Shutoff of host transcription triggers a toxin-antitoxin system to cleave phage RNA and abort infection

Toxin-antitoxin (TA) systems are widespread in bacteria, but their activation mechanisms and bona fide targets remain largely unknown. Here, we characterize a type III TA system, toxIN, that protects E. coli against multiple bacteriophages, including T4. Using RNA sequencing, we find that the endoribonuclease ToxN is activated following T4 infection and blocks phage development primarily by cleaving viral mRNAs and inhibiting their translation. ToxN activation arises from T4-induced shutoff of host transcription, specifically of toxIN, leading to loss of the intrinsically unstable toxI antitoxin. Transcriptional shutoff is necessary and sufficient for ToxN activation. Notably, toxIN does not strongly protect against another phage, T7, which incompletely blocks host transcription. Thus, our results reveal a critical trade-off in blocking host transcription: it helps phage commandeer host resources but can activate potent defense systems. More generally, our results now reveal the native targets of an RNase toxin and activation mechanism of a phage-defensive TA system.

Automated summary

Research has found that toxin-antitoxin system toxIN can protect E. coli against bacteriophages, with ToxN being activated following T4 infection to inhibit phage development by cleaving viral mRNAs. Transcriptional shutoff is crucial for ToxN activation, but toxIN does not provide strong protection against T7 phage, indicating a critical trade-off in blocking host transcription.