Persister formation driven by tisb-dependent membrane depolarization

Abstract

The membrane-depolarizing toxin TisB encoded by the chromosomal type I toxin-antitoxin (TA) locus tisB/istR-1 can induce a persister state in Escherichia coli. While transcription of tisB is effectively induced by DNA damage as part of the SOS response, efficient TisB translation requires processing of the mRNA to an active species that works through ribosome standby. This latter step is inhibited by the RNA antitoxin, IstR-1. This regulatory complexity contributes to a delay in toxin production under stress conditions and favors phenotypic heterogeneity in terms of membrane depolarization. Removing the layer of translational inhibition by cis- and trans-regulatory RNA elements increases the likelihood of depolarization and, as a consequence, triggers higher levels of persisters. The tisB/istR-1 locus represents a useful model system for “persistence by depolarization” and considerably contributes to our understanding of how bacteria control persistence as a strategy to encounter stress and maintain survival on the population level.