Alderwick Luke J, Harrison James, Lloyd Georgina S, Birch Helen L
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Cold Spring Harb Perspect Med. 2015 Mar 27;5(8):a021113. doi: 10.1101/cshperspect.a021113.
The mycobacterial bacillus is encompassed by a remarkably elaborate cell wall structure. The mycolyl-arabinogalactan-peptidoglycan (mAGP) complex is essential for the viability of Mycobacterium tuberculosis and maintains a robust basal structure supporting the upper "myco-membrane." M. tuberculosis peptidoglycan, although appearing to be unexceptional at first glance, contains a number of unique molecular subtleties that become particularly important as the TB-bacilli enters into nonreplicative growth during dormancy. Arabinogalactan, a highly branched polysaccharide, serves to connect peptidoglycan with the outer mycolic acid layer, and a variety of unique glycolsyltransferases are used for its assembly. In this review, we shall explore the microbial chemistry of this unique heteropolysacchride, examine the molecular genetics that underpins its fabrication, and discuss how the essential biosynthetic process might be exploited for the development of future anti-TB chemotherapies.
分枝杆菌杆菌被一个极其复杂的细胞壁结构所包围。霉菌酸 - 阿拉伯半乳聚糖 - 肽聚糖(mAGP)复合物对于结核分枝杆菌的生存能力至关重要,并维持一个强大的基础结构以支撑上层的“霉菌膜”。结核分枝杆菌的肽聚糖,尽管乍一看似乎并无特别之处,但包含许多独特的分子细微差别,当结核杆菌在休眠期间进入非复制性生长时,这些细微差别变得尤为重要。阿拉伯半乳聚糖是一种高度分支的多糖,用于将肽聚糖与外部的霉菌酸层连接起来,并且多种独特的糖基转移酶被用于其组装。在这篇综述中,我们将探索这种独特杂多糖的微生物化学,研究其合成基础的分子遗传学,并讨论如何利用这个必需的生物合成过程来开发未来的抗结核化疗药物。