Stress Can Induce Transcription of Toxin-Antitoxin Systems without Activating Toxin

Toxin-antitoxin (TA) systems are ubiquitous genetic elements in bacterial genomes, but their functions are controversial. Although they are frequently postulated to regulate cell growth following stress, few null phenotypes for TA systems have been reported. Here, we show that TA transcript levels can increase substantially in response to stress, but toxin is not liberated. We find that the growth of an Escherichia coli strain lacking ten TA systems encoding endoribonuclease toxins is not affected following exposure to six stresses that each trigger TA transcription. Additionally, using RNA sequencing, we find no evidence of mRNA cleavage following stress. Stress-induced transcription arises from antitoxin degradation and relief of transcriptional autoregulation. Importantly, although free antitoxin is readily degraded in vivo, antitoxin bound to toxin is protected from proteolysis, preventing release of active toxin. Thus, transcription is not a reliable marker of TA activity, and TA systems do not strongly promote survival following individual stresses. [Display omitted] •Diverse stress conditions induce transcription of bacterial toxin-antitoxin systems•Growth and RNA-seq assays demonstrate that stress does not activate toxins•Stress can trigger antitoxin degradation and relief from transcriptional repression•New antitoxin synthesis and proteolytically stable TA complexes prevent toxin release The toxin-antitoxin (TA) systems encoded on bacterial chromosomes have long been thought to act as effectors of a cellular stress response system. LeRoux et al. find that, despite strong transcriptional induction following various stress treatments, the toxins of TA systems are not activated under these conditions.