title: Action-mechanism of trichoderin A, an anti-dormant mycobacterial aminolipopeptide from marine sponge-derived Trichoderma sp.
abstract: In the course of our search for anti-dormant mycobacterial substances from marine organisms, we previously isolated three new aminolipopeptides, named trichoderins A, A1 and B, from the culture of the marine sponge-derived fungus of Trichoderma sp. and determined their chemical structures. To identify the gene that could confer a resistance to trichoderin A, we prepared transformants of Mycobacterium (M.) smegmatis, which were transformed with the genomic DNA library of M. bovis BCG constructed in the multi-copy shuttle cosmid pYUB145. 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. In addition, trichoderin A reduced ATP contents in M. bovis BCG. These findings elucidated that the anti-mycobacterial activity of trichoderins comes from the inhibition of ATP synthesis.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565–0871, Japan.
authors.forename: Patamaporn
authors.initials: P
authors.lastname: Pruksakorn
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.forename: William Robert
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D003360:Cosmids; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015723:Gene Library; D016678:Genome; D055666:Lipopeptides / Q000494:pharmacology*; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000235:genetics*; D011161:Porifera / Q000382:microbiology*; D014170:Transformation, Genetic; D014242:Trichoderma / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D055666:Lipopeptides; C551822:trichoderin A; D000255:Adenosine Triphosphate