Mycolic acids: deciphering and targeting the Achilles' heel of the tubercle bacillus.
Mycolic acids: deciphering and targeting the Achilles' heel of the tubercle bacillus.
复制标题
分枝菌酸：破译并瞄准结核杆菌的致命弱点。
DOI：
10.1111/mmi.13101
复制
发表时间：
2015-10
影响因子：
3.6
通讯作者：
Bhatt A
中科院分区：
文献类型：
--
作者：
Nataraj V;Varela C;Javid A;Singh A;Besra GS;Bhatt A
分枝菌酸是在分枝杆菌（包括结核杆菌）富含脂质的细胞壁中发现的独特的长链脂肪酸。参与分枝菌酸生物合成的酶对于活力和毒力至关重要，代表了药物开发的新靶标。鉴于耐多药和广泛耐药的分枝杆菌菌株的增加，这与对全球健康的影响尤其相关。 结核。在这篇综述中，我们讨论了我们对分枝菌酸合成方式的理解的最新进展，特别是专门的脂肪酸合酶复合物的潜在作用。此外，我们还参考了一些关于抗 MmpL3 的多种化合物靶向该转运蛋白的报告，研究了最近报道的分枝菌酸转运蛋白 MmpL3 的作用。 结核病活动。此外，我们考虑了最近的发现，将分枝菌酸生物合成置于细菌的细胞生物学背景中，即其与细菌细胞骨架的定位和协调，以及其在维持细胞包膜完整性之外的作用。
Mycolic acids are unique long chain fatty acids found in the lipid‐rich cell walls of mycobacteria including the tubercle bacillus M ycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development. This is particularly relevant to the impact on global health given the rise of multidrug resistant and extensively drug resistant strains of M . tuberculosis. In this review, we discuss recent advances in our understanding of how mycolic acid are synthesised, especially the potential role of specialised fatty acid synthase complexes. Also, we examine the role of a recently reported mycolic acid transporter MmpL3 with reference to several reports of the targeting of this transporter by diverse compounds with anti‐M . tuberculosis activity. Additionally, we consider recent findings that place mycolic acid biosynthesis in the context of the cell biology of the bacterium, viz its localisation and co‐ordination with the bacterial cytoskeleton, and its role beyond maintaining cell envelope integrity.