Dual Effect: High NADH Levels Contribute to Efflux-Mediated Antibiotic Resistance but Drive Lethality Mediated by Reactive Oxygen Species.

ABSTRACT: In light of the antibiotic crisis, emerging strategies to sensitize bacteria to available antibiotics should be explored. Several studies on the mechanisms of killing suggest that bactericidal antibiotic activity is enforced through the generation of reactive oxygen species (ROS-lethality hypothesis). Here, we artificially manipulated the redox homeostasis of the model opportunistic pathogen Pseudomonas aeruginosa using specific enzymes that catalyze either the formation or oxidation of NADH. Increased NADH levels led to the activation of antibiotic efflux pumps and high levels of antibiotic resistance. However, higher NADH levels also resulted in increased intracellular ROS and amplified antibiotic killing. Our results demonstrate that growth inhibition and killing activity are mediated v

SUBMITTER: Arce-Rodriguez A 

PROVIDER: S-EPMC8764520 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature