title: Anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of Melophlus sp.
abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a major world health problem that is responsible for the deaths of 1.5 million people each year. In addition, the requirement for long-term therapy to cure TB complicates treatment of the disease. One of the major reasons for the extended chemotherapeutic regimens and wide epidemicity of TB is that M. tuberculosis has the ability to persist in a dormant state. We therefore established a new screening system to search for substances with activity against dormant mycobacteria using M. smegmatis and M. bovis BCG cultivated in medium containing propionate as sole carbon source to induce dormancy. Subsequently, melophlins A (1), G (2), H (3), and I (4), tetramic acid derivatives, were re-discovered from the Indonesian marine sponge of Melophlus sp. as anti-dormant mycobacterial substances. Moreover, target analysis of melophlin A indicated that it targeted the BCG1083 protein of putative exopolyphosphatase and the BCG1321c protein of diadenosine 5',5‴-P(1),P(4)-tetraphosphate phosphorylase.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan. araim@phs.osaka-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kamiya
authors.affiliation: Department of Chemistry, Faculty of Science, Lampung University, Jl. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar Lampung, 35145, Indonesia.
authors.forename: Andi
authors.initials: A
authors.lastname: Setiawan
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka, 565-0871, Japan. kobayasi@phs.osaka-u.ac.jp.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011760:Pyrrolidinones / Q000737:chemistry*
chemical_list: D000473:Alkanes; D000995:Antitubercular Agents; D011760:Pyrrolidinones; C546381:melophlin A; C009435:tetramic acid
keywords: Antibiotic; Carbon source; Dormant; Marine sponge; Melophlin; Tuberculosis