Bacterial retrons encode phage-defending tripartite toxin–antitoxin systems

Jacob Bobonis, Karin Mitosch, André Mateus, Nicolai Karcher, George Kritikos, Joel Selkrig, Matylda Zietek, Vivian Monzon, Birgit Pfalz, Sarela Garcia-Santamarina, Marco Galardini, Anna Sueki, Callie Kobayashi, Frank Stein, Alex Bateman, Georg Zeller, Mikhail M. Savitski, Johanna R. Elfenbein (), Helene L. Andrews-Polymenis () and Athanasios Typas ()
Additional contact information
Jacob Bobonis: European Molecular Biology Laboratory
Karin Mitosch: European Molecular Biology Laboratory
André Mateus: European Molecular Biology Laboratory
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
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
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
Johanna R. Elfenbein: University of Wisconsin-Madison
Helene L. Andrews-Polymenis: Texas A&M University
Athanasios Typas: European Molecular Biology Laboratory

Nature, 2022, vol. 609, issue 7925, 144-150

Abstract: 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.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05091-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:609:y:2022:i:7925:d:10.1038_s41586-022-05091-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-05091-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().