Common sensor and diverse effectors: regulation of bacterial antiphage immunity by retron systems

Bacteria employ a sophisticated arsenal of immune systems to counter bacteriophage infection. Among these systems, retron antiphage systems have emerged as a widespread class of reverse transcriptase (RT)-associated regulatory modules. Retrons are genetic elements encoding an RT and a structured noncoding RNA (ncRNA), which together generate multicopy single-stranded DNA (msDNA). In antiphage defense, an RT-msDNA module associates with its cognate effector protein to form a tripartite complex, which typically functions as a toxin-antitoxin system. Recent studies reveal a consistent defense mechanism: RT-msDNA complex functions as a molecular sentinel that senses phage-encoded triggers and regulates effector activation. Perturbation of RT-msDNA unleashes diverse cytotoxic effectors, thus inducing abortive infection (Abi) to restrict viral propagation. This review summarizes recent advances in retron activation mechanisms, effector diversity, and structural assembly, providing a comprehensive perspective on retron-mediated immunity.