分枝杆菌噬菌体裂解系统及其相关蛋白的研究进展

Advances in the study of mycobacteriophage lysis cassettes and their related proteins

噬菌体进化出多种裂解系统,以裂解宿主菌的细胞壁来释放子代噬菌体,并进行下一轮感染。与常见的Endolysin-Holin裂解系统不同,分枝杆菌噬菌体裂解系统由LysinA、LysinB及Holin蛋白组成。分枝杆菌具有特殊的细胞壁结构,其具有非典型的A1γ型肽聚糖,且在肽聚糖外有一层致密的分枝菌酸。LysinA可以裂解宿主菌的肽聚糖层;LysinB具有酯酶活性,裂解分枝菌酸与阿拉伯半乳聚糖之间的共价键-分枝酰阿拉伯半乳聚糖苷键;而Holin蛋白属于小分子极性跨膜蛋白,可在细胞膜形成稳定的跨膜孔。在噬菌体感染晚期,LysinA及LysinB蛋白正是通过此孔到达细胞壁发挥作用。与其他革兰阳性菌噬菌体不同,外源添加LysinA/LysinB不能有效裂解其宿主菌。本文综述了分枝杆菌噬菌体裂解系统相关蛋白的研究进展,并着重介绍了LyinA蛋白的保守的结构域,以期为分枝杆菌噬菌体及其相关蛋白的研究与临床应用带来新思路。

Bacteriophage has evolved a variety of lysis systems to digest the bacterial cell wall in order to release progeny phages and carry out the next round of infection.Unlike the common endolysin-holin system,the lysis system of mycobacteriophages consists of LysinA,LysinB,and Holin proteins.The cell wall structure of a mycobacterium contains atypical A1 gamma type peptidoglycan and a mycolic acid-rich outer membrane covalently attached to the arabinogalactanpeptidoglycan complex.Lysin A hydrolyzes peptidoglycan,and Lysin B,a novel mycolylarabinogalactan esterase,cleaves the mycolylarabinogalactan bond to release free mycolic acids.Holins are small molecular transmembrane proteins that control the length of the infective cycle and are associated with a collapse of the membrane potential and permeabilization of the membrane.This allows LysinA and LysinB proteins to gain access to the membrane＇s substrate,the cell wall,immediately resulting in destruction of murein and bursting of the cell.Addition of exogenous LysinA/LysinB does not result in the lysis of mycobacteria as it does with Gram-positive bacteria.This paper reviews advances in the study of proteins related to the mycobacteriophage lysis system,with an emphasis on the conserved domain of the LysinA protein.This paper will provide new ideas for research on and clinical use of mycobacteriophages and their related proteins.