title: Prevalence of amino acid changes in the yvqF, vraSR, graSR, and tcaRAB genes from vancomycin intermediate resistant Staphylococcus aureus.
abstract: Vancomycin intermediate Staphylococcus aureus (VISA) strains are increasingly prevalent in the hospital setting, and are of major concern in the treatment of methicillin-resistant S. aureus infections. Multiple mutations in vancomycin-susceptible S. aureus (VSSA) strains likely led to the emergence of VISA, and point mutations in the agr, orf1, yvqF, vraSR, graSR, and tcaRAB genes of VISA strains have been shown to contribute to glycopeptide resistance. Therefore, we investigated point mutations in these genes from 87 VISA and 27 VSSA clinical strains isolated from Korean hospitals. All strains were assigned an agr type (I, II, or III) on the basis of multiplex PCR, with the majority of VISA strains belonging to agr groups I and II. Sequencing revealed amino acid changes in vraS from VISA strains which were not present in the VSSA strains. The E59D substitution in the vraR gene occurred in 36.3% of VSSA/agrI and 92.7% of VISA/agrI strains, suggesting that this mutation associated with emergence of VISA/agrI strains. VISA strains were classified into 31 mutation patterns according to mutations in the yvqF, vraSR, graSR, and tcaRAB genes. In addition, the mutation patterns were correlated with agr and sequence type (ST). The most prevalent pattern included agr type I (ST 72) strains with E59D (vraR), L26F and T224I (graS), D148Q (graR), and L218P, R283H and G312D (tcaA) amino acid substitutions. The minimum inhibitory concentration (MIC) range of mutation pattern 5 toward oxacillin and imipenem was much lower than that of patterns 6 and 24. These results improve our understanding of emergence of VISA strains.
authors.affiliation: Division of Antimicrobial Resistance, Center for Infectious Diseases, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Yoo
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Gi Su
authors.initials: GS
authors.lastname: Kang
authors.forename: Hwa Su
authors.initials: HS
authors.lastname: Kim
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Yoo
authors.forename: Yeong Seon
authors.initials: YS
authors.lastname: Lee
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D017354:Point Mutation; D056910:Republic of Korea / Q000453:epidemiology; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C478170:VraR protein, Staphylococcus aureus; C478169:VraS protein, Staphylococcus aureus; D014640:Vancomycin