Peptidoglycan recognition proteins kill bacteria by activating protein-sensing two-component systems
Peptidoglycan recognition proteins kill bacteria by activating protein-sensing two-component systems
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DOI：
10.1038/nm.2357
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发表时间：
2011-06-01
期刊：
影响因子：
82.9
通讯作者：
Dziarski, Roman
中科院分区：
文献类型：
--
作者：
Kashyap, Des Raj;Wang, Minhui;Dziarski, Roman
哺乳动物肽聚糖识别蛋白（PGRP）与抗菌凝集素类似，可以结合细菌细胞壁并通过未知机制杀死细菌。我们发现 PGRP 在细胞分裂过程中子细胞分离部位进入革兰氏阳性细胞壁。在枯草芽孢杆菌中，PGRP 激活 CssR-CssS 双组分系统，该系统检测并处理通常从细菌细胞中输出的错误折叠蛋白质。这种激活导致膜去极化、细胞内肽聚糖、蛋白质、RNA 和 DNA 合成的停止以及羟基自由基的产生，这些自由基是细菌死亡的原因。 PGRP 还结合大肠杆菌的外膜并激活功能上同源的 CpxA-CpxR 双组分系统，从而杀死细菌。我们排除其他潜在的杀菌机制，包括抑制细胞外肽聚糖合成、肽聚糖水解和膜透化。因此，我们揭示了一种以前未知的机制，结合细胞壁或外膜的先天免疫蛋白利用细菌应激防御反应来杀死细菌。
Mammalian peptidoglycan recognition proteins (PGRPs), similar to antimicrobial lectins, bind the bacterial cell wall and kill bacteria through an unknown mechanism. We show that PGRPs enter the Gram-positive cell wall at the site of daughter cell separation during cell division. In Bacillus subtilis, PGRPs activate the CssR-CssS two-component system that detects and disposes of misfolded proteins that are usually exported out of bacterial cells. This activation results in membrane depolarization, cessation of intracellular peptidoglycan, protein, RNA and DNA synthesis, and production of hydroxyl radicals, which are responsible for bacterial death. PGRPs also bind the outer membrane of Escherichia coli and activate the functionally homologous CpxA-CpxR two-component system, which kills the bacteria. We exclude other potential bactericidal mechanisms, including inhibition of extracellular peptidoglycan synthesis, hydrolysis of peptidoglycan and membrane permeabilization. Thus, we reveal a previously unknown mechanism by which innate immunity proteins that bind the cell wall or outer membrane exploit the bacterial stress defense response to kill bacteria.