| Project/Area Number |
25860329
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Kim Hyun 国立感染症研究所, その他部局等, 主任研究官 (90648817)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 結核菌 / 薬剤耐性菌 / X線回析 / 立体構造解析 / DNAジャイレース / ニューキノロン / X線回折 |
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| Outline of Final Research Achievements |
Emergence of multidrug-resistant (MDR) tuberculosis is becoming an increasing public health problem and poses a serious threat to TB control. Therefore, novel anti-TB drugs are needed urgently. The outbreak of MDR-TB leads fluoroquinolones to becoming an important second-line anti-TB agent. The major target of FQs is DNA gyrase consisted of two subunits GyrA and GyrB. FQs-gyrase interaction site is thought to be located at QRDRs in GyrA and GyrB where the majority of mutations conferring resistance to FQs exist. Recently, FQs-resistant M. tuberculosis is dramatically increased. However, the mechanisms of correlation between MtDNA gyrase and FQs-resistance are still not clearly understood. In this study, we examined and investigated an association between FQs and mutants GyrA subunits from Beijing strain by using inhibition assays. Furthermore, we demonstrated the different structures of MtDNA gyrases, between H37Rv and Beijing strain DNA GyrA (N-term) from structural analysis.
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