2025/11/13 by Zhikang Dai, Chang Liu, Yanjing Wang +9 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Environmental Science · #Bacterial Genetics and Biotechnology #Bacteriophages and microbial interactions #Bacillus and Francisella bacterial research
paper · doi:10.1093/nar/gkaf1173
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.