Elucidation and clinical application of stringent response controlling an MRSA infectious disease
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 |
Section | 一般 |
Research Field |
Infectious disease medicine
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Research Institution | Juntendo University |
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 |
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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Report
(5 results)
Research Products
(60 results)
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[Journal Article] Rapid and easy detection of low-level resistance to vancomycin in methicillin-resistant Staphylococcus aureus by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.2018
Author(s)
Asakura K, Azechi T, Sasano H, Matsui H, Hanaki H, Miyazaki M, Takata T, Sekine M, Takaku T, Ochiai T, Komatsu N, Shibayama K, Katayama Y, Yahara K.
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Journal Title
PLoS One.
Volume: 13(3)
Issue: 3
Pages: e0194212-e0194212
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The Mechanism of Resistance to Vancomycin in slow-VISA Possibly Responsible for Recurrent MRSA Infection2016
Author(s)
○Yuki Katayama, Yoshifumi Aiba, Miwa Sekine, Motoyasu Miyazaki, Tohru Takata, Miki Matsuo, Takuya Azechi, Tomomi Hishinuma, Hideaki Hanaki, and Keiichi Hiramatsu
Organizer
ASM Microb and ICAAC 2016
Place of Presentation
Boston Convention and Exhibition Center (Boston, MA, US)
Year and Date
2016-06-16
Related Report
Int'l Joint Research
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[Presentation] なぜ難治性MRSA感染症は再燃するのか2015
Author(s)
○Yuki Katayama, Tomomi Hishinuma, Yoshifumi Aiba, Takashi Sasaki, Miwa Sekine, Takashi Sasaki, Miki Matsuo and Keiichi Hiramatsu
Organizer
第16回Pharmaco-Hematology シンポジウム
Place of Presentation
日本薬学会長い記念ホール(東京都渋谷区)
Year and Date
2015-05-13
Related Report
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