Molecular Epidemiology of Staphylococcus aureus in China Reveals the Key Gene Features Involved in Epidemic Transmission and Adaptive Evolution

Staphylococcus aureus is a Gram-positive pathogen that causes various infections in humans and domestic animals. In China, S. aureus is the most common Gram-positive pathogen that causes clinical infections. However, there are few comprehensive genome-based molecular epidemiology studies to investigate the genotypic background of the major S. aureus clones that are epidemic in China. Here, four S. aureus isolates that were recovered from hospital personnel were sequenced. In combination with whole-genome sequencing (WGS) data of 328 S. aureus strains as references, we performed a comprehensive molecular epidemiology study to reveal the molecular epidemic characterization of S. aureus that is epidemic in China. It was found that 332 S. aureus isolates were phylogenetically categorized into 4 major epidemic groups with different epidemiology phenotypes. Each group has exclusive features in virulence genotypic profiles, antimicrobial resistance genotypic profiles, core and pangenome features representing the differences involved in genetic features, evolutionary processes, and potential future evolutionary directions. Moreover, a comparative core genome analysis of 332 S. aureus isolates indicated several key genes that contributed to differences in molecular epidemic characterization and promoted the adaptive evolutionary process of each group. This study provides a comprehensive understanding of molecular epidemiological characteristics and adaptive evolutionary directions of major S. aureus clones that are epidemic in China. IMPORTANCE Staphylococcus aureus is an important Gram-positive pathogen that is epidemic worldwide and causes various infections in humans and domestic animals. However, there has been relatively little research on comprehensive molecular epidemiology in China. In this research, we reconstructed the phylogenetic relationship based on whole-genome data of strains almost all over China, screened for resistance and virulence genes, and took core and pan genome analysis to perform a comprehensive molecular epidemiology study of S. aureus that is epidemic in China. Our results highlight that there are 4 major epidemic groups with different epidemiology phenotypes after phylogenetic categorization with exclusive genetic features in virulence genotypic profiles, antimicrobial-resistance genotypic profiles, and core and pangenome features, and we found key gene features involved in epidemic transmission and adaptive evolution. Our findings are critical in describing molecular characteristic profiles of S. aureus infection, which could update existing preventive measures and take appropriate strategies.