Bistable expression of a toxin-antitoxin system located in a cryptic prophage of Escherichia coliO157:H7

Dukas Jurenas, Nathan Fraikin, Frédéric Goormaghtigh, Pieter De Bruyn, Alexandra Vandervelde, Thomas Jove, Daniel Charlier, Remy Loris, Laurence Van Melderen

Research output: Contribution to journalArticle

Abstract

Type II toxin-antitoxin systems (TA) are classically composed of two genes encoding a toxic protein and a cognate antitoxin protein. Both genes are organized in an operon whose transcription is autoregulated at the level of transcription by the antitoxin-toxin complex thanks to the antitoxin DNA-binding domain. Here we investigated the transcriptional regulation of a particular toxin-antitoxin (TA) system located in the immunity region of a cryptic lambdoid prophage in the E. coli O157:H7 EDL933 strain. This non-canonical paaA2-parE2 TA operon contains a third gene - paaR2 - encoding a transcriptional regulator that controls the TA expression. We provide evidence that the PaaR2 is a transcriptional regulator that shares functional similarities to the lambda CI repressor. Furthermore, expression of the paaA2-parE2 TA operon is further regulated by two other transcriptional regulators analogous to Cro and CII encoded within the same region. These results show that the paaA2-parE2 TA does not regulate its own expression but is rather embedded in an intricate lambdoid prophage-like regulation network. Using single-cell analysis and time-lapse microscopy, we observed that the entire locus exhibits bistability, which generates diversity of expression in the population. However, no detectable activity of the ParE2 toxin was observed in cells showing an increase of paaA2-parE2 transcription. This reinforces the idea that increase of transcription of TA systems is not coupled to toxin activity. In line with our previous data showing that the paaR2-paaA2-parE2 locus is able to mediate plasmid addiction, we propose that this TA system is rather involved in genomic stabilization.
Original languageEnglish
JournalmBio
Publication statusPublished - Nov 2021

Keywords

  • Toxin-Antitoxin module
  • Bacteriophage
  • Transcription regulation
  • Single cell analysis
  • Genome stabilization

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