| Project/Area Number |
09044342
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
GOTOH Naomasa Kyoto Pharmaceutical University, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (30121156)
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| Co-Investigator(Kenkyū-buntansha) |
PECHERE Jean ジュネーブ大学, 医学部, 教授
POOLE R.Keith Queen's University, Department of Microbiology and Immunoblogy, Associate Profes, 医学部, 助教授
TSUDA Masataka Okayama University, Faculty of Science, Associate Professor, 理学部, 助教授 (90172022)
TSUJIMOTO Hideto Kyoto Pharmaceutical University, Faculty of Pharmacy, Research Assistant, 薬学部, 助手 (10257777)
NISHINO Takeshi Kyoto Pharmaceutical University, Faculty of Pharmacy, Professor, 薬学部, 教授 (50097838)
PECHERE Jean-Claude Geneve University, Department of Genetics and Microbiology
KEITH Poole クイーンズ大学, 医学部, 助教授
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| Project Period (FY) |
1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1997: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Pseudomonas aeruginosa / multidrug resistance / multidrug efflux / deletion system / MexA-MexB-OprM / MexC-MexD-OprJ / Multidrug resistance / Deletion system / Multidrug efflux system |
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| Research Abstract |
We have obtained the following results in the investigation of multidrug efflux systems in which endow multidrug resistance in Pseudomonas aeruginosa. Moreover, we developed a new genetical system for deletion of a defined region on the chromosome. Isogenic mutants from a laboratory strain PAOl were constructed using this deletion systems and used in this study.
1. In addition to the two multidrug efflux operons mexA-mexB-oprM and mexC-mexD-oprJ,an efflux operonmexE-mexF-opeN found to be encoded on the chromosome of P.aeruginosa.
2. Characterization of mutants lacking the mexA-mexB-oprM region clearly indicated that the MexC-MexD-OprJ efflux system is involved in resistance to the ordinary cephems as well as fluoroquinolones and the fourth generation cephems, but not to carbenicillin and aztreonam.
3. The functional replacement between OprJ and OprM,and the role of the inner membrane-associated components MexCD,but not the outer membrane component OprJ,as a determinant endowing substrate specificity.
4. These systems contribute to emergence of multidrug resistant strains during treatment of infections caused by P.aeruginosa.
We believe our results provide important information for further investigation of the molecular structure of the multidrug efflux system.
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