Screen for signatures of positive selection in the core genome of Staphylococcus epidermidis

Staphylococcus epidermidis is a commensal skin bacterium and the leading cause of medical-device-associated infections. Although previous studies have investigated the phylogenetic diversity of the species, the level of positive selection on the core genome has yet to be explored in S. epidermidis. Here, we present a comprehensive genome-wide screen for signatures of positive selection in this species. A curated dataset of 1,003 whole-genome sequences was created, which represented the global diversity of S. epidermidis, including all previously identified clades and genetic clusters. A 100-strain subset, which retained the diversity of the collection, was created by pruning the species-level tree with treemmer; core genes present in all genomes were extracted with Roary and used for positive selection analysis (n=826). Site-level analysis was performed using PAML with omegaMap for confirmation. Selection along branches separating clades A and B was investigated using PAML branch-site models and HyPhy. PAML site analysis revealed 16 genes under selection, including 6 hypothetical genes, most of which were linked to metabolism or transport. Several genes were associated with antimicrobial resistance, including ileS, which confers resistance to mupirocin. Nearly a third of the genes under selection were components of interconnected pathways that collectively provide essential cofactors for the NirB enzyme subunit. No genes showed evidence of positive selection in both the PAML and HyPhy branch-site analyses. Our analysis reveals the extent to which positive selection is operating on the core genome of S. epidermidis, driving clade-associated mutations in multiple core genes, and identifies candidate genes that may have important roles in the fitness of the species.