2014 Fiscal Year Final Research Report
Mechanisms of quinolone resistance in Acinetobacter spp. and screening of a novel antibacterial drug target
| Project/Area Number |
24590533
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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 |
Bacteriology (including Mycology)
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| Research Institution | Nihon Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KAKU Mitsuo 東北大学, 医学系研究科, 教授 (40224357)
YAMADA Sakuo 川崎医科大学, 医学部, 准教授 (00122458)
KAWAI Mako 姫路獨協大学, 薬学部, 准教授 (40533922)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 薬剤耐性機構 / キノロン薬 / アシネトバクター / 耐性変異 / DNA gyrase / DNA topoisomeraseⅣ / レボフロキサシン / ナリジクス酸 |
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| Outline of Final Research Achievements |
In order to elucidate the mechanisms of quinolone resistance in Acinetobacter spp., spontaneous mutants with various patterns of resistance to levofloxacin(LVFX) and nalidixic acid(NA) were isolated from Acinetobacter baumannii ATCC19606 by stepwise selection with LVFX. Most mutants were less resistant to LVFX than to NA, and some mutants resistant to LVFX were hypersusceptible to NA. The first-step mutants had a point mutation only in gyrA. These results indicate that the primary target of LVFX are DNA gyrase, but not DNA topoisomeraseⅣ. The characterization of the spontaneous mutants demonstrates that in addition to the previously reported alterations in GyrA and ParC, an unkown efflux pump and probably other unkown mechanisms contribute to quinolone resistance in A. baumannii.
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| Free Research Field |
化学療法学
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