P-62 潜在性結核菌に有効な抗菌物質の探索とゲノムDNAライブラリーを利用する標的分子の解明(ポスター発表の部)

• 荒井 雅吉

  阪大院薬

• 山野 喜

  阪大院薬

• 韓 智秀

  阪大院薬

• Pruksakorn Patamaporn

  阪大院薬

• 小林 資正

  阪大院薬

書誌事項

タイトル別名

• P-62 Search for anti-dormant mycobacterial substances and analysis of their target molecule using genomic DNA library(Poster Presentation)

抄録

It is now generally accepted that the requirement for minimum 6 months treatment for Tuberculosis is due to the difficulty in eradicating dormant states of M. tuberculosis. Although physiology of the latent M. tuberculosis infections is still unclear, hypoxic condition was found to induce a dormant state of Mycobacterium sp., which has a drug susceptibility profile resembling that of the latent M. tuberculosis infection. Based on these findings, we have established a screening system for anti-dormant mycobacterial substances. As a result of screening, we isolated three new aminolipopeptides, named trichoderins A (1), A1 (2), and B (3) from a marine sponge-derived fungus of Trichoderma sp. Trichonderins showed potent anti-mycobacterial activity against M. smegmatis and M. bovis BCG under standard aerobic growth condition as well as dormancy-inducing hypoxic condition, with MICs in the range of 0.02-1.56 μg/mL. In addition, we also isolated the marine spongian diterpene alkaloids, agelasines B (4), C (5), and D (6), as anti-dormant mycobacterial substances with MICs in the range of 0.8-12.5 μg/mL. On the other hand, it is known that the transformant, which over-expresses the target molecule of anti-microbial compound, becomes resistant to the compound. In order to identify the gene that could confer a resistance to trichoderin A (1) or agelasine D (6), the transformants of M. smegmatis, which over-expressed the genes of M. bovis BCG randomly, were prepared by geomic DNA library of M. bovis BCG. Then, the transformant of M. smegmatis, which over-expressed a part of genes that coded mycobacterial ATP synthase, was found to exhibit a resistance to trichoderin A (1). In addition, trichoderin A (1) reduced ATP contents in M. bovis BCG. These findings suggested that the anti-mycobacterial activity of trichoderin A (1) might come from the inhibition of ATP synthesis. In the case of agelasine D (6), the four genes, BCG3184c, 3185c, 3186c and 3187c, were identified as candidates for target molecule of agelasine D (6) according to the analysis of cosmids in the agelasine D (6)-resistant transformants.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 54 (0), 639-644, 2012

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390001206079527296
• NII論文ID: 110010013900
• DOI: 10.24496/tennenyuki.54.0_639
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可