| Project/Area Number |
17K08403
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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 |
Environmental and hygienic pharmacy
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| Research Institution | Daiichi University, College of Pharmaceutical Sciences |
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Principal Investigator |
Ogawa Wakano 第一薬科大学, 薬学部, 教授 (90397878)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 多剤排出ポンプ / 薬剤耐性 / 転写制御 / トランスクリプトーム / 抗菌薬多剤耐性 / 2成分転写制御系 / 肺炎桿菌 / 細菌 / 抗菌薬耐性 / 転写発現解析 / 発現解析 |
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| Outline of Final Research Achievements |
Transcriptome analysis was performed on multidrug-resistant K. pneumoniae Em16-1. Compared to the parental strain ATCC10031, forty-four genes were significantly up-regulated. In the mutant strain Em16-1, we observed elevated expression of kdrAB as well as kexD. Therefore, it is highly possible that the expression of kdrAB is self-controlled by itself. Increased expression of genes related to phosphate transport and phosphate utilization was observed in Em16-1. Increased expression of the enzyme gene arnBCADTEF, which synthesizes 4-amino-4-deoxy-L-arabinose from uridine diphosphate glucuronic acid for LPS modification, was also observed.
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| Academic Significance and Societal Importance of the Research Achievements |
KdrABにより発現制御されうる遺伝子群を同定した。これらの遺伝子の一部は、コリスチン耐性株でも発現上昇が報告されていた。従って、KdrBの変異は多剤排出ポンプKexD発現を上昇させるのみでなく、コリスチン耐性化に関わる遺伝子群の発現を上昇させることが示唆された。一方で、Em16-1ではコリスチン耐性の上昇は認められなかった。この結果からコリスチン耐性化とKdrABの間には、別の因子が介在している可能性が考えられ、本研究は肺炎桿菌の抗菌薬耐性について、新たな知見を与えるものである。
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