A Molecular characterization and virulence profiles of Staphylococcus aureus bloodstream infection and their associations with clinical prognosis: a comparative analysis of MSSA/MRSA and predominant ST188/ST398

Abstract Objective The study explores correlations of molecular epidemiology and virulence with Staphylococcus aureus bloodstream infection (SA-BSI), informing pathogenesis and clinical risk management. Methods A retrospective cohort study enrolled 81 patients diagnosed with SA-BSI admitted to a tertiary hospital in Ningbo from January 2021 to December 2025. Whole-genome sequencing, antimicrobial susceptibility testing, semi-quantitative biofilm assay, and in vitro hemolytic activity test were performed on all clinical isolates. Results Multilocus sequence typing (MLST) showed that ST188 (14 isolates) and ST398 (10 isolates) were the predominant clones. All ST188 isolates belonged to methicillin-susceptible Staphylococcus aureus (MSSA), while 50% of the ST398 isolates were methicillin-resistant Staphylococcus aureus (MRSA), showing a statistically significant difference in the MRSA proportion between the two groups. The multivariate analysis revealed that MRSA was an independent risk factor for poor prognosis in patients with SA-BSI. In vitro virulence gene profiling showed that the ST188 isolates possessed markedly higher biofilm-forming ability but lower hemolytic activity than the ST398 isolates; when stratified by MRSA/MSSA, no statistically significant difference was noted in biofilm-forming ability and hemolytic activity between the two groups. The drug resistance gene analysis showed that the resistance gene mecA was a key molecular marker for distinguishing MSSA from MRSA. IV and V were the main SCCmec elements. The virulence factor analysis revealed that MRSA isolates often harbored significant deletions of genes encoding the extracellular serine protease and exotoxin genes, such as splABCDEF, set17, set25, set34, lukD, and lukE. Compared with ST188 isolates, most of the ST398 isolates also showed deletions of the gene cluster splABCDEF that encoded the extracellular serine protease. In addition, the exotoxin gene clusters significantly differed between the two STs: ST398 isolates mainly carried the exotoxin genes set1 and set3-set6, while ST188 isolates predominately carried set16-set19, set21-set26, set34, as well as genes such as lukD and lukE. All MRSA isolates within the ST398 clonal lineage belonged to cgST24977. Conclusion MRSA is an independent influential factor for unfavorable prognosis in patients with SA-BSI. ST188 and ST398 exhibit differentiated virulence strategies, which are significant for clinical anti-infective treatment decisions and the development of hosital infection control strategies.