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A bacterial toxin-antitoxin system as a native defence element against RNA phages

Nikolic, Nela1; Pleška, Maroš2; Bergmiller, Tobias3; Guet, Călin4

Published May 27, 2025 on Dryad. https://doi.org/10.5061/dryad.zgmsbccq5

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Abstract

Bacteria have evolved a wide range of defence strategies to protect themselves against bacterial viruses (phages). Most known bacterial antiphage defence systems target phages with DNA genomes, which raises the question of how bacteria defend against phages with RNA genomes. Bacterial toxin-antitoxin systems that cleave intracellular RNA under stress could potentially protect bacteria against RNA phages, but this has not been explored experimentally. In this study, we investigated the role of a model toxin-antitoxin system, MazEF, in protecting Escherichia coli against two RNA phage species. When challenged with these phages, native presence of mazEF moderately reduced population susceptibility and increased survival of individual E. coli cells. Genomic analysis further revealed an underrepresentation of the MazF cleavage site in genomes of RNA phages infecting E. coli, indicating selection against cleavage. These results show that, in addition to other physiological roles, RNA-degrading toxin-antitoxin systems may serve as a native defence system against RNA phages.