P-81 感染部位環境に着目した評価系を用いる新規抗結核活性物質の探索と作用メカニズムの解析(ポスター発表の部)
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概要
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Tuberculosis (TB) is one of the most common causes of morbidity and death in HIV-positive adults living less-developed countries. Eight million new TB cases and two million deaths by TB are estimated each year. It is now generally accepted that the requirement for minimum 6 months treatment for TB is due to the difficulty in eradicating non-replicating persistent Mycobacterium tuberculosis in the granuloma of infected region. Therefore, the lead compounds, which are effective to M. tuberculosis in both active state and dormant state, are urgently needed. It is also important to explore new targets for drug against M. tuberculosis in the dormant state. Then, we established a screening system in hypoxic condition inducing dormant state based on environment of infected region. Resulting the screening, halicyclamine A was re-discovered as a lead for anti-tuberculosis agent from a marine sponge of Haliclona sp. on the guidance of the constructed bioassay. Halicyclamine A showed growth inhibition against M. smegmatis and M. bovis BCG with MICs in the range of 1.0μg/ml-2.5μg/ml under both aerobic condition and hypoxic condition inducing dormant state, and the growth inhibitory activity of halicyclamine A was bactericidal. In order to elucidate action-mechanism of halicyclamine A, transformants of M. smegmatis, which over-expressed the genes of M. bovis BCG randomly, were prepared by gnomic DNA library of M. bovis BCG. As a result, the target molecule of halicylamine A was clarified to be included in the genome of M. bovis BCG from 2920.549kb to 2933.210kb.
- 2008-09-01
著者
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小林 資正
大阪大学大学院薬学研究科
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荒井 雅吉
大阪大学大学院薬学研究科
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荒井 雅吉
阪大院薬
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惣坊 真理
阪大院薬
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石田 俊介
阪大院薬
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Pruksakorn Patamaporn
阪大院薬
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小林 資正
阪大院薬
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Kobayashi Masao
Pharmaceutical Research Laboratory Tanabe Seiyaku Co. Ltd.
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