近日來自美國印第安納大學(xué)醫(yī)學(xué)院的研究人員在新研究中揭示了機(jī)體先天防御系統(tǒng)中的一組蛋白質(zhì)通過誘導(dǎo)細(xì)菌自殺防止入侵機(jī)體的機(jī)制。這一研究發(fā)現(xiàn)為開發(fā)出針對抗生素耐受性細(xì)菌的新抗菌治療指明了新方向,。相關(guān)研究論文發(fā)表在5月22日的《自然—醫(yī)學(xué)》（Nature Medicine）雜志上,。
PGRPs
肽聚糖識別蛋白(PGRPs)是一類可識別肽聚糖和含肽聚糖的細(xì)菌的模式識別受體，過去的研究證實PGRPs在天然免疫中發(fā)揮著重要的識別和調(diào)節(jié)功能,。
早在2001年第安納大學(xué)醫(yī)學(xué)院微生物學(xué)及免疫學(xué)教授Roman Dziarski就與他的同事生物化學(xué)和分子生物學(xué)系副教授Dipika Gupta首次克隆了PGRP基因,。隨后，研究人員證實PGRP廣泛地存在于從昆蟲到哺乳動物等物種中,，在機(jī)體的先天免疫系統(tǒng)中起重要作用,。
PGRP蛋白通常表達(dá)于血液的吞噬細(xì)胞及皮膚、口腔,、腸道及其他與外界有著直接或間接接觸的組織中,。在某些組織中PGRPs參與維持機(jī)體與某些有益菌的相對平衡。一些研究表明PGRP蛋白質(zhì)缺失可導(dǎo)致炎性腸病,。然而直到現(xiàn)在科學(xué)家們對于PGRPs靶向殺死細(xì)菌的機(jī)制并不是很清楚,。
在這篇文章中，Dziarski領(lǐng)導(dǎo)的研究小組證實PGRPs是通過結(jié)合到細(xì)菌細(xì)胞壁的特異性位點,，進(jìn)而利用一種稱為“蛋白質(zhì)傳感雙組份系統(tǒng)”（protein-sensing two-component system）的細(xì)菌防御機(jī)制靶向性誘導(dǎo)細(xì)菌發(fā)生自殺反應(yīng)的,。正常情況下細(xì)菌通常利用這一系統(tǒng)檢測并清除例如PGRPs一類的“畸形”蛋白質(zhì)。而當(dāng)無法清除PGRPs時,，細(xì)菌則會啟動自殺反應(yīng),。
“這種抗菌機(jī)制與其他例如免疫系統(tǒng)白細(xì)胞采用的抗菌機(jī)制完全不同。我們的研究發(fā)現(xiàn)為開發(fā)出新的抗菌策略提供了一個新方向,，”Dziarski說,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature Medicine DOI:10.1038/nm.2357
Peptidoglycan recognition proteins kill bacteria by activating protein-sensing two-component systems
Des Raj Kashyap; Minhui Wang; Li-Hui Liu; Geert-Jan Boons; Dipika Gupta; Roman Dziarski
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.
