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2018 Fiscal Year Final Research Report

Elucidation and clinical application of stringent response controlling an MRSA infectious disease

Research Project

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Project/Area Number 15K09581
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionJuntendo University

Principal Investigator

KATAYAMA YUKI  順天堂大学, 医学部, 助教 (60365591)

Research Collaborator AZECHI takuya  
ASAKURA kouta  
SASANO hiroshi  
Project Period (FY) 2015-04-01 – 2019-03-31
KeywordsMRSA / Vancomycin / slow-VISA / stringent response / Infectious Disease / rpoB / staphylococcus
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.

Free Research Field

感染症学 微生物学

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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Published: 2020-03-30  

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