Spontaneous TisB toxin expression modulates Escherichia coli metabolic adaptation during growth transitions.

Abstract

Escherichia coli TisB/IstR1 is a type I toxin-antitoxin system. The TisB toxin targets the inner membrane and disrupts the proton motive force (PMF). Under normal growth conditions, tisB transcription is repressed by the LexA SOS repressor, and IstR1 blocks its translation. DNA damage lifts LexA repression, allowing tisB mRNA to overcome IstR1 inhibition and produce TisB. Although spontaneous tisB expression has been reported, its physiological significance remains unclear. We show that tisB is spontaneously induced and TisB is synthesized during the transition to stationary phase, coinciding with decreased LexA repression and a transient decline in istR1 promoter activity. Deletion of tisB does not affect exponential growth but delays entry into and exit from stationary phase, reduces fitness under nutrient limitation and alkaline pH, and impairs stringent response induction, intracellular pH homeostasis, and glycogen accumulation-phenotypes consistent with metabolic dysregulation. These findings indicate that low-level spontaneous TisB production modulates metabolism during the transition to stationary phase. By collapsing the PMF, TisB attenuates nutrient uptake and promotes early stringent-response-driven dormancy before nutrient exhaustion. Our results reveal a physiological role for TisB, positioning it as a metabolic rheostat that fine-tunes adaptation to environmental fluctuations.