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Traits convenient for persistence may be fixed by mutation thus turning these mutants into microevolution endpoints. The feasibility that stable, non-encapsulated<jats:italic>S. aureus<\/jats:italic>mutants can regain expression of key virulence factors for survival in the bloodstream was investigated.<jats:italic>S. aureus agr<\/jats:italic>mutant HU-14 (IS<jats:italic>256<\/jats:italic>insertion in<jats:italic>agrC<\/jats:italic>) from a patient with chronic osteomyelitis was passed through the bloodstream using a bacteriemia mouse model and derivative P3.1 was obtained. Although IS<jats:italic>256<\/jats:italic>remained inserted in<jats:italic>agrC<\/jats:italic>, P3.1 regained production of capsular polysaccharide type 5 (CP5) and staphyloxanthin<jats:italic>.<\/jats:italic>Furthermore, P3.1 expressed higher levels of<jats:italic>asp23\/<\/jats:italic>SigB when compared with parental strain HU-14. Strain P3.1 displayed decreased osteoclastogenesis capacity, thus indicating decreased adaptability to bone compared with strain HU-14 and exhibited a trend to be more virulent than parental strain HU-14. Strain P3.1 exhibited the loss of one IS<jats:italic>256<\/jats:italic>copy, which was originally located in the HU-14 noncoding region between<jats:italic>dnaG<\/jats:italic>(DNA primase) and<jats:italic>rpoD<\/jats:italic>(<jats:italic>sigA)<\/jats:italic>. This loss may be associated with the observed phenotype change but the mechanism remains unknown. In conclusion,<jats:italic>S. aureus<\/jats:italic>organisms that escape the infected bone may recover the expression of key virulence factors through a rapid microevolution pathway involving SigB regulation of key virulence factors.<\/jats:p>","DOI":"10.1038\/s41598-020-70671-1","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T10:04:26Z","timestamp":1598263466000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Acapsular Staphylococcus aureus with a non-functional agr regains capsule expression after passage through the bloodstream in a bacteremia mouse model"],"prefix":"10.1038","volume":"10","author":[{"given":"Carlos M.","family":"Suligoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo E.","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Katharina","family":"Gehrke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Yebra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa I.","family":"G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindy","family":"Wendler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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