Clade-specific adaptation and global spread of Staphylococcus aureus ST188 with emergence of a multidrug-resistant MRSA sublineage.

Staphylococcus aureus sequence type (ST) 188 is a globally distributed lineage frequently associated with colonization and bloodstream infection in both humans and animals, yet its evolutionary dynamics and genomic adaptations remain poorly understood. In this study, we conducted a comprehensive genomic analysis of 808 ST188 isolates collected from 24 countries between 2004 and 2023. Phylogenetic reconstruction identified seven clades, with clades I and VII showing independent clonal expansions in China. Frequent cross-regional, international, and cross-host transmission events were observed, supporting the emergence of ST188 as a host-generalist lineage. A distinct methicillin-resistant S. aureus subclade within clade VI likely emerged from a methicillin-susceptible ancestor through the acquisition of SCCmec IVa. This event was accompanied by co-acquisition of resistance transposon Tn6636 and fluoroquinolone-resistance mutations, alongside truncation of the adhesion-related gene sraP and loss of the serine protease genes splDE. Preliminary phenotypic assays confirmed reduced adhesion and colonization in clade VI isolates. Comparative analysis revealed clade-specific patterns of mobile genetic elements, including vertical inheritance of SaPI1 and SaPI2 in the Chinese subclade of clade VII. In contrast, the novel prophage φST188-1, found exclusively in clade VII isolates, appeared to have been independently acquired. However, accessory genome variation across clades was limited, and the overall population structure was primarily shaped by core genome single-nucleotide polymorphisms. These findings provide a detailed view of the evolution and adaptation of ST188, underscore the role of clade-specific resistance and virulence patterns, and highlight the importance of continued genomic surveillance of this emerging lineage.

Importance: The global emergence of Staphylococcus aureus 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 SCCmec 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 S. aureus emerging from traditionally susceptible lineages.