Dissecting the genetic features and evolution of Staphylococcus aureus sequence type 88: a global perspective

Staphylococcus aureus sequence type (ST) 88, encompassing both methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) phenotypes, is globally prevalent and commonly associated with skin and soft tissue infections. Despite its widespread occurrence, comprehensive genomic studies on this clone remain scarce. In this study, we performed detailed genomic analyses on 130 ST88 isolates derived from severe bloodstream infections alongside 275 publicly available ST88 sequences. Our phylogenetic analysis identified four distinct clades, with evidence suggesting independent evolution and significant clonal expansion of ST88 in China, particularly within clade I, which appeared to have emerged circa 1964. We documented notable interregional, international, and even intercontinental transmission of ST88 isolates. Variability in the distribution of SCCmec and spa types was observed across clades. Our in silico analyses indicated distinct patterns in the distribution of resistance genes, virulence genes, and mobile genetic elements among the clades, with clade I notably harboring the highest prevalence of the intact sraP gene and an independently acquired novel prophage, φST88-1. Conversely, clade IV exhibited deletions within the sasC gene, with certain sub-clades lacking the sdrDE and fnbB genes, underscoring the superior adhesive capabilities of clade I. In vitro experiments confirmed enhanced biofilm formation in clade I isolates, although the levels of hemolysis and cytotoxicity were similar across clades. Pan-genome-wide association study revealed that core SNPs, rather than the accessory genome, are the primary contributors to the diversification of the ST88 clades. These findings enrich our understanding of the genetic foundations underpinning the transmission dynamics and phenotypic diversity of ST88 clones globally.IMPORTANCEUnderstanding the evolution and transmission of Staphylococcus aureus ST88 clones is critically important due to their spread within food, hospital, and community environments, leading to significant health issues. Despite its prevalence, detailed genomic insights into ST88, particularly regarding its diversity and evolutionary dynamics, have been lacking. Our comprehensive genomic analysis of 130 ST88 isolates from severe bloodstream infections, alongside 275 sequences from public databases, significantly advances our understanding of this pathogen. We identified four distinct evolutionary clades, demonstrating the independent evolution and substantial clonal expansion of ST88 in China, as well as its ability to spread across regions and continents. The diversity among the isolates was evident in their unique profiles of SCCmec elements, antibiotic resistance genes, virulence genes, and mobile genetic elements. Our findings underscore the critical role of core genomic variations over accessory elements in driving the diversification of ST88. This enhanced understanding provides new insights that could inform more effective control strategies, crucial for developing interventions to combat the global spread of this formidable pathogen.