小柯机器人

噬菌体抗CBASS和抗Pycsar核酸酶破坏细菌免疫力
2022-04-15 15:56
来源：小柯机器人

近日，美国哈佛大学Philip J. Kranzusch及其课题组发现，噬菌体抗CBASS和抗Pycsar核酸酶破坏细菌免疫力。2022年4月8日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现，噬菌体编码的抗CBASS（Acb）和抗Pycsar（Apyc）蛋白通过专门降解激活宿主免疫的环状核苷酸信号来对抗防御。通过对大肠杆菌和枯草杆菌的57个噬菌体进行生化筛选，研究人员发现来自噬菌体T4的Acb1和来自噬菌体SBSphiJ的Apyc1是免疫规避蛋白不同家族的创始成员。Acb1与3′3′-cGAMP复合物的晶体结构确定了一种与金属无关的腺苷碱3′水解机制，使其能够广泛识别和降解环状二核苷酸和三核苷酸CBASS信号。Apyc1的结构揭示了一种金属依赖性的cNMP磷酸二酯酶，它利用宽松的特异性来针对Pycsar环状嘧啶单核苷酸信号。
 
结果表明，Acb1和Apyc1阻止下游效应器的激活，并在体内保护CBASS和Pycsar防御。活跃的Acb1和Apyc1酶在系统发育不同的噬菌体中是保守的，表明裂解宿主的环状核苷酸信号是噬菌体生物学中免疫规避的一个关键策略。
 
据了解，CBASS和Pycsar是不同细菌中的抗噬菌体防御系统，使用环状核苷酸信号诱导细胞死亡并阻止病毒传播。噬菌体使用多种策略来击败宿主的CRISPR和限制性修饰系统，但没有已知的机制来逃避CBASS和Pycsar的免疫。
 
附：英文原文
 
Title: Phage anti-CBASS and anti-Pycsar nucleases subvert bacterial immunity

Author: Hobbs, Samuel J., Wein, Tanita, Lu, Allen, Morehouse, Benjamin R., Schnabel, Julia, Leavitt, Azita, Yirmiya, Erez, Sorek, Rotem, Kranzusch, Philip J.

Issue&Volume: 2022-04-08

Abstract: CBASS and Pycsar are anti-phage defense systems in diverse bacteria that use cyclic nucleotide signals to induce cell death and prevent viral propagation1,2. Phages use multiple strategies to defeat host CRISPR and restriction-modification systems3–10, 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 defense by specifically degrading cyclic nucleotide signals that activate host immunity. Using a biochemical screen of 57 phages in E. coli and B. 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′-cGAMP define a mechanism of metal-independent hydrolysis 3′ of adenosine bases, enabling broad recognition and degradation of cyclic di- and trinucleotide CBASS signals. Structures of Apyc1 reveal a metal-dependent cNMP 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 defense in vivo. Active Acb1 and Apyc1 enzymes are conserved in phylogenetically diverse phages, demonstrating cleavage of host cyclic nucleotide signals is a key strategy of immune evasion in phage biology.

DOI: 10.1038/s41586-022-04716-y

Source: https://www.nature.com/articles/s41586-022-04716-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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

分享到:

0