Rousseau Cécile, Sirakova Tatiana D, Dubey Vinod S, Bordat Yann, Kolattukudy Pappachan E, Gicquel Brigitte, Jackson Mary
Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Biomolecular Science Center, Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32816-2360, USA.
Microbiology (Reading). 2003 Jul;149(Pt 7):1837-1847. doi: 10.1099/mic.0.26278-0.
The cell envelope of pathogenic mycobacteria is highly distinctive in that it contains a large number of structurally related very long multiple methyl-branched fatty acids. These complex molecules are thought to play important roles in cell envelope organization and virulence. The genetic and enzymic characterization of the polyketide synthase Mas, which is responsible for the synthesis of one such family of fatty acids (the mycocerosic acids), paved the way towards the identification of other enzymes involved in the synthesis of methyl-branched fatty acids in M. tuberculosis. In an effort to elucidate the origin of these complex fatty acids and their possible involvement in pathogenesis, the two mas-like polyketide genes pks5 and pks7 were disrupted in M. tuberculosis and the effects of their inactivation on fatty acid composition and virulence were analysed. While the disruption of pks7 resulted in a mutant deficient in the production of phthiocerol dimycocerosates, the cell envelope composition of the pks5 mutant was found to be identical to that of the wild-type parental strain M. tuberculosis H37Rv. Interestingly, both the pks5 and pks7 mutants displayed severe growth defects in mice.
致病性分枝杆菌的细胞壁非常独特，因为它含有大量结构相关的超长多甲基支链脂肪酸。这些复杂分子被认为在细胞壁组织和毒力中发挥重要作用。聚酮合酶Mas负责合成其中一类脂肪酸（霉菌酸），对其进行遗传和酶学表征，为鉴定参与结核分枝杆菌甲基支链脂肪酸合成的其他酶铺平了道路。为了阐明这些复杂脂肪酸的来源及其可能参与发病机制的情况，在结核分枝杆菌中破坏了两个类mas聚酮基因pks5和pks7，并分析了它们失活对脂肪酸组成和毒力的影响。虽然pks7的破坏导致一个缺乏结核菌醇二霉菌酸酯产生的突变体，但发现pks5突变体的细胞壁组成与野生型亲本菌株结核分枝杆菌H37Rv相同。有趣的是，pks5和pks7突变体在小鼠中均表现出严重的生长缺陷。
