Comparison of Genetic Features and Evolution of Global and Chinese Strains of Community-Associated Methicillin-Resistant Staphylococcus aureus ST22

Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 22, especially the epidemic MRSA-15 (EMRSA-15), has been one of the most important disease-causing clones transmitting rapidly within and between hospitals globally. However, the genetic features and evolution of Chinese MRSA ST22 remain to be determined. Herein, we performed comparative genomics analysis of 12 ST22 community-associated (CA) MRSA isolates from China with 9 Chinese ST22 CA-MSSA isolates and 284 ST22 genomes from global sources, to clarify the genotypic features and potential transmission of MRSA ST22 strains isolated in China. Phylogenetic reconstruction and time estimation suggested that the Chinese subclade emerged around 2006, and the ST22-SCCmec V clone may have evolved from the native ST22-MSSA clone rather than spread from other regions, indicating that the Chinese ST22-MRSA-V clone is independent of the EMRSA-15 and Gaza clone, with differences in lukSF-PV and tsst-1 carriage. Virulence assays suggested that the ST22-MRSA clone was highly virulent, displaying higher or similar virulence potential as MSSA ST22 predecessors and the epidemic USA300 and ST22-MSSA. However, two nonsense mutations caused by a frameshift in agrC were identified in two ST22-MSSA isolates, resulting in a significant attenuation of virulence. RT-qPCR also demonstrated that the high virulence potential of these ST22 strains may be attributed to elevated expression of agr. This study provides insight into the epidemiology of the novel and highly virulent CA-MRSA ST22 clones. IMPORTANCE Staphylococcus aureus sequence type 22 (ST22) is the main HA-MRSA clone spreading in Europe. It has strong capacity to supplant and replace other formerly epidemic MRSA clones. Previous work has described genotypic characteristics of ST22 belonging to EMRSA-15 and Gaza clone; however, the genetic feature and virulence potential of Chinese spread of ST22 strains are still limited. We conducted a detailed analysis of genomic evolution of global ST22 strains, to clarify the genotypic features and potential transmission of MRSA ST22 strains isolated from China. Our results suggested that the Chinese subclade is highly virulent, and emerged around 2006. We also demonstrated that the ST22-SCCmec V may have evolved from the native ST22-MSSA clone rather than spread from other regions, and the high virulence potential of these ST22 strains may be attributed to the high expression of agr based on the results of virulence assays of Chinese ST22 clones. Our findings are of great importance for providing insights into the epidemiology and pathogenicity of global and Chinese ST22 clones.