Global genetic diversity and Asian clades evolution: a phylogeographic study of Staphylococcus aureus sequence type 5

Staphylococcus aureus sequence type (ST) 5 has spread worldwide; however, phylogeographic studies on the evolution of global phylogenetic and Asian clades of ST5 are lacking. This study included 368 ST5 genome sequences, including 111 newly generated sequences. Primary phylogenetic analysis suggested that there are five clades, and geographical clustering of ST5 methicillin-resistant S. aureus (MRSA) was linked to the acquisition of S. aureus pathogenicity islands (SaPIs; enterotoxin gene island) and integration of the prophage φSa3. The most recent common ancestor of global S. aureus ST5 dates back to the mid-1940s, coinciding with the clinical introduction of penicillin. Bayesian phylogeographic inference allowed to ancestrally trace the Asian ST5 MRSA clade to Japan, which may have spread to major cities in China and Korea in the 1990s. Based on a pan-genome-wide association study, the emergence of Asian ST5 clades was attributed to the gain of prophages, SaPIs, and plasmids, as well as the coevolution of resistance genes. Clade IV displayed greater genomic diversity than the Asian MRSA clades. Collectively, our study provides in-depth insights into the global evolution of S. aureus ST5 mainly in China and the United States and reveals that different S. aureus ST5 clades have arisen independently in different parts of the world, with limited geographic dispersal across continents.