| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| 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.
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