Bacterial toxin-antitoxin system MazEF as a native defense mechanism against RNA phages in Escherichia coli

Abstract

Bacteria have evolved a wide range of defense strategies to protect themselves against bacterial viruses (phages). However, the known mechanisms almost exclusively target phages with DNA genomes. While several bacterial toxin-antitoxin systems have been considered to cleave single-stranded bacterial RNA in response to stressful conditions, their role in protecting bacteria against phages with single-stranded RNA genomes has not been studied. Here we investigate the role of a representative toxin-antitoxin system, MazEF, in protecting Escherichia coli against two RNA phages - MS2 and Q{beta}. Our population-level experiments revealed that a mazEF deletion strain is more susceptible to RNA phage infection than the wild-type. At the single-cell level, deletion of the mazEF locus significantly shortened the time to lysis of individual bacteria challenged with RNA phage. At the genomic level, we found that the adenine-cytosine-adenine sequence, directly recognized and cleaved by the MazF toxin, is systematically underrepresented in the genomes of RNA phages that are known to infect E. coli, indicating selection for decreased probability of cleavage. These results suggest that in addition to other physiological roles, RNA-degrading toxin-antitoxin modules can function as a primitive immune system against RNA phages.