Molecular epidemiology of clinical Staphylococcus aureus infections: circulating CC398 lineage with human-adapted genomic signatures and virulent ST5-SCCmec II MRSA

Clinical Staphylococcus aureus infections, such as pneumonia and bloodstream infections, pose significant threats and potentially lead to fatal outcomes. Most clinical isolates harbor multiple virulence factors and antimicrobial resistance genes. This study focused on S. aureus strains isolated from clinically documented infections at a Chinese tertiary hospital between 2018 and 2023. Using whole-genome sequencing, we characterized the genomic epidemiology of 262 strains. In addition, long-read sequencing and Bayesian analysis were used to characterize the genomic features associated with clonal distribution of S. aureus isolates. We identified ST239-III, ST398-V, ST59-IV, and ST5-II as the predominant methicillin-resistant S. aureus (MRSA) clones, which belong to clonal complexes CC5, CC8, CC59, and CC398. Majority of CC5 strains were distinguished by their carriage of the toxic shock syndrome toxin-1 gene tst-1 , phiN315-like hlb -converting prophages, and type II SCC mec . Notably, most tst-1 -positive ST5-MRSA-SCC mec II isolates exhibited a small colony variant phenotype with reduced growth rate, attenuated hemolytic activity, and enhanced biofilm formation, suggesting a potential role in persistent infections. In contrast, CC8 strains were prevalent due to the typical multidrug-resistant profile of ST239 lineage. Interestingly, the dominant CC398 isolates belonged to a human-adapted clade, underscoring its clinical relevance in nosocomial settings. These results showed CC5, CC8, and CC398 as the dominant clones in clinical isolates and offered preliminary genomic observations on their adaptive and pathogenic-related characteristics.