{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:47:21Z","timestamp":1782913641555,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFC2609700"],"award-info":[{"award-number":["2025YFC2609700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFC2609702"],"award-info":[{"award-number":["2025YFC2609702"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Clinical\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    infections, such as pneumonia and bloodstream infections, pose significant threats and potentially lead to fatal outcomes. Most clinical isolates harbor multiple virulence factors and antimicrobial resistance genes. This study focused on\n                    <jats:italic>S. aureus<\/jats:italic>\n                    strains isolated from clinically documented infections at a Chinese tertiary hospital between 2018 and 2023. Using whole-genome sequencing, we characterized the genomic epidemiology of 262 strains. In addition, long-read sequencing and Bayesian analysis were used to characterize the genomic features associated with clonal distribution of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    isolates. We identified ST239-III, ST398-V, ST59-IV, and ST5-II as the predominant methicillin-resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    (MRSA) clones, which belong to clonal complexes CC5, CC8, CC59, and CC398. Majority of CC5 strains were distinguished by their carriage of the toxic shock syndrome toxin-1 gene\n                    <jats:italic>tst-1<\/jats:italic>\n                    , phiN315-like\n                    <jats:italic>hlb<\/jats:italic>\n                    -converting prophages, and type II SCC\n                    <jats:italic>mec<\/jats:italic>\n                    . Notably, most\n                    <jats:italic>tst-1<\/jats:italic>\n                    -positive ST5-MRSA-SCC\n                    <jats:italic>mec<\/jats:italic>\n                    II isolates exhibited a small colony variant phenotype with reduced growth rate, attenuated hemolytic activity, and enhanced biofilm formation, suggesting a potential role in persistent infections. In contrast, CC8 strains were prevalent due to the typical multidrug-resistant profile of ST239 lineage. Interestingly, the dominant CC398 isolates belonged to a human-adapted clade, underscoring its clinical relevance in nosocomial settings. These results showed CC5, CC8, and CC398 as the dominant clones in clinical isolates and offered preliminary genomic observations on their adaptive and pathogenic-related characteristics.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1818812","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:11:41Z","timestamp":1782911501000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular epidemiology of clinical Staphylococcus aureus infections: circulating CC398 lineage with human-adapted genomic signatures and virulent ST5-SCCmec II MRSA"],"prefix":"10.3389","volume":"17","author":[{"given":"Qichen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Second Affiliated Hospital Zhejiang University, School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjiao","family":"Liu","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]},{"name":"Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI Research","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhu","family":"Liang","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]},{"name":"Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI Research","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Second Affiliated Hospital Zhejiang University, School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyin","family":"Zhou","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Jin","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Second Affiliated Hospital Zhejiang University, School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxi","family":"Wang","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqing","family":"Deng","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]},{"name":"Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI Research","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Second Affiliated Hospital Zhejiang University, School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Pei","sequence":"additional","affiliation":[{"name":"BGI Research","place":["Beijing, China"]},{"name":"Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI Research","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e65088","DOI":"10.7554\/elife.65088","article-title":"Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3","volume":"10","author":"Beghini","year":"2021","journal-title":"eLife"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1093\/jac\/dkaa345","article-title":"ResFinder 4.0 for predictions of phenotypes from genotypes","volume":"75","author":"Bortolaia","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e1006650","DOI":"10.1371\/journal.pcbi.1006650","article-title":"BEAST 2.5: an advanced software platform for Bayesian evolutionary analysis","volume":"15","author":"Bouckaert","year":"2019","journal-title":"PLoS Comput. Biol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e0117523","DOI":"10.1128\/aac.01175-23","article-title":"Global genetic diversity and Asian clades evolution: a phylogeographic study of Staphylococcus aureus sequence type 5","volume":"68","author":"Chen","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref7","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing, 34th Edition. CLSI Document M100","year":"2024"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"E1647","DOI":"10.1073\/pnas.1204307109","article-title":"Coordinated phenotype switching with large-scale chromosome flip-flop inversion observed in bacteria","volume":"109","author":"Cui","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2666","DOI":"10.1093\/bioinformatics\/bty149","article-title":"NanoPack: visualizing and processing long-read sequencing data","volume":"34","author":"De Coster","year":"2018","journal-title":"Bioinformatics"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"5526","DOI":"10.1038\/s41467-024-49644-9","article-title":"Time-calibrated phylogenetic and chromosomal mobilome analyses of Staphylococcus aureus CC398 reveal geographical and host-related evolution","volume":"15","author":"Fernandez","year":"2024","journal-title":"Nat. Commun."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"20135","DOI":"10.1073\/pnas.1904861116","article-title":"Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections","volume":"116","author":"Guerillot","year":"2019","journal-title":"Proc. Natl. Acad. Sci. 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Microb. Infect."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.12688\/wellcomeopenres.14826.1","article-title":"Open-access bacterial population genomics: BIGSdb software, the PubMLST.Org website and their applications","volume":"3","author":"Jolley","year":"2018","journal-title":"Wellcome Open Res."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e00612","DOI":"10.1128\/mSphere.00612-17","article-title":"SCCmecFinder, a web-based tool for typing of staphylococcal cassette chromosome mec in Staphylococcus aureus using whole-genome sequence data","volume":"3","author":"Kaya","year":"2018","journal-title":"mSphere"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e00020","DOI":"10.1128\/CMR.00020-18","article-title":"Methicillin-resistant Staphylococcus aureus: molecular characterization, evolution, and epidemiology","volume":"31","author":"Lakhundi","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"18033","DOI":"10.1038\/nrdp.2018.33","article-title":"Methicillin-resistant Staphylococcus aureus","volume":"4","author":"Lee","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.micpath.2016.10.028","article-title":"Staphylococcal chromosomal cassettes mec (SCCmec): a mobile genetic element in methicillin-resistant Staphylococcus aureus","volume":"101","author":"Liu","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e03117","DOI":"10.1128\/spectrum.03117-22","article-title":"Pan-genome analysis of Staphylococcus aureus reveals key factors influencing genomic plasticity","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiol. Spectrum"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e00673-23","DOI":"10.1128\/msphere.00673-23","article-title":"\u0392-Hemolysin, not agrA mutation, inhibits the hemolysis of \u03b1-hemolysin in Staphylococcus aureus laboratory and clinical strains","volume":"9","author":"Liu","year":"2024","journal-title":"mSphere"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1056\/nejm199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1001\/archinternmed.2008.603","article-title":"Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the international collaboration on endocarditis-prospective cohort study","volume":"169","author":"Murdoch","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e74819","DOI":"10.7554\/eLife.74819","article-title":"Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA","volume":"11","author":"Murray","year":"2022","journal-title":"eLife"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0037125","DOI":"10.1128\/msystems.00371-25","article-title":"Longitudinal surveillance of the molecular evolution of methicillin-resistant Staphylococcus aureus isolates from pediatric patients in Shanghai, China, from 2013 to 2022","volume":"10","author":"Pan","year":"2025","journal-title":"mSystems"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e1005595","DOI":"10.1371\/journal.pcbi.1005595","article-title":"Unicycler: resolving bacterial genome assemblies from short and long sequencing reads","volume":"13","author":"Phillippy","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1159\/000516645","article-title":"The role of hlb-converting bacteriophages in Staphylococcus aureus host adaption","volume":"31","author":"Rohmer","year":"2021","journal-title":"Microb. Phys."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e8582","DOI":"10.1371\/journal.pone.0008582","article-title":"Population structure of a hybrid clonal group of methicillin-resistant Staphylococcus aureus, ST239-MRSA-III","volume":"5","author":"Smyth","year":"2010","journal-title":"PLoS One"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s44259-024-00032-9","article-title":"Demographic fluctuations in bloodstream Staphylococcus aureus lineages configure the mobile gene pool and antimicrobial resistance","volume":"2","author":"Souza","year":"2024","journal-title":"NPJ Antimicrob Resist."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"765317","DOI":"10.3389\/fmicb.2022.765317","article-title":"The association between onset of staphylococcal non-menstrual toxic shock syndrome with inducibility of toxic shock syndrome toxin-1 production","volume":"13","author":"Taki","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","article-title":"Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research","volume":"17","author":"Turner","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1128\/JB.188.4.1310-1315.2006","article-title":"The innate immune modulators staphylococcal complement inhibitor and chemotaxis inhibitory protein of Staphylococcus aureus are located on \u03b2-hemolysin-converting bacteriophages","volume":"188","author":"van Wamel","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1080\/22221751.2022.2032373","article-title":"Methicillin-resistant Staphylococcus aureus in China: a multicentre longitudinal study and whole-genome sequencing","volume":"11","author":"Wang","year":"2022","journal-title":"Emerg Microbes Infect."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e000132","DOI":"10.1099\/mgen.0.000132","article-title":"Completing bacterial genome assemblies with multiplex MinION sequencing","volume":"3","author":"Wick","year":"2017","journal-title":"Microb. Genom."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"100972","DOI":"10.1016\/j.lanwpc.2023.100972","article-title":"Burden of infectious diseases and bacterial antimicrobial resistance in China: a systematic analysis for the global burden of disease study 2019","volume":"43","author":"Zhang","year":"2019","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.3389\/fmicb.2019.01388","article-title":"Molecular typing and variations in amount of tst gene expression of TSST-1-producing clinical Staphylococcus aureus isolates","volume":"10","author":"Zhao","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"101178","DOI":"10.1016\/j.drup.2024.101178","article-title":"Reshaping the battlefield: a decade of clonal wars among Staphylococcus aureus in China","volume":"78","author":"Zhou","year":"2025","journal-title":"Drug Resist. 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