{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:51:40Z","timestamp":1791255100691,"version":"4.1.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T00:00:00Z","timestamp":1441152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"DOI":"10.1371\/journal.pbio.1002229","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T18:32:00Z","timestamp":1441218720000},"page":"e1002229","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":140,"title":["Evolutionary Trade-Offs Underlie the Multi-faceted Virulence of Staphylococcus aureus"],"prefix":"10.1371","volume":"13","author":[{"given":"Maisem","family":"Laabei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Catrin","family":"Uhlemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin D.","family":"Lowy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise D.","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Ouadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Feil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry A.","family":"Thorpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnabas","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Dordel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Holden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina A.","family":"Votintseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Bowden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick W.","family":"Crook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette C.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Recker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth C.","family":"Massey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,9,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1365-2958.1991.tb00723.x","article-title":"Pore-forming cytolysins of gram-negative bacteria","volume":"5","author":"RA Welch","year":"1991","journal-title":"Mol Microbiol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/MMBR.60.1.167-215.1996","article-title":"Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion","volume":"60","author":"CL Sears","year":"1996","journal-title":"Microbiol Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1128\/CMR.13.1.16-34.2000","article-title":"Exotoxins of Staphylococcus aureus","volume":"13","author":"MM Dinges","year":"2000","journal-title":"Clin Microbiol Rev"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/nature07822","article-title":"Toxin B is essential for virulence of Clostridium difficile","volume":"458","author":"D Lyras","year":"2009","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev.micro.112408.134309","article-title":"Basis of virulence in community-associated methicillin-resistant Staphylococcus aureus","volume":"64","author":"M Otto","year":"2010","journal-title":"Annu Rev Microbiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1038\/nrmicro1289","article-title":"Immune evasion by staphylococci","volume":"3","author":"TJ Foster","year":"2005","journal-title":"Nat Rev Microbiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.tim.2005.10.002","article-title":"Staphylococcal innate immune evasion","volume":"13","author":"SH Rooijakkers","year":"2005","journal-title":"Trends Microbiol"},{"issue":"Suppl 5","key":"ref8","doi-asserted-by":"crossref","first-page":"S350","DOI":"10.1086\/533591","article-title":"Pathogenesis of methicillin-resistant Staphylococcus aureus infection","volume":"46","author":"RJ Gordon","year":"2008","journal-title":"Clin Infect Dis"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"FD Lowy","year":"1998","journal-title":"N Engl J Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1128\/JB.184.5.1430-1437.2002","article-title":"In vitro serial passage of Staphylococcus aureus: changes in physiology, virulence factor production, and agr nucleotide sequence","volume":"184","author":"GA Somerville","year":"2002","journal-title":"J Bacteriol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"15876","DOI":"10.1073\/pnas.0705653104","article-title":"Social cheating in Pseudomonas aeruginosa quorum sensing","volume":"104","author":"KM Sandoz","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e1004298","DOI":"10.1371\/journal.ppat.1004298","article-title":"Production of an attenuated phenol-soluble modulin variant unique to the MRSA clonal complex 30 increases severity of bloodstream infection","volume":"10","author":"GY Cheung","year":"2014","journal-title":"PLoS Pathog"},{"issue":"12","key":"ref13","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1093\/infdis\/jiu554","article-title":"Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus","volume":"211","author":"HR Rose","year":"2014","journal-title":"J Infect Dis"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1093\/infdis\/jis483","article-title":"Nasal carriage as a source of agr-defective Staphylococcus aureus bacteremia","volume":"206","author":"DS Smyth","year":"2012","journal-title":"J Infect Dis"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1086\/423145","article-title":"Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein","volume":"190","author":"VG Fowler Jr.","year":"2004","journal-title":"J Infect Dis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1099\/mic.0.2007\/011874-0","article-title":"agr function in clinical Staphylococcus aureus isolates","volume":"154","author":"KE Traber","year":"2008","journal-title":"Microbiology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1086\/656915","article-title":"Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus","volume":"202","author":"B Shopsin","year":"2010","journal-title":"J Infect Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.tim.2008.05.002","article-title":"The role of virulence determinants in community-associated MRSA pathogenesis","volume":"16","author":"BA Diep","year":"2008","journal-title":"Trends Microbiol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1471-2180-14-31","article-title":"Hyperexpression of alpha-hemolysin explains enhanced virulence of sequence type 93 community-associated methicillin-resistant Staphylococcus aureus","volume":"14","author":"KY Chua","year":"2014","journal-title":"BMC Microbiol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1128\/IAI.70.1.127-133.2002","article-title":"Staphylococcus aureus agr and sarA functions are required for invasive infection but not inflammatory responses in the lung","volume":"70","author":"G Heyer","year":"2002","journal-title":"Infect Immun"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1128\/IAI.63.9.3373-3380.1995","article-title":"Role of the accessory gene regulator (agr) in pathogenesis of staphylococcal osteomyelitis","volume":"63","author":"AF Gillaspy","year":"1995","journal-title":"Infect Immun"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1172\/JCI117530","article-title":"Diminished virulence of a sar-\/agr- mutant of Staphylococcus aureus in the rabbit model of endocarditis","volume":"94","author":"AL Cheung","year":"1994","journal-title":"J Clin Invest"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1128\/IAI.61.9.3879-3885.1993","article-title":"The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine arthritis model","volume":"61","author":"A Abdelnour","year":"1993","journal-title":"Infect Immun"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1093\/infdis\/jir845","article-title":"Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant Staphylococcus aureus by interfering with the agr quorum sensing system","volume":"205","author":"JK Rudkin","year":"2012","journal-title":"J Infect Dis"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1073\/pnas.1113219109","article-title":"Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease","volume":"109","author":"BC Young","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6738","DOI":"10.1073\/pnas.1401006111","article-title":"Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community","volume":"111","author":"AC Uhlemann","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1096\/fj.12-220509","article-title":"C5L2: a controversial receptor of complement anaphylatoxin, C5a","volume":"27","author":"R Li","year":"2013","journal-title":"FASEB J"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"5231","DOI":"10.1128\/JB.05454-11","article-title":"Rsp inhibits attachment and biofilm formation by repressing fnbA in Staphylococcus aureus MW2","volume":"193","author":"MG Lei","year":"2011","journal-title":"J Bacteriol"},{"key":"ref29","first-page":"e00537","article-title":"A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes","volume":"4","author":"PD Fey","year":"2013","journal-title":"MBio"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1101\/gr.165415.113","article-title":"Predicting the virulence of MRSA from its genome sequence","volume":"24","author":"M Laabei","year":"2014","journal-title":"Genome Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1128\/JB.00987-10","article-title":"Staphylococcus aureus ClpC divergently regulates capsule via sae and codY in strain newman but activates capsule via codY in strain UAMS-1 and in strain Newman with repaired saeS","volume":"193","author":"TT Luong","year":"2011","journal-title":"J Bacteriol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1128\/MMBR.00005-09","article-title":"At the crossroads of bacterial metabolism and virulence factor synthesis in Staphylococci","volume":"73","author":"GA Somerville","year":"2009","journal-title":"Microbiol Mol Biol Rev"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nrmicro732","article-title":"The damage-response framework of microbial pathogenesis","volume":"1","author":"A Casadevall","year":"2003","journal-title":"Nat Rev Microbiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1078\/1438-4221-00112","article-title":"Regulation of virulence determinants in Staphylococcus aureus","volume":"291","author":"S Arvidson","year":"2001","journal-title":"Int J Med Microbiol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.femsre.2003.09.003","article-title":"Regulation of virulence determinants in Staphylococcus aureus: complexity and applications","volume":"28","author":"S Bronner","year":"2004","journal-title":"FEMS Microbiol Rev"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"7413","DOI":"10.4049\/jimmunol.1000675","article-title":"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus","volume":"185","author":"FH Pilsczek","year":"2010","journal-title":"J Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1128\/AEM.05316-11","article-title":"Expression of virulence factors by Staphylococcus aureus grown in serum","volume":"77","author":"Y Oogai","year":"2011","journal-title":"Appl Environ Microbiol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e18617","DOI":"10.1371\/journal.pone.0018617","article-title":"Global changes in Staphylococcus aureus gene expression in human blood","volume":"6","author":"N Malachowa","year":"2011","journal-title":"PLoS One"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e1002606","DOI":"10.1371\/journal.ppat.1002606","article-title":"Inactivation of staphylococcal phenol soluble modulins by serum lipoprotein particles","volume":"8","author":"BG Surewaard","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jinf.2013.10.015","article-title":"Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies","volume":"68","author":"AJ Kaasch","year":"2014","journal-title":"J Infect"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1056\/NEJMoa1109910","article-title":"Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak","volume":"366","author":"CU Koser","year":"2012","journal-title":"N Engl J Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1128\/JCM.03332-12","article-title":"Outbreak investigation using high-throughput genome sequencing within a diagnostic microbiology laboratory","volume":"51","author":"NL Sherry","year":"2013","journal-title":"J Clin Microbiol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1002129","DOI":"10.1371\/journal.ppat.1002129","article-title":"The impact of recombination on dN\/dS within recently emerged bacterial clones","volume":"7","author":"S Castillo-Ramirez","year":"2011","journal-title":"PLoS Pathog"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"R126","DOI":"10.1186\/gb-2012-13-12-r126","article-title":"Phylogeographic variation in recombination rates within a global clone of methicillin-resistant Staphylococcus aureus","volume":"13","author":"S Castillo-Ramirez","year":"2012","journal-title":"Genome Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"11923","DOI":"10.1073\/pnas.1305559110","article-title":"Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter","volume":"110","author":"SK Sheppard","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/ng.2747","article-title":"Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis","volume":"45","author":"MR Farhat","year":"2013","journal-title":"Nat Genet"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ng.3148","article-title":"Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis","volume":"47","author":"RL Marvig","year":"2015","journal-title":"Nat Genet"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13073-014-0109-z","article-title":"Characterizing the genetic basis of bacterial phenotypes using genome-wide association studies: a new direction for bacteriology","volume":"6","author":"TD Read","year":"2014","journal-title":"Genome Med"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1093\/gbe\/evu092","article-title":"Dissecting vancomycin-intermediate resistance in staphylococcus aureus using genome-wide association","volume":"6","author":"MT Alam","year":"2014","journal-title":"Genome Biol Evol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e1003959","DOI":"10.1371\/journal.ppat.1003959","article-title":"Clonal expansion during Staphylococcus aureus infection dynamics reveals the effect of antibiotic intervention","volume":"10","author":"G McVicker","year":"2014","journal-title":"PLoS Pathog"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1128\/JCM.00156-08","article-title":"Identification of factors contributing to T-cell toxicity of Staphylococcus aureus clinical isolates","volume":"46","author":"J Collins","year":"2008","journal-title":"J Clin Microbiol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0140-6736(06)68231-7","article-title":"Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus","volume":"367","author":"BA Diep","year":"2006","journal-title":"Lancet"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1126\/science.1198545","article-title":"Rapid pneumococcal evolution in response to clinical interventions","volume":"331","author":"NJ Croucher","year":"2011","journal-title":"Science"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"e1000964","DOI":"10.1371\/journal.ppat.1000964","article-title":"Staphylococcus aureus host cell invasion and virulence in sepsis is facilitated by the multiple repeats within FnBPA","volume":"6","author":"AM Edwards","year":"2010","journal-title":"PLoS Pathog"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nprot.2013.163","article-title":"Identification and quantification of aminophospholipid molecular species on the surface of apoptotic and activated cells","volume":"9","author":"CP Thomas","year":"2014","journal-title":"Nat Protoc"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"e71151","DOI":"10.1371\/journal.pone.0071151","article-title":"Emergence of daptomycin resistance in daptomycin-naive rabbits with methicillin-resistant Staphylococcus aureus prosthetic joint infection is associated with resistance to host defense cationic peptides and mprF polymorphisms","volume":"8","author":"NN Mishra","year":"2013","journal-title":"PLoS One"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1128\/IAI.65.3.890-896.1997","article-title":"Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates","volume":"65","author":"W Ziebuhr","year":"1997","journal-title":"Infect Immun"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1086\/285289","article-title":"Long-term experimental evolution in Escherichia coli. I. Adaptation and divergence during 2,000 generations","volume":"138","author":"RE Lenski","year":"1991","journal-title":"The American Naturalist"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pbio.1002229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T22:32:24Z","timestamp":1599517944000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.1002229"}},"subtitle":[],"editor":[{"given":"David S.","family":"Schneider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,9,2]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.1002229","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,2]]}}}