Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, 94720, USA.
J Microbiol. 2013 Oct;51(5):619-26. doi: 10.1007/s12275-013-3092-y. Epub 2013 Sep 14.
The lipid-rich cell wall of Mycobacterium tuberculosis, the agent of tuberculosis, serves as an effective barrier against many chemotherapeutic agents and toxic host cell effector molecules, and it may contribute to the mechanism of persistence. Mycobacterium tuberculosis strains mutated in a 13-gene operon called mce1, which encodes a putative ABC lipid transporter, induce aberrant granulomatous response in mouse lungs. Because of the postulated role of the mce1 operon in lipid importation, we compared the cell wall lipid composition of wild type and mce1 operon mutant M. tuberculosis H37Rv strains. High resolution mass spectrometric analyses of the mce1 mutant lipid extracts showed unbound mycolic acids to accumulate in the cell wall. Quantitative analysis revealed a 10.7 fold greater amount of free mycolates in the mutant compared to that of the wild type strain. The free mycolates were comprised of alpha, methoxy and keto mycolates in the ratio 1:0.9:0.6, respectively. Since the mce1 operon is regulated in vivo, the free mycolates that accumulate during infection may serve as a barrier for M. tuberculosis against toxic products and contribute to the pathogen's persistence.
结核分枝杆菌（Mycobacterium tuberculosis）的富含脂质的细胞壁是结核病的病原体，它作为许多化学治疗药物和毒性宿主细胞效应分子的有效屏障，可能有助于其持续存在的机制。在一个称为 mce1 的 13 基因操纵子中发生突变的结核分枝杆菌菌株，该操纵子编码一个假定的 ABC 脂质转运蛋白，会在小鼠肺部引起异常的肉芽肿反应。由于 mce1 操纵子在脂质摄取中的假定作用，我们比较了野生型和 mce1 操纵子突变型 M. tuberculosis H37Rv 菌株的细胞壁脂质组成。对 mce1 突变体脂质提取物的高分辨率质谱分析表明，未结合的分枝菌酸在细胞壁中积累。定量分析显示，突变体中游离的分枝菌酸含量比野生型菌株高 10.7 倍。游离的分枝菌酸由α、甲氧基和酮分枝菌酸组成，比例分别为 1:0.9:0.6。由于 mce1 操纵子在体内受到调控，因此在感染过程中积累的游离分枝菌酸可能成为结核分枝杆菌对抗毒性产物的屏障，并有助于病原体的持续存在。
