Strain-level genomic analysis of Staphylococcus epidermidis across multiple body sites in healthy females

Staphylococcus epidermidis is a ubiquitous skin commensal that also colonizes the nasal and oral cavities, as well as the gastrointestinal and urinary tracts. Although prior studies have found genetic variation between S. epidermidis from infections and commensal strains, prior studies also have found that individual strains can inhabit multiple sites within an individual. None of these studies, however, have considered urogenital isolates. Here, we collected samples from 76 healthy female participants and performed whole-genome sequencing on 114 S. epidermidis isolates from the skin, nasal cavity, oral cavity, and urine. Pairwise average nucleotide identity (ANI) revealed instances of identical strains (>99.99% ANI) across multiple body sites within individuals and, in some cases, between individuals. Accessory genome functional profiles showed no clustering by anatomical site, indicating limited niche specialization and a broadly shared accessory gene pool. Intact prophages were shared among isolates, consistent with a fluid, mobile accessory genome. Although multinomial logistic regression using gene-cluster presence/absence identified site-associated gene enrichment, the model achieved low accuracy in predicting isolation source from publicly available genomes. The absence of strong evidence for niche-specific adaptation among isolates from healthy individuals supports the species’ generalist lifestyle and genetic diversity. This study advances our understanding of S. epidermidis population structure in healthy hosts, including the urinary tract.