Identification of genetic factors responsible for multidrug resistance of methicillin-resistant Staphylococcus aureus (MRSA)

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Juntendo University
• Principal Investigator: MATSUO Miki 順天堂大学, 医学部, 助教 (70320322)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬剤耐性機構 / 黄色ブドウ球菌 / 耐性変異 / VISA / MRSA / バンコマイシン / slow-VISA

Outline of Final Research Achievements

Vancomycin-intermediate Staphylococcus aureus (VISA) affects the sensitivity of not only glycopeptides (vancomycin and teicoplanin) but also daptomycin. To understand the overall vancomycin resistance mechanism of VISA, we performed whole genome sequencing of 45 VISA strains isolated by vancomycin selection, and identified mutations using a comparative genome analysis. The results indicated that mutations in rpoB and rpoC genes, in addition of two-component regulatory systems, led to changes in the flow of metabolites, and caused increased peptidoglycan production and reduced autolytic activity. We also found that the functional alteration of the genes in multiple metabolic pathways in addition to those with regulatory functions can achieve hVISA-to-VISA phenotypic conversion. This explains the high frequencies of hVISA-to-VISA conversion and the characteristic shape of the population curves of hetero-VISA strains.

Free Research Field

細菌学、分子生物学