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Identification of a Toxin-Antitoxin System That Contributes to Persister Formation by Reducing NAD in Pseudomonas aeruginosa.

ABSTRACT: Bacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type II TA systems in the persister formation of a Pseudomonas aeruginosa wild-type strain PA14. Overexpression of a toxin gene PA14_51010 or deletion of the cognate antitoxin gene PA14_51020 increased the bacterial tolerance to antibiotics. Co-overexpression of PA14_51010 and PA14_51020 or simultaneous deletion of the two genes resulted in a wild-type level survival rate following antibiotic treatment. The two genes were located in the same operon that was repressed by PA14_51020. We further demonstrated the interaction between PA14_51010 and PA14_51020. Sequence analysis revealed that PA14_51010 contained a conserved RES domain. Overexpression of PA14_51010 reduced the intracellular level of nicotinamide adenine dinucleotide (NAD⁺). Mutation of the RES domain abolished the abilities of PA14_51010 in reducing NAD⁺ level and promoting persister formation. In addition, overproduction of NAD⁺ by mutation in an nrtR gene counteracted the effect of PA14_51010 overexpression in promoting persister formation. In combination, our results reveal a novel TA system that contributes to persister formation through reducing the intracellular NAD⁺ level in P. aeruginosa.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8065639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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