Phage anti-CBASS and anti-Pycsar nucleases subvert bacterial immunity.
Phage anti-CBASS and anti-Pycsar nucleases subvert bacterial immunity.
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DOI：
10.1038/s41586-022-04716-y
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发表时间：
2022-05
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
基于环核苷酸的抗噬菌体信号系统(CBASS)和用于抗噬菌体抗性的嘧啶环酶系统(PYCSAR)是不同细菌中的抗噬菌体防御系统，它们使用环核苷酸信号来诱导细胞死亡和防止病毒传播。噬菌体使用几种策略来击败宿主CRISPR和限制性内切酶修改系统，但尚不知道有什么机制可以逃避CBass和Pycsar免疫。在这里，我们展示了噬菌体编码抗CBass(ACB)和抗Pycsar(Apyc)蛋白，这些蛋白通过特异性地降解激活宿主免疫的环核苷酸信号来抵消防御。通过对大肠杆菌和枯草芽孢杆菌中57个噬菌体的生化筛选，我们发现噬菌体T4中的Acb1和噬菌体SBSphiJ中的Apyc1是不同免疫逃避蛋白家族的创始成员。Acb1与3‘-3’-环GMP-AMP形成的配合物中的晶体结构定义了腺苷碱基3‘-金属非依赖的水解机制，使环二核苷酸和三核苷酸CBASS信号能够被广泛识别和降解。Apyc1的结构揭示了一种金属依赖的环NMP磷酸二酯酶，它使用松弛的特异性来靶向Pycsar环嘧啶单核苷酸信号。我们在体内表明，Acb1和Apyc1阻止下游效应器的激活，并保护其免受CBass和Pycsar的防御。活性Acb1和Apyc1酶在不同系统发育的噬菌体中是保守的，表明切割宿主环核苷酸信号是噬菌体生物学中免疫逃避的关键策略。一项使用两个细菌物种的57个噬菌体的生化筛选的研究识别和表征了使噬菌体能够逃避CBass和Pycsar免疫系统的蛋白质，并描述了相关的机制。
The cyclic oligonucleotide-based antiphage signalling system (CBASS) and the pyrimidine cyclase system for antiphage resistance (Pycsar) are antiphage defence systems in diverse bacteria that use cyclic nucleotide signals to induce cell death and prevent viral propagation. Phages use several strategies to defeat host CRISPR and restriction-modification systems, but no mechanisms are known to evade CBASS and Pycsar immunity. Here we show that phages encode anti-CBASS (Acb) and anti-Pycsar (Apyc) proteins that counteract defence by specifically degrading cyclic nucleotide signals that activate host immunity. Using a biochemical screen of 57 phages in Escherichia coli and Bacillus subtilis, we discover Acb1 from phage T4 and Apyc1 from phage SBSphiJ as founding members of distinct families of immune evasion proteins. Crystal structures of Acb1 in complex with 3′3′-cyclic GMP–AMP define a mechanism of metal-independent hydrolysis 3′ of adenosine bases, enabling broad recognition and degradation of cyclic dinucleotide and trinucleotide CBASS signals. Structures of Apyc1 reveal a metal-dependent cyclic NMP phosphodiesterase that uses relaxed specificity to target Pycsar cyclic pyrimidine mononucleotide signals. We show that Acb1 and Apyc1 block downstream effector activation and protect from CBASS and Pycsar defence in vivo. Active Acb1 and Apyc1 enzymes are conserved in phylogenetically diverse phages, demonstrating that cleavage of host cyclic nucleotide signals is a key strategy of immune evasion in phage biology. A study using a biochemical screen of 57 phages in two bacterial species identifies and characterizes proteins enabling phages to evade CBASS and Pycsar immune systems, and describes the mechanisms involved.
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影响因子：
14.9
作者：
Letunic I;Bork P
通讯作者：
Bork P
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16
作者：
Lau, Rebecca K.;Ye, Qiaozhen;Corbett, Kevin D.
通讯作者：
Corbett, Kevin D.
DOI：
10.1126/science.aar4120
发表时间：
2018-03-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Doron S;Melamed S;Ofir G;Leavitt A;Lopatina A;Keren M;Amitai G;Sorek R
通讯作者：
Sorek R
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC