| Project/Area Number |
16390131
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | OKYAMA UNIVERSITY |
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Principal Investigator |
TSUCHIYA Tomofusa Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 大学院医歯薬学総合研究科, 教授 (80012673)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Teruo Okayama University, Graduate School of Medicine, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (80304327)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | multidrug resistant bacteria / multidrug efflux pump / MRSA / P.aeruginosa / analysis of total picture / inhibitor of efflux pump / K.pneumoniae / skyrin / 排出ポンプ阻害物質 / 感染症 / 抗生物質 / 耐性系阻害薬 / 系統的解析 / ポンプ阻害剤 / 有効物質 |
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| Research Abstract |
Infections by multidrug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Pseudomonas aeruginosa, Klebsiella pneumoniae are serious problems. Multidrug efflux pumps are most importantly involved in the multidrug resistance in multidrug resistant bacteria. We systematically investigated the multidrug efflux pumps of such bacteria. Based on genome sequence of MRSA N315, we cloned all of the 37 genes for tentative multidrug efflux pumps, and characterized the pumps. Also we investigated expression of the 37 genes in MRSA N315, and made clear which ones are really expressed in N315 cells and really contributing to the multidrug resistance. Thus, total picture of multidrug efflux pumps was made clear in MRSA N315. RND-type multidrug efflux pumps play major role in multidrug resistance in P aeruginosa. We cloned all of the 11 possible genes for RND-type multidrug efflux pumps in P aeruginosa PAO1 with which genome sequence is available. We characterized all of the hitherto uncharacterized pumps. Thus, total picture of RND-type multidrug efflux pumps was made clear. We isolated mutants of P.aeruginosa with elevated resistance to multiple antimicrobial agents. We cloned genes responsible for the multidrug resistance from chromosome of the mutants, expressed the genes and characterized the pumps. We identified the mutated portion of each gene for multidrug efflux pump. Genes for multidrug efflux pumps were also cloned from chromosome of K.pneumoniae, VRE, Vibrio parahaemolyticus and V.cholerae non-O1. We characterized many multidrug efflux pumps. We constructed mutants lacking genes for the multidrug efflux pumps, and investigated physiological roles of the pumps.
We found inhibitors for the multidrug efflux pumps, skyrin and baicalein.
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