Evolutionary history of S. aureus using 10,257 single isolates

Most new pathogens of humans and animals arise via switching events from distinct host-species. However, our understanding of the evolutionary and ecological drivers of successful host-adaptation, expansion and dissemination are limited. Staphylococcus aureus is a major bacterial pathogen of humans and a leading cause of mastitis in dairy cows worldwide. Here we trace the evolutionary history of bovine S. aureus using a global dataset of 10,257 S. aureus genomes including 1,896 bovine isolates from 32 countries in 6 continents. We identified 7 major contemporary endemic clones of S. aureus causing bovine mastitis around the world and traced them back to 4 independent host-jump events from humans that occurred up to 2,500 years ago. Individual clones emerged and underwent clonal expansion from the mid-19th to late 20th century coinciding with the commercialisation and industrialisation of dairy farming, and older lineages have become globally-distributed via established cattle trade links. Importantly, we identified lineage-dependent differences in the frequency of host transmission events between humans and cows in both directions revealing high risk clones threatening veterinary and human health. Finally, pan-genome network analysis revealed that some bovine S. aureus lineages contained distinct sets of bovine-associated genes, consistent with multiple trajectories to host-adaptation via gene acquisition. Taken together, we have dissected the evolutionary history of a major endemic pathogen of livestock providing a comprehensive temporal, geographic and gene-level perspective of its remarkable success.