Genomic Analysis of Heterogeneous Vancomycin-Intermediate Strains from Different Clonal Lineages in South Korea.

Recent genomic studies of methicillin-resistant (MRSA) have revealed genetic diversity in the various clonal lineages. Along with clinical concerns of MRSA infection, infection with heterogeneous vancomycin-intermediate (hVISA) is closely associated with treatment failure. In this study, we investigated the magnitude of genetic variation and features at the genomic level of hVISA strains isolated in South Korea. Four hVISA strains were analyzed by molecular epidemiology, antimicrobial susceptibility, and whole-genome sequencing methods, and they were compared with the reference VISA and vancomycin-susceptible strains in the same clonal lineage. The epidemiologic features of hVISA strains were closely related to the ST5 and ST239 clones. Comparative analysis of the whole genome showed genetic mutations, particularly in two-component systems (TCSs) and transcriptional regulators. Genetic mutations in were commonly found in both ST5- (F545L, E378K, T500K) and ST239-related (E424D, T492R) hVISA strains. hVISA strains in the ST5 clonal lineage contained mutations in TCS genes, including the , , and loci, whereas ST239-related strains harbored different genetic variations in , , and . This study suggests that the diverse genetic variation of TCSs and transcriptional regulators are involved in reduced vancomycin susceptibility through different mechanisms in each clonal lineage.