Drugging evolution of antibiotic resistance at a regulatory network hub.

ABSTRACT: Evolution of antibiotic resistance is a world health crisis, fueled by new mutations. Drugs to slow mutagenesis could, as cotherapies, prolong the shelf-life of antibiotics, yet evolution-slowing drugs and drug targets have been underexplored and ineffective. Here, we used a network-based strategy to identify drugs that block hubs of fluoroquinolone antibiotic-induced mutagenesis. We identify a U.S. Food and Drug Administration- and European Medicines Agency-approved drug, dequalinium chloride (DEQ), that inhibits activation of the Escherichia coli general stress response, which promotes ciprofloxacin-induced (stress-induced) mutagenic DNA break repair. We uncover the step in the pathway inhibited: activation of the upstream "stringent" starvation stress response, and find that DEQ

SUBMITTER: Zhai Y 

PROVIDER: S-EPMC10289659 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature