A Hypervirulent Community‐Associated Methicillin‐Resistant Staphylococcus aureus Sequence Type 59 Strain Shows Enhanced Cytotoxicity and Accessory Gene Regulator Activation Compared With Strain USA300

Background Different clonal groups of methicillin‐resistant Staphylococcus aureus (MRSA), particularly community‐acquired MRSA (CA‐MRSA), have caused widespread outbreaks and transmission in various regions. Methods We used the North American CA‐MRSA epidemic strain USA300, the Asian CA‐MRSA epidemic strain YNSA7, and ATCC43300 as research subjects. The genomic structural variations were analyzed, along with the transcriptomics and metabolomics of these MRSA clonal strains. Cytotoxicity assays were conducted on these strains. Results The genome of YNSA7 was more similar to that of USA300, with better collinearity and fewer InDels, translocations, and inversions in the genomic structure. The transcriptome and metabolome revealed differences in gene expression profiles and metabolic products among the three MRSA strains. GO and KEGG enrichment indicated that the YNSA7 strain was enriched primarily in bacterial two‐component systems, including representative genes of agrB and agrC , as well as virulence factors such as seb and fnbB . Coculture assays with RAW264.7 macrophages revealed that the YNSA7 strain exhibited greater cytotoxicity than the USA300 and ATCC43300 strains did. Additionally, the two‐component system represented by the agr system of the cocultured YNSA7 strain also exhibited high expression levels, with downstream regulatory factors and virulence factors of the agr system also showing higher expression levels than USA300 and ATCC43300. Conclusions The application of multiomics in this study elucidated the genomic structural characteristics and biological features of different clonal groups of MRSA strains. These findings provide insights into the transmission and prevalence of these strains.