GENETIC CHANGES IN LOCAL METHICILIN RESISTANT Staphylococcus aureus LEADING TO HETRO-VANCOMYCIN SUSCEPTIBILITY

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), which emerged as a major nosocomial pathogen, is now spreading rapidly worldwide. Moreover, treatment of S. aureus infections is becoming more complicated. The emergence of glycopeptide resistance in S. aureus is considered to be a serious threat around the world, since current treatment of serious infections caused by MRSA relies mainly upon the administration of glycopeptide antibiotics. To understand the mechanism of vancomycin resistance, resulting from multiple mutations, in clinically isolated S. aureus. Complete sequences of multiple genes, including two-component vancomycin histidine kinase sensors (VraS), vancomycin response regulator (VraR), teacoplanin resistant gene (trf AB ) were compared with those of their susceptible strain. Further genetic analysis was performed on 9 vancomycin- resistance S. aureus (VRSA) revealed that a single point mutations leading to amino acid substitutions in a gene: vraS, encoding a two-component histidine kinase sensor. The accumulation of the mutation in proteins VraR regulator, correlated with further increases in the glycopeptide MIC. Genetic analysis of 9 VRSA isolates also identified the predominant amino acid substitutions in VraS: 5 isolates revealed mutations in VraS gene, followed by 3 isolates with mutations in Vra R Finally the present research provides novel insights into genetic diversity of VraSR mutants among clinical S. aureus isolates with variable susceptibility to vancomycin.