Bacterial defense systems and host ecology drive the evolution of intra-species lineages

Horizontal gene transfer (HGT) is a major driver of diversity in bacterial populations. However, our understanding of its impact on the evolution of intra-species lineages is limited. The multi-host bacterial pathogen Staphylococcus aureus is differentiated into genetic lineages known as clonal complexes (CC) with variable host and disease tropisms. Here, we demonstrate that CCs exhibit extensive variation in pangenome size, structure, and gene flow, influenced by both genetic and ecological barriers to HGT. Examination of pangenome openness for each CC revealed remarkable variation that correlated strongly with host-species promiscuity. Notably, CCs were defined by horizontally acquired defense systems, and genetic subpopulations have diverged by changes to their type I restriction-modification (R-M) system repertoire, suggesting a role in lineage emergence. Overall, our data indicate a key role of HGT of defense systems in promoting the differentiation of S. aureus into lineages, with host ecology as a major driver of accessory genome variation.