Year: 2025
Type: article
Abstract: Retrons have been recently identified as bacterial defense systems that employ a tripartite of reverse transcriptase, non-coding RNA (ncRNA) and its derived multi-copy single stranded DNA (msDNA) to sequester effector activity. Phage invasion activates retrons, triggering effector activity and inducing abortive infection and cell growth arrest. Ec78 differs from other retrons by leveraging the Septu defense system, a stand-alone ATPase–nuclease pair (PtuAB), by reshaping the phage sensing and molecular assembly processes of PtuAB. To elucidate how Ec78 hijacks PtuAB, we determined electron cryomicroscopy structures of Ec78 as well as the retron-displaced PtuAB. We show that the Ec78-associated ATPase, PtuA, acquired unique elements that enable its interactions with the reverse transcriptase and the msDNA, and self-assembly when displaced by the retron. By biochemical and mutational analyses, we also show that the retron-displaced PtuAB forms a tetramer, unlike its stand-alone counterpart, that restricts the host. However, in the presence of the retron, the retron-displaced PtuAB confers a well-controlled immune response, eliciting ATP hydrolysis- and msDNA-regulated targeting to host factors. Our studies reveal an evolutionary principle for retrons to co-opt conserved enzyme modules for defense in response to different cellular needs. Wang et al. combine structural and biochemical analyses to show how a bacterial defense system, Ec78 retron, employs reverse-transcriptase-derived DNA to regulate an ATPase–nuclease pair for phage defense.
Authors: Bing Wang, Renee D. Hoffman, Ya-Ming Hou, Hong Li
Institutions: Van Andel Institute, Thomas Jefferson University
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W4415731715