Evolutionary dynamics of the accessory genomes of .

is a ubiquitous commensal and opportunistic bacterial pathogen that can cause a wide gamut of infections, which are exacerbated by the presence of multidrug-resistant and methicillin-resistant . is genetically heterogeneous and consists of numerous distinct lineages. Using 558 complete genomes of , we aim to determine how the accessory genome content among phylogenetic lineages of is structured and has evolved. Bayesian hierarchical clustering identified 10 sequence clusters, of which seven contained major sequence types (ST 1, 5, 8, 30, 59, 239, and 398). The seven sequence clusters differed in their accessory gene content, including genes associated with antimicrobial resistance and virulence. Focusing on the two largest clusters, BAPS8 and BAPS10, and each consisting mostly of ST5 and ST8, respectively, we found that the structure and connected components in the co-occurrence networks of accessory genomes varied between them. These differences are explained, in part, by the variation in the rates at which the two sequence clusters gained and lost accessory genes, with the highest rate of gene accumulation occurring recently in their evolutionary histories. We also identified a divergent group within BAPS10 that has experienced high gene gain and loss early in its history. Together, our results show highly variable and dynamic accessory genomes in that are structured by the history of the specific lineages that carry them.IMPORTANCE is an opportunistic, multi-host pathogen that can cause a variety of benign and life-threatening infections. Our results revealed considerable differences in the structure and evolution of the accessory genomes of major lineages within . Such genomic variation within a species can have important implications on disease epidemiology, pathogenesis of infection, and interactions with the vertebrate host. Our findings provide important insights into the underlying genetic basis for the success of as a highly adaptable and resistant pathogen, which will inform current efforts to control and treat staphylococcal diseases.