| Project/Area Number |
15K09581
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Infectious disease medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Research Collaborator |
AZECHI takuya
ASAKURA kouta
SASANO hiroshi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | MRSA / Vancomycin / slow-VISA / stringent response / Infectious Disease / rpoB / staphylococcus / 薬剤耐性 / 難治感染症 / バンコマイシン / VISA / 緊縮応答 / 薬剤耐性菌 / rpoB 遺伝子 / ppGpp / 難治性感染症 / 院内感染 / 抗MRSA薬 |
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| Outline of Final Research Achievements |
The slow-vancomycin-intermediate Staphylococcus aureus (VISA) strains can be difficult to detect because prolonged incubation is required and the phenotype is unstable. We found that mupirocin induced stable expression of vancomycin resistance. On the basis of these results, we developed a method for detection of slow-VISA using by mupirocin 0.032 ug/ml (Patent Application No. PCT/JP2017/008975filed on March 7, 2017). Using this method, we detected 53 (15.6%) slow-VISA isolates among clinical MRSA isolates. In contrast, the VISA phenotype was detected in fewer than 1% of isolates. Moreover, we revealed that slow-VISA strains survive in small numbers among hVISA isolates according to deep-sequencing analysis, and when the cells are incubated again in the presence of vancomycin. The existence of this slow-VISA parent population may result in a recurrent MRSA infection. These findings may account in part for the recurrence and persistence of slow-VISA in MRSA infection.
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| Academic Significance and Societal Importance of the Research Achievements |
Antimicrobial Resistance;AMRによる死亡者数は2050年にガンによる死亡者数を越えると想定されている (G7 OECD report,2015)。そこでWHOや主要国首脳会議から抗菌薬使用制限が提言され、本邦も2020年までに「数十％の抗菌薬耐性菌の減少」の成果指標を設定した（感染症対策閣僚会議, 2016）。特に本邦におけるMRSAのヒトにおける検出の割合は、他国と比較して高い(WHO 2014)。本研究では、新規高度薬剤耐性の国際基準を確立し、耐性化機構の解明、検出方法、実用化に向けた治療戦略の臨床開発を遂行し AMRアクションプランの成果指標に貢献した。
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