Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.

ABSTRACT: Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides. While actively growing P. aeruginosa cells compensate for NatT-mediated NAD⁺ deficiency by inducing the NAD⁺ salvage pathway, NAD depletion generates drug-tolerant persisters under nutrient-limited conditions. Our structural and biochemical analyses propose a model for NatT toxin activation and aut

SUBMITTER: Santi I 

PROVIDER: S-EPMC11535050 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature