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Using periprosthetic joint infection (PJI) as a model, a prospective study was designed to quantify genetic variation among <jats:italic>S. aureus<\/jats:italic> strains both among and within patients. Whole genome sequencing and multilocus sequence typing was performed to genotype these two populations at high resolution. In nasal cultures, 78% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 63% could be classified in these common clonal complexes. The PJI cultures had a larger proportion of atypical strains, and these atypical strains were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (<jats:italic>ebh, fnbA, clfA<\/jats:italic>, and <jats:italic>clfB<\/jats:italic>) systematically distinguished later PJI isolates from the first PJI isolate from each patient. Repeated mutations in <jats:italic>S. aureus<\/jats:italic> genes associated with extracellular matrix binding were identified, suggesting adaptive, parallel evolution of <jats:italic>S. aureus<\/jats:italic> during the development of PJI.<\/jats:p>","DOI":"10.1002\/jor.25031","type":"journal-article","created":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T16:45:42Z","timestamp":1615653942000},"page":"420-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>Staphylococcus aureus<\/i> genotype variation among and within periprosthetic joint infections"],"prefix":"10.1002","volume":"40","author":[{"given":"Dongzhu","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Arthritis and Arthroplasty Design Group University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly 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