Abstract Background Staphylococcus epidermidis , typically regarded as a harmless commensal, has become one of the major causes of nosocomial infections, including ocular, skin, medical device-associated and bloodstream infections. Therefore, we analyze its population structure through genomic analysis integrated with metadata. Results We performed whole-genome sequencing-based population genomic analyses by integrating 1742 publicly available S. epidermidis genomes (accessed by August 2025) with 94 newly sequenced isolates. Our analyses revealed that S. epidermidis represents a species complex composed of four phylogenetic lineages (phylogroups 1-4) with diverse clonal backgrounds and a broad global distribution. The species harbors an open pan-genome and demonstrates a strong capacity to acquire novel genetic traits through mobile genetic elements. Extensive antimicrobial resistance and substantial virulence potential were observed across lineages. Notably, phylogroup 1, dominated by ST 2, exhibited a 97.8% detection rate of the methicillin resistance gene mecA , likely driven by clonal expansion and horizontal gene transfer, identifying it as a high-risk lineage. The analysis of enriched genes in blood-derived strains showed that the adaptability of S. epidermidis in bloodstream-associated environments is controlled by multiple genes, involving antimicrobial resistance, cell wall remodeling, environmental adaptation, and core metabolism. Conclusions This study provides a comprehensive population genomic framework for S. epidermidis , elucidating its population structure, genomic diversity, antimicrobial resistance, and virulence-associated genetic features. These findings offer valuable insights into the evolutionary dynamics and pathogenic potential of S. epidermidis and provide an important genomic resource to inform infection control strategies and clinical management.
Yang et al. (Thu,) studied this question.