Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids

被引：58

作者：

Morbidoni, HR

Vilchèze, C

Kremer, L

Bittman, R

Sacchettini, JC

Jacobs, WR

机构：

[1] Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[2] Univ Montpellier 2, Lab Dynam Mol Interact Membranaires, F-34095 Montpellier 05, France

[3] Queens Coll City Univ New York, Dept Chem & Biochem, Flushing, NY 11367 USA

[4] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA

来源：

CHEMISTRY & BIOLOGY | 2006年 / 13卷 / 03期

关键词：

D O I：

10.1016/j.chembiol.2006.01.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

2-Hexadecynoic acid and 2-octadecynoic acid have cidal activity against Mycobacterium smegmatis and Mycobacterium bovis BCG. At subinhibitory concentrations, M. smegmatis rapidly transformed [1-C-14]-2-hexadecynoic acid into endogenous fatty acids and elongated them into mycolic acids. Toxic concentrations of 2-hexadecynoic acid resulted in accumulation of 3-ketohexadecanoic acid, which blocked fatty acid biosynthesis, and 3-hexadecynoic acid, an inhibitor of fatty acid degradation. The combination of these two metabolites is necessary to achieve the inhibition of M. smegmatis. We conclude that 2- and 3-hexa/octadecynoic acids inhibit mycolic acid biosynthesis, fatty acid biosynthesis, and fatty acid degradation, pathways of significant importance for mycobacteria.

引用

页码：297 / 307

页数：11

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