Hijacking anaerobic metabolism to restore antibiotic efficacy in <i>Pseudomonas aeruginosa</i>.

ABSTRACT: Bacterial pathogens regularly encounter oxygen (O₂) limitation at sites of infection in the human body. Many pathogens exhibit antibiotic recalcitrance under low O₂ conditions, spotlighting the need for new therapeutics that are effective in O₂-limited environments. We demonstrate that several classes of antibiotics display limited toxicity against hypoxic cultures of the opportunistic pathogen, Pseudomonas aeruginosa, where the pathogen exhibits antibiotic tolerance. In O₂-limited host environments, many pathogens employ nitrate respiration, marking this anaerobic bacterial metabolism as an excellent drug target. Chlorate is a nitrate analog that hijacks nitrate respiration to kill P. aeruginosa. Chlorate acts as a prodrug: nitrate

SUBMITTER: Gentry-Lear Z 

PROVIDER: S-EPMC12542746 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature