{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:55:08Z","timestamp":1787064908028,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Translational Science Training T32 program","award":["1T32TR004544-01"],"award-info":[{"award-number":["1T32TR004544-01"]}]},{"name":"Translational Science Training T32 program","award":["UL1TR002645"],"award-info":[{"award-number":["UL1TR002645"]}]},{"name":"Translational Science Training T32 program","award":["NIA\/NIH K23-AG066933"],"award-info":[{"award-number":["NIA\/NIH K23-AG066933"]}]},{"name":"National Center for Advancing Translational Sciences, National Institutes of Health","award":["1T32TR004544-01"],"award-info":[{"award-number":["1T32TR004544-01"]}]},{"name":"National Center for Advancing Translational Sciences, National Institutes of Health","award":["UL1TR002645"],"award-info":[{"award-number":["UL1TR002645"]}]},{"name":"National Center for Advancing Translational Sciences, National Institutes of Health","award":["NIA\/NIH K23-AG066933"],"award-info":[{"award-number":["NIA\/NIH K23-AG066933"]}]},{"name":"National Institutes of Aging","award":["1T32TR004544-01"],"award-info":[{"award-number":["1T32TR004544-01"]}]},{"name":"National Institutes of Aging","award":["UL1TR002645"],"award-info":[{"award-number":["UL1TR002645"]}]},{"name":"National Institutes of Aging","award":["NIA\/NIH K23-AG066933"],"award-info":[{"award-number":["NIA\/NIH K23-AG066933"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs), yet the bacterial genomic adaptations underlying the transition from nasal colonization to invasive infection remain incompletely defined. We sequenced and analyzed 157 S. aureus isolates (126 from SSTIs and 31 from asymptomatic nasal colonization) from a primary care network in South Texas. Using genome-wide association studies, non-synonymous single-nucleotide variant (NSNV) profiling, and machine learning, we identified strain-specific adaptations in metabolic and regulatory pathways. SSTI isolates exhibited significant enrichment of nitrogen assimilation, purine biosynthesis, menaquinone production, and anaerobic respiration genes. Elevated copy number and colocalization of phage-linked metabolic genes\u2014including nirB, narH, and nifR3\u2014suggest a pathoadaptive genomic island supporting infection-specific energy generation. The enrichment of \u03b1\/\u03b2-hydrolase domain-encoding genes was associated with clinical severity. To quantify severity, we developed the Purulent Ulcer Skin (PUS) score, which integrates wound size, drainage, and erythema. The \u03b1\/\u03b2-hydrolase and lipoprotein genes were significantly associated with higher PUS scores (higher SSTI severity) and phage-encoded virulence gene products were linked to larger wound size. Machine learning prioritized purL and other metabolic loci as key infection classifiers. NSNVs and unitig-level changes co-localized within nutrient transport, stress resistance, and cytolytic genes, supporting a model of multi-layered genomic selection. Metagenomic assemblies of nasal microbiota were enriched for Staphylococcus, Enterococcus, and Micrococcus species, core metabolic pathways, and taxon-specific virulence determinants. This underscores the roles of metabolic and virulent co-networks within nasal commensals and their adaptive capacity for pathogenic transition. These findings provide a potential genomic blueprint of S. aureus pathoadaptation during SSTI and are a step towards the development of novel therapeutic targets.<\/jats:p>","DOI":"10.3390\/microorganisms13092023","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:18:15Z","timestamp":1756484295000},"page":"2023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pathoadapative Genomic Determinants of Staphylococcus aureus Community Skin Infections and Nasal Colonization"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-0216","authenticated-orcid":false,"given":"Cody A.","family":"Black","sequence":"first","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-3670","authenticated-orcid":false,"given":"Wonhee","family":"So","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Benavides","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8921-2971","authenticated-orcid":false,"given":"Julianne A.","family":"Mercer","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-2407","authenticated-orcid":false,"given":"Steven S.","family":"Dallas","sequence":"additional","affiliation":[{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"},{"name":"Department of Pathology and Laboratory Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"},{"name":"Department of Microbiology, University Health System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Shurko","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Bandy","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6571-8835","authenticated-orcid":false,"given":"Benjamin A.","family":"Encino","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina S.","family":"Lipscomb","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7133-4329","authenticated-orcid":false,"given":"Adriana","family":"Vargus","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-4787","authenticated-orcid":false,"given":"Christopher R.","family":"Frei","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"},{"name":"South Texas Veterans Health Care System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace C.","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Antonio, TX 78229, USA"},{"name":"South Texas Veterans Health Care System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jinf.2022.12.028","article-title":"All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: Results of GWAS and experimental animal 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