Bacteriophages inhibit and evade cGAS-like immune function in bacteria

文献类型： 外文期刊

第一作者： Huiting, Erin

作者： Huiting, Erin;Silas, Sukrit;Carion, Heloise;Bondy-Denomy, Joseph;Luo, Zhaorong;An, Na;Feng, Yue;Ren, Jie;Zhou, Yu;Fraser, James S.;Bondy-Denomy, Joseph;Bondy-Denomy, Joseph

作者机构：

期刊名称：CELL （ 影响因子：64.5； 五年影响因子：57.5 ）

ISSN： 0092-8674

年卷期： 2023 年 186 卷 4 期

页码：

收录情况： SCI

摘要： A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2',3'-cGAMP and activates the effector STING. Diverse bacteria contain cGAS-like enzymes that produce cy-clic oligonucleotides and induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether bacteria harboring CBASS antagonize and co -evolve with phages is unknown. Here, we identified an endogenous cGAS-like enzyme in Pseudomonas aer-uginosa that generates 3 ',3 '-cGAMP during phage infection, signals to a phospholipase effector, and limits phage replication. In response, phages express an anti-CBASS protein ("Acb2") that forms a hexamer with three 3',3'-cGAMP molecules and reduces phospholipase activity. Acb2 also binds to molecules pro-duced by other bacterial cGAS-like enzymes (3 ',3 '-cUU/UA/UG/AA) and mammalian cGAS (2',3'-cGAMP), suggesting broad inhibition of cGAS-based immunity. Upon Acb2 deletion, CBASS blocks lytic phage repli-cation and lysogenic induction, but rare phages evade CBASS through major capsid gene mutations. Alto-gether, we demonstrate endogenous CBASS anti-phage function and strategies of CBASS inhibition and evasion.

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