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。
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