Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis
Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis
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DOI：
10.1016/s1472-9792(02)00089-6
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发表时间：
2003-01-01
期刊：
影响因子：
3.2
通讯作者：
Brennan, PJ
中科院分区：
文献类型：
--
作者：
Brennan, PJ
分枝杆菌细胞壁的大部分早期结构定义。是在20世纪60年代和70年代开始的。有很长一段时间没有活动，但最近在NMR和质谱方面的发展，结核杆菌基因组的分析和定义不仅使人们对分枝杆菌细胞壁及其脂质的结构，而且对基本的遗传学和生物合成有了全面的了解。我们现在对细胞壁结构的理解相当于一个巨大的“核心”，该核心由肽聚糖组成，肽聚糖通过接头单元（L-Rha-D-GlcNAc-P）共价连接到线性半乳呋喃上，然后连接到高度支化的阿拉伯呋喃的几条链上，然后连接到分枝菌酸上。分枝菌酸的方向垂直于膜的平面，并提供了一个真正特殊的脂质屏障，负责结核杆菌的许多生理和疾病诱导方面。嵌入在这种脂质环境中的脂质，吸引了研究人员超过50年：phthiocerol dimycerosate，脐带因子/dimycolyltrehalose，sulfolipids，磷脂酰肌醇甘露糖苷等知识，他们的角色在“信号”事件，发病机制，免疫反应，现在正在出现，有时零敲碎打，有时在一个有组织的方式。一些更有趣的观察是那些证明，myocardial acids被识别的CD 1-限制性T细胞，抗原85，最强大的保护性抗原之一的结核杆菌，是一个mycolyltransferase，和脂阿拉伯甘露聚糖（LAM），当“帽”与短甘露寡糖，参与吞噬结核杆菌。结核分枝杆菌基因组的定义极大地帮助了我们确定所有这些外来分子的生物合成途径：分枝菌酸、分枝菌蜡酸、苯硫代蜡醇、LAM和聚异戊二烯磷酸盐。例如，我们知道，整个核心的合成是在十异戊二烯基-P上起始的，同时合成接头单元，然后伴随着半乳聚糖和阿拉伯聚糖链的延伸，同时该中间体通过细胞质膜转运。这些事件的最后步骤，分枝菌酸的附着和连接肽聚糖，等待定义，并将被证明是新一代抗结核药物的优秀目标。(C)2003年由Elsevier Science Ltd.出版
Much of the early structural definition of the cell wall of Mycobacterium spp. was initiated in the 1960s and 1970s. There was a long period of inactivity, but more recent developments in NMR and mass spectral, analysis and definition of the A tuberculosis genome have resulted in a thorough understanding, not only of the structure of the mycobacterial cell wall and its lipids but also the basic genetics and biosynthesis. Our understanding nowadays of cell-wall architecture amounts to a massive "core" comprised of peptidoglycan covalently attached via a linker unit (L-Rha-D-GlcNAc-P) to a linear galactofuran, in turn attached to several strands of a highly branched arabinofuran, in turn attached to mycolic acids. The mycolic acids are oriented perpendicular to the plane of the membrane and provide a truly special lipid barrier responsible for many of the physiological and disease-inducing aspects of A tuberculosis. Intercalated within this lipid environment are the lipids that have intrigued researchers for over five decades: the phthiocerol dimycocerosate, cord factor/dimycolyltrehalose, the sulfolipids, the phosphatidytinositol mannosides, etc. Knowledge of their roles in "signaling" events, in pathogenesis, and in the immune response is now emerging, sometimes piecemeal and sometimes in an organized fashion. Some of the more intriguing observations are those demonstrating that mycotic acids are recognized by CD1-restricted T-cells, that antigen 85, one of the most powerful protective antigens of A tuberculosis, is a mycolyltransferase, and that lipoarabinomannan (LAM), when "capped" with short mannose oligosaccharides, is involved in phagocytosis of A tuberculosis. Definition of the genome of A tuberculosis has greatly aided efforts to define the biosynthetic pathways for all of these exotic molecules: the mycolic acids, the mycocerosates, phthiocerol, LAM, and the polyprenyl phosphates. For example, we know that synthesis of the entire core is initiated on a decaprenyl-P with synthesis of the linker unit, and then there is concomitant extension of the galactan and arabinan chains while this intermediate is transported through the cytoplasmic membrane. The final steps in these events, the attachment of mycolic acids and ligation to peptidoglycan, await definition and will prove to be excellent targets for a new generation of anti-tuberculosis drugs. (C) 2003 Published by Elsevier Science Ltd.