references.bib

@article{menzies_signal_2006,
	title = {Signal transduction and nuclear responses in {Staphylococcus} aureus-induced expression of human beta-defensin 3 in skin keratinocytes},
	volume = {74},
	issn = {0019-9567},
	doi = {10.1128/IAI.00389-06},
	abstract = {The human beta-defensin 3 (hBD-3) is an inducible epithelial peptide antibiotic that has potent antistaphylococcal activity. Infection of skin epithelial cells with viable Staphylococcus aureus, a common skin pathogen, induces increased gene expression of hBD-3 and other antimicrobial peptides. The aim of this study was to identify signaling pathways and nuclear responses that contribute to the gene expression of hBD-3 in primary human keratinocytes upon contact with S. aureus. Increased hBD-3 peptide was observed by immunofluorescence microscopy in keratinocytes exposed to S. aureus and to lipoteichoic acid (LTA). Both are ligands for the cell surface Toll-like receptor 2 (TLR2), and thus the contribution of TLR2 signaling in hBD-3 expression was examined. Functional inhibition of TLR2 prior to S. aureus stimulation significantly decreased hBD-3 mRNA levels by 37\%, attesting to the involvement of this surface receptor in the initial recognition and downstream signaling for hBD-3 expression. Treatment of keratinocytes with a p38 mitogen-activated protein kinase (MAPK) inhibitor prior to either S. aureus or LTA stimulation was associated with reduced hBD-3 mRNA transcripts and peptide. We also propose a role for the MAPK-regulated transcriptional activating protein 1 in S. aureus-induced hBD-3 gene expression. Combined, these studies indicate a role for TLR2 signaling and MAPK activation in the upregulation of hBD-3 and demonstrate the innate immune capacity of skin keratinocytes under conditions of S. aureus challenge to enhance the local expression of this antistaphylococcal peptide antibiotic.},
	language = {eng},
	number = {12},
	journal = {Infection and immunity},
	author = {Menzies, Barbara E and Kenoyer, Aimee},
	month = dec,
	year = {2006},
	pmid = {16954397},
	keywords = {beta-Defensins, Cells, Cultured, gene expression, Humans, Keratinocytes, Lipopolysaccharides, p38 Mitogen-Activated Protein Kinases, RNA, Messenger, signal transduction, Skin, Staphylococcus aureus, Teichoic Acids, Toll-like receptor 2, Transcription Factor AP-1, Transcription, Genetic},
	pages = {6847--6854}
}

@article{chen_secreted_2013,
	title = {Secreted {Proteases} {Control} {Autolysin}-mediated {Biofilm} {Growth} of {Staphylococcus} aureus},
	volume = {288},
	issn = {1083-351X},
	doi = {10.1074/jbc.M113.502039},
	abstract = {Staphylococcus epidermidis, a commensal of humans, secretes Esp protease to prevent Staphylococcus aureus biofilm formation and colonization. Blocking S. aureus colonization may reduce the incidence of invasive infectious diseases; however, the mechanism whereby Esp disrupts biofilms is unknown. We show here that Esp cleaves autolysin (Atl)-derived murein hydrolases and prevents staphylococcal release of DNA, which serves as extracellular matrix in biofilms. The three-dimensional structure of Esp was revealed by x-ray crystallography and shown to be highly similar to that of S. aureus V8 (SspA). Both atl and sspA are necessary for biofilm formation, and purified SspA cleaves Atl-derived murein hydrolases. Thus, S. aureus biofilms are formed via the controlled secretion and proteolysis of autolysin, and this developmental program appears to be perturbed by the Esp protease of S. epidermidis.},
	language = {eng},
	number = {41},
	journal = {The Journal of biological chemistry},
	author = {Chen, Chen and Krishnan, Vengadesan and Macon, Kevin and Manne, Kartik and Narayana, Sthanam V L and Schneewind, Olaf},
	month = oct,
	year = {2013},
	pmid = {23970550},
	pages = {29440--29452}
}

@article{holland_differential_2009,
	title = {Differential innate immune responses of a living skin equivalent model colonized by {Staphylococcus} epidermidis or {Staphylococcus} aureus},
	volume = {290},
	issn = {1574-6968},
	shorttitle = {Differential innate immune responses of a living skin equivalent model colonized by {Staphylococcus} epidermidis or {Staphylococcus} aureus},
	doi = {10.1111/j.1574-6968.2008.01402.x},
	journal = {FEMS microbiology letters},
	author = {Holland, D.B. and Bojar, R.A. and Farrar, M.D. and Holland, K.T.},
	year = {2009},
	note = {2},
	pages = {149--155},
	file = {Holland et al_2009_Differential innate immune responses of a living skin equivalent model.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/HC7MUHG9/Holland et al_2009_Differential innate immune responses of a living skin equivalent model.pdf:application/pdf;j.1574-6968.2008.01402.x.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/M7RQW377/j.1574-6968.2008.01402.x.pdf:application/pdf}
}

@article{von_eiff_nasal_2001,
	title = {Nasal {Carriage} as a {Source} of {Staphylococcus} aureus {Bacteremia}},
	volume = {344},
	issn = {0028-4793},
	url = {http://www.nejm.org/doi/full/10.1056/NEJM200101043440102},
	doi = {10.1056/NEJM200101043440102},
	abstract = {Staphylococcus aureus is one of the most common causes of both endemic and epidemic infections acquired in hospitals, which result in substantial morbidity and mortality. In U.S. hospitals in the National Nosocomial Infections Surveillance system, S. aureus accounted for up to 13 percent of isolates recovered from patients with nosocomial infections from 1979 through 1995, and the percentage has increased in recent years.1,2 Community-acquired infections with S. aureus are also common.2,3 Multidrug-resistant strains of staphylococci have been reported with increasing frequen-cy worldwide, including isolates that are resistant to methicillin, lincosamides, macrolides, aminoglycosides, fluoroquinolones, or combinations of these . . .},
	number = {1},
	urldate = {2013-07-29},
	journal = {New England Journal of Medicine},
	author = {von Eiff, Christof and Becker, Karsten and Machka, Konstanze and Stammer, Holger and Peters, Georg},
	year = {2001},
	pmid = {11136954},
	pages = {11--16},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/VDWRPWTP/von Eiff et al. - 2001 - Nasal Carriage as a Source of Staphylococcus aureu.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/TSMR6WAW/NEJM200101043440102.html:text/html}
}

@article{knobloch_evaluation_2002,
	title = {Evaluation of different detection methods of biofilm formation in {Staphylococcus} aureus},
	volume = {191},
	issn = {0300-8584, 1432-1831},
	url = {http://link.springer.com.proxy.uchicago.edu/article/10.1007/s00430-002-0124-3},
	doi = {10.1007/s00430-002-0124-3},
	abstract = {The icaADBC gene locus of Staphylococcus aureus and its polysaccharide intercellular adhesin (PIA/PNSG) were recently identified, but biofilm formation has rarely been detected in vitro. In this study we evaluated a tissue culture plate (TCP) assay and a tube test, as well as Congo red agar, using the two basic media trypticase soy broth (TSB) and brain heart infusion (BHI) broth with different sugar supplements for detection of biofilm formation in 128 ica-positive S. aureus isolates. Of the S. aureus strains, 57.1\% displayed a biofilm-positive phenotype under optimized conditions in the TCP test. The tube test correlated well with the TCP test for strongly biofilm-producing strains, whereas weak producers were not safely discriminated from biofilm-negative strains. Screening on Congo red agar displayed a strong correlation with the TCP and the tube test for only 3.8\%, and is therefore not recommended for investigation of biofilm formation in S. aureus.},
	language = {en},
	number = {2},
	urldate = {2013-11-12},
	journal = {Medical Microbiology and Immunology},
	author = {Knobloch, Johannes K.-M. and Horstkotte, Matthias A. and Rohde, Holger and Mack, Dietrich},
	month = oct,
	year = {2002},
	keywords = {Staphylococcus aureus Biofilm Congo red},
	pages = {101--106},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/XWC746B7/Knobloch et al. - 2002 - Evaluation of different detection methods of biofi.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/5ISBDNDR/10.html:text/html}
}

@article{stark_organotypic_1999,
	title = {Organotypic {Keratinocyte} {Cocultures} in {Defined} {Medium} with {Regular} {Epidermal} {Morphogenesis} and {Differentiation}},
	volume = {112},
	copyright = {© 1999 Nature Publishing Group},
	issn = {0022-202X},
	url = {http://www.nature.com/jid/journal/v112/n5/full/5600451a.html},
	doi = {10.1046/j.1523-1747.1999.00573.x},
	abstract = {Skin equivalents formed by keratinocytes cocultured with fibroblasts embedded in collagen lattices represent promising tools for mechanistic studies of skin physiology, for pharmacotoxicologic testing, and for the use as skin substitutes in wound treatment. Such cultures would be superior in defined media to avoid interference with components of serum or tissue extracts. Here we demonstrate that a defined medium (supplemented keratinocyte defined medium) supports epidermal morphogenesis in organotypic cocultures equally well as serum-containing medium (mixture of Ham's F12 and Dulbecco's modified Eagle's medium), as documented by hallmarks of the epidermal phenotype studied by immunofluorescence and electron microscopy. In both cases regularly structured, orthokeratinized epithelia evolved with similar kinetics. Morphology in mixture of Ham's F12 and Dulbecco's modified Eagle's medium was slightly hyperplastic, and keratins 1 and 10 synthesis less co-ordinated than in supplemented keratinocyte defined medium, but a consistently inverted sequence of expression of keratins 1 and 10 was found in either medium. The late differentiation markers filaggrin, involucrin, keratin 2e, and transglutaminase 1 corresponded in their typical distribution in upper suprabasal layers. Keratin 16 persisted under both conditions indicating the activated epidermal state. Keratinocyte proliferation was comparable in both media, whereas fibroblast multiplication and proliferation was delayed and reduced in supplemented keratinocyte defined medium. In both media, ultrastructural features of epidermal differentiation as well as reconstitution of a basement membrane occurred similarly. Immature lamellar bodies and cytoplasmatic vacuoles, however, indicated an impaired lipid metabolism in supplemented keratinocyte defined medium. Nevertheless, these defined organotypic cocultures provide a suitable basis for in vitro skin models to study molecular mechanisms of tissue homeostasis and for use in pharmacotoxicologic testing.},
	language = {en},
	number = {5},
	urldate = {2013-07-30},
	journal = {Journal of Investigative Dermatology},
	author = {Stark, Hans-Jürgen and Baur, Markus and Breitkreutz, Dirk and Mirancea, Nicolae and Fusenig, Norbert E.},
	month = may,
	year = {1999},
	keywords = {epithelial proliferation, fibroblast dynamics, serum-free cultivation, skin equivalents},
	pages = {681--691},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/3D2JASQJ/Stark et al. - 1999 - Organotypic Keratinocyte Cocultures in Defined Med.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/2RAWAPNZ/5600451a.html:text/html}
}

@article{liu_human_2002,
	title = {Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation},
	volume = {118},
	issn = {0022-202X},
	doi = {10.1046/j.0022-202x.2001.01651.x},
	abstract = {Intact human epidermis resists invasion by pathogenic microbes but the biochemical basis of its resistance is not well understood. Recently, an antimicrobial peptide, human beta-defensin-2, was discovered in inflamed epidermis. We used a recombinant baculovirus/insect cell system to produce human beta-defensin-2 and confirmed that at micromolar concentrations it has a broad spectrum of antimicrobial activity, with the striking exception of Staphylococcus aureus. Immunostaining with a polyclonal antibody to human beta-defensin-2 showed that the expression of human beta-defensin-2 peptide by human keratinocytes required differentiation of the cells (either by increased calcium concentration or by growth and maturation in epidermal organotypic culture) as well as a cytokine or bacterial stimulus. Interleukin-1alpha, interleukin-1beta, or live Pseudomonas aeruginosa proved to be the most effective stimuli whereas other bacteria and cytokines had little or no ability to induce human beta-defensin-2 synthesis. In interleukin-1alpha-stimulated epidermal cultures, human beta-defensin-2 first appeared in the cytoplasm in differentiated suprabasal layers of skin, next in a more peripheral web-like distribution in the upper layers of the epidermis, and then over a few days migrated to the stratum corneum. By semiquantitative Western blot analysis of epidermal lysates, the average concentration of human beta-defensin-2 in stimulated organotypic epidermal culture reached 15--70 microg per gram of tissue, i.e., 3.5-16 microM, well within the range required for antimicrobial activity. Because of the restricted pattern of human beta-defensin-2 distribution in the epidermis, its local concentration must be much higher. Defensins and other antimicrobial peptides of inflamed epidermis are likely to play an important antimicrobial role in host defense against cutaneous pathogens.},
	language = {eng},
	number = {2},
	journal = {The Journal of investigative dermatology},
	author = {Liu, Alice Y and Destoumieux, Delphine and Wong, Annie V and Park, Christina H and Valore, Erika V and Liu, Lide and Ganz, Tomas},
	month = feb,
	year = {2002},
	pmid = {11841544},
	keywords = {Anti-Bacterial Agents, Bacterial Physiological Phenomena, beta-Defensins, Cell Differentiation, Cells, Cultured, Humans, interleukin-1, Keratinocytes, Organ Culture Techniques, recombinant proteins, Tissue Distribution},
	pages = {275--281}
}

@article{mermel_methicillin-resistant_2011,
	title = {Methicillin-{Resistant} {Staphylococcus} aureus {Colonization} at {Different} {Body} {Sites}: a {Prospective}, {Quantitative} {Analysis}},
	volume = {49},
	issn = {0095-1137, 1098-660X},
	shorttitle = {Methicillin-{Resistant} {Staphylococcus} aureus {Colonization} at {Different} {Body} {Sites}},
	url = {http://jcm.asm.org/content/49/3/1119},
	doi = {10.1128/JCM.02601-10},
	abstract = {We quantified methicillin-resistant Staphylococcus aureus (MRSA) carriage. The greater the log10 count in samples from the nares, the greater the likelihood that other body sites had been colonized. Log10 counts among body sites were correlated. The greatest sensitivity value (98\%) was determined for the combined results from 2 sites: the nares and the groin.},
	language = {en},
	number = {3},
	urldate = {2013-07-30},
	journal = {Journal of Clinical Microbiology},
	author = {Mermel, Leonard A. and Cartony, Jennifer M. and Covington, Pauline and Maxey, Gail and Morse, Dan},
	month = mar,
	year = {2011},
	pmid = {21209169},
	pages = {1119--1121},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/PPZJVJMW/Mermel et al. - 2011 - Methicillin-Resistant Staphylococcus aureus Coloni.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/DT3UMCQ4/1119.html:text/html}
}

@article{burian_regulatory_2010,
	title = {Regulatory {Adaptation} of {Staphylococcus} aureus during {Nasal} {Colonization} of {Humans}},
	volume = {5},
	url = {http://dx.doi.org/10.1371/journal.pone.0010040},
	doi = {10.1371/journal.pone.0010040},
	abstract = {The nasopharynx is the main ecological niche of the human pathogen Staphylococcus aureus. Although colonization of the nares is asymptomatic, nasal carriage is a known risk factor for endogenous staphylococcal infection. We quantified S. aureus mRNA levels in nose swabs of persistent carriers to gain insight into the regulatory adaptation of the bacterium to the nasal environment. We could elucidate a general response of the pathogen to the surrounding milieu independent of the strain background or the human host. Colonizing bacteria preferentially express molecules necessary for tissue adherence or immune-evasion whereas toxins are down regulated. From the analysis of regulatory loci we found evidence for a predominate role of the essential two-component system WalKR of S. aureus. The results suggest that during persistent colonization the bacteria are metabolically active with a high cell surface turnover. The increased understanding of bacterial factors that maintain the colonization state can open new therapeutic options to control nasal carriage and subsequent infections.},
	number = {4},
	urldate = {2013-07-27},
	journal = {PLoS ONE},
	author = {Burian, Marc and Wolz, Christiane and Goerke, Christiane},
	month = apr,
	year = {2010},
	pages = {e10040},
	file = {PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/7R7TUGFD/Burian et al. - 2010 - Regulatory Adaptation of Staphylococcus aureus dur.pdf:application/pdf;PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/I7XDDTAP/Burian et al. - 2010 - Regulatory Adaptation of Staphylococcus aureus dur.pdf:application/pdf;PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/X2FQP8TX/Burian et al. - 2010 - Regulatory Adaptation of Staphylococcus aureus dur.pdf:application/pdf;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/98MZMC6M/infodoi10.1371journal.pone.html:text/html;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CM3CSS6R/infodoi10.1371journal.pone.html:text/html;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/K8P92HNZ/infodoi10.1371journal.pone.html:text/html}
}

@article{haugwitz_pore-forming_2006,
	title = {Pore-forming {Staphylococcus} aureus alpha-toxin triggers epidermal growth factor receptor-dependent proliferation},
	volume = {8},
	issn = {1462-5814 (Print) 1462-5814 (Linking)},
	shorttitle = {Pore-forming {Staphylococcus} aureus alpha-toxin triggers epidermal growth factor receptor-dependent proliferation},
	doi = {10.1111/j.1462-5822.2006.00733.x},
	abstract = {Staphylococcal alpha-toxin is an archetypal killer protein that homo-oligomerizes in target cells to create small transmembrane pores. The membrane-perforating beta-barrel motif is a conserved attack element of cytolysins of Gram-positive and Gram-negative bacteria. Following the recognition that nucleated cells can survive membrane permeabilization, a profile of abundant transcripts was obtained in transiently perforated keratinocytes. Several immediate early genes were found to be upregulated, reminiscent of the cellular response to growth factors. Cell cycle analyses revealed doubling of S + G2/M phase cells 26 h post toxin treatment. Determination of cell counts uncovered that after an initial drop, numbers increased to exceed the controls after 2 days. A non-lytic alpha-toxin mutant remained without effect. The alpha-toxin pore is too small to allow egress of cytosolic growth factors, and evidence was instead obtained for growth signalling via the epidermal growth factor receptor (EGFR). Inhibition of the EGFR or of EGFR-proligand-processing blocked the mitogenic effect of alpha-toxin. Western blots with phospho-specific antibodies revealed activation of the EGFR, and of the adapter protein Shc. Immediate early response and proliferation upon transient plasma membrane pore formation by bacterial toxins may represent a novel facet of the complex interaction between pathogen and host.},
	language = {eng},
	journal = {Cell Microbiol},
	author = {Haugwitz, U. and Bobkiewicz, W. and Han, S. R. and Beckmann, E. and Veerachato, G. and Shaid, S. and Biehl, S. and Dersch, K. and Bhakdi, S. and Husmann, M.},
	month = oct,
	year = {2006},
	note = {10},
	keywords = {Adaptor proteins, Adaptor Proteins, Signal Transducing/metabolism, Bacterial toxins, Blotting, Western, Cell Cycle, Cell line, Cell Line, Transformed, Cell Proliferation, Cytotoxins/metabolism, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Profiling, Hemolysin Proteins, Humans, Keratinocytes/cytology/ metabolism/microbiology, Mitogens/pharmacology, Receptor, Epidermal Growth Factor/ metabolism, Reverse Transcriptase Polymerase Chain Reaction, Shc Signaling Adaptor Proteins, Signal Transduction, Staphylococcus aureus/ physiology, Transfection},
	pages = {1591--600},
	file = {pore forming triggers spidermal growth factor.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/EUUE4UV5/pore forming triggers spidermal growth factor.pdf:application/pdf}
}

@article{holland_microbial_2008,
	title = {Microbial colonization of an in vitro model of a tissue engineered human skin equivalent a novel approach},
	volume = {279},
	issn = {1574-6968},
	shorttitle = {Microbial colonization of an in vitro model of a tissue engineered human skin equivalent–a novel approach},
	doi = {10.1111/j.1574-6968.2007.01021.x},
	journal = {FEMS microbiology letters},
	author = {Holland, D.B. and Bojar, R.A. and Jeremy, A.H.T. and Ingham, E. and Holland, K.T.},
	year = {2008},
	note = {1},
	pages = {110--115},
	file = {j.1574-6968.2007.01021.x.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/47MFFMTQ/j.1574-6968.2007.01021.x.pdf:application/pdf}
}

@article{bae_staphylococcus_2004,
	title = {Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing},
	volume = {101},
	issn = {0027-8424},
	shorttitle = {Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing},
	doi = {10.1073/pnas.0404728101},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	author = {Bae, T. and Banger, A.K. and Wallace, A. and Glass, E.M. and Åslund, F. and Schneewind, O. and Missiakas, D.M.},
	year = {2004},
	note = {33},
	pages = {12312--12317},
	file = {PNAS-2004-Bae-12312-7.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/RIUSJR6G/PNAS-2004-Bae-12312-7.pdf:application/pdf}
}

@article{mazmanian_staphylococcus_1999,
	title = {Staphylococcus aureus {Sortase}, an {Enzyme} that {Anchors} {Surface} {Proteins} to the {Cell} {Wall}},
	volume = {285},
	issn = {0036-8075, 1095-9203},
	url = {http://www.sciencemag.org/content/285/5428/760},
	doi = {10.1126/science.285.5428.760},
	abstract = {Surface proteins of Gram-positive bacteria are linked to the bacterial cell wall by a mechanism that involves cleavage of a conserved Leu-Pro-X-Thr-Gly (LPXTG) motif and that occurs during assembly of the peptidoglycan cell wall. A Staphylococcus aureus mutant defective in the anchoring of surface proteins was isolated and shown to carry a mutation in the srtA gene. Overexpression of srtA increased the rate of surface protein anchoring, and homologs of srtA were found in other pathogenic Gram-positive bacteria. The protein specified bysrtA, sortase, may be a useful target for the development of new antimicrobial drugs.},
	language = {en},
	number = {5428},
	urldate = {2013-08-01},
	journal = {Science},
	author = {Mazmanian, Sarkis K. and Liu, Gwen and Ton-That, Hung and Schneewind, Olaf},
	month = jul,
	year = {1999},
	pmid = {10427003},
	pages = {760--763},
	file = {Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/6R66J6D2/760.html:text/html}
}

@article{elias_epidermal_1983,
	title = {Epidermal {Lipids}, {Barrier} {Function}, and {Desquamation}},
	volume = {80},
	copyright = {© 1983 Nature Publishing Group},
	url = {http://www.nature.com.proxy.uchicago.edu/jid/journal/v80/n1s/abs/jid198312a.html},
	doi = {10.1038/jid.1983.12},
	abstract = {Based on recent morphologic, histochemical, and biochemical data, we propose a heterogeneous two-compartment model of the stratum corneum that ascribes a special role for intercellular lipids in the regulation of stratum corneum barrier function and desquamation. The evidence in favor of the model and several predictions based on the model are surveyed in this review.},
	urldate = {2013-07-31},
	journal = {Journal of Investigative Dermatology},
	author = {Elias, Peter M.},
	month = jun,
	year = {1983},
	keywords = {cutaneous biology, dendritic cells, dermatitis, epidermis, keratinocyte, melanocyte, psoriasis, skin cancer, skin disease},
	pages = {44s--49s},
	file = {Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/8Q4H9E42/jid198312a.html:text/html}
}

@article{monk_transforming_2012,
	title = {Transforming the {Untransformable}: {Application} of {Direct} {Transformation} {To} {Manipulate} {Genetically} {Staphylococcus} aureus and {Staphylococcus} epidermidis},
	volume = {3},
	issn = {, 2150-7511},
	shorttitle = {Transforming the {Untransformable}},
	url = {http://mbio.asm.org/content/3/2/e00277-11},
	doi = {10.1128/mBio.00277-11},
	abstract = {The strong restriction barrier present in Staphylococcus aureus and Staphylococcus epidermidis has limited functional genomic analysis to a small subset of strains that are amenable to genetic manipulation. Recently, a conserved type IV restriction system termed SauUSI (which specifically recognizes cytosine methylated DNA) was identified as the major barrier to transformation with foreign DNA. Here we have independently corroborated these findings in a widely used laboratory strain of S. aureus. Additionally, we have constructed a DNA cytosine methyltransferase mutant in the high-efficiency Escherichia coli cloning strain DH10B (called DC10B). Plasmids isolated from DC10B can be directly transformed into clinical isolates of S. aureus and S. epidermidis. We also show that the loss of restriction (both type I and IV) in an S. aureus USA300 strain does not have an impact on virulence. Circumventing the SauUSI restriction barrier, combined with an improved deletion and transformation protocol, has allowed the genetic manipulation of previously untransformable strains of these important opportunistic pathogens.
IMPORTANCE Staphylococcal infections place a huge burden on the health care sector due both to their severity and also to the economic impact of treating the infections because of prolonged hospitalization. To improve the understanding of Staphylococcus aureus and Staphylococcus epidermidis infections, we have developed a series of improved techniques that allow the genetic manipulation of strains that were previously refractory to transformation. These developments will speed up the process of mutant construction and increase our understanding of these species as a whole, rather than just a small subset of strains that could previously be manipulated.},
	language = {en},
	number = {2},
	urldate = {2013-11-29},
	journal = {mBio},
	author = {Monk, Ian R. and Shah, Ishita M. and Xu, Min and Tan, Man-Wah and Foster, Timothy J.},
	month = may,
	year = {2012},
	pmid = {22434850},
	pages = {e00277--11},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CJ7AF568/Monk et al. - 2012 - Transforming the Untransformable Application of D.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/948C3I2K/e00277-11.html:text/html}
}

@article{walsh_clumping_2004,
	title = {Clumping factor {B}, a fibrinogen-binding {MSCRAMM} (microbial surface components recognizing adhesive matrix molecules) adhesin of {Staphylococcus} aureus, also binds to the tail region of type {I} cytokeratin 10},
	volume = {279},
	issn = {0021-9258},
	shorttitle = {Clumping factor {B}, a fibrinogen-binding {MSCRAMM} (microbial surface components recognizing adhesive matrix molecules) adhesin of {Staphylococcus} aureus, also binds to the tail region of type {I} cytokeratin 10},
	journal = {Journal of Biological Chemistry},
	author = {Walsh, E.J. and O'brien, L.M. and Liang, X. and Hook, M. and Foster, T.J.},
	year = {2004},
	note = {49},
	pages = {50691--50699},
	file = {J. Biol. Chem.-2004-Walsh-50691-9.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/P8UE4MDI/J. Biol. Chem.-2004-Walsh-50691-9.pdf:application/pdf}
}

@article{bhattacharyya_colonization_1998,
	title = {Colonization of living skin equivalents by {Malassezia} furfur},
	volume = {36},
	issn = {1369-3786},
	abstract = {Initial colonization events and yeast-hyphal transformation by Malassezia furfur were observed using living skin equivalent (LSE) models for growth. Yeast cells were inoculated onto the LSEs which were incubated in CO2-independent media at 37 degreesC for variable lengths of time. Assessment of fungal growth and invasion was by light- and scanning electron microscopy (SEM). Viability counts of M. furfur were determined by a method of washing and serial dilution. Yeast cells had retained their viability and increased in number approximately twofold over a 4-day period of incubation. Yeast-to-hyphal transition was not achieved in this model. Random destruction of the uppermost layers of the stratum corneum was observed in the presence of M. furfur. LSEs therefore appear to be a promising model for mechanisms of growth of cutaneous organisms.},
	language = {eng},
	number = {1},
	journal = {Medical mycology: official publication of the International Society for Human and Animal Mycology},
	author = {Bhattacharyya, T and Edward, M and Cordery, C and Richardson, M D},
	month = feb,
	year = {1998},
	pmid = {9776807},
	keywords = {Animals, Cells, Cultured, Collagen, Humans, Infant, Newborn, Keratinocytes, Kinetics, Malassezia, Male, Microscopy, Electron, Scanning, Rats, Skin, Time Factors},
	pages = {15--19},
	file = {Bhattacharyya et al_1998_Colonization of living skin equivalents by Malassezia furfur.doc:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/VJ79WMVG/Bhattacharyya et al_1998_Colonization of living skin equivalents by Malassezia furfur.doc:application/msword;Bhattacharyya et al_1998_Colonization of living skin equivalents by Malassezia furfur.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/MXAHADNT/Bhattacharyya et al_1998_Colonization of living skin equivalents by Malassezia furfur.pdf:application/pdf}
}

@article{popov_three-dimensional_2014,
	title = {Three-dimensional human skin models to understand {Staphylococcus} aureus skin colonization and infection},
	volume = {5},
	url = {http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00041/full},
	doi = {10.3389/fimmu.2014.00041},
	abstract = {Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue.},
	urldate = {2014-09-11},
	journal = {Microbial Immunology},
	author = {Popov, Lauren and Kovalski, Joanna and Grandi, Guido and Bagnoli, Fabio and Amieva, Manuel R.},
	year = {2014},
	keywords = {Colonization, MRSA, organ culture, Skin, Staphylococcus aureus},
	pages = {41},
	file = {Popov et al_2014_Three-dimensional human skin models to understand Staphylococcus aureus skin.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/3Z9CVMH9/Popov et al_2014_Three-dimensional human skin models to understand Staphylococcus aureus skin.pdf:application/pdf}
}

@article{harvey_formulation_2010,
	title = {Formulation and stability of a novel artificial human sweat under conditions of storage and use},
	volume = {24},
	issn = {0887-2333},
	url = {http://www.sciencedirect.com/science/article/pii/S088723331000158X},
	doi = {10.1016/j.tiv.2010.06.016},
	abstract = {A limitation of most artificial sweat formulations used for in vitro assessment of chemical release from materials in contact with skin have little biological relevance to human sweat. The purposes of this paper are to provide guidance for preparation of a novel artificial sweat with chemical constituents at concentrations that match human sweat and to characterize chemical stability. The artificial sweat was characterized under conditions of use (with and without sebum at 36 °C) and storage (without sebum at −4, 4, and 23 °C) over 28 days by gas chromatography–mass spectroscopy, high-performance liquid chromatography, enzymatic assay kits, and ion-selective electrodes. Seven indicator constituents were tracked: sodium, chloride, glucose, lactic acid, urea, pantothenic acid, and alanine. With or without sebum at 36 °C, the sweat solvent was chemically stable for 14 days. Storage by refrigeration at 4 °C retained the chemical integrity of the solvent longest. Based on these results, the solvent should be used within 14 days of preparation. The artificial sweat model presented herein is most similar to human sweat and has applications as a dissolution solvent, donor solution in diffusion cells, or vehicle for patch testing. This sweat model may aid researchers in understanding potential release and percutaneous absorption of chemicals in contact with human skin surface liquids.},
	number = {6},
	urldate = {2013-07-30},
	journal = {Toxicology in Vitro},
	author = {Harvey, Christopher J. and LeBouf, Ryan F. and Stefaniak, Aleksandr B.},
	month = sep,
	year = {2010},
	keywords = {Artificial sweat, Human sweat, Skin, Skin surface film liquids},
	pages = {1790--1796},
	file = {ScienceDirect Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/4UBWINGR/Harvey et al. - 2010 - Formulation and stability of a novel artificial hu.pdf:application/pdf;ScienceDirect Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/8F4R782B/S088723331000158X.html:text/html}
}

@article{simpson_rna_2010,
	title = {{RNA} interference in keratinocytes and an organotypic model of human epidermis},
	volume = {585},
	shorttitle = {{RNA} interference in keratinocytes and an organotypic model of human epidermis},
	journal = {Methods Mol. Biol},
	author = {Simpson, C.L. and Kojima, S. and Getsios, S.},
	year = {2010},
	pages = {127--146},
	file = {Simpson et al_2010_RNA interference in keratinocytes and an organotypic model of human epidermis.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/M99CWUHS/Simpson et al_2010_RNA interference in keratinocytes and an organotypic model of human epidermis.pdf:application/pdf}
}

@article{mempel_invasion_2002,
	title = {Invasion of human keratinocytes by {Staphylococcus} aureus and intracellular bacterial persistence represent haemolysin independent virulence mechanisms that are followed by features of necrotic and apoptotic keratinocyte cell death},
	volume = {146},
	issn = {1365-2133},
	journal = {British Journal of Dermatology},
	author = {Mempel, M. and Schnopp, C. and Hojka, M. and Fesq, H. and Weidinger, S. and Schaller, M. and Korting, HC and Ring, J. and Abeck, D.},
	year = {2002},
	note = {6},
	pages = {943--951},
	file = {invasion of human keratinocytes.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/HE2STRGW/invasion of human keratinocytes.pdf:application/pdf}
}

@article{secor_staphylococcus_2011,
	title = {Staphylococcus aureus {Biofilm} and {Planktonic} cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes},
	volume = {11},
	issn = {1471-2180},
	shorttitle = {Staphylococcus aureus {Biofilm} and {Planktonic} cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes},
	journal = {BMC microbiology},
	author = {Secor, P.R. and James, G.A. and Fleckman, P. and Olerud, J.E. and McInnerney, K. and Stewart, P.S.},
	year = {2011},
	note = {1},
	pages = {143},
	file = {1471-2180-11-143.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/TCI6JFPR/1471-2180-11-143.pdf:application/pdf}
}

@article{soong_staphylococcus_2012,
	title = {Staphylococcus aureus {Activation} of {Caspase} 1/{Calpain} {Signaling} {Mediates} {Invasion} {Through} {Human} {Keratinocytes}},
	volume = {205},
	issn = {0022-1899},
	shorttitle = {Staphylococcus aureus {Activation} of {Caspase} 1/{Calpain} {Signaling} {Mediates} {Invasion} {Through} {Human} {Keratinocytes}},
	journal = {Journal of Infectious Diseases},
	author = {Soong, G. and Chun, J. and Parker, D. and Prince, A.},
	year = {2012},
	note = {10},
	pages = {1571--1579},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/W99G23T3/Soong et al. - 2012 - Staphylococcus aureus Activation of Caspase 1Calp.pdf:application/pdf;J Infect Dis.-2012-Soong-1571-9.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/DRQWAS8B/J Infect Dis.-2012-Soong-1571-9.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/M22DRF8C/1571.html:text/html}
}

@article{toshkova_significance_2001,
	title = {The significance of nasal carriage of {Staphylococcus} aureus as risk factor for human skin infections},
	volume = {202},
	issn = {1574-6968},
	url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.2001.tb10774.x/abstract},
	doi = {10.1111/j.1574-6968.2001.tb10774.x},
	abstract = {The present study was designed to investigate the significance and the relationship between nasal carriage of Staphylococcus aureus and staphylococcal skin infections. Thirty-one S. aureus strains, isolated from 12 patients with chronic and recurrent skin infections, one patient with septicemia and one patient with otitis externa were studied. The staphylococcal strains were isolated from the site of infection and from the anterior nares of each patient. The identity of both strains of each pair could be demonstrated by determination of phenotypic properties and by genotyping of the isolates. The phenotypic properties included hemolytic activities, antibiotic resistance data, and the production of enterotoxins. The identity was additionally confirmed by phage-typing, by determination of the size and the number of repeats of the X region of spa gene, by determination of gene polymorphisms of coa gene and by macrorestriction analysis of the chromosomal DNA of the isolates by pulsed-field gel electrophoresis. The present results showed an identity of the S. aureus obtained from anterior nares and from skin infection of each patient indicating the importance of nasal carriage of these bacteria for development of human skin infection.},
	language = {en},
	number = {1},
	urldate = {2013-10-23},
	journal = {FEMS Microbiology Letters},
	author = {Toshkova, K and Annemuller, C and Akineden, O and Lammler, Ch},
	year = {2001},
	keywords = {Genotyping, Phenotyping, skin infection, Staphylococcus aureus},
	pages = {17--24},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/RNSPHFHX/Toshkova et al. - 2001 - The significance of nasal carriage of Staphylococc.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/BBNNTRI3/full.html:text/html}
}

@article{obrien_staphylococcus_2002,
	title = {Staphylococcus aureus clumping factor {B} ({ClfB}) promotes adherence to human type {I} cytokeratin 10: implications for nasal colonization},
	volume = {4},
	issn = {1462-5822},
	shorttitle = {Staphylococcus aureus clumping factor {B} ({ClfB}) promotes adherence to human type {I} cytokeratin 10: implications for nasal colonization},
	journal = {Cellular microbiology},
	author = {O'Brien, L.M. and Walsh, E.J. and Massey, R.C. and Peacock, S.J. and Foster, T.J.},
	year = {2002},
	note = {11},
	pages = {759--770},
	file = {j.1462-5822.2002.00231.x.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/BCZ7H5FH/j.1462-5822.2002.00231.x.pdf:application/pdf}
}

@article{breij_three-dimensional_2012,
	title = {Three-{Dimensional} {Human} {Skin} {Equivalent} as a {Tool} {To} {Study} {Acinetobacter} baumannii {Colonization}},
	volume = {56},
	issn = {0066-4804, 1098-6596},
	url = {http://aac.asm.org/content/56/5/2459},
	doi = {10.1128/AAC.05975-11},
	abstract = {Acinetobacter baumannii can colonize body surfaces of hospitalized patients. From these sites, invasion into the host and spread to other patients and the hospital environment may occur. The eradication of the organism from the patient's skin is an important infection control strategy during epidemic and endemic episodes. In this study, a three-dimensional (3D), air-exposed human epidermal skin equivalent was exploited to study Acinetobacter skin colonization. We characterized the adherence of A. baumannii ATCC 19606T and Acinetobacter junii RUH2228T to and biofilm formation on the skin equivalent and the responses to these bacteria. Furthermore, we assessed the ability of the disinfectant chlorhexidine to decolonize the skin equivalents. The results revealed that both strains replicated on the stratum corneum for up to 72 h but did not invade the epidermis. A. baumannii, in contrast to A. junii, formed large biofilms on the stratum corneum. Bacterial colonization did not affect keratinocyte activation, proliferation, or differentiation, nor did it induce a strong inflammatory response. Disinfection with chlorhexidine solution resulted in complete eradication of A. baumannii from the skin, without detrimental effects. This 3D model is a promising tool to study skin colonization and to evaluate the effects of novel disinfectant and antimicrobial strategies.},
	language = {en},
	number = {5},
	urldate = {2013-08-23},
	journal = {Antimicrobial Agents and Chemotherapy},
	author = {Breij, Anna de and Haisma, Elisabeth M. and Rietveld, Marion and Ghalbzouri, Abdelouahab El and Broek, Peterhans J. van den and Dijkshoorn, Lenie and Nibbering, Peter H.},
	month = may,
	year = {2012},
	pmid = {22290957},
	pages = {2459--2464},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/TGVSQKD9/Breij et al. - 2012 - Three-Dimensional Human Skin Equivalent as a Tool .pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/TD8P4946/2459.html:text/html}
}

@article{deleo_molecular_2011,
	title = {Molecular differentiation of historic phage-type 80/81 and contemporary epidemic {Staphylococcus} aureus},
	volume = {108},
	issn = {1091-6490 (Electronic) 0027-8424 (Linking)},
	shorttitle = {Molecular differentiation of historic phage-type 80/81 and contemporary epidemic {Staphylococcus} aureus},
	doi = {10.1073/pnas.1111084108},
	abstract = {Staphylococcus aureus is a bacterial pathogen known to cause infections in epidemic waves. One such epidemic was caused by a clone known as phage-type 80/81, a penicillin-resistant strain that rose to world prominence in the late 1950s. The molecular underpinnings of the phage-type 80/81 outbreak have remained unknown for decades, nor is it understood why related S. aureus clones became epidemic in hospitals in the early 1990s. To better understand the molecular basis of these epidemics, we sequenced the genomes of eight S. aureus clinical isolates representative of the phage-type 80/81 clone, the Southwest Pacific clone [a community-associated methicillin-resistant S. aureus (MRSA) clone], and contemporary S. aureus clones, all of which are genetically related and belong to the same clonal complex (CC30). Genome sequence analysis revealed that there was coincident divergence of these clones from a recent common ancestor, a finding that resolves controversy about the evolutionary history of the lineage. Notably, we identified nonsynonymous SNPs in genes encoding accessory gene regulator C (agrC) and alpha-hemolysin (hla)--molecules important for S. aureus virulence--that were present in virtually all contemporary CC30 hospital isolates tested. Compared with the phage-type 80/81 and Southwest Pacific clones, contemporary CC30 hospital isolates had reduced virulence in mouse infection models, the result of SNPs in agrC and hla. We conclude that agr and hla (along with penicillin resistance) were essential for world dominance of phage-type 80/81 S. aureus, whereas key SNPs in contemporary CC30 clones restrict these pathogens to hospital settings in which the host is typically compromised.},
	language = {eng},
	journal = {Proc Natl Acad Sci U S A},
	author = {DeLeo, F. R. and Kennedy, A. D. and Chen, L. and Bubeck Wardenburg, J. and Kobayashi, S. D. and Mathema, B. and Braughton, K. R. and Whitney, A. R. and Villaruz, A. E. and Martens, C. A. and Porcella, S. F. and McGavin, M. J. and Otto, M. and Musser, J. M. and Kreiswirth, B. N.},
	month = nov,
	year = {2011},
	note = {44},
	keywords = {Bacteriophages, Bacteriophages/ classification/genetics, Disease Outbreaks, Genome, Bacterial, Genome, Viral, Humans, Mutation, Phylogeny, Polymorphism, Single Nucleotide, Staphylococcal Infections/ epidemiology, Staphylococcus aureus/genetics/pathogenicity/ virology, Virulence},
	pages = {18091--6},
	file = {molecular differentiation of historic and comtemporary mrsa.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/TKAHPCXI/molecular differentiation of historic and comtemporary mrsa.pdf:application/pdf}
}

@article{bose_contribution_2012,
	title = {Contribution of the {Staphylococcus} aureus {Atl} {AM} and {GL} {Murein} {Hydrolase} {Activities} in {Cell} {Division}, {Autolysis}, and {Biofilm} {Formation}},
	volume = {7},
	url = {http://dx.doi.org/10.1371/journal.pone.0042244},
	doi = {10.1371/journal.pone.0042244},
	abstract = {The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM) and a glucosaminidase (GL). Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable to the parental strain, but showed clumping phenotypes and lysis profiles that were distinct from the parental strain and each other, suggesting distinct roles in cell wall metabolism. Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development. Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm. The results of this study provide insight into the relative contributions of AM and GL in S. aureus and demonstrate the contribution of Atl-mediated lysis in biofilm development.},
	number = {7},
	urldate = {2014-03-25},
	journal = {PLoS ONE},
	author = {Bose, Jeffrey L. and Lehman, McKenzie K. and Fey, Paul D. and Bayles, Kenneth W.},
	month = jul,
	year = {2012},
	pages = {e42244},
	file = {PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/HBHJVEJX/Bose et al. - 2012 - Contribution of the Staphylococcus aureus Atl AM a.pdf:application/pdf;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/4MKQC63M/infodoi10.1371journal.pone.html:text/html}
}

@article{boles_agr-mediated_2008,
	title = {agr-{Mediated} {Dispersal} of {Staphylococcus} aureus {Biofilms}},
	volume = {4},
	url = {http://dx.plos.org/10.1371/journal.ppat.1000052},
	doi = {10.1371/journal.ppat.1000052},
	abstract = {Author SummaryA biofilm is a surface-attached community of cells bound together by an extracellular matrix. In a bacterial infection, biofilm-encased cells are protected from antibiotic therapy and host immune response, and these encased cells can develop into a chronic infection. Staphylococcus aureus is a prominent bacterial pathogen known to form biofilms on many medical implants and host tissues. In this report, we demonstrate that repression of the S. aureus quorum-sensing system is required to form a biofilm, and quorum-sensing reactivation in established biofilms disperses the cells. Genetic and molecular analysis demonstrates that quorum-sensing is activated before and required for the detachment mechanism. Detachment is protease-mediated, as established biofilms are sensitive to a non-specific protease and quorum-sensing activation increases the production of extracellular proteases. Using mutations in the protease genes, we show that these secreted enzymes are required for the detachment mechanism. These findings denote that S. aureus quorum-sensing can function as a dispersal mechanism to colonize new sites, and our results suggest this mechanism could be modulated to treat recalcitrant biofilms.},
	number = {4},
	urldate = {2014-03-25},
	journal = {PLoS Pathog},
	author = {Boles, Blaise R. and Horswill, Alexander R.},
	month = apr,
	year = {2008},
	pages = {e1000052},
	file = {PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/22SAR85Z/Boles and Horswill - 2008 - agr-Mediated Dispersal of Staphylococcus aureus Bi.pdf:application/pdf;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/2I5M6KTX/infodoi10.1371journal.ppat.html:text/html}
}

@article{nolte_development_1993,
	title = {Development of a stratum corneum and barrier function in an organotypic skin culture},
	volume = {285},
	issn = {0340-3696, 1432-069X},
	url = {http://link.springer.com.proxy.uchicago.edu/article/10.1007/BF00376819},
	doi = {10.1007/BF00376819},
	abstract = {The stratum corneum of human skin is responsible for maintaining the epidermal permeability barrier. We have developed a bilayered skin culture (SC) which forms a corneum 35 ± 1 cell layers thick 21 days after being raised to the air-liquid (A/L) interface. By the 7th day after raising to the A/L interface the corneocytes were irregularly shaped and had cross-sectional areas (CSA) of ≧300 Μm2. By the 21st day the corneocytes had assumed polygonal shapes and had a CSA (100–250 Μm2) similar to that of human foreskin. The total lipid (TL) content of the corneum averaged 5–7\% of the lyophilized weight. Ceramide content increased from 20\% of TL at day 7 of A/L interface culture to 30\% at day 21. Triglycerides decreased from 43\% to 17\% of TL during the same period. Free fatty acids comprised 5.5\% of TL at day 21 of A/L interface culture. The intercorneocyte spaces contained stacks of lipid lamellae. However, the stacks lacked the Landmann unit repeat. Abnormal lamellar structures were observed in both the intra- and extracorneocyte spaces. Transepidermal water loss (TEWL) was {\textgreater}4 mg/cm2 per h throughout the culture period. Lipid supplementation of the culture medium and culturing in a low humidity environment improved barrier function by 50\%. However, the effects were not additive. The SC developed a near-normal corneum, but did not achieve barrier competence, due at least partially to abnormalities in lipid composition and organization. Improvement of barrier function with lipid supplementation or low humidity indicates that modifications of the culture environment may facilitate the SC in assembling a permeability barrier equivalent to human skin.},
	language = {en},
	number = {8},
	urldate = {2014-02-25},
	journal = {Archives of Dermatological Research},
	author = {Nolte, C. J. M. and Oleson, M. A. and Bilbo, P. R. and Parenteau, N. L.},
	month = nov,
	year = {1993},
	keywords = {barrier function, Corneocyte, Dermatology, Lipid, Skin, stratum corneum},
	pages = {466--474},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/NWHNSUHV/Nolte et al. - 1993 - Development of a stratum corneum and barrier funct.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/K4AIT4CC/10.html:text/html}
}

@article{kiedrowski_nuclease_2011,
	title = {Nuclease {Modulates} {Biofilm} {Formation} in {Community}-{Associated} {Methicillin}-{Resistant} {Staphylococcus} aureus},
	volume = {6},
	url = {http://dx.doi.org/10.1371/journal.pone.0026714},
	doi = {10.1371/journal.pone.0026714},
	abstract = {Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of the nuc gene was increased in a sigB mutant, repressed by glucose supplementation, and was unaffected by the agr quorum-sensing system. A FRET assay for Nuc activity was developed and confirmed the regulatory results. A USA300 nuc mutant was constructed and displayed an enhanced biofilm-forming capacity, and the nuc mutant also accumulated more high molecular weight eDNA than the WT and regulatory mutant strains. Inactivation of nuc in the USA300 sigB mutant background partially repaired the sigB biofilm-negative phenotype, suggesting that nuc expression contributes to the inability of the mutant to form biofilm. To test the generality of the nuc mutant biofilm phenotypes, the mutation was introduced into other S. aureus genetic backgrounds and similar increases in biofilm formation were observed. Finally, using multiple S. aureus strains and regulatory mutants, an inverse correlation between Nuc activity and biofilm formation was demonstrated. Altogether, our findings confirm the important role for eDNA in the S. aureus biofilm matrix and indicates Nuc is a regulator of biofilm formation.},
	number = {11},
	urldate = {2014-03-25},
	journal = {PLoS ONE},
	author = {Kiedrowski, Megan R. and Kavanaugh, Jeffrey S. and Malone, Cheryl L. and Mootz, Joe M. and Voyich, Jovanka M. and Smeltzer, Mark S. and Bayles, Kenneth W. and Horswill, Alexander R.},
	month = nov,
	year = {2011},
	pages = {e26714},
	file = {PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/9FQ4P8VR/Kiedrowski et al. - 2011 - Nuclease Modulates Biofilm Formation in Community-.pdf:application/pdf;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/K9QUWP9C/infodoi10.1371journal.pone.html:text/html}
}

@article{periasamy_how_2012,
	title = {How {Staphylococcus} aureus biofilms develop their characteristic structure},
	volume = {109},
	issn = {0027-8424, 1091-6490},
	url = {http://www.pnas.org/content/109/4/1281},
	doi = {10.1073/pnas.1115006109},
	abstract = {Biofilms cause significant problems in the environment and during the treatment of infections. However, the molecular mechanisms underlying biofilm formation are poorly understood. There is a particular lack of knowledge about biofilm maturation processes, such as biofilm structuring and detachment, which are deemed crucial for the maintenance of biofilm viability and the dissemination of cells from a biofilm. Here, we identify the phenol-soluble modulin (PSM) surfactant peptides as key biofilm structuring factors in the premier biofilm-forming pathogen Staphylococcus aureus. We provide evidence that all known PSM classes participate in structuring and detachment processes. Specifically, absence of PSMs in isogenic S. aureus psm deletion mutants led to strongly impaired formation of biofilm channels, abolishment of the characteristic waves of biofilm detachment and regrowth, and loss of control of biofilm expansion. In contrast, induced expression of psm loci in preformed biofilms promoted those processes. Furthermore, PSMs facilitated dissemination from an infected catheter in a mouse model of biofilm-associated infection. Moreover, formation of the biofilm structure was linked to strongly variable, quorum sensing-controlled PSM expression in biofilm microenvironments, whereas overall PSM production remained constant to ascertain biofilm homeostasis. Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease.},
	language = {en},
	number = {4},
	urldate = {2014-03-25},
	journal = {Proceedings of the National Academy of Sciences},
	author = {Periasamy, Saravanan and Joo, Hwang-Soo and Duong, Anthony C. and Bach, Thanh-Huy L. and Tan, Vee Y. and Chatterjee, Som S. and Cheung, Gordon Y. C. and Otto, Michael},
	month = jan,
	year = {2012},
	pmid = {22232686},
	pages = {1281--1286},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/H4KMUDIW/Periasamy et al. - 2012 - How Staphylococcus aureus biofilms develop their c.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/GX4T8NFC/1281.html:text/html}
}

@article{bachelor_transcriptional_2014,
	title = {Transcriptional profiling of epidermal barrier formation in vitro},
	volume = {73},
	issn = {0923-1811},
	url = {http://www.sciencedirect.com/science/article/pii/S0923181113003629},
	doi = {10.1016/j.jdermsci.2013.11.004},
	abstract = {Barrier function is integral to the health of epithelial tissues. Currently, there is a broad need to develop and improve our knowledge with regard to barrier function for reversal of mild skin irritation and dryness. However, there are few in vitro models that incorporate modulations of both lipids and epidermal differentiation programs for pre-clinical testing to aid in the understanding of barrier health.
We have generated a reconstituted epidermis on a decellularized dermis (DED) and characterized its barrier properties relative to human epidermis in order to determine its utility for modeling barrier formation and repair.
We followed the process of epidermal differentiation and barrier formation through immunocytochemistry and transcriptional profiling. We examined barrier functionality through measurements of surface pH, lipid composition, stratum corneum water content, and the ability to demonstrate topical dose-dependent exclusion of surfactant.
Transcriptional profiling of the epidermal model during its formation reveals temporal patterns of gene expression associated with processes regulating barrier function. The profiling is supported by gradual formation and maturation of a stratum corneum and expression of appropriate markers of epidermis development. The model displays a functional barrier and a water gradient between the stratum corneum and viable layers, as determined by confocal Raman spectroscopy. The stratum corneum layer displays a normal acidic pH and an appropriate composition of barrier lipids.
The epidermal model demonstrates its utility as an investigative tool for barrier health and provides a window into the transcriptional regulation of multiple aspects of barrier formation.},
	number = {3},
	urldate = {2014-02-24},
	journal = {Journal of Dermatological Science},
	author = {Bachelor, Michael and Binder, Robert L. and Cambron, R. Thomas and Kaczvinsky, Joseph R. and Spruell, Russell and Wehmeyer, Kenneth R. and Reilman, Raymond and Adams, Rachel and Tiesman, Jay P. and Wang, Yu and Bascom, Charles C. and Isfort, Robert J. and DiColandrea, Teresa},
	month = mar,
	year = {2014},
	keywords = {Barrier, Epidermal differentiation, Genomics, skin equivalent},
	pages = {187--197},
	file = {ScienceDirect Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/23FUVHWQ/Bachelor et al. - 2014 - Transcriptional profiling of epidermal barrier for.pdf:application/pdf;ScienceDirect Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/5UNRKJWI/S0923181113003629.html:text/html}
}

@article{simonetti_visualization_1995,
	title = {Visualization of diffusion pathways across the stratum corneum of native and in-vitro-reconstructed epidermis by confocal laser scanning microscopy},
	volume = {287},
	issn = {0340-3696, 1432-069X},
	url = {http://link.springer.com.proxy.uchicago.edu/article/10.1007/BF00373430},
	doi = {10.1007/BF00373430},
	abstract = {Confocal laser scanning microscopy is a technique that permits the direct visualization in unfixed material of diffusion pathways and the cellular distribution of fluorescent markers after topical applications. This approach, in which the tissue specimen is optically sectioned, allows the study of changes in distribution pattern of applied compounds depending on the vehicle, time and depth without the interference of chemical alterations induced by most of the current techniques used for such studies. Using this technique the permeability properties of in-vitro-reconstructed epidermis were compared with those of the native counterpart. The epidermis was reconstructed by culturing human adult keratinocytes at the air-liquid interface either on fibroblast-populated collagen or on de-epidermized dermis. A fluorescent probe — Nile red (NR) — was applied in three different vehicles — polyethylene glycol (PEG) with a molecule mass of 400 (Da), propylene glycol (PG) and dimethyl sulphoxide (DMSO) — which perturb the SC barrier function to different extents. When NR was applied in PEG and PG on native epidermis, the amount of NR penetrating into and through the SC was very low, but was markedly increased when NR was applied in DMSO. Unlike native epidermis, the reconstructed epidermis allowed rapid NR penetration after the application in any of the solvents used. Furthermore, NR applied on reconstructed epidermis, was distributed quite homogeneously between the cellular and the intercellular spaces throughout the SC, suggesting that not only intercellular lipid structures but also the properties of the cornified envelopes differed markedly from those found in native epidermis. The differences in transport pathways between reconstructed and native epidermis may be partially ascribed to the culture conditions used, since incubation of freshly isolated epidermis under the same culture conditions as used for the reconstruction of the epidermis also leads to profound changes in the NR diffusion pathways.},
	language = {en},
	number = {5},
	urldate = {2014-05-18},
	journal = {Archives of Dermatological Research},
	author = {Simonetti, O. and Kempenaar, J. A. and Ponec, M. and Hoogstraate, A. J. and Bialik, W. and Schrijvers, A. H. G. J. and Boddé, H. E.},
	month = may,
	year = {1995},
	keywords = {Confocal laser scanning microscopy, Dermatology, Diffusion pathways, epidermis, Epidermis reconstruction (in vitro), stratum corneum},
	pages = {465--473},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/U25XPA2Z/Simonetti et al. - 1995 - Visualization of diffusion pathways across the str.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CJUS255P/BF00373430.html:text/html}
}

@article{faergemann_new_1989,
	title = {A {New} {Model} for {Growth} and {Filament} {Production} of {Pityrosporum} {Ovale} ({Orbiculare}) on {Human} {Stratum} {Corneum} {In} {Vitro}},
	volume = {92},
	copyright = {© 1989 Nature Publishing Group},
	issn = {0022-202X},
	url = {http://www.nature.com.proxy.uchicago.edu/jid/journal/v92/n1/abs/5613483a.html},
	doi = {10.1111/1523-1747.ep13071328},
	abstract = {A new model for the production of hyphae in Pityrosporum ovale in vitro is described. P. ovale was cultured on human stratum corneum pieces placed directly on a culture medium. The highest number of hyphae (24\%) was seen after 6 d of incubation at 37°C in a microaerophilic environment. There was a variation between the strains tested. This model opened possibilities to study the filamentous form of P. ovale in vitro. The effect of antimycotics and variation in antigens may be investigated and compared to the yeast form.},
	number = {1},
	urldate = {2014-02-25},
	journal = {Journal of Investigative Dermatology},
	author = {Faergemann, Jan},
	month = jan,
	year = {1989},
	pages = {117--119},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/WXVQU3WD/Faergemann - 1989 - A New Model for Growth and Filament Production of .pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/JSJ6C4EX/5613483a.html:text/html}
}

@article{krismer_nutrient_2014,
	title = {Nutrient {Limitation} {Governs} {Staphylococcus} aureus {Metabolism} and {Niche} {Adaptation} in the {Human} {Nose}},
	volume = {10},
	url = {http://dx.doi.org/10.1371/journal.ppat.1003862},
	doi = {10.1371/journal.ppat.1003862},
	abstract = {Author SummaryMany severe bacterial infections are caused by endogenous pathogens colonizing human body surfaces. Eradication of notorious pathogens such as Staphylococcus aureus from risk patients has become an important preventive strategy. However, efficient decolonization agents are rare, and the living conditions of colonizing pathogens have hardly been studied. Using a combined metabolomics and transcriptomics approach, we explored the metabolism of S. aureus during colonization of its preferred niche, the human nose. Based on nasal metabolite profiles, a synthetic nasal medium (SNM3) was composed, enabling steady growth of S. aureus but not of staphylococcal species preferentially colonizing the human skin. Marker gene expression was similar in SNM3 and the human nose, and genome-wide expression analysis revealed that amino acid biosynthesis, in particular that of methionine, is critical for S. aureus during colonization. An inhibitor of methionine biosynthesis had anti-staphylococcal activity in SNM3 but not in complex media, and transcription of the S. aureus target enzyme was strongly up-regulated in human noses. Furthermore, mutants defective in methionine biosynthesis exhibited strongly compromised nasal colonisation capacities in a cotton rat model. Altogether, our results indicate that the elucidation of in vivo metabolism of pathogens may lead to the identification of new antimicrobial targets and compounds.},
	number = {1},
	urldate = {2014-01-22},
	journal = {PLoS Pathog},
	author = {Krismer, Bernhard and Liebeke, Manuel and Janek, Daniela and Nega, Mulugeta and Rautenberg, Maren and Hornig, Gabriele and Unger, Clemens and Weidenmaier, Christopher and Lalk, Michael and Peschel, Andreas},
	month = jan,
	year = {2014},
	pages = {e1003862},
	file = {PLoS Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/RIJKRSRG/Krismer et al. - 2014 - Nutrient Limitation Governs Staphylococcus aureus .pdf:application/pdf;PLoS Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/KDV9C2SG/infodoi10.1371journal.ppat.html:text/html}
}

@article{nakatsuji_microbiome_2013,
	title = {The microbiome extends to subepidermal compartments of normal skin},
	volume = {4},
	copyright = {© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
	url = {http://www.nature.com.proxy.uchicago.edu/ncomms/journal/v4/n2/full/ncomms2441.html},
	doi = {10.1038/ncomms2441},
	abstract = {Commensal microbes on the skin surface influence the behaviour of cells below the epidermis. We hypothesized that bacteria or their products exist below the surface epithelium and thus permit physical interaction between microbes and dermal cells. Here to test this hypothesis, we employed multiple independent detection techniques for bacteria including quantitative PCR, Gram staining, immunofluorescence and in situ hybridization. Bacteria were consistently detectable within the dermis and dermal adipose of normal human skin. Sequencing of DNA from dermis and dermal adipose tissue identified bacterial 16S ribosomal RNA reflective of a diverse and partially distinct microbial community in each skin compartment. These results show the microbiota extends within the dermis, therefore, enabling physical contact between bacteria and various cells below the basement membrane. These observations show that normal commensal bacterial communities directly communicate with the host in a tissue previously thought to be sterile.},
	language = {en},
	urldate = {2014-10-30},
	journal = {Nature Communications},
	author = {Nakatsuji, Teruaki and Chiang, Hsin-I. and Jiang, Shangi B. and Nagarajan, Harish and Zengler, Karsten and Gallo, Richard L.},
	month = feb,
	year = {2013},
	keywords = {Biological sciences, immunology, Microbiology},
	pages = {1431},
	file = {Nakatsuji et al_2013_The microbiome extends to subepidermal compartments of normal skin.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/AQDMMTQW/Nakatsuji et al_2013_The microbiome extends to subepidermal compartments of normal skin.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/6DBKNXE6/ncomms2441.html:text/html}
}

@article{oneill_novel_2008,
	title = {A {Novel} {Staphylococcus} aureus {Biofilm} {Phenotype} {Mediated} by the {Fibronectin}-{Binding} {Proteins}, {FnBPA} and {FnBPB}},
	volume = {190},
	issn = {0021-9193},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395027/},
	doi = {10.1128/JB.00167-08},
	abstract = {Device-associated infections involving biofilm remain a persistent clinical problem. We recently reported that four methicillin-resistant Staphylococcus aureus (MRSA) strains formed biofilm independently of the icaADBC-encoded exopolysaccharide. Here, we report that MRSA biofilm development was promoted under mildly acidic growth conditions triggered by the addition of glucose to the growth medium. Loss of sortase, which anchors LPXTG-containing proteins to peptidoglycan, reduced the MRSA biofilm phenotype. Furthermore introduction of mutations in fnbA and fnbB, which encode the LPXTG-anchored multifunctional fibrinogen and fibronectin-binding proteins, FnBPA and FnBPB, reduced biofilm formation by several MRSA strains. However, these mutations had no effect on biofilm formation by methicillin-sensitive S. aureus strains. FnBP-promoted biofilm occurred at the level of intercellular accumulation and not primary attachment. Mutation of fnbA or fnbB alone did not substantially affect biofilm, and expression of either gene alone from a complementing plasmid in fnbA fnbB mutants restored biofilm formation. FnBP-promoted biofilm was dependent on the integrity of SarA but not through effects on fnbA or fnbB transcription. Using plasmid constructs lacking regions of FnBPA to complement an fnbAB mutant revealed that the A domain alone and not the domain required for fibronectin binding could promote biofilm. Additionally, an A-domain N304A substitution that abolished fibrinogen binding did not affect biofilm. These data identify a novel S. aureus biofilm phenotype promoted by FnBPA and FnBPB which is apparently independent of the known ligand-binding activities of these multifunctional surface proteins.},
	number = {11},
	urldate = {2014-04-24},
	journal = {Journal of Bacteriology},
	author = {O'Neill, Eoghan and Pozzi, Clarissa and Houston, Patrick and Humphreys, Hilary and Robinson, D. Ashley and Loughman, Anthony and Foster, Timothy J. and O'Gara, James P.},
	month = jun,
	year = {2008},
	pmid = {18375547},
	pmcid = {PMC2395027},
	pages = {3835--3850},
	file = {PubMed Central Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/Q2ZR6RS3/O'Neill et al. - 2008 - A Novel Staphylococcus aureus Biofilm Phenotype Me.pdf:application/pdf}
}

@article{wardenburg_surface_2007,
	title = {Surface {Proteins} and {Exotoxins} {Are} {Required} for the {Pathogenesis} of {Staphylococcus} aureus {Pneumonia}},
	volume = {75},
	issn = {0019-9567, 1098-5522},
	url = {http://iai.asm.org/content/75/2/1040},
	doi = {10.1128/IAI.01313-06},
	abstract = {A model of Staphylococcus aureus-induced pneumonia in adult, immunocompetent C57BL/6J mice is described. This model closely mimics the clinical and pathological features of pneumonia in human patients. Using this system, we defined a role for S. aureus strain Newman surface proteins and secreted exotoxins in pneumonia-related mortality.},
	language = {en},
	number = {2},
	urldate = {2014-05-01},
	journal = {Infection and Immunity},
	author = {Wardenburg, Juliane Bubeck and Patel, Ravi J. and Schneewind, Olaf},
	month = feb,
	year = {2007},
	pmid = {17101657},
	pages = {1040--1044},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/4G69IFFZ/Wardenburg et al. - 2007 - Surface Proteins and Exotoxins Are Required for th.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CBNV64JA/1040.html:text/html;Wardenburg et al_2007_Surface Proteins and Exotoxins Are Required for the Pathogenesis of.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/RNAR5SK4/Wardenburg et al_2007_Surface Proteins and Exotoxins Are Required for the Pathogenesis of.pdf:application/pdf}
}

@article{ya-xian_number_1999,
	title = {Number of cell layers of the stratum corneum in normal skin – relationship to the anatomical location on the body, age, sex and physical parameters},
	volume = {291},
	issn = {0340-3696, 1432-069X},
	url = {http://link.springer.com.proxy.uchicago.edu/article/10.1007/s004030050453},
	doi = {10.1007/s004030050453},
	language = {en},
	number = {10},
	urldate = {2014-04-04},
	journal = {Archives of Dermatological Research},
	author = {Ya-Xian, Z. and Suetake, T. and Tagami, H.},
	month = nov,
	year = {1999},
	keywords = {Corneocyte, Key words Cell layer, Normal skin, Regional difference, stratum corneum},
	pages = {555--559},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/JE59E5NK/Ya-Xian et al. - 1999 - Number of cell layers of the stratum corneum in no.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/PEIBCA7Q/10.html:text/html}
}

@article{ten_broeke-smits_hair_2010,
	title = {Hair follicles as a niche of {Staphylococcus} aureus in the nose; is a more effective decolonisation strategy needed?},
	volume = {76},
	issn = {0195-6701},
	url = {http://www.sciencedirect.com/science/article/pii/S0195670110003336},
	doi = {10.1016/j.jhin.2010.07.011},
	abstract = {Summary
Staphylococcus aureus is the major cause of surgical site infections, and meticillin-resistant S. aureus (MRSA) is increasingly accounting for infections worldwide. Preventing surgical site infections by screening and decolonising positive patients reduces the number of infections, but does not completely eradicate the risk. A balance between prevention, costs and the chance of mupirocin-resistant S. aureus needs to be evaluated and decolonisation strategies optimised. It is essential to know the site of S. aureus during colonisation. In this study, for the first time the exact location of S. aureus in the human nose was determined using a histological approach. We showed the presence of S. aureus in the cornified layer of squamous epithelium, associated keratin and mucous debris and within hair follicles in the vestibulum nasi. The presence of S. aureus in hair follicles suggests that this could be the niche from which relapses occur after decolonisation. Decolonisation strategies might have to be reconsidered.},
	number = {3},
	urldate = {2014-09-11},
	journal = {Journal of Hospital Infection},
	author = {ten Broeke-Smits, N. J. P. and Kummer, J. A. and Bleys, R. L. A. W. and Fluit, A. C. and Boel, C. H. E.},
	month = nov,
	year = {2010},
	keywords = {Mupirocin, Nasal colonisation, Staphylococcus aureus},
	pages = {211--214},
	file = {ScienceDirect Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/U6597U6T/S0195670110003336.html:text/html;ten Broeke-Smits et al_2010_Hair follicles as a niche of Staphylococcus aureus in the nose\; is a more.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/U7NSNW8C/ten Broeke-Smits et al_2010_Hair follicles as a niche of Staphylococcus aureus in the nose\; is a more.pdf:application/pdf}
}

@article{wertheim_risk_2004,
	title = {Risk and outcome of nosocomial {Staphylococcus} aureus bacteraemia in nasal carriers versus non-carriers},
	volume = {364},
	issn = {0140-6736},
	url = {http://www.sciencedirect.com/science/article/pii/S0140673604168979},
	doi = {10.1016/S0140-6736(04)16897-9},
	abstract = {Summary
Staphylococcus aureus is the second most frequent cause of nosocomial blood infections. We screened 14 008 non-bacteraemic, non-surgical patients for S aureus nasal carriage at admission, and monitored them for development of bacteraemia. Nosocomial S aureus bacteraemia was three times more frequent in S aureus carriers (40/3420, 1·2\%) than in non-carriers (41/10 588, 0·4\%; relative risk 3·0, 95\% CI 2·0–4·7). However, in bacteraemic patients, all-cause mortality was significantly higher in non-carriers (19/41, 46\%) than in carriers (seven/40, 18\%, p=0·005). Additionally, S aureus bacteraemia-related death was significantly higher in non-carriers than in carriers (13/41 [32\%] vs three/40 [8\%], p=0·006). S aureus nasal carriers and non-carriers differ significantly in risk and outcome of nosocomial S aureus bacteraemia. Genotyping revealed that 80\% of strains causing bacteraemia in carriers were endogenous.},
	number = {9435},
	urldate = {2014-09-11},
	journal = {The Lancet},
	author = {Wertheim, Heiman FL and Vos, Margreet C and Ott, Alewijn and van Belkum, Alex and Voss, Andreas and Kluytmans, Jan AJW and van Keulen, Peter HJ and Vandenbroucke-Grauls, Christina MJE and Meester, Marlene HM and Verbrugh, Henri A},
	month = aug,
	year = {2004},
	pages = {703--705},
	file = {ScienceDirect Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/XJFJ4RJI/S0140673604168979.html:text/html;Wertheim et al_2004_Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/3HAUX979/Wertheim et al_2004_Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal.pdf:application/pdf}
}

@article{schwartz_functional_2012,
	title = {Functional {Amyloids} {Composed} of {Phenol} {Soluble} {Modulins} {Stabilize} {Staphylococcus} aureus {Biofilms}},
	volume = {8},
	issn = {1553-7366},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369951/},
	doi = {10.1371/journal.ppat.1002744},
	abstract = {Staphylococcus aureus is an opportunistic pathogen that colonizes the skin and mucosal surfaces of mammals. Persistent staphylococcal infections often involve surface-associated communities called biofilms. Here we report the discovery of a novel extracellular fibril structure that promotes S. aureus biofilm integrity. Biochemical and genetic analysis has revealed that these fibers have amyloid-like properties and consist of small peptides called phenol soluble modulins (PSMs). Mutants unable to produce PSMs were susceptible to biofilm disassembly by matrix degrading enzymes and mechanical stress. Previous work has associated PSMs with biofilm disassembly, and we present data showing that soluble PSM peptides disperse biofilms while polymerized peptides do not. This work suggests the PSMs' aggregation into amyloid fibers modulates their biological activity and role in biofilms., Most people know Staphylococcus aureus as a highly infectious “Super Bug”, but many are not aware that S. aureus non-infectiously colonizes much of the population in the nose, among other bodily niches. It is not well understood how and why S. aureus is able to adapt and readily switch between the commensal and pathogenic lifestyle within the host; however, the capacity to accumulate into multicellular aggregates is a hallmark associated with both lifestyles. In this work, we demonstrate that S. aureus produces extracellular fibers in multicellular biofilm communities, and that these fibers help the bacterial community to withstand physical stresses. Surprisingly, these fibers consist of small peptides called phenol soluble modulins (PSMs) that have previously been implicated in biofilm disassembly and virulence. We demonstrate that accumulation of PSM peptides into fibers modulates their ability to disperse biofilms. Thus, PSMs fulfill dual and opposing roles that are modulated by amyloid-like aggregation. Staphylococci have never before been shown to produce this kind of extracellular structure, and our findings may have a profound impact on our understanding of S. aureus physiology. We have found that these structures are composed of known virulence factors, which indicates a common pathway between infectious and static lifestyles in the body.},
	number = {6},
	urldate = {2014-11-26},
	journal = {PLoS Pathogens},
	author = {Schwartz, Kelly and Syed, Adnan K. and Stephenson, Rachel E. and Rickard, Alexander H. and Boles, Blaise R.},
	month = jun,
	year = {2012},
	pmid = {22685403},
	pmcid = {PMC3369951},
	file = {PubMed Central Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/9IE9UFCJ/Schwartz et al. - 2012 - Functional Amyloids Composed of Phenol Soluble Mod.pdf:application/pdf}
}

@article{beenken_mutation_2003,
	title = {Mutation of {sarA} in {Staphylococcus} aureus {Limits} {Biofilm} {Formation}},
	volume = {71},
	issn = {0019-9567},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC161964/},
	doi = {10.1128/IAI.71.7.4206-4211.2003},
	abstract = {Mutation of sarA resulted in a reduced capacity to form a biofilm in six of the eight Staphylococcus aureus strains we tested (UAMS-1, UAMS-601, SA113, SC-01, S6C, and DB). The exceptions were Newman, which formed a poor biofilm under all conditions, and RN6390, which consistently formed a biofilm only after mutation of agr. Mutation of agr in other strains had little impact on biofilm formation. In every strain other than Newman, including RN6390, simultaneous mutation of sarA and agr resulted in a phenotype like that observed with the sarA mutants. Complementation studies using a sarA clone confirmed that the defect in biofilm formation was due to the sarA mutation.},
	number = {7},
	urldate = {2015-02-26},
	journal = {Infection and Immunity},
	author = {Beenken, Karen E. and Blevins, Jon S. and Smeltzer, Mark S.},
	month = jul,
	year = {2003},
	pmid = {12819120},
	pmcid = {PMC161964},
	pages = {4206--4211},
	file = {Beenken et al_2003_Mutation of sarA in Staphylococcus aureus Limits Biofilm Formation.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/7S3DPPAG/Beenken et al_2003_Mutation of sarA in Staphylococcus aureus Limits Biofilm Formation.pdf:application/pdf}
}

@article{yarwood_quorum_2004,
	title = {Quorum {Sensing} in {Staphylococcus} aureus {Biofilms}},
	volume = {186},
	issn = {0021-9193},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC355980/},
	doi = {10.1128/JB.186.6.1838-1850.2004},
	abstract = {Several serious diseases are caused by biofilm-associated Staphylococcus aureus, infections in which the accessory gene regulator (agr) quorum-sensing system is thought to play an important role. We studied the contribution of agr to biofilm development, and we examined agr-dependent transcription in biofilms. Under some conditions, disruption of agr expression had no discernible influence on biofilm formation, while under others it either inhibited or enhanced biofilm formation. Under those conditions where agr expression enhanced biofilm formation, biofilms of an agr signaling mutant were particularly sensitive to rifampin but not to oxacillin. Time lapse confocal scanning laser microscopy showed that, similar to the expression of an agr-independent fluorescent reporter, biofilm expression of an agr-dependent reporter was in patches within cell clusters and oscillated with time. In some cases, loss of fluorescence appeared to coincide with detachment of cells from the biofilm. Our studies indicate that the role of agr expression in biofilm development and behavior depends on environmental conditions. We also suggest that detachment of cells expressing agr from biofilms may have important clinical implications.},
	number = {6},
	urldate = {2015-02-27},
	journal = {Journal of Bacteriology},
	author = {Yarwood, Jeremy M. and Bartels, Douglas J. and Volper, Esther M. and Greenberg, E. Peter},
	month = mar,
	year = {2004},
	pmid = {14996815},
	pmcid = {PMC355980},
	pages = {1838--1850},
	file = {PubMed Central Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/6442TGXS/Yarwood et al. - 2004 - Quorum Sensing in Staphylococcus aureus Biofilms.pdf:application/pdf}
}

@article{recsei_regulation_1986,
	title = {Regulation of exoprotein gene expression in {Staphylococcus} aureus by agr},
	volume = {202},
	issn = {0026-8925, 1432-1874},
	url = {http://link.springer.com.proxy.uchicago.edu/article/10.1007/BF00330517},
	doi = {10.1007/BF00330517},
	abstract = {Insertion of the erythromycin-resistance transposon Tn551 into the Staphylococcus aureus chromosome at a site which maps between the purB and ilv loci has a pleiotrophic effect on the production of a number of extracellular proteins. Production of alpha, beta and delta hemolysin, toxic shock syndrome toxin (TSST-1) and staphylokinase was depressed about fifty-fold while protein A production was elevated twenty-fold. Hybridization analysis showed that the defect in expression of TSST-1 and alpha hemolysin was at the transcriptional level. Inability of the mutant strain to express either a cloned TSST-1 gene or the chromosomal gene indicates that the transposon has inactivated a trans-active positive control element. This element has been designated agr for accessory gene regulator.},
	language = {en},
	number = {1},
	urldate = {2015-03-03},
	journal = {Molecular and General Genetics MGG},
	author = {Recsei, P. and Kreiswirth, B. and O'Reilly, M. and Schlievert, P. and Gruss, A. and Novick, R. P.},
	month = jan,
	year = {1986},
	keywords = {Biochemistry, general, Cell Biology, Exoproteins, Gene regulation, Microbial Genetics and Genomics, Pathogenicity, Pletotropism, S. aureus},
	pages = {58--61},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/XPWQ2MXE/Recsei et al. - 1986 - Regulation of exoprotein gene expression in Staphy.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/JBXM2JPM/10.html:text/html}
}

@article{peng_cloning_1988,
	title = {Cloning, characterization, and sequencing of an accessory gene regulator (agr) in {Staphylococcus} aureus.},
	volume = {170},
	issn = {0021-9193, 1098-5530},
	url = {http://jb.asm.org/content/170/9/4365},
	abstract = {We have previously identified a gene in Staphylococcus aureus, agr, whose activity is required for high-level post-exponential-phase expression of a series of secreted proteins. In this paper, we describe the cloning of this gene in Escherichia coli by using an inserted transposon (Tn551) as a cloning probe. The cloned gene, consisting of a 241-codon open reading frame containing the site of the transposon insertion, was recloned to an S. aureus vector, pSK265, and shown to be functional in S. aureus. Activity was evaluated by determinations of alpha-hemolysin, beta-hemolysin, and toxic shock syndrome toxin-1 production in early-stationary-phase cultures. The cloned gene showed considerable variation with respect to different exoproteins and different host strains compared with the chromosomal agr determinant; this variation could not be attributed to the higher copy number of the cloned gene and probably reflects inapparent subtleties of the regulatory system.},
	language = {en},
	number = {9},
	urldate = {2015-03-03},
	journal = {Journal of Bacteriology},
	author = {Peng, H. L. and Novick, R. P. and Kreiswirth, B. and Kornblum, J. and Schlievert, P.},
	month = sep,
	year = {1988},
	pmid = {2457579},
	pages = {4365--4372},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/DBK2R9K4/Peng et al. - 1988 - Cloning, characterization, and sequencing of an ac.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/SGQAJI2K/4365.html:text/html}
}

@article{novick_theagr_1995,
	title = {Theagr {P}2 operon: {An} autocatalytic sensory transduction system {inStaphylococcus} aureus},
	volume = {248},
	issn = {0026-8925, 1432-1874},
	shorttitle = {Theagr {P}2 operon},
	url = {http://link.springer.com.proxy.uchicago.edu/article/10.1007/BF02191645},
	doi = {10.1007/BF02191645},
	abstract = {The synthesis of virulence factors and other exoproteins inStaphylococcus aureus is controlled by the global regulator,agr. Expression of secreted proteins is up-regulated in the postexponential growth phase, whereas expression of surface proteins is down-regulated byagr. Theagr locus consists of two divergent operons, transcribed from neighboring but non-overlapping promoters, P2 and P3. The P2 operon sequence, reported here, contains 4 open reading frames,agr A, C, D, andB, of whichA andC appear to encode proteins of a classical 2-component signal transduction pathway. The P3 operon specifies a 0.5 kb transcript, RNA III, which is the actual effector of theagr response, and, incidentally, encodes theagr-regulated peptide δ-hemolysin. Transcriptional fusions have shown that both P2 and P3 areagr sensitive (function in anagr + but not in anagr background) and deletion analysis has shown that all four of the P2 ORFs are involved;agrA andagrC seem to be absolutely required for the transcriptional activation of theagr locus, whereasagrB andagrD seem to be partially required. Since transcription of P2 requires P2 operon products, the P2 operon is autocatalytic, and is thus admirably suited to the need for rapid production of exo-proteins at a time when overall growth is coming to a halt.},
	language = {en},
	number = {4},
	urldate = {2015-04-07},
	journal = {Molecular and General Genetics MGG},
	author = {Novick, R. P. and Projan, S. J. and Kornblum, J. and Ross, H. F. and Ji, G. and Kreiswirth, B. and Vandenesch, F. and Moghazeh, S. and Novick, R. P.},
	month = aug,
	year = {1995},
	keywords = {Biochemistry, general, Cell Biology, Microbial Genetics and Genomics},
	pages = {446--458},
	file = {Novick et al_1995_Theagr P2 operon.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/7GFC4HGZ/Novick et al_1995_Theagr P2 operon.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/BP2CETCT/BF02191645.html:text/html}
}

@article{soong_methicillin-resistant_2015,
	title = {Methicillin-{Resistant} {Staphylococcus} aureus {Adaptation} to {Human} {Keratinocytes}},
	volume = {6},
	issn = {, 2150-7511},
	url = {http://mbio.asm.org/content/6/2/e00289-15},
	doi = {10.1128/mBio.00289-15},
	abstract = {Skin is the most common site of Staphylococcus aureus infection. While most of these infections are self-limited, recurrent infections are common. Keratinocytes and recruited immune cells participate in skin defense against infection. We postulated that S. aureus is able to adapt to the milieu within human keratinocytes to avoid keratinocyte-mediated clearance. From a collection of S. aureus isolated from chronically infected patients with atopic dermatitis, we noted 22\% had an agr mutant-like phenotype. Using several models of human skin infection, we demonstrate that toxin-deficient, agr mutants of methicillin-resistant S. aureus (MRSA) USA300 are able to persist within keratinocytes by stimulating autophagy and evading caspase-1 and inflammasome activation. MRSA infection induced keratinocyte autophagy, as evidenced by galectin-8 and LC3 accumulation. Autophagy promoted the degradation of inflammasome components and facilitated staphylococcal survival. The recovery of more than 58\% agr or RNAIII mutants (P {\textless} 0.0001) of an inoculum of wild-type (WT) MRSA from within wortmannin-treated keratinocytes compared to control keratinocytes reflected the survival advantage for mutants no longer expressing agr-dependent toxins. Our results illustrate the dynamic interplay between S. aureus and keratinocytes that can result in the selection of mutants that have adapted specifically to evade keratinocyte-mediated clearance mechanisms.
IMPORTANCE Human skin is a major site of staphylococcal infection, and keratinocytes actively participate in eradication of these pathogens. We demonstrate that methicillin-resistant Staphylococcus aureus (MRSA) is ingested by keratinocytes and activates caspase-1-mediated clearance through pyroptosis. Toxin-deficient MRSA mutants are selected within keratinocytes that fail to induce caspase-1 activity and keratinocyte-mediated clearance. These intracellular staphylococci induce autophagy that enhances their intracellular survival by diminishing inflammasome components. These findings suggest that S. aureus mutants, by exploiting autophagy, can persist within human keratinocytes.},
	language = {en},
	number = {2},
	urldate = {2015-04-22},
	journal = {mBio},
	author = {Soong, Grace and Paulino, Franklin and Wachtel, Sarah and Parker, Dane and Wickersham, Matthew and Zhang, Dongni and Brown, Armand and Lauren, Christine and Dowd, Margaret and West, Emily and Horst, Basil and Planet, Paul and Prince, Alice},
	month = may,
	year = {2015},
	pmid = {25900653},
	pages = {e00289--15},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/BVH5UGSC/Soong et al. - 2015 - Methicillin-Resistant Staphylococcus aureus Adapta.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CWV9A5H7/e00289-15.html:text/html;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/XH87H2HX/e00289-15.html:text/html;Soong et al_2015_Methicillin-Resistant Staphylococcus aureus Adaptation to Human Keratinocytes.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/VTQXHV7N/Soong et al_2015_Methicillin-Resistant Staphylococcus aureus Adaptation to Human Keratinocytes.pdf:application/pdf}
}

@article{mack_intercellular_1996,
	title = {The intercellular adhesin involved in biofilm accumulation of {Staphylococcus} epidermidis is a linear beta-1,6-linked glucosaminoglycan: purification and structural analysis.},
	volume = {178},
	issn = {0021-9193},
	shorttitle = {The intercellular adhesin involved in biofilm accumulation of {Staphylococcus} epidermidis is a linear beta-1,6-linked glucosaminoglycan},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC177636/},
	abstract = {The primary attachment to polymer surfaces followed by accumulation in multilayered cell clusters leads to biofilm production of Staphylococcus epidermidis, which is thought to contribute to virulence in biomaterial-related infections. We purified a specific polysaccharide antigen of biofilm-producing S. epidermidis 1457 and RP62A, which was recently shown to have a function in the accumulative phase of biofilm production by mediating intercellular adhesion (D. Mack, M. Nedelmann, A. Krokotsch, A. Schwarzkopf, J. Heesemann, and R. Laufs, Infect. Immun. 62:3244-3253, 1994). Following Sephadex G-200 gel filtration, this antigen was separated by Q-Sepharose chromatography into a major polysaccharide, polysaccharide I ({\textgreater} 80\%), which did not bind to Q-Sepharose, and a minor polysaccharide, polysaccharide II ({\textless} 20\%), which was moderately anionic. As shown by chemical analyses and nuclear magnetic resonance spectroscopy, polysaccharide I is a linear homoglycan of at least 130 beta-1,6-linked 2-deoxy-2-amino-D-glucopyranosyl residues. On average, 80 to 85\% of them are N acetylated; the rest are non-N-acetylating and positively charged. Chain cleavage by deamination with HNO2 revealed a more or less random distribution of the non-N-acetylated glucosaminyl residues, with some prevalence of glucosaminyl-rich sequences. Cation-exchange chromatography separated molecular species whose content of non-N-acetylated glucosaminyl residues varied between 2 and 26\%. Polysaccharide II is structurally related to polysaccharide I but has a lower content of non-N-acetylated D-glucosaminyl residues and contains phosphate and ester-linked succinate, rendering it anionic. Enzyme-linked immunosorbent assay inhibition with various monosaccharides revealed the beta-anomeric form and the acetylated amino group of the D-glucosaminyl residues as important for reactivity with the specific antiserum. The unbranched polysaccharide structure favors long-range contacts and interactions between polysaccharide strands and the cell wall and/or lectin-like proteins, leading to intercellular adhesion and biofilm accumulation. The structure of the polysaccharide is, so far, considered to be unique and, according to its function, is referred to as S. epidermidis polysaccharide intercellular adhesin (PIA).},
	number = {1},
	urldate = {2015-05-09},
	journal = {Journal of Bacteriology},
	author = {Mack, D and Fischer, W and Krokotsch, A and Leopold, K and Hartmann, R and Egge, H and Laufs, R},
	month = jan,
	year = {1996},
	pmid = {8550413},
	pmcid = {PMC177636},
	pages = {175--183},
	file = {Mack et al_1996_The intercellular adhesin involved in biofilm accumulation of Staphylococcus.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/D7CEACGB/Mack et al_1996_The intercellular adhesin involved in biofilm accumulation of Staphylococcus.pdf:application/pdf}
}

@article{quinn_subversion_2009,
	title = {Subversion of interleukin-1-mediated host defence by a nasal carrier strain of {Staphylococcus} aureus},
	volume = {128},
	issn = {0019-2805},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753939/},
	doi = {10.1111/j.1365-2567.2008.02952.x},
	abstract = {Staphylococcus aureus, a major source of nosocomial and community-acquired infections, has a nasal carriage rate exceeding 25\% in the human population. To elucidate host–pathogen interactions pertaining to nasal carriage, we examined the role of interleukin-1 (IL-1) in the colonization of human nasal epithelial cells (NEC) by a nasal carrier strain and a non-carrier strain of S. aureus. Using an organotypic model of the nasal epithelium, we observed that inoculation with a non-carrier strain of S. aureus induced production of IL-1 from NEC, but the expression of this cytokine was significantly reduced when NEC were inoculated with a carrier strain. Moreover, both IL-1α and IL-1β significantly decreased the growth of the nasal carrier strain of S. aureus (P{\textless} 0·001, n= 17 to n= 25); however the growth of the non-carrier strain was unaffected. Interestingly, it was found that several nasal carrier strains of S. aureus form quorum-dependent biofilms, which can be partially inhibited when preincubated with IL-1α. Taken together these data suggest that, although nasal carrier strains of S. aureus are sensitive to IL-1, they display a significant colonization advantage by both preventing the host from expressing IL-1 and elaborating a protective biofilm.},
	number = {1 Pt 2},
	urldate = {2015-05-14},
	journal = {Immunology},
	author = {Quinn, Gerry A and Tarwater, Patrick M and Cole, Alexander M},
	month = sep,
	year = {2009},
	pmid = {19740308},
	pmcid = {PMC2753939},
	pages = {e222--e229},
	file = {Quinn et al_2009_Subversion of interleukin-1-mediated host defence by a nasal carrier strain of.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/U9FNXPIP/Quinn et al_2009_Subversion of interleukin-1-mediated host defence by a nasal carrier strain of.pdf:application/pdf}
}

@article{schneewind_cell_1993,
	title = {Cell wall sorting signals in surface proteins of gram-positive bacteria.},
	volume = {12},
	issn = {0261-4189},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC413927/},
	abstract = {Staphylococcal protein A is anchored to the cell wall, a unique cellular compartment of Gram-positive bacteria. The sorting signal sufficient for cell wall anchoring consists of an LPXTG motif, a C-terminal hydrophobic domain and a charged tail. Homologous sequences are found in many surface proteins of Gram-positive bacteria and we explored the universality of these sequences to serve as cell wall sorting signals. We show that several signals are able to anchor fusion proteins to the staphylococcal cell wall. Some signals do not sort effectively, but acquire sorting activity once the spacing between the LPXTG motif and the charged tail has been increased to span the same length as in protein A. Thus, signals for cell wall anchoring in Gram-positive bacteria are as universal as signal (leader) sequences.},
	number = {12},
	urldate = {2015-07-10},
	journal = {The EMBO Journal},
	author = {Schneewind, O and Mihaylova-Petkov, D and Model, P},
	month = dec,
	year = {1993},
	pmid = {8223489},
	pmcid = {PMC413927},
	pages = {4803--4811},
	file = {PubMed Central Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/GFFAJTXK/Schneewind et al. - 1993 - Cell wall sorting signals in surface proteins of g.pdf:application/pdf}
}

@article{mansbridge_penetration_1993,
	title = {Penetration of lucifer yellow into human skin: a lateral diffusion channel in the stratum corneum.},
	volume = {41},
	issn = {0022-1554, 1551-5044},
	shorttitle = {Penetration of lucifer yellow into human skin},
	url = {http://jhc.sagepub.com/content/41/6/909},
	doi = {10.1177/41.6.8315281},
	abstract = {We investigated the penetration of Lucifer Yellow into human and murine epidermis in 4-mm punch biopsies by incubation in dye solution. Lucifer Yellow was taken up freely by the dermis but penetrated only slightly into keratinocytes of the basal and suprabasal layers. However, progressive lateral diffusion was observed in the lowest layers of the stratum corneum, extending a distance of 1 mm in 6 hr. Under high magnification, Lucifer Yellow appeared to lie within rather than between corneocytes of this layer. Control samples stained with Lucifer Yellow after sectioning showed no preferential binding of the dye in this region. We concluded that the localization of staining was the result of diffusion from the cut edge of the stratum corneum. Lucifer Yellow penetration was insensitive to PMSF, 1:10 phenanthroline, or N-ethyl maleimide and was also observed in an in vivo injury, indicating that it was not an artifact of proteolytic or degenerative changes. In contrast, horseradish peroxidase failed to penetrate, suggesting molecular size limitation to channel entry. Diffusion of Lucifer Yellow beneath the stratum corneum marks a pathway for the lateral movement of small molecules of potential importance in the normal physiology of the skin, drug delivery, and pathology.},
	language = {en},
	number = {6},
	urldate = {2015-08-06},
	journal = {Journal of Histochemistry \& Cytochemistry},
	author = {Mansbridge, J. N. and Knapp, A. M.},
	month = jun,
	year = {1993},
	pmid = {8315281},
	pages = {909--914},
	file = {Mansbridge_Knapp_1993_Penetration of lucifer yellow into human skin.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CRBMBC6I/Mansbridge_Knapp_1993_Penetration of lucifer yellow into human skin.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/F77QW3P8/909.html:text/html}
}

@article{merriman_novel_2015,
	title = {Novel {Staphylococcus} aureus {Secreted} {Protein} {Alters} {Keratinocyte} {Proliferation} and {Elicits} a {Proinflammatory} {Response} {In} {Vitro} and {In} {Vivo}},
	volume = {54},
	issn = {0006-2960},
	url = {http://dx.doi.org/10.1021/acs.biochem.5b00523},
	doi = {10.1021/acs.biochem.5b00523},
	abstract = {Staphylococcus aureus is a leading cause of surgical site infections that results in increased hospital stays due to the development of chronic wounds. Little is known about factors involved in S. aureus? ability to prevent wounds from healing. We discovered a novel secreted protein produced by a surgical site isolate of S. aureus that prevents keratinocyte proliferation. The protein has a molecular weight of 15.7 kDa and an isoelectric point of 8.9. The cloned and purified protein has cytotoxic and proinflammatory properties, as shown in vitro and in vivo. Potent biological effects on keratinocytes and rabbit skin suggest that this protein may play an important role in preventing re-epithelialization. Its lack of homology to known exotoxins suggests that this protein is novel, and this observation is likely to open a new field of research in S. aureus exotoxins. Due to its cytotoxic activities, we call this new protein ε-cytotoxin.},
	number = {31},
	urldate = {2015-09-30},
	journal = {Biochemistry},
	author = {Merriman, Joseph A. and Klingelhutz, Aloysius J. and Diekema, Daniel J. and Leung, Donald Y. M. and Schlievert, Patrick M.},
	month = aug,
	year = {2015},
	pages = {4855--4862},
	file = {ACS Full Text PDF w/ Links:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/323EAMW6/Merriman et al. - 2015 - Novel Staphylococcus aureus Secreted Protein Alter.pdf:application/pdf;ACS Full Text Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/8UH4HACX/acs.biochem.html:text/html}
}

@article{fitzpatrick_evidence_2005,
	title = {Evidence for {icaADBC}-{Independent} {Biofilm} {Development} {Mechanism} in {Methicillin}-{Resistant} {Staphylococcus} aureus {Clinical} {Isolates}},
	volume = {43},
	issn = {0095-1137},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1081404/},
	doi = {10.1128/JCM.43.4.1973-1976.2005},
	abstract = {Synthesis of a polysaccharide adhesin by icaADBC-encoded enzymes is currently the best-understood mechanism of staphylococcal biofilm development. In four methicillin-resistant Staphylococcus aureus isolates, environmental activation of icaADBC did not always correlate with increased biofilm production. Moreover, glucose-mediated biofilm development in these isolates was icaADBC independent. Apparently, an environmentally regulated, ica-independent mechanism(s) of biofilm development exists in S. aureus clinical isolates.},
	number = {4},
	urldate = {2015-08-11},
	journal = {Journal of Clinical Microbiology},
	author = {Fitzpatrick, Fidelma and Humphreys, Hilary and O'Gara, James P.},
	month = apr,
	year = {2005},
	pmid = {15815035},
	pmcid = {PMC1081404},
	pages = {1973--1976},
	file = {Fitzpatrick et al_2005_Evidence for icaADBC-Independent Biofilm Development Mechanism in.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/E7ZNTQ7Q/Fitzpatrick et al_2005_Evidence for icaADBC-Independent Biofilm Development Mechanism in.pdf:application/pdf;Fitzpatrick et al_2005_Evidence for icaADBC-Independent Biofilm Development Mechanism in.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/BFPCDCUR/Fitzpatrick et al_2005_Evidence for icaADBC-Independent Biofilm Development Mechanism in.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/9AXBBQPV/1973.html:text/html;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/ZSBJM22J/1973.html:text/html}
}

@article{cramton_intercellular_1999,
	title = {The {Intercellular} {Adhesion} (ica) {Locus} {Is} {Present} in {Staphylococcus} aureus and {Is} {Required}  for {Biofilm} {Formation}},
	volume = {67},
	issn = {0019-9567},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC96900/},
	abstract = {Nosocomial infections that result in the formation of biofilms on the surfaces of biomedical implants are a leading cause of sepsis and are often associated with colonization of the implants by Staphylococcus epidermidis. Biofilm formation is thought to require two sequential steps: adhesion of cells to a solid substrate followed by cell-cell adhesion, creating multiple layers of cells. Intercellular adhesion requires the polysaccharide intercellular adhesin (PIA), which is composed of linear β-1,6-linked glucosaminylglycans and can be synthesized in vitro from UDP-N-acetylglucosamine by products of the intercellular adhesion (ica) locus. We have investigated a variety of Staphylococcus aureus strains and find that all strains tested contain the ica locus and that several can form biofilms in vitro. Sequence comparison with the S. epidermidis ica genes revealed 59 to 78\% amino acid identity. Deletion of the ica locus results in a loss of the ability to form biofilms, produce PIA, or mediate N-acetylglucosaminyltransferase activity in vitro. Cross-species hybridization experiments revealed the presence of icaA in several other Staphylococcus species, suggesting that cell-cell adhesion and the potential to form biofilms is conserved within this genus.},
	number = {10},
	urldate = {2015-11-15},
	journal = {Infection and Immunity},
	author = {Cramton, Sarah E. and Gerke, Christiane and Schnell, Norbert F. and Nichols, Wright W. and Götz, Friedrich},
	month = oct,
	year = {1999},
	pmid = {10496925},
	pmcid = {PMC96900},
	pages = {5427--5433},
	file = {Cramton et al_1999_The Intercellular Adhesion (ica) Locus Is Present in Staphylococcus aureus and.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/SCQG6P6Z/Cramton et al_1999_The Intercellular Adhesion (ica) Locus Is Present in Staphylococcus aureus and.pdf:application/pdf}
}

@article{caiazza_alpha-toxin_2003,
	title = {Alpha-{Toxin} {Is} {Required} for {Biofilm} {Formation} by {Staphylococcus} aureus},
	volume = {185},
	issn = {0021-9193, 1098-5530},
	url = {http://jb.asm.org/content/185/10/3214},
	doi = {10.1128/JB.185.10.3214-3217.2003},
	language = {en},
	number = {10},
	urldate = {2015-10-08},
	journal = {Journal of Bacteriology},
	author = {Caiazza, Nicky C. and O'Toole, G. A.},
	month = may,
	year = {2003},
	pmid = {12730182},
	pages = {3214--3217},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/4SJ4AMUG/Caiazza and O'Toole - 2003 - Alpha-Toxin Is Required for Biofilm Formation by S.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CWEJG6EH/3214.html:text/html}
}

@article{reijer_detection_2016,
	title = {Detection of {Alpha}-{Toxin} and {Other} {Virulence} {Factors} in {Biofilms} of {Staphylococcus} aureus on {Polystyrene} and a {Human} {Epidermal} {Model}},
	volume = {11},
	issn = {1932-6203},
	url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145722},
	doi = {10.1371/journal.pone.0145722},
	abstract = {Background \& Aim   The ability of  Staphylococcus aureus  to successfully colonize (a)biotic surfaces may be explained by biofilm formation and the actions of virulence factors. The aim of the present study was to establish the presence of 52 proteins, including virulence factors such as alpha-toxin, during biofilm formation of five different (methicillin resistant)  S .  aureus  strains on Leiden human epidermal models (LEMs) and polystyrene surfaces (PS) using a competitive Luminex-based assay.       Results   All five  S .  aureus  strains formed biofilms on PS, whereas only three out of five strains formed biofilms on LEMs. Out of the 52 tested proteins, six functionally diverse proteins (ClfB, glucosaminidase, IsdA, IsaA, SACOL0688 and nuclease) were detected in biofilms of all strains on both PS and LEMs. At the same time, four toxins (alpha-toxin, gamma-hemolysin B and leukocidins D and E), two immune modulators (formyl peptide receptor-like inhibitory protein and Staphylococcal superantigen-like protein 1), and two other proteins (lipase and LytM) were detectable in biofilms by all five  S .  aureus  strains on LEMs, but not on PS. In contrast, fibronectin-binding protein B (FnbpB) was detectable in biofilms by all  S .  aureus  biofilms on PS, but not on LEMs. These data were largely confirmed by the results from proteomic and transcriptomic analyses and in case of alpha-toxin additionally by GFP-reporter technology.       Conclusion   Functionally diverse virulence factors of (methicillin-resistant)  S .  aureus  are present during biofilm formation on LEMs and PS. These results could aid in identifying novel targets for future treatment strategies against biofilm-associated infections.},
	number = {1},
	urldate = {2016-01-08},
	journal = {PLOS ONE},
	author = {Reijer, P. M. den and Haisma, E. M. and Toom, N. A. Lemmens-den and Willemse, J. and Koning, R. A. and Demmers, J. a. A. and Dekkers, D. H. W. and Rijkers, E. and Ghalbzouri, A. El and Nibbering, P. H. and Wamel, W. van},
	month = jan,
	year = {2016},
	pages = {e0145722},
	file = {Full Text PDF:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/PK4KJBVK/Reijer et al. - 2016 - Detection of Alpha-Toxin and Other Virulence Facto.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/BAHRKRIX/article.html:text/html}
}

@article{malcolm_demonstration_1980,
	title = {The demonstration of bacteria on and within the stratum corneum using scanning electron microscopy},
	volume = {102},
	issn = {1365-2133},
	url = {http://onlinelibrary.wiley.com.proxy.uchicago.edu/doi/10.1111/j.1365-2133.1980.tb08139.x/abstract},
	doi = {10.1111/j.1365-2133.1980.tb08139.x},
	abstract = {Using scanning electron microscopy it has been possible to demonstrate the location of bacteria on and within the stratum corneum of the human foot. Biopsies taken either by sectioning or by removing stratum corneum with cyanoacrylate ester adhesive were examined using a Jeol JSM-T20 scanning electron microscope. Bacteria could be seen easily on specimens from skin which had been occluded to increase the number of bacteria present. On the surface, bacteria were scattered widely in small colonies (usually containing less than ten bacteria). Although bacteria could be seen around the orifice of sweat ducts they did not preferentially favour these sites. Within the stratum corneum, bacteria could be found as relatively large colonies but these were usually associated with sweat ducts or the underside of the furrows in the skin surface. This study suggests that, in normal skin, bacteria are able to colonize both the surface and the depths of the stratum corneum.},
	language = {en},
	number = {3},
	urldate = {2016-03-22},
	journal = {British Journal of Dermatology},
	author = {Malcolm, S. A. and Hughes, T. C.},
	month = mar,
	year = {1980},
	pages = {267--275},
	file = {Malcolm_Hughes_1980_The demonstration of bacteria on and within the stratum corneum using scanning.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/J2UIS4WK/Malcolm_Hughes_1980_The demonstration of bacteria on and within the stratum corneum using scanning.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/NSNRBWED/abstract\;jsessionid=5494C93FFE54F1F526E3FBBCB04DA89D.html:text/html}
}

@article{hohl_expression_1993,
	title = {Expression patterns of loricrin in various species and tissues},
	volume = {54},
	issn = {0301-4681},
	url = {http://www.sciencedirect.com/science/article/pii/S0301468111601072},
	doi = {10.1111/j.1432-0436.1993.tb01585.x},
	abstract = {In this study we analyzed the expression patterns of loricrin in various species and tissues using immunohistochemistry, immunoblotting and Northern blots. Loricrin is a glycine-, serine- and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal mouse and human epidermis. Later on in differentiation, loricrin becomes cross-linked as a major component into the cornified cell envelope by the formation of Nɛ -(γ-glutamyl)lysine isopeptide bonds. This process either occurs directly or by the intermediate accumulation in L-keratohyaline granules of mouse epidermis and human acrosyringia. Loricrin was identified in all mammalian species analyzed by virtue of its highly conserved carboxy-terminal sequences revealing an electric mobility of ∼60 kDa in rodents, rabbit and cow and of ∼35 kDa in lamb and human on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Loricrin is expressed in the granular layer of all mammalian orthokeratinizing epithelia tested including oral, esophageal and fore-stomach mucosa of rodents, tracheal squamous metaplasia of vitamin A deficient hamster and estrogen induced squamous vaginal epithelium of ovary ectomized rats. Loricrin is also expressed in a few parakeratinizing epithelia such as BBN [N-butyl-N-(4–hydroxybutyl)nitrosamine]-induced murine bladder carcinoma and a restricted subset of oral and single vaginal epithelial cells in higher mammals. Our results provide further evidence that the program of squamous differentiation in internal epithelia of the upper alimentary tract in rodents and higher mammals differ remarkably. In addition, we also have noted the distinct distribution patterns of human loricrin and involucrin, another major precursor protein of the cornified cell envelope.},
	number = {3},
	urldate = {2016-04-19},
	journal = {Differentiation},
	author = {Hohl, Daniel and Olano, Barbara Ruf and de Viragh, Pierre A. and Huber, Marcel and Detrisac, Carol J. and Schnyder, Urs W. and Roop, Dennis R.},
	month = oct,
	year = {1993},
	pages = {25--34}
}

@article{kaplan_low_2012,
	title = {Low {Levels} of beta-{Lactam} {Antibiotics} {Induce} {Extracellular} {DNA} {Release} and {Biofilm} {Formation} in {Staphylococcus} aureus},
	volume = {3},
	issn = {2150-7511},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419523/},
	doi = {10.1128/mBio.00198-12},
	abstract = {Subminimal inhibitory concentrations of antibiotics have been shown to induce bacterial biofilm formation. Few studies have investigated antibiotic-induced biofilm formation in Staphylococcus aureus, an important human pathogen. Our goal was to measure S. aureus biofilm formation in the presence of low levels of β-lactam antibiotics. Fifteen phylogenetically diverse methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains were employed. Methicillin, ampicillin, amoxicillin, and cloxacillin were added to cultures at concentrations ranging from 0× to 1× MIC. Biofilm formation was measured in 96-well microtiter plates using a crystal violet binding assay. Autoaggregation was measured using a visual test tube settling assay. Extracellular DNA was quantitated using agarose gel electrophoresis. All four antibiotics induced biofilm formation in some strains. The amount of biofilm induction was as high as 10-fold and was inversely proportional to the amount of biofilm produced by the strain in the absence of antibiotics. MRSA strains of lineages USA300, USA400, and USA500 exhibited the highest levels of methicillin-induced biofilm induction. Biofilm formation induced by low-level methicillin was inhibited by DNase. Low-level methicillin also induced DNase-sensitive autoaggregation and extracellular DNA release. The biofilm induction phenotype was absent in a strain deficient in autolysin (atl). Our findings demonstrate that subminimal inhibitory concentrations of β-lactam antibiotics significantly induce autolysin-dependent extracellular DNA release and biofilm formation in some strains of S. aureus., The widespread use of antibiotics as growth promoters in agriculture may expose bacteria to low levels of the drugs. The aim of this study was to investigate the effects of low levels of antibiotics on bacterial autoaggregation and biofilm formation, two processes that have been shown to foster genetic exchange and antibiotic resistance. We found that low levels of β-lactam antibiotics, a class commonly used in both clinical and agricultural settings, caused significant autoaggregation and biofilm formation by the important human pathogen Staphylococcus aureus. Both processes were dependent on cell lysis and release of DNA into the environment. The effect was most pronounced among multidrug-resistant strains known as methicillin-resistant S. aureus (MRSA). These results may shed light on the recalcitrance of some bacterial infections to antibiotic treatment in clinical settings and the evolution of antibiotic-resistant bacteria in agricultural settings.},
	number = {4},
	urldate = {2016-05-04},
	journal = {mBio},
	author = {Kaplan, Jeffrey B. and Izano, Era A. and Gopal, Prerna and Karwacki, Michael T. and Kim, Sangho and Bose, Jeffrey L. and Bayles, Kenneth W. and Horswill, Alexander R.},
	month = jul,
	year = {2012},
	pmid = {22851659},
	pmcid = {PMC3419523}
}

@article{noble_aspects_1964,
	title = {Some aspects of nasal carriage of staphylococci},
	volume = {17},
	issn = {0021-9746},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC480678/},
	abstract = {The nasal carrier status of 3,736 patients was determined throughout their stay in hospital. The carrier rate on admission, which was highest in patients under 20 years of age, did not appear to vary with season., The carriage of strains resistant to penicillin increased with the patients' stay in hospital from 13·\% on admission to 20·5\% on discharge, and the acquisition of these strains was enhanced by the administration of antibiotics., Patients discharged from hospital carrying strains of staphylococci acquired in hospital lost them more readily than patients discharged carrying the strain which they had carried on admission, 31\% of those discharged carrying strains resistant to penicillin and tetracycline being readmitted carrying these strains compared with 69\% of those discharged carrying strains sensitive to these antibiotics.},
	number = {1},
	urldate = {2016-05-09},
	journal = {Journal of Clinical Pathology},
	author = {Noble, W. C. and Williams, R. E. O. and Jevons, M. Patricia and Shooter, R. A.},
	month = jan,
	year = {1964},
	pmid = {14100010},
	pmcid = {PMC480678},
	pages = {79--83},
	file = {Noble et al_1964_Some aspects of nasal carriage of staphylococci.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/98TAS58W/Noble et al_1964_Some aspects of nasal carriage of staphylococci.pdf:application/pdf}
}

@article{williams_healthy_1963,
	title = {Healthy {Carriage} {Of} {Staphylococcus} {Aureus}: {Its} {Prevalence} {And} {Importance}},
	volume = {27},
	shorttitle = {{HEALTHY} {CARRIAGE} {OF} {STAPHYLOCOCCUS} {AUREUS}},
	url = {http://www-ncbi-nlm-nih-gov.proxy.uchicago.edu/pmc/articles/PMC441169/},
	number = {1},
	urldate = {2016-05-10},
	journal = {Bacteriological Reviews},
	author = {Williams, R. E. O.},
	month = mar,
	year = {1963},
	pmid = {14000926},
	pages = {56},
	file = {Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/R9V7HBJT/PMC441169.html:text/html;Williams_1963_HEALTHY CARRIAGE OF STAPHYLOCOCCUS AUREUS.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/ZP4IZ3Q6/Williams_1963_HEALTHY CARRIAGE OF STAPHYLOCOCCUS AUREUS.pdf:application/pdf}
}

@article{lovell_skin_1945,
	title = {Skin bacteria: {Their} role in contamination and infection of wounds},
	volume = {51},
	issn = {0272-5533},
	shorttitle = {Skin bacteria},
	url = {http://dx.doi.org/10.1001/archsurg.1945.01230040083002},
	doi = {10.1001/archsurg.1945.01230040083002},
	abstract = {There are seven main sources of contamination of clean operative wounds, namely, instruments, drapes, hands of operating personnel, droplet infection from nose and throat, suture material, air-borne bacteria and organisms in the skin. Hart,1 Meleney,2 Weaver,3 Dandy4 and many others have carried out investigations to prove the existence of these sources of contamination and have devised methods of combating all of them with the exception of bacteria of the skin. In a previous publication,5 it has been shown that most of the transient organisms of the skin are superficial and can be removed by mechanical and chemical cleansing. The resident bacteria are situated so deep in the hair follicles and sebaceous glands that they cannot be removed by mechanical means without injury to the skin. The antiseptics generally used do not penetrate sufficiently to reach the organisms located in the deeper parts of these structures.},
	number = {2},
	urldate = {2016-05-10},
	journal = {Archives of Surgery},
	author = {Lovell, DL},
	month = sep,
	year = {1945},
	pages = {78--80},
	file = {LOVELL DL_1945_Skin bacteria.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/GAWFB4FD/LOVELL DL_1945_Skin bacteria.pdf:application/pdf}
}

@article{lovell_skin_1945-1,
	title = {Skin {Bacteria}-{Their} {Location} {With} {Reference} {To} {Skin} {Sterilization}},
	volume = {80},
	number = {2},
	journal = {Surgery Gynecology \& Obstetrics},
	author = {Lovell, DL},
	year = {1945},
	pages = {174--177}
}

@article{polakowska_virulence_2012,
	series = {Danger signals and immunity},
	title = {The virulence of {Staphylococcus} aureus correlates with strain genotype in a chicken embryo model but not a nematode model},
	volume = {14},
	issn = {1286-4579},
	url = {http://www.sciencedirect.com/science/article/pii/S1286457912002377},
	doi = {10.1016/j.micinf.2012.09.006},
	abstract = {Staphylococcus aureus infections are of major importance in human and veterinary medicine. Studies of the virulence of this bacterium are complicated by inconsistent results obtained in different animal models. We searched for an uncomplicated and inexpensive model suitable to study virulence of poultry strains of S. aureus using a genome-wide approach. We determined that a useful model would clearly differentiate strains of high and low virulence, and that this would generally correlate with the genetic relatedness among strains. To this end Gallus gallus (chicken) embryo and Caenorhabditis elegans (nematode) models were selected, and their response to challenge by a set of well-characterized Staphylococcus strains was evaluated. The chicken embryo model allowed to determine variation in virulence among strains of poultry and human origin. The survival of embryos ranged from 0\% to almost 100\% for the various strains. In contrast, variation in virulence of most strains in the nematode model was comparable, regardless of their origin or genotype, demonstrating limited usefulness of this model. Most importantly, a clear correlation was found between the virulence level in the embryo model and the genotype of the tested poultry strains. Our findings indicate the potential usefulness of embryo model for future identification of host-specific adaptations and virulence factors in S. aureus.},
	number = {14},
	urldate = {2016-06-01},
	journal = {Microbes and Infection},
	author = {Polakowska, Klaudia and Lis, Marcin W. and Helbin, Weronika M. and Dubin, Grzegorz and Dubin, Adam and Niedziolka, Jerzy W. and Miedzobrodzki, Jacek and Wladyka, Benedykt},
	month = nov,
	year = {2012},
	keywords = {Caenorhabditis elegans, Chicken embryo, Host–pathogen interaction, Infection model, Nematode, Staphylococcus aureus},
	pages = {1352--1362},
	file = {Polakowska et al_2012_The virulence of Staphylococcus aureus correlates with strain genotype in a.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/WNXK73JS/Polakowska et al_2012_The virulence of Staphylococcus aureus correlates with strain genotype in a.pdf:application/pdf;ScienceDirect Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/W2DNKHAK/S1286457912002377.html:text/html}
}

@article{kiedrowski_development_2016,
	title = {Development of an in vitro colonization model to investigate {Staphylococcus} aureus interactions with airway epithelia},
	volume = {18},
	copyright = {© 2015 John Wiley \& Sons Ltd},
	issn = {1462-5822},
	url = {http://onlinelibrary.wiley.com.proxy.uchicago.edu/doi/10.1111/cmi.12543/abstract},
	doi = {10.1111/cmi.12543},
	abstract = {Staphylococcus aureus is a bacterial pathogen responsible for a wide range of diseases and is also a human commensal colonizing the upper respiratory tract. Strains belonging to the clonal complex group CC30 are associated with colonization, although the colonization state itself is not clearly defined. In this work, we developed a co-culture model with S. aureus colonizing the apical surface of polarized human airway epithelial cells. The S. aureus are grown at the air–liquid interface to allow an in-depth evaluation of a simulated colonization state. Exposure to wild-type, S. aureus bacteria or conditioned media killed airway epithelial cells within 1 day, while mutant S. aureus strains lacking alpha-toxin (hla) persisted on viable cells for at least 2 days. Recent S. aureus CC30 isolates are natural hla mutants, and we observed that these strains displayed reduced toxicity toward airway epithelial cells. Quantitative real-time polymerase chain reaction of known virulence factors showed the expression profile of S. aureus grown in co-culture correlates with results from previous human colonization studies. Microarray analysis indicated significant shifts in S. aureus physiology in the co-culture model toward lipid and amino acid metabolism. The development of the in vitro colonization model will enable further study of specific S. aureus interactions with the host epithelia.},
	language = {en},
	number = {5},
	urldate = {2016-06-09},
	journal = {Cellular Microbiology},
	author = {Kiedrowski, Megan R. and Paharik, Alexandra E. and Ackermann, Laynez W. and Shelton, Annie U. and Singh, Sachinkumar B. and Starner, Timothy D. and Horswill, Alexander R.},
	month = may,
	year = {2016},
	pages = {720--732},
	file = {Kiedrowski et al_2016_Development of an in vitro colonization model to investigate Staphylococcus.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/HHHVVKZU/Kiedrowski et al_2016_Development of an in vitro colonization model to investigate Staphylococcus.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/M77W28VP/abstract\;jsessionid=C5143FA1B52C19DED7901AA06A2944B7.html:text/html}
}

@article{miko_high_2012,
	title = {High prevalence of colonization with {Staphylococcus} aureus clone {USA}300 at multiple body sites among sexually transmitted disease clinic patients: an unrecognized reservoir},
	volume = {14},
	issn = {1286-4579},
	shorttitle = {High prevalence of colonization with {Staphylococcus} aureus clone {USA}300 at multiple body sites among sexually transmitted disease clinic patients},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662241/},
	doi = {10.1016/j.micinf.2012.06.004},
	abstract = {Extranasal colonization is increasingly recognized as an important reservoir for Staphylococcus aureus among high-risk populations. We conducted a cross-sectional study of multiple body site colonization among 173 randomly selected STD clinic patients in Baltimore, Maryland. Staphylococcal carriage at extranasal sites, including the oropharynx, groin, rectum, and genitals, was common among study subjects. The USA300 clone was particularly associated with multiple sites of colonization compared with non-USA300 strains (p = .01). Given their high burden of multi-site colonization and confluence of established staphylococcal risk factors, STD clinic patients may represent a community-based reservoir for S. aureus and be well suited for innovative infection control initiatives.},
	number = {12},
	urldate = {2016-06-10},
	journal = {Microbes and infection / Institut Pasteur},
	author = {Miko, Benjamin A. and Uhlemann, Anne-Catrin and Gelman, Amanda and Lee, Caroline J. and Hafer, Cory A. and Sullivan, Sean B. and Shi, Qiuhu and Miller, Maureen and Zenilman, Jonathan and Lowy, Franklin D.},
	month = oct,
	year = {2012},
	pmid = {22728758},
	pmcid = {PMC3662241},
	pages = {1040--1043},
	file = {Miko et al_2012_High prevalence of colonization with Staphylococcus aureus clone USA300 at.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/3RA8ENMW/Miko et al_2012_High prevalence of colonization with Staphylococcus aureus clone USA300 at.pdf:application/pdf}
}

@article{matoltsy_desmosomes_1975,
	title = {Desmosomes, {Filaments}, {And} {Keratohyaline} {Granules}: {Their} {Role} {In} {The} {Stabilization} {And} {Keratinization} of {The} {Epidermis}},
	volume = {65},
	issn = {0022-202X},
	shorttitle = {Desmosomes, {Filaments}, {And} {Keratohyaline} {Granules}},
	url = {http://www.sciencedirect.com/science/article/pii/S0022202X15445580},
	doi = {10.1111/1523-1747.ep12598093},
	abstract = {Components of desmosomes, filaments, and keratohyaline granules were studied by electron microscope and biochemical methods to clarify their role in the stabilization and keratinization of the epidermis. Isolated desmosomes are composed of 76\% protein, 17\% carbohydrate, and 10\% lipid. The bulk of protein consists of a “spectrin”-like fibrous protein, presumably present in the plaque, and of glycoproteins in the desmosomal interspace. The main component of filaments, prekeratin, is a low-sulfur α-protein composed of a pair of three-chain subunits with non-α-helical segments separated by 200 Å-long α-helical regions. The major component of isolated keratohyaline granules, the amorphous particulate material, is formed by a high-sulfur protein with a single-type of polypeptide chain. polypeptide chains comparable to those found in prekeratin and keratohyaline granules were recovered from extracts of horny cells. Within the living part of the epidermis, filaments hypothetically form a cytoskeletal system which is anchored to desmosomes by a filamentous plaque protein. Glycoproteins are involved in the formation of strong junctions between the cells which enable the living part of the epidermis to respond as a whole to mechanical stress. The stratum corneum is stabilized by a similar system in a consolidated state which is less extensible. Horny cells are enveloped by a thickened membrane and the interfilamentous spaces are filled with various proteins, including the sulfur-rich amorphous protein found in keratohyaline granules.},
	number = {1},
	urldate = {2016-06-10},
	journal = {Journal of Investigative Dermatology},
	author = {Matoltsy, A Gedeon},
	month = jul,
	year = {1975},
	pages = {127--142},
	file = {Matoltsy_1975_Desmosomes, Filaments, And Keratohyaline Granules.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/6GN3DT97/Matoltsy_1975_Desmosomes, Filaments, And Keratohyaline Granules.pdf:application/pdf;ScienceDirect Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/6CEWMFCB/S0022202X15445580.html:text/html}
}

@article{anderl_role_2000,
	title = {Role of {Antibiotic} {Penetration} {Limitation} in {Klebsiella} pneumoniae {Biofilm} {Resistance} to {Ampicillin} and {Ciprofloxacin}},
	volume = {44},
	issn = {0066-4804, 1098-6596},
	url = {http://aac.asm.org/content/44/7/1818},
	doi = {10.1128/AAC.44.7.1818-1824.2000},
	abstract = {The penetration of two antibiotics, ampicillin and ciprofloxacin, through biofilms developed in an in vitro model system was investigated. The susceptibilities of biofilms and corresponding freely suspended bacteria to killing by the antibiotics were also measured. Biofilms of Klebsiella pneumoniae were developed on microporous membranes resting on agar nutrient medium. The susceptibilities of planktonic cultures and biofilms to 10 times the MIC were determined. Antibiotic penetration through biofilms was measured by assaying the concentration of antibiotic that diffused through the biofilm to an overlying filter disk. Parallel experiments were performed with a mutant K. pneumoniae strain in which β-lactamase activity was eliminated. For wild-type K. pneumoniae grown in suspension culture, ampicillin and ciprofloxacin MICs were 500 and 0.18 μg/ml, respectively. The log reductions in the number of CFU of planktonic wild-type bacteria after 4 h of treatment at 10 times the MIC were 4.43 ± 0.33 and 4.14 ± 0.33 for ampicillin and ciprofloxacin, respectively. Biofilms of the same strain were much less susceptible, yielding log reductions in the number of CFU of −0.06 ± 0.06 and 1.02 ± 0.04 for ampicillin and ciprofloxacin, respectively, for the same treatment. The number of CFU in the biofilms after 24 h of antibiotic exposure was not statistically different from the number after 4 h of treatment. Ampicillin did not penetrate wild-typeK. pneumoniae biofilms, whereas ciprofloxacin and a nonreactive tracer (chloride ion) penetrated the biofilms quickly. The concentration of ciprofloxacin reached the MIC throughout the biofilm within 20 min. Ampicillin penetrated biofilms formed by a β-lactamase-deficient mutant. However, the biofilms formed by this mutant were resistant to ampicillin treatment, exhibiting a 0.18 ± 0.07 log reduction in the number of CFU after 4 h of exposure and a 1.64 ± 0.33 log reduction in the number of CFU after 24 h of exposure. Poor penetration contributed to wild-type biofilm resistance to ampicillin but not to ciprofloxacin. The increased resistance of the wild-type strain to ciprofloxacin and the mutant strain to ampicillin and ciprofloxacin could not be accounted for by antibiotic inactivation or slow diffusion since these antibiotics fully penetrated the biofilms. These results suggest that some other resistance mechanism is involved for both agents.},
	language = {en},
	number = {7},
	urldate = {2016-06-10},
	journal = {Antimicrobial Agents and Chemotherapy},
	author = {Anderl, Jeff N. and Franklin, Michael J. and Stewart, Philip S.},
	month = jul,
	year = {2000},
	pmid = {10858336},
	pages = {1818--1824},
	file = {Anderl et al_2000_Role of Antibiotic Penetration Limitation in Klebsiella pneumoniae Biofilm.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/B8HUE3JI/Anderl et al_2000_Role of Antibiotic Penetration Limitation in Klebsiella pneumoniae Biofilm.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/QI42829B/1818.html:text/html}
}

@article{ranjit_staphylococcus_2011,
	title = {Staphylococcus aureus {CidA} and {LrgA} {Proteins} {Exhibit} {Holin}-{Like} {Properties}},
	volume = {193},
	issn = {0021-9193, 1098-5530},
	url = {http://jb.asm.org/content/193/10/2468},
	doi = {10.1128/JB.01545-10},
	abstract = {The Staphylococcus aureus cid and lrg operons are known to be involved in biofilm formation by controlling cell lysis and the release of genomic DNA, which ultimately becomes a structural component of the biofilm matrix. Although the molecular mechanisms controlling cell death and lysis are unknown, it has been hypothesized that the cidA and lrgA genes encode holin- and antiholin-like proteins and function to regulate these processes similarly to bacteriophage-induced death and lysis. In this study, we focused on the biochemical and molecular characterization of CidA and LrgA with the goal of testing the holin model. First, membrane fractionation and fluorescent protein fusion studies revealed that CidA and LrgA are membrane-associated proteins. Furthermore, similarly to holins, CidA and LrgA were found to oligomerize into high-molecular-mass complexes whose formation was dependent on disulfide bonds formed between cysteine residues. To determine the function of disulfide bond-dependent oligomerization of CidA, an S. aureus mutant in which the wild-type copy of the cidA gene was replaced with the cysteine mutant allele was generated. As determined by β-galactosidase release assays, this mutant exhibited increased cell lysis during stationary phase, suggesting that oligomerization has a negative impact on this process. When analyzed for biofilm development and maturation, this mutant displayed increased biofilm adhesion in a static assay and a greater amount of dead-cell accumulation during biofilm maturation. These studies support the model that CidA and LrgA proteins are bacterial holin-/antiholin-like proteins that function to control cell death and lysis during biofilm development.},
	language = {en},
	number = {10},
	urldate = {2016-06-10},
	journal = {Journal of Bacteriology},
	author = {Ranjit, Dev K. and Endres, Jennifer L. and Bayles, Kenneth W.},
	month = may,
	year = {2011},
	pmid = {21421752},
	pages = {2468--2476},
	file = {Ranjit et al_2011_Staphylococcus aureus CidA and LrgA Proteins Exhibit Holin-Like Properties.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/THHZJCX9/Ranjit et al_2011_Staphylococcus aureus CidA and LrgA Proteins Exhibit Holin-Like Properties.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/WNNXQ5RS/2468.html:text/html}
}

@article{foulston_extracellular_2014,
	title = {The {Extracellular} {Matrix} of {Staphylococcus} aureus {Biofilms} {Comprises} {Cytoplasmic} {Proteins} {That} {Associate} with the {Cell} {Surface} in {Response} to {Decreasing} {pH}},
	volume = {5},
	issn = {, 2150-7511},
	url = {http://mbio.asm.org/content/5/5/e01667-14},
	doi = {10.1128/mBio.01667-14},
	abstract = {Biofilm formation by Staphylococcus aureus involves the formation of an extracellular matrix, but the composition of this matrix has been uncertain. Here we report that the matrix is largely composed of cytoplasmic proteins that reversibly associate with the cell surface in a manner that depends on pH. We propose a model for biofilm formation in which cytoplasmic proteins are released from cells in stationary phase. These proteins associate with the cell surface in response to decreasing pH during biofilm formation. Rather than utilizing a dedicated matrix protein, S. aureus appears to recycle cytoplasmic proteins that moonlight as components of the extracellular matrix.
IMPORTANCE Staphylococcus aureus is a leading cause of multiantibiotic-resistant nosocomial infections and is often found growing as a biofilm in catheters and chronic wounds. Biofilm formation is an important pathogenicity strategy that enhances resistance to antimicrobials, thereby limiting treatment options and ultimately contributing to increased morbidity and mortality. Cells in a biofilm are held together by an extracellular matrix that consists in whole or in part of protein, but the nature of the proteins in the S. aureus matrix is not well understood. Here we postulate that S. aureus recycles proteins from the cytoplasm to form the extracellular matrix. This strategy, of cytoplasmic proteins moonlighting as matrix proteins, could allow enhanced flexibility and adaptability for S. aureus in forming biofilms under infection conditions and could promote the formation of mixed-species biofilms in chronic wounds.},
	language = {en},
	number = {5},
	urldate = {2016-06-10},
	journal = {mBio},
	author = {Foulston, Lucy and Elsholz, Alexander K. W. and DeFrancesco, Alicia S. and Losick, Richard},
	month = oct,
	year = {2014},
	pmid = {25182325},
	pages = {e01667--14},
	file = {Foulston et al_2014_The Extracellular Matrix of Staphylococcus aureus Biofilms Comprises.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/9X82EKVX/Foulston et al_2014_The Extracellular Matrix of Staphylococcus aureus Biofilms Comprises.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/E6MJKMME/e01667-14.html:text/html}
}

@article{schindelin_fiji:_2012,
	title = {Fiji: an open-source platform for biological-image analysis},
	volume = {9},
	copyright = {© 2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
	issn = {1548-7091},
	shorttitle = {Fiji},
	url = {http://www.nature.com.proxy.uchicago.edu/nmeth/journal/v9/n7/full/nmeth.2019.html},
	doi = {10.1038/nmeth.2019},
	abstract = {Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.},
	language = {en},
	number = {7},
	urldate = {2016-06-23},
	journal = {Nature Methods},
	author = {Schindelin, Johannes and Arganda-Carreras, Ignacio and Frise, Erwin and Kaynig, Verena and Longair, Mark and Pietzsch, Tobias and Preibisch, Stephan and Rueden, Curtis and Saalfeld, Stephan and Schmid, Benjamin and Tinevez, Jean-Yves and White, Daniel James and Hartenstein, Volker and Eliceiri, Kevin and Tomancak, Pavel and Cardona, Albert},
	month = jul,
	year = {2012},
	keywords = {Imaging, Software},
	pages = {676--682},
	file = {Schindelin et al_2012_Fiji.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/DV8J5MMU/Schindelin et al_2012_Fiji.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/PRB493G4/nmeth.2019.html:text/html}
}

@article{williams_skin_1946,
	title = {Skin and nose carriage of bacteriophage types of {Staph}. aureus},
	volume = {58},
	issn = {1555-2039},
	url = {http://onlinelibrary.wiley.com.proxy.uchicago.edu/doi/10.1002/path.1700580214/abstract},
	doi = {10.1002/path.1700580214},
	language = {en},
	number = {2},
	urldate = {2016-06-25},
	journal = {The Journal of Pathology and Bacteriology},
	author = {Williams, R. E. O.},
	month = apr,
	year = {1946},
	pages = {259--268},
	file = {Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/9X9FQSSV/abstract.html:text/html;Williams_1946_Skin and nose carriage of bacteriophage types of Staph.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/AH4ENGEV/Williams_1946_Skin and nose carriage of bacteriophage types of Staph.pdf:application/pdf}
}

@article{bubeck_wardenburg_poring_2007,
	title = {Poring over pores: alpha-hemolysin and {Panton}-{Valentine} leukocidin in {Staphylococcus} aureus pneumonia},
	volume = {13},
	copyright = {© 2007 Nature Publishing Group},
	issn = {1078-8956},
	shorttitle = {Poring over pores},
	url = {http://www.nature.com.proxy.uchicago.edu/nm/journal/v13/n12/full/nm1207-1405.html},
	doi = {10.1038/nm1207-1405},
	abstract = {Nature Medicine is the premier journal for biomedical research. Respected internationally for the quality of its papers on areas ranging from infectious disease to cancer and neurodegeneration, Nature Medicine aims to bridge the gap between basic research and medical advances and is consistently ranked the number one journal by the Institute of Scientific Investigation in the Medicine, Research and Experimental category.},
	number = {12},
	urldate = {2016-07-22},
	journal = {Nature Medicine},
	author = {Bubeck Wardenburg, Juliane and Bae, Taeok and Otto, Michael and DeLeo, Frank R. and Schneewind, Olaf},
	month = dec,
	year = {2007},
	pages = {1405--1406},
	file = {Bubeck Wardenburg et al_2007_Poring over pores.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/CA3UJTFU/Bubeck Wardenburg et al_2007_Poring over pores.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/IGW2DXVX/nm1207-1405.html:text/html}
}

@article{nair_whole-genome_2011,
	title = {Whole-{Genome} {Sequencing} of {Staphylococcus} aureus {Strain} {RN}4220, a {Key} {Laboratory} {Strain} {Used} in {Virulence} {Research}, {Identifies} {Mutations} {That} {Affect} {Not} {Only} {Virulence} {Factors} but {Also} the {Fitness} of the {Strain}},
	volume = {193},
	issn = {0021-9193, 1098-5530},
	url = {http://jb.asm.org/content/193/9/2332},
	doi = {10.1128/JB.00027-11},
	abstract = {Staphylococcus aureus RN4220, a cloning intermediate, is sometimes used in virulence, resistance, and metabolic studies. Using whole-genome sequencing, we showed that RN4220 differs from NCTC8325 and contains a number of genetic polymorphisms that affect both virulence and general fitness, implying a need for caution in using this strain for such studies.},
	language = {en},
	number = {9},
	urldate = {2016-09-11},
	journal = {Journal of Bacteriology},
	author = {Nair, Dhanalakshmi and Memmi, Guido and Hernandez, David and Bard, Jonathan and Beaume, Marie and Gill, Steven and Francois, Patrice and Cheung, Ambrose L.},
	month = may,
	year = {2011},
	pmid = {21378186},
	pages = {2332--2335},
	file = {Nair et al_2011_Whole-Genome Sequencing of Staphylococcus aureus Strain RN4220, a Key.pdf:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/5XE59ZU6/Nair et al_2011_Whole-Genome Sequencing of Staphylococcus aureus Strain RN4220, a Key.pdf:application/pdf;Snapshot:/home/danwchan/.mozilla/firefox/3x20cw5z.default/zotero/storage/T3AZAT95/2332.html:text/html}
}

@misc{chan_organotypic_2016,
	title = {Organotypic {Model}},
	url = {osf.io/gmxye},
	publisher = {Open Science Framework},
	author = {Chan, Daniel},
	year = {2016}
}

@book{r_core_team_r:_2015,
	address = {Vienna, Austria},
	title = {R: {A} {Language} and {Environment} for {Statistical} {Computing}},
	url = {http://www.R-project.org/},
	publisher = {R Foundation for Statistical Computing},
	author = {{R Core Team}},
	year = {2015}
}