Bistability in type I toxin-antitoxin systems may lead to stress-induced persister formation.

ABSTRACT: Antibiotic persistence, characterized by a dormant subpopulation of bacterial cells that causes chronic and recurrent infections, remains poorly understood despite being recognized nearly a century ago. Toxin-antitoxin (TA) systems, which include a toxin and an antitoxin, are promising candidates for elucidating persister formation. We present the first theoretical model of persister formation driven by type I TA systems, in which the antitoxin is a small RNA molecule. Our analyses and simulations reveal two steady states-low toxin (normal growth) and high toxin (persistence)-with stochastic switching between them. Bistability requires both positive and negative feedback mediated by inhibition of antitoxin degradation. We derive stability diagrams that map mechanistic properties to system

SUBMITTER: Markovic S 

PROVIDER: S-EPMC12848306 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature