9vh1

Publication Abstract from PubMed

Retrons are bacterial antiphage defense systems comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and cognate effector proteins. The RT synthesizes multicopy single-stranded DNA (msDNA) from the ncRNA template to detect phage invasion. This study focuses on Retron-Eco7, which integrates retron-based sensing with the effector module of Septu-a characterized antiphage system in which the PtuAB complex mediates nuclease-dependent defense. However, the activation mechanism of this hybrid system remains unclear. Here, we determined cryo-electron microscopy structures of the RT-msDNA-PtuAB quaternary complex and the PtuAB binary complex in Retron-Eco7. Structural analyses reveal that the DNA stem-loop of msDNA extensively interacts with PtuA subunits via electrostatic interactions. We establish Retron-Eco7 as a novel toxin-antitoxin system, in which RT-msDNA acts as the antitoxin, directly binding and neutralizing the PtuAB toxin. Furthermore, we identified a phage-encoded flap endonuclease as a trigger for Retron-Eco7 activation, which cleaves msDNA to release the PtuAB toxin. Our findings demonstrate the diversity in bacterial retron defense systems and uncover a novel activation mechanism of the Septu-derived retron toxin-antitoxin system.

Phage nuclease-mediated defense activation of the bacterial Retron-Eco7 toxin-antitoxin system.,Dai Z, Liu C, Wang Y, Chen X, Fu X, Yang K, Zhu R, Jia X, Chen Y, Tao P, Guan Z, Zou T Nucleic Acids Res. 2025 Nov 13;53(21):gkaf1173. doi: 10.1093/nar/gkaf1173. PMID:41277685^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.