Detection of positive selection driving antimicrobial resistance in the core genome of Staphylococcus epidermidis

Staphylococcus epidermidis is a commensal skin organism and leading cause of medical-device associated infections. Although previous research has investigated the phylogenetic diversity of the species, the level of positive selection on the core genome has yet to be explored. Here, we present the first core genome-wide screen of positive selection in the species. A curated dataset of 1003 whole-genome sequences (WGS) was created which represented the global diversity of the species, including all previously identified clades and genetic clusters (GCs). 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 were also investigated using PAML branch-site models and HyPhy. PAML site analysis revealed 17 genes under selection, including six hypothetical genes, most of which were linked to metabolism or transport. Several genes were associated with antimicrobial resistance, such as ileS which confers resistance to mupirocin. cysG and sirC, which catalyse the first two steps in the synthesis of siroheme, were also under selection. Two genes were found to be under selection at the branch-site level by both PAML and HyPhy, of which only one, rhtC, has been functionally characterised. Our analysis reveals the extent to which positive selection is operating on the core genome and identifies candidate genes which may have important roles in the fitness of the species.