小柯机器人

细菌反转录子编码噬菌体防御的三方毒素-抗毒素系统
2022-07-24 00:44
来源：小柯机器人

德国欧洲分子生物学实验室Athanasios Typas等研究人员合作发现，细菌反转录子编码噬菌体防御的三方毒素-抗毒素系统。2022年7月18日，《自然》杂志在线发表了这项成果。

据研究人员介绍，反转录子是原核生物的遗传逆转录元件，编码一种逆转录酶（RT），产生多拷贝单链DNA（msDNA）。尽管几十年来对msDNA的生物合成进行了研究，但反转录子的功能和生理作用仍然难以确定。
 
研究人员发现，鼠疫沙门氏菌的反转录子-Sen2编码一种附属毒素蛋白，并将其重新命名为RcaT。RcaT被RT-msDNA抗毒素复合物中和，在msDNA生物合成紊乱的情况下变得活跃。RT需要与RcaT结合，而msDNA需要促成抗毒素的活性。高度普遍的含RcaT的反转录子家族构成了一种新型的含三方DNA的毒素/抗毒素系统（TA）。为了了解它们的生理作用，研究人员开发了TAC/TIC（毒素激活/抑制共轭），这是一种高通量的反向遗传学方法，可以确定TA难以捉摸的分子触发因子和阻断因子。通过将TAC/TIC应用于Retron-Sen2，研究人员确定了多个来自噬菌体的此类蛋白质。
 
研究人员证明，与噬菌体有关的触发因子直接修改msDNA，从而激活RcaT并抑制细菌生长。相反，原噬菌体蛋白通过直接阻断RcaT来规避反转录子。一致的是，反转录子-TA作为中止感染的抗噬菌体防御系统，与平行报告一致。因此，RcaT-反转录子是三方DNA调节的TA，它利用RT-msDNA复合物作为抗毒素和噬菌体蛋白活动的传感因子。
 
附：英文原文
 
Title: Bacterial retrons encode phage-defending tripartite toxin–antitoxin systems

Author: Bobonis, Jacob, Mitosch, Karin, Mateus, Andr, Karcher, Nicolai, Kritikos, George, Selkrig, Joel, Zietek, Matylda, Monzon, Vivian, Pfalz, Birgit, Garcia-Santamarina, Sarela, Galardini, Marco, Sueki, Anna, Kobayashi, Callie, Stein, Frank, Bateman, Alex, Zeller, Georg, Savitski, Mikhail M., Elfenbein, Johanna R., Andrews-Polymenis, Helene L., Typas, Athanasios

Issue&Volume: 2022-07-18

Abstract: Retrons are prokaryotic genetic retroelements, encoding a reverse transcriptase (RT) that produces multi-copy single-stranded DNA (msDNA1). Despite decades of research on msDNA biosynthesis2, the function and physiological role of retrons remained elusive. We show that Retron-Sen2 of Salmonella Typhimurium encodes an accessory toxin protein, which we rename RcaT. RcaT is neutralized by the RT-msDNA antitoxin complex, becoming active upon perturbations of msDNA biosynthesis. The RT is required for binding to RcaT, and the msDNA for enabling the antitoxin activity. The highly prevalent RcaT-containing retron family constitutes a new type of tripartite DNA-containing toxin/antitoxin systems (TAs). To understand their physiological role, we developed TAC/TIC (Toxin Activation/Inhibition Conjugation), a high-throughput reverse genetics approach that identifies the elusive molecular triggers and blockers of TAs. By applying TAC/TIC to Retron-Sen2 we identified multiple such proteins of phage origin. We demonstrate that phage-related triggers directly modify the msDNA, thereby activating RcaT and inhibiting bacterial growth. In contrast, prophage proteins circumvent retrons by directly blocking RcaT. Consistently, retron-TAs act as abortive-infection anti-phage defense systems, in line with parallel reports3,4. Thus, RcaT-retrons are tripartite DNA-regulated TAs, which use the RT-msDNA complex both as antitoxin and as a sensor of phage protein activities.

DOI: 10.1038/s41586-022-05091-4

Source: https://www.nature.com/articles/s41586-022-05091-4

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

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