Clade-specific adaptation and global spread of <i>Staphylococcus aureus</i> ST188 with emergence of a multidrug-resistant MRSA sublineage

The global emergence of <i>Staphylococcus aureus</i> ST188 poses new challenges to public health due to its ability to infect both humans and animals and spread across regions and continents. Despite its growing prevalence, little has been known about its evolutionary history and dissemination patterns. In this study, we analyzed 808 ST188 genomes from 24 countries and found evidence of frequent cross-regional and cross-host transmission. Two major clades, showing clear clonal expansion, were dominated by isolates from China. We also identified a newly emerged methicillin-resistant subclade likely derived from a methicillin-susceptible ancestor, characterized by the acquisition of SCC<i>mec</i> IVa, multiple resistance genes, and fluoroquinolone-resistance mutations. This subclade exhibited reduced adhesion and colonization capacity due to structural loss of key virulence genes. These findings provide new insights into the clade-specific adaptation and global spread of ST188 and underscore the need for genomic surveillance of multidrug-resistant <i>S. aureus</i> emerging from traditionally susceptible lineages.