{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:17:26Z","timestamp":1787501846085,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012394","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000}}],"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["SINGH19R0"],"award-info":[{"award-number":["SINGH19R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30 DK089507"],"award-info":[{"award-number":["P30 DK089507"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K23 AR080209"],"award-info":[{"award-number":["K23 AR080209"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is a facultative intracellular pathogen of human macrophages, which facilitates chronic infection. The genotypes, pathways, and mutations influencing that phenotype remain incompletely explored. Here, we used two distinct strategies to ascertain\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    gene mutations affecting pathogenesis in macrophages. First, we analyzed isolates collected serially from chronic cystic fibrosis (CF) respiratory infections. We found that\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    strains evolved greater macrophage invasion capacity during chronic human infection. Bacterial genome-wide association studies (GWAS) identified 127 candidate genes for which mutation was significantly associated with macrophage pathogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In parallel, we passaged laboratory\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    strains\n                    <jats:italic>in vitro<\/jats:italic>\n                    to select for increased infection of human THP-1 derived macrophages, which identified 15 candidate genes by whole-genome sequencing. Functional validation of candidate genes using isogenic transposon mutant knockouts and CRISPR interference (CRISPRi) knockdowns confirmed virulence contributions from 37 of 39 tested genes (95%) implicated by\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies and 7 of 10 genes (70%) ascertained from\n                    <jats:italic>in vitro<\/jats:italic>\n                    selection, with one gene in common to the two strategies. Validated genes included 17 known virulence factors (39%) and 27 newly identified by our study (61%), some encoding functions not previously associated with macrophage pathogenesis. Most genes (80%) positively impacted macrophage invasion when disrupted, consistent with the phenotype readily arising from loss-of-function mutations\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This work reveals genes and mechanisms that contribute to\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    infection of macrophages, highlights differences in mutations underlying convergent phenotypes arising from\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    systems, and supports the relevance of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    macrophage pathogenesis during chronic respiratory infection in CF. Additional studies will be needed to illuminate the exact mechanisms by which implicated mutations affect their phenotypes.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012394","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T14:00:37Z","timestamp":1720706437000},"page":"e1012394","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical and in vitro models identify distinct adaptations enhancing Staphylococcus aureus pathogenesis in human macrophages"],"prefix":"10.1371","volume":"20","author":[{"given":"Dustin R.","family":"Long","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yu","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsi","family":"Penewit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Almazan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Hodgson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nova F.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe H.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janessa D.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Waalkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wolter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-6992","authenticated-orcid":true,"given":"Stephen J.","family":"Salipante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ppat.1012394.ref001","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.620339","article-title":"The Role of Macrophages in Staphylococcus aureus Infection.620339","volume":"11","author":"GR Pidwill","year":"2021","journal-title":"Front Immunol"},{"issue":"8","key":"ppat.1012394.ref002","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.ijmm.2013.09.012","article-title":"Extended Staphylococcus aureus persistence in cystic fibrosis is associated with bacterial adaptation","volume":"303","author":"N Hirschhausen","year":"2013","journal-title":"Int J Med Microbiol"},{"issue":"4","key":"ppat.1012394.ref003","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1099\/00222615-45-4-294","article-title":"Persistence of Staphylococcus aureus strains among cystic fibrosis patients over extended periods of time","volume":"45","author":"C Branger","year":"1996","journal-title":"J Med Microbiol"},{"issue":"9","key":"ppat.1012394.ref004","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1164\/rccm.202003-0735OC","article-title":"Polyclonality, Shared Strains, and Convergent Evolution in Chronic Cystic Fibrosis Staphylococcus aureus Airway Infection","volume":"203","author":"DR Long","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"ppat.1012394.ref005","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1097\/INF.0000000000000204","article-title":"Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolated in serial cultures from the respiratory tract of children with cystic fibrosis.","volume":"33","author":"D Al-Zubeidi","year":"2014","journal-title":"Pediatr Infect Dis J."},{"issue":"5","key":"ppat.1012394.ref006","doi-asserted-by":"crossref","first-page":"O285","DOI":"10.1111\/1469-0691.12406","article-title":"Intravenous antibiotics given for 2 weeks do not eradicate persistent Staphylococcus aureus clones in cystic fibrosis patients","volume":"20","author":"C Andersen","year":"2014","journal-title":"Clin Microbiol Infect"},{"issue":"10","key":"ppat.1012394.ref007","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1002\/bies.201400080","article-title":"Staphylococcus aureus chronic and relapsing infections: Evidence of a role for persister cells: An investigation of persister cells, their formation and their role in S. aureus disease","volume":"36","author":"BP Conlon","year":"2014","journal-title":"Bioessays"},{"issue":"8","key":"ppat.1012394.ref008","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ijmm.2010.08.003","article-title":"Adaptation of Staphylococcus aureus to the cystic fibrosis lung","volume":"300","author":"C Goerke","year":"2010","journal-title":"Int J Med Microbiol"},{"issue":"4","key":"ppat.1012394.ref009","doi-asserted-by":"crossref","first-page":"e1004870","DOI":"10.1371\/journal.ppat.1004870","article-title":"Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections.","volume":"11","author":"L Tuchscherr","year":"2015","journal-title":"PLoS Pathog."},{"key":"ppat.1012394.ref010","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fcimb.2018.00018","article-title":"Mutation of Agr Is Associated with the Adaptation ofStaphylococcus aureusto the Host during Chronic Osteomyelitis","volume":"8","author":"CM Suligoy","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"ppat.1012394.ref011","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1128\/CMR.00042-09","article-title":"Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and","volume":"23","author":"BP Howden","year":"2010","journal-title":"Clinical Implications. Clinical Microbiology Reviews"},{"key":"ppat.1012394.ref012","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fcimb.2012.00043","article-title":"Intracellular Staphylococcus aureus: live-in and let die","volume":"2","author":"M Fraunholz","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"issue":"8","key":"ppat.1012394.ref013","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0966-842X(00)01803-5","article-title":"Is Staphylococcus aureus an intracellular pathogen","volume":"8","author":"FD Lowy","year":"2000","journal-title":"Trends Microbiol"},{"issue":"2","key":"ppat.1012394.ref014","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tim.2008.11.005","article-title":"Staphylococcus aureus: new evidence for intracellular persistence","volume":"17","author":"C Garzoni","year":"2009","journal-title":"Trends Microbiol"},{"issue":"3","key":"ppat.1012394.ref015","doi-asserted-by":"crossref","first-page":"e12997","DOI":"10.1111\/cmi.12997","article-title":"In or out: Phagosomal escape of Staphylococcus aureus","volume":"21","author":"A Moldovan","year":"2019","journal-title":"Cellular Microbiology"},{"issue":"8","key":"ppat.1012394.ref016","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1080\/21505594.2017.1361089","article-title":"Investigating intracellular persistence of Staphylococcus aureus within a murine alveolar macrophage cell line","volume":"8","author":"A Lacoma","year":"2017","journal-title":"Virulence"},{"issue":"3","key":"ppat.1012394.ref017","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrmicro2508","article-title":"Are bloodstream leukocytes Trojan Horses for the metastasis of Staphylococcus aureus","volume":"9","author":"GE Thwaites","year":"2011","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"ppat.1012394.ref018","doi-asserted-by":"crossref","first-page":"e1409","DOI":"10.1371\/journal.pone.0001409","article-title":"A potential new pathway for Staphylococcus aureus dissemination: the silent survival of S. aureus phagocytosed by human monocyte-derived macrophages.","volume":"3","author":"M Kubica","year":"2008","journal-title":"PLoS ONE."},{"issue":"8","key":"ppat.1012394.ref019","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.ijmm.2014.07.013","article-title":"Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation","volume":"304","author":"J Kalinka","year":"2014","journal-title":"Int J Med Microbiol"},{"issue":"11","key":"ppat.1012394.ref020","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1093\/cid\/ciz106","article-title":"Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence","volume":"69","author":"X Tan","year":"2019","journal-title":"Clinical Infectious Diseases"},{"issue":"5","key":"ppat.1012394.ref021","article-title":"Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia","volume":"85","author":"C Li","year":"2017","journal-title":"Infect Immun"},{"issue":"10","key":"ppat.1012394.ref022","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1111\/cmi.12582","article-title":"Adaptive processes of Staphylococcus aureus isolates during the progression from acute to chronic bone and joint infections in patients: S. aureus adaptation during BJI","volume":"18","author":"S Trouillet-Assant","year":"2016","journal-title":"Cellular Microbiology"},{"key":"ppat.1012394.ref023","doi-asserted-by":"crossref","first-page":"121632","DOI":"10.1016\/j.biomaterials.2022.121632","article-title":"Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based infection model.","volume":"287","author":"F Siwczak","year":"2022","journal-title":"Biomaterials."},{"key":"ppat.1012394.ref024","doi-asserted-by":"crossref","first-page":"341","DOI":"10.22203\/eCM.v025a24","article-title":"Intra-cellular Staphylococcus aureus alone causes infection in vivo","volume":"25","author":"T Hamza","year":"2013","journal-title":"Eur Cell Mater"},{"issue":"4","key":"ppat.1012394.ref025","first-page":"249","article-title":"Intracellular residency is frequently associated with recurrent Staphylococcus aureus rhinosinusitis.","volume":"44","author":"I Plouin-Gaudon","year":"2006","journal-title":"Rhinology.Dec"},{"key":"ppat.1012394.ref026","doi-asserted-by":"crossref","first-page":"667387","DOI":"10.3389\/fimmu.2021.667387","article-title":"Making the Most of the Host; Targeting the Autophagy Pathway Facilitates Staphylococcus aureus Intracellular Survival in Neutrophils.","volume":"12","author":"EG Vozza","year":"2021","journal-title":"Front Immunol.Jun 16"},{"key":"ppat.1012394.ref027","article-title":"Intracellular Staphylococcus aureus and host cell death pathways","author":"YM Soe","year":"2021","journal-title":"Cellular Microbiology"},{"issue":"4","key":"ppat.1012394.ref028","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1128\/AAC.01145-08","article-title":"Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Pharmacodynamic Evaluation and Comparison with Isogenic Normal-Phenotype and Revertant Strains","volume":"53","author":"HA Nguyen","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ppat.1012394.ref029","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.intimp.2014.08.002","article-title":"THP-1 cell line: an in vitro cell model for immune modulation approach","volume":"23","author":"W Chanput","year":"2014","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"ppat.1012394.ref030","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."},{"issue":"11","key":"ppat.1012394.ref031","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1038\/nprot.2013.132","article-title":"CRISPR interference (CRISPRi) for sequence-specific control of gene expression.","volume":"8","author":"MH Larson","year":"2013","journal-title":"Nat Protoc"},{"issue":"3","key":"ppat.1012394.ref032","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1128\/AAC.02330-15","article-title":"Optimized In Vitro Antibiotic Susceptibility Testing Method for Small-Colony Variant Staphylococcus aureus","volume":"60","author":"MR Precit","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"21","key":"ppat.1012394.ref033","first-page":"1970","article-title":"National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011.","volume":"173","author":"R Dantes","journal-title":"JAMA Intern Med. 2013 Nov 25"},{"issue":"9","key":"ppat.1012394.ref034","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cmi.2016.06.020","article-title":"Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain","volume":"22","author":"M Strobel","year":"2016","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"ppat.1012394.ref035","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1101\/gr.214346.116","article-title":"ABySS 2.0: resource-efficient assembly of large genomes using a Bloom filter","volume":"27","author":"SD Jackman","year":"2017","journal-title":"Genome Res"},{"issue":"22","key":"ppat.1012394.ref036","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: rapid large-scale prokaryote pan genome analysis","volume":"31","author":"AJ Page","year":"2015","journal-title":"Bioinformatics"},{"issue":"4","key":"ppat.1012394.ref037","first-page":"e000056","article-title":"SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments.","volume":"2","author":"AJ Page","year":"2016","journal-title":"Microb Genom.Apr"},{"issue":"1","key":"ppat.1012394.ref038","first-page":"1","article-title":"Matching methods for causal inference: A review and a look forward.","volume":"25","author":"EA Stuart","year":"2010","journal-title":"Stat Sci.Feb 1"},{"issue":"4","key":"ppat.1012394.ref039","first-page":"1530","article-title":"Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester","volume":"42","author":"S Tsuchiya","year":"1982","journal-title":"Cancer Res"},{"issue":"1","key":"ppat.1012394.ref040","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/aji.12129","article-title":"Effect of culture conditions on the phenotype of THP-1 monocyte cell line","volume":"70","author":"PB Aldo","year":"2013","journal-title":"Am J Reprod Immunol"},{"issue":"1\u20132","key":"ppat.1012394.ref041","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jim.2013.11.006","article-title":"Reduced PMA enhances the responsiveness of transfected THP-1 macrophages to polarizing stimuli","volume":"402","author":"MB Mae\u00df","year":"2014","journal-title":"J Immunol Methods"},{"issue":"5","key":"ppat.1012394.ref042","first-page":"e00119","article-title":"Alternative Enzyme Protection Assay To Overcome the Drawbacks of the Gentamicin Protection Assay for Measuring Entry and Intracellular Survival of Staphylococci","volume":"87","author":"JH Kim","year":"2019","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1012394.ref043","doi-asserted-by":"crossref","DOI":"10.1093\/jacamr\/dlac011","article-title":"Evolution of cefiderocol resistance in Stenotrophomonas maltophilia using in vitro serial passage techniques","volume":"4","author":"BJ Werth","year":"2022","journal-title":"JAC Antimicrob Resist"},{"issue":"1","key":"ppat.1012394.ref044","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"JT Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"issue":"3","key":"ppat.1012394.ref045","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"SF Altschul","year":"1990","journal-title":"J Mol Biol"},{"issue":"6","key":"ppat.1012394.ref046","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ijmm.2017.11.011","article-title":"Aureo Wiki \u2013 The repository of the Staphylococcus aureus research and annotation community","volume":"308","author":"S Fuchs","year":"2018","journal-title":"International Journal of Medical Microbiology"},{"issue":"1","key":"ppat.1012394.ref047","first-page":"595","volume":"11","author":"KA Jolley","year":"2010","journal-title":"BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics"},{"issue":"24","key":"ppat.1012394.ref048","doi-asserted-by":"crossref","first-page":"4310","DOI":"10.1093\/bioinformatics\/bty539","article-title":"pyseer: a comprehensive tool for microbial pangenome-wide association studies","volume":"34","author":"JA Lees","year":"2018","journal-title":"Bioinformatics"},{"issue":"3","key":"ppat.1012394.ref049","doi-asserted-by":"crossref","first-page":"e9490","DOI":"10.1371\/journal.pone.0009490","article-title":"FastTree 2 \u2013Approximately Maximum-Likelihood Trees for Large Alignments.","volume":"5","author":"MN Price","year":"2010","journal-title":"PLoS ONE."},{"issue":"3","key":"ppat.1012394.ref050","doi-asserted-by":"crossref","first-page":"e0053822","DOI":"10.1128\/iai.00538-22","article-title":"In Vitro Selection Identifies Staphylococcus aureus Genes Influencing Biofilm Formation","volume":"91","author":"DR Long","year":"2023","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1012394.ref051","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00067-18","article-title":"Efficient and Scalable Precision Genome Editing inStaphylococcus aureusthrough Conditional Recombineering and CRISPR\/Cas9-Mediated Counterselection.","volume":"9","author":"K Penewit","year":"2018","journal-title":"MBio."},{"issue":"15","key":"ppat.1012394.ref052","doi-asserted-by":"crossref","first-page":"7429","DOI":"10.1093\/nar\/gkt520","article-title":"Programmable repression and activation of bacterial gene expression using an engineered CRISPR-Cas system","volume":"41","author":"D Bikard","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"ppat.1012394.ref053","doi-asserted-by":"crossref","first-page":"e0024324","DOI":"10.1128\/jcm.00243-24","article-title":"Development of advanced control material for reverse transcription-mediated bacterial nucleic acid amplification tests","volume":"62","author":"JD Lewis","year":"2024","journal-title":"J Clin Microbiol"},{"issue":"W1","key":"ppat.1012394.ref054","doi-asserted-by":"crossref","first-page":"W242","DOI":"10.1093\/nar\/gky354","article-title":"CRISPOR: intuitive guide selection for CRISPR\/Cas9 genome editing experiments and screens","volume":"46","author":"JP Concordet","year":"2018","journal-title":"Nucleic Acids Research"},{"issue":"2","key":"ppat.1012394.ref055","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41596-021-00639-6","article-title":"CRISPRi-seq for genome-wide fitness quantification in bacteria.","volume":"17","author":"V de Bakker","year":"2022","journal-title":"Nat Protoc."},{"issue":"10","key":"ppat.1012394.ref056","doi-asserted-by":"crossref","first-page":"e0022823","DOI":"10.1128\/iai.00228-23","article-title":"Transposon sequencing identifies genes impacting Staphylococcus aureus invasion in a human macrophage model","volume":"91","author":"HY Lo","year":"2023","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1012394.ref057","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1128\/AEM.03803-14","article-title":"New shuttle vector-based expression system to generate polyhistidine-tagged fusion proteins in Staphylococcus aureus and Escherichia coli","volume":"81","author":"S Schwendener","year":"2015","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"ppat.1012394.ref058","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nbt1172","article-title":"Engineering and characterization of a superfolder green fluorescent protein","volume":"24","author":"JD P\u00e9delacq","year":"2006","journal-title":"Nat Biotechnol"},{"key":"ppat.1012394.ref059","volume":"111","author":"W. Strober","year":"2015","journal-title":"Trypan Blue Exclusion Test of Cell Viability. Curr Protoc Immunol"},{"issue":"2","key":"ppat.1012394.ref060","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1165\/rcmb.2018-0389OC","article-title":"Metabolic Adaptation in Methicillin-Resistant Staphylococcus aureus Pneumonia","volume":"61","author":"SJ Gabryszewski","year":"2019","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ppat.1012394.ref061","first-page":"3119","article-title":"Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls.","volume":"10","author":"JE San","year":"2020","journal-title":"Microbiol"},{"issue":"1","key":"ppat.1012394.ref062","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ajhg.2014.06.009","article-title":"Rare-variant association analysis: study designs and statistical tests","volume":"95","author":"S Lee","year":"2014","journal-title":"Am J Hum Genet"},{"issue":"1","key":"ppat.1012394.ref063","doi-asserted-by":"crossref","first-page":"16923","DOI":"10.1038\/srep16923","article-title":"Efficient Test and Visualization of Multi-Set Intersections.","volume":"5","author":"M Wang","year":"2015","journal-title":"Sci Rep."},{"issue":"19","key":"ppat.1012394.ref064","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1128\/JB.00948-12","article-title":"Phenotype switching is a natural consequence of Staphylococcus aureus replication","volume":"194","author":"AM Edwards","year":"2012","journal-title":"J Bacteriol"},{"issue":"6","key":"ppat.1012394.ref065","first-page":"302","article-title":"Variant subpopulations of Staphylococcus aureus as cause of persistent and recurrent infections.","volume":"3","author":"RA Proctor","year":"1994","journal-title":"Infect Agents Dis."},{"key":"ppat.1012394.ref066","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.meegid.2013.04.020","article-title":"Evolution of Staphylococcus aureus during human colonization and infection","volume":"21","author":"JR Fitzgerald","year":"2014","journal-title":"Infect Genet Evol"},{"issue":"4","key":"ppat.1012394.ref067","doi-asserted-by":"crossref","first-page":"e5210","DOI":"10.1371\/journal.pone.0005210","article-title":"Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors.","volume":"4","author":"J Koziel","year":"2009","journal-title":"PLoS ONE."},{"issue":"16","key":"ppat.1012394.ref068","doi-asserted-by":"crossref","first-page":"5976","DOI":"10.1128\/JB.00592-07","article-title":"Staphylococcus aureus ArcR controls expression of the arginine deiminase operon","volume":"189","author":"J Makhlin","year":"2007","journal-title":"J Bacteriol"},{"issue":"27","key":"ppat.1012394.ref069","doi-asserted-by":"crossref","first-page":"13563","DOI":"10.1073\/pnas.1904280116","article-title":"The purine biosynthesis regulator PurR moonlights as a virulence regulator in Staphylococcus aureus","volume":"116","author":"WE Sause","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"ppat.1012394.ref070","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1128\/JB.00928-09","article-title":"Golden pigment production and virulence gene expression are affected by metabolisms in Staphylococcus aureus","volume":"192","author":"L Lan","year":"2010","journal-title":"J Bacteriol"},{"issue":"4","key":"ppat.1012394.ref071","doi-asserted-by":"crossref","first-page":"e01447","DOI":"10.1128\/mBio.01447-14","article-title":"Inactivation of thyA in Staphylococcus aureus attenuates virulence and has a strong impact on metabolism and virulence gene expression","volume":"5","author":"A Kriegeskorte","year":"2014","journal-title":"mBio"},{"issue":"2","key":"ppat.1012394.ref072","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"},{"issue":"12","key":"ppat.1012394.ref073","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.3390\/antibiotics10121555","article-title":"The Role of Staphylococcus aureus YycFG in Gene Regulation, Biofilm Organization and Drug Resistance.","volume":"10","author":"S Wu","year":"2021","journal-title":"Antibiotics (Basel)."},{"key":"ppat.1012394.ref074","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ijbiomac.2018.01.047","article-title":"Autolysin mediated adherence of Staphylococcus aureus with Fibronectin, Gelatin and Heparin","volume":"110","author":"C Porayath","year":"2018","journal-title":"Int J Biol Macromol"},{"issue":"6","key":"ppat.1012394.ref075","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1128\/IAI.00133-11","article-title":"Role of fibronectin-binding proteins A and B in in vitro cellular infections and in vivo septic infections by Staphylococcus aureus","volume":"79","author":"H Shinji","year":"2011","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1012394.ref076","first-page":"e00590","article-title":"MgrA Negatively Impacts Staphylococcus aureus Invasion by Regulating Capsule and FnbA. Freitag NE, editor","volume":"87","author":"MG Lei","year":"2019","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1012394.ref077","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1574-6968.2006.00229.x","article-title":"Clumping factor A of Staphylococcus aureus inhibits phagocytosis by human polymorphonuclear leucocytes","volume":"258","author":"J Higgins","year":"2006","journal-title":"FEMS Microbiology Letters"},{"issue":"6","key":"ppat.1012394.ref078","doi-asserted-by":"crossref","first-page":"E870","DOI":"10.3390\/microorganisms8060870","article-title":"YycH and YycI Regulate Expression of Staphylococcus aureus Autolysins by Activation of WalRK Phosphorylation.","volume":"8","author":"M Gajdiss","year":"2020","journal-title":"Microorganisms."},{"issue":"12","key":"ppat.1012394.ref079","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1111\/j.1462-5822.2010.01506.x","article-title":"A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor","volume":"12","author":"N Hirschhausen","year":"2010","journal-title":"Cell Microbiol"},{"issue":"22","key":"ppat.1012394.ref080","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"},{"issue":"1","key":"ppat.1012394.ref081","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3390\/biomedicines10010035","article-title":"VraSR Regulatory System Contributes to the Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in a 3D-Skin Model and Skin Infection of Humanized Mouse Model.","volume":"10","author":"N Barua","year":"2021","journal-title":"Biomedicines."},{"issue":"3","key":"ppat.1012394.ref082","doi-asserted-by":"crossref","first-page":"e1003201","DOI":"10.1371\/journal.ppat.1003201","article-title":"The KdpD\/KdpE two-component system: integrating K+ homeostasis and virulence.","volume":"9","author":"ZN Freeman","year":"2013","journal-title":"PLoS Pathog."},{"issue":"6","key":"ppat.1012394.ref083","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1128\/IAI.73.6.3415-3421.2005","article-title":"Role of Staphylococcus aureus global regulators sae and sigmaB in virulence gene expression during device-related infection","volume":"73","author":"C Goerke","year":"2005","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1012394.ref084","doi-asserted-by":"crossref","first-page":"e03081","DOI":"10.1128\/mBio.03081-19","article-title":"Stochastic Expression of Sae-Dependent Virulence Genes during Staphylococcus aureus Biofilm Development Is Dependent on SaeS","volume":"11","author":"EA DelMain","year":"2020","journal-title":"mBio"},{"key":"ppat.1012394.ref085","first-page":"45","volume":"10","author":"D Yang","year":"2019","journal-title":"A Genome-Wide Screen Identifies Factors Involved in S. aureus-Induced Human Neutrophil Cell Death and Pathogenesis. Front Immunol"},{"key":"ppat.1012394.ref086","article-title":"The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis","author":"YQ Xiong","year":"2024","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1012394.ref087","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/21505594.2021.1875683","article-title":"YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus.","volume":"12","author":"A Paudel","year":"2021","journal-title":"Virulence"},{"issue":"11","key":"ppat.1012394.ref088","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1042\/BCJ20170132","article-title":"Hiding in plain sight: immune evasion by the staphylococcal protein SdrE","volume":"474","author":"AB Herr","year":"2017","journal-title":"Biochemical Journal"},{"issue":"8","key":"ppat.1012394.ref089","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1093\/infdis\/jiaa251","article-title":"The ClpXP Protease Contributes to Staphylococcus aureus Pneumonia","volume":"222","author":"GL Kim","year":"2020","journal-title":"J Infect Dis"},{"issue":"11","key":"ppat.1012394.ref090","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00337-17","article-title":"Identification of Staphylococcus aureus Factors Required for Pathogenicity and Growth in Human Blood","volume":"85","author":"J Connolly","year":"2017","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1012394.ref091","doi-asserted-by":"crossref","first-page":"e00002","DOI":"10.1128\/IAI.00002-19","article-title":"MroQ Is a Novel Abi-Domain Protein That Influences Virulence Gene Expression in Staphylococcus aureus via Modulation of Agr Activity","volume":"87","author":"S Marroquin","year":"2019","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1012394.ref092","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1128\/IAI.03122-14","article-title":"Protein A is released into the Staphylococcus aureus culture supernatant with an unprocessed sorting signal","volume":"83","author":"DP O\u2019Halloran","year":"2015","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1012394.ref093","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1073\/pnas.1317181111","article-title":"Release of protein A from the cell wall of Staphylococcus aureus","volume":"111","author":"S Becker","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1012394.ref094","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1128\/JB.188.1.211-222.2006","article-title":"Transposon Disruption of the Complex I NADH Oxidoreductase Gene (snoD) in Staphylococcus aureus Is Associated with Reduced Susceptibility to the Microbicidal Activity of Thrombin-Induced Platelet Microbicidal Protein 1","volume":"188","author":"AS Bayer","year":"2006","journal-title":"J Bacteriol"},{"issue":"7","key":"ppat.1012394.ref095","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1128\/JB.187.7.2249-2256.2005","article-title":"Staphylococcus aureus NfrA (SA0367) Is a Flavin Mononucleotide-Dependent NADPH Oxidase Involved in Oxidative Stress Response","volume":"187","author":"K Streker","year":"2005","journal-title":"J Bacteriol"},{"issue":"1","key":"ppat.1012394.ref096","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.micpath.2008.10.004","article-title":"Helicobacter pylori mutants defective in the clpP ATP-dependant protease and the chaperone clpA display reduced macrophage and murine survival","volume":"46","author":"MF Loughlin","year":"2009","journal-title":"Microb Pathog"},{"issue":"5","key":"ppat.1012394.ref097","article-title":"Roles of Staphylococcus aureus Mnh1 and Mnh2 Antiporters in Salt Tolerance, Alkali Tolerance, and","volume":"200","author":"M Vaish","year":"2018","journal-title":"Pathogenesis. J Bacteriol"},{"key":"ppat.1012394.ref098","doi-asserted-by":"crossref","first-page":"145268","DOI":"10.1016\/j.gene.2020.145268","article-title":"A genomic analysis of osmotolerance in Staphylococcus aureus","volume":"767","author":"D Casey","year":"2021","journal-title":"Gene"},{"issue":"39","key":"ppat.1012394.ref099","doi-asserted-by":"crossref","first-page":"13664","DOI":"10.1074\/jbc.RA120.014371","article-title":"FmhA and FmhC of Staphylococcus aureus incorporate serine residues into peptidoglycan cross-bridges","volume":"295","author":"S Willing","year":"2020","journal-title":"J Biol Chem"},{"issue":"5","key":"ppat.1012394.ref100","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S1368-7646(98)80048-4","article-title":"Role of fem factors in methicillin resistance","volume":"1","author":"B Berger-B\u00e4chi","year":"1998","journal-title":"Drug Resist Updat"},{"issue":"4","key":"ppat.1012394.ref101","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrmicro1861","article-title":"Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions","volume":"6","author":"C Weidenmaier","year":"2008","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"ppat.1012394.ref102","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.tim.2020.05.017","article-title":"Wall Teichoic Acid in Staphylococcus aureus Host Interaction","volume":"28","author":"R van Dalen","year":"2020","journal-title":"Trends in Microbiology"},{"issue":"5","key":"ppat.1012394.ref103","doi-asserted-by":"crossref","DOI":"10.1093\/femsre\/fuac025","article-title":"Staphylococcus aureus cell wall maintenance\u2014the multifaceted roles of peptidoglycan hydrolases in bacterial growth, fitness, and virulence","volume":"46","author":"M Wang","year":"2022","journal-title":"FEMS Microbiol Rev"},{"issue":"3","key":"ppat.1012394.ref104","doi-asserted-by":"crossref","first-page":"e1009468","DOI":"10.1371\/journal.ppat.1009468","article-title":"Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction","volume":"17","author":"JAF Sutton","year":"2021","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1012394.ref105","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1111\/j.1469-0691.2010.03250.x","article-title":"Bacterial hypermutation in cystic fibrosis, not only for antibiotic resistance","volume":"16","author":"A Oliver","year":"2010","journal-title":"Clinical Microbiology and Infection"},{"key":"ppat.1012394.ref106","article-title":"Genomic analysis identifies novel Pseudomonas aeruginosa resistance genes under selection during inhaled aztreonam therapy in vivo","author":"K Mclean","journal-title":"Antimicrobial Agents and Chemotherapy"},{"issue":"5","key":"ppat.1012394.ref107","doi-asserted-by":"crossref","first-page":"e19970","DOI":"10.1371\/journal.pone.0019970","article-title":"Dysfunctional CFTR Alters the Bactericidal Activity of Human Macrophages against Pseudomonas aeruginosa.","volume":"6","author":"PD Porto","year":"2011","journal-title":"PLoS ONE"},{"issue":"6","key":"ppat.1012394.ref108","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1183\/09031936.99.14613409","article-title":"Determinants of chronic infection with Staphylococcus aureus in patients with bronchiectasis","volume":"14","author":"PL Shah","year":"1999","journal-title":"Eur Respir J"},{"issue":"6","key":"ppat.1012394.ref109","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1086\/432735","article-title":"Evidence of an intracellular reservoir in the nasal mucosa of patients with recurrent Staphylococcus aureus rhinosinusitis","volume":"192","author":"S Clement","year":"2005","journal-title":"J Infect Dis"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012394","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T18:20:56Z","timestamp":1732386056000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012394"}},"subtitle":[],"editor":[{"given":"Alice","family":"Prince","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":109,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012394","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}