Author
Listed:
- Jacob Bobonis
(European Molecular Biology Laboratory
Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences)
- Karin Mitosch
(European Molecular Biology Laboratory)
- André Mateus
(European Molecular Biology Laboratory
The Laboratory for Molecular Infection Medicine Sweden (MIMS))
- Nicolai Karcher
(European Molecular Biology Laboratory)
- George Kritikos
(European Molecular Biology Laboratory)
- Joel Selkrig
(European Molecular Biology Laboratory)
- Matylda Zietek
(European Molecular Biology Laboratory)
- Vivian Monzon
(European Molecular Biology Laboratory)
- Birgit Pfalz
(European Molecular Biology Laboratory)
- Sarela Garcia-Santamarina
(European Molecular Biology Laboratory
Institute of Chemical and Biological Technology António Xavier)
- Marco Galardini
(TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI))
- Anna Sueki
(European Molecular Biology Laboratory
University of Basel)
- Callie Kobayashi
(Texas A&M University)
- Frank Stein
(European Molecular Biology Laboratory)
- Alex Bateman
(European Molecular Biology Laboratory)
- Georg Zeller
(European Molecular Biology Laboratory)
- Mikhail M. Savitski
(European Molecular Biology Laboratory
European Molecular Biology Laboratory
European Molecular Biology Laboratory)
- Johanna R. Elfenbein
(University of Wisconsin-Madison)
- Helene L. Andrews-Polymenis
(Texas A&M University)
- Athanasios Typas
(European Molecular Biology Laboratory
European Molecular Biology Laboratory)
Abstract
Retrons are prokaryotic genetic retroelements encoding a reverse transcriptase that produces multi-copy single-stranded DNA1 (msDNA). Despite decades of research on the biosynthesis of msDNA2, the function and physiological roles of retrons have remained unknown. Here we show that Retron-Sen2 of Salmonella enterica serovar Typhimurium encodes an accessory toxin protein, STM14_4640, which we renamed as RcaT. RcaT is neutralized by the reverse transcriptase–msDNA antitoxin complex, and becomes active upon perturbation of msDNA biosynthesis. The reverse transcriptase is required for binding to RcaT, and the msDNA is required for the antitoxin activity. The highly prevalent RcaT-containing retron family constitutes a new type of tripartite DNA-containing toxin–antitoxin system. To understand the physiological roles of such toxin–antitoxin systems, we developed toxin activation–inhibition conjugation (TAC-TIC), a high-throughput reverse genetics approach that identifies the molecular triggers and blockers of toxin–antitoxin systems. By applying TAC-TIC to Retron-Sen2, we identified multiple trigger and blocker proteins of phage origin. We demonstrate that phage-related triggers directly modify the msDNA, thereby activating RcaT and inhibiting bacterial growth. By contrast, prophage proteins circumvent retrons by directly blocking RcaT. Consistently, retron toxin–antitoxin systems act as abortive infection anti-phage defence systems, in line with recent reports3,4. Thus, RcaT retrons are tripartite DNA-regulated toxin–antitoxin systems, which use the reverse transcriptase–msDNA complex both as an antitoxin and as a sensor of phage protein activities.
Suggested Citation
Jacob Bobonis & Karin Mitosch & André Mateus & Nicolai Karcher & George Kritikos & Joel Selkrig & Matylda Zietek & Vivian Monzon & Birgit Pfalz & Sarela Garcia-Santamarina & Marco Galardini & Anna Sue, 2022.
"Bacterial retrons encode phage-defending tripartite toxin–antitoxin systems,"
Nature, Nature, vol. 609(7925), pages 144-150, September.
Handle:
RePEc:nat:nature:v:609:y:2022:i:7925:d:10.1038_s41586-022-05091-4
DOI: 10.1038/s41586-022-05091-4
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- Aa Haeruman Azam & Kohei Kondo & Kotaro Chihara & Tomohiro Nakamura & Shinjiro Ojima & Wenhan Nie & Azumi Tamura & Wakana Yamashita & Yo Sugawara & Motoyuki Sugai & Longzhu Cui & Yoshimasa Takahashi &, 2024.
"Evasion of antiviral bacterial immunity by phage tRNAs,"
Nature Communications, Nature, vol. 15(1), pages 1-10, December.
- Yunxue Guo & Kaihao Tang & Brandon Sit & Jiayu Gu & Ran Chen & Xinqi Shao & Shituan Lin & Zixian Huang & Zhaolong Nie & Jianzhong Lin & Xiaoxiao Liu & Weiquan Wang & Xinyu Gao & Tianlang Liu & Fei Liu, 2024.
"Control of lysogeny and antiphage defense by a prophage-encoded kinase-phosphatase module,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:609:y:2022:i:7925:d:10.1038_s41586-022-05091-4. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.