The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.
The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.
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分枝杆菌糖苷水解酶 LamH 能够释放荚膜阿拉伯甘露聚糖并刺激生长。
DOI：
10.1101/2023.10.26.563968
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Franklin A
中科院分区：
文献类型：
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作者：
Franklin A
分枝杆菌糖脂是驱动宿主-病原体相互作用的重要细胞包膜结构。可以说，最重要的是脂阿拉伯甘露聚糖（LAM）及其前体脂甘露聚糖（LM），它们通过未知的机制从细菌运输到宿主。阿拉伯甘露聚糖被认为是这些分子的囊状衍生物，缺乏脂质锚。然而，这种物质产生的机制尚未阐明。在这里，我们描述了一种糖苷水解酶家族76酶的鉴定，我们称之为LamH（结核分枝杆菌中的Rv 0365 c），它特异性地切割LM和LAM中的α− 1，6-甘露糖苷键，驱动其输出到释放其磷脂酰肌醇甘露糖苷脂质锚的胶囊。出乎意料的是，我们发现这种酶的催化活性对于从稳定期培养物有效退出是重要的，这可能暗示阿拉伯甘露聚糖是生长相变的信号。最后，我们证明了LamH对M的重要性。结核菌在巨噬细胞中存活。
Mycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are trafficked from the bacterium to the host via unknown mechanisms. Arabinomannan is thought to be a capsular derivative of these molecules, lacking a lipid anchor. However, the mechanism by which this material is generated has yet to be elucidated. Here, we describe the identification of a glycoside hydrolase family 76 enzyme that we term LamH (Rv0365c inMycobacterium tuberculosis) which specifically cleaves α−1,6-mannoside linkages within LM and LAM, driving its export to the capsule releasing its phosphatidyl-myo-inositol mannoside lipid anchor. Unexpectedly, we found that the catalytic activity of this enzyme is important for efficient exit from stationary phase cultures, potentially implicating arabinomannan as a signal for growth phase transition. Finally, we demonstrate that LamH is important forM. tuberculosissurvival in macrophages.