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Here, using bioinformatic analyses accounting for population structure, we determined genomic traits (genes, SNPs and k-<\/jats:italic>mers) that distinguish \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> causing prosthetic-joint infections (PJIs) from commensal isolates from nares, by analysing whole-genome sequencing data from \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> from PJIs prospectively collected over 10 years in Sweden, and contemporary \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> from the nares of patients scheduled for arthroplasty surgery. Previously suggested virulence determinants and the presence of genes and mutations linked to antimicrobial resistance (AMR) were also investigated. Publicly available \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> sequences were used for international extrapolation and validation of findings. Our data show that \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> causing PJIs differed from nasal isolates not by virulence but by traits associated with resistance to compounds used in prevention of PJIs: \u03b2-lactams, aminoglycosides and chlorhexidine. Almost a quarter of the PJI isolates did not belong to any of the previously described major nosocomial lineages, but the AMR-related traits were also over-represented in these isolates, as well as in international \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> isolates originating from PJIs. Genes previously associated with virulence in \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> were over-represented in individual lineages, but failed to reach statistical significance when adjusted for population structure. Our findings suggest that the current strategies for prevention of PJIs select for nosocomial MDR \n \n S. epidermidis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> lineages that have arisen from horizontal gene transfer of AMR-related traits into multiple genetic backgrounds.<\/jats:p>","DOI":"10.1099\/mgen.0.000504","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T15:25:31Z","timestamp":1610551531000},"source":"Crossref","is-referenced-by-count":29,"title":["Comparative genomics of Staphylococcus epidermidis from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence"],"prefix":"10.1099","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2867-1044","authenticated-orcid":false,"given":"Emeli","family":"M\u00e5nsson","sequence":"first","affiliation":[{"name":"Centre for Clinical Research, Hospital of V\u00e4stmanland, Region V\u00e4stmanland \u2013 Uppsala 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