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研究揭示cGAMP信号保护细菌免受病毒感染机制
2019-09-19 14:04

以色列魏茨曼科学研究所Rotem Sorek和Gil Amitai合作发现了环GMP-AMP(cGAMP)信号保护细菌免受病毒感染的机制。 相关论文于2019年9月18日在线发表于《自然》。

研究者发现cGAMP信号是细菌中常见的抗噬菌体防御系统的一部分。细菌cGAS防御系统由四个基因操纵子组成,包括相关的磷脂酶、类似真核生物E1 / E2的结构域和JAB。研究证明这个操纵子可以抵抗多种噬菌体。噬菌体感染引发cGAMP产生,其反过来激活磷脂酶,导致在完成噬菌体复制之前细菌膜完整性丧失和细胞死亡。

该系统的不同模式在超过10%的原核基因组中存在,并且研究显示具有磷脂酶以外的其他效应物变体也可以防止噬菌体感染。这项研究表明,真核生物cGAS-STING抗病毒途径在微生物防御噬菌体方面具有古老的进化根源。

据研究人员介绍,cGAS-STING途径是动物细胞自主先天免疫系统的核心组成部分。 cGAS蛋白(环状GMP-AMP合酶)是细胞质病毒DNA的传感器,在检测到DNA时,产生环状GMP-AMP信号分子,其结合STING蛋白并激活免疫应答。在细菌中也检测到cGAMP产生,并且霍乱弧菌已经显示出磷脂酶活性,降解细菌内膜。然而,它的生物学作用仍然未知。

附:英文原文

Title: Cyclic GMP–AMP signalling protects bacteria against viral infection

Author: Daniel Cohen, Sarah Melamed, Adi Millman, Gabriela Shulman, Yaara Oppenheimer-Shaanan, Assaf Kacen, Shany Doron, Gil Amitai, Rotem Sorek

Issue&Volume: 2019-09-18

Abstract: 

The cGAS–STING pathway is a central component of the cell-autonomous innate immune system in animals1,2. The cGAS protein (cyclic GMP–AMP synthase) is a sensor of cytosolic viral DNA and, upon DNA sensing, produces a cyclic GMP–AMP (cGAMP) signalling molecule that binds the STING protein and activates the immune response3–5. cGAMP production has also been detected in bacteria6, and in Vibrio cholerae has been shown to activate a phospholipase that degrades the inner bacterial membrane7; however, its biological role remains unknown. Here we show that cGAMP signalling is part of an anti-phage defence system that is common in bacteria. This system is composed of a four-gene operon that codes for the bacterial cGAS, the associated phospholipase, and two enzymes with the eukaryotic-like domains E1/E2 and JAB. We show that this operon confers resistance against a wide array of phages. Phage infection triggers cGAMP production, which, in turn, activates the phospholipase leading to loss of membrane integrity and cell death before completion of phage reproduction. Diverged versions of this system appear in more than 10% of prokaryotic genomes, and we show that variants with effectors other than phospholipase also protect against phage infection. Our results suggest that the eukaryotic cGAS–STING antiviral pathway has ancient evolutionary roots in microbial defence against phages.

DOI: 10.1038/s41586-019-1605-5

Source:https://www.nature.com/articles/s41586-019-1605-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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