ArticlemBio2022
Dual Effect: High NADH Levels Contribute to Efflux-Mediated Antibiotic Resistance but Drive Lethality Mediated by Reactive Oxygen Species.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- TheVirulence · 2026Article
- Metabolic adaptations in antibiotic-resistantMicrobiology spectrum · 2026Article
- Targeting serine metabolism boosts antimycobacterial immunity during Mycobacterium tuberculosis H37Rv infection.Molecules and cells · 2026Article
- Metabolism-Based Biomarkers for Rapid Phenotypic Antibiotic Susceptibility Testing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Design of Poly-Catechol Biodynamers for Potentiation of Antibiotic Efficacy against Drug-Resistant Bacteria.Biomacromolecules · 2026Article
- Sequential eradication of bacterial persisters: integrating phytochemical pharmacology with microenvironment-responsive delivery strategies.Frontiers in microbiology · 2026Review
- Effects of L-cysteine on the synthesis and secretion of extracellular pigments in submerged fermentation ofFrontiers in microbiology · 2026Article
- Bacterial secondary metabolites as resistance-modifying adjuvants: microbial origins, molecular mechanisms, and translational relevance.Frontiers in microbiology · 2026Review
- Beyond RNA modification: a novel role for tRNA modifying enzyme in oxidative stress response and metabolism.Nucleic acids research · 2025Article
- Adaptation to cinnamaldehyde shapesJournal of bacteriology · 2025Article
- Metabolic Rewiring of Bacterial Pathogens in Response to Antibiotic Pressure-A Molecular Perspective.International journal of molecular sciences · 2025Review
- Article
- Exogenous NADH promotes the bactericidal effect of aminoglycoside antibiotics againstVirulence · 2024Article
- Optimised stress - intensification of pyocyanin production with zinc oxide nanoparticles.Microbial cell factories · 2024Article
- Cell wall disruption, membrane damage, and decrease in the expression of Yrp1 virulence factor inIranian journal of microbiology · 2023Article
- Article
- Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription.PLoS pathogens · 2023Article
- Article
- Bacterial metabolism and susceptibility to cell wall-active antibiotics.Advances in microbial physiology · 2023Review
- The Neisseria gonorrhoeae type IV pilus promotes resistance to hydrogen peroxide- and LL-37-mediated killing by modulating the availability of intracellular, labile iron.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 via different mechanisms. Furthermore, the profound changes in bioenergetics produced low-virulence phenotypes characterized by reduced interbacterial signaling controlled pathogenicity traits. Our results pave the way for a more effective infection resolution and add an antivirulence strategy to maximize chances to combat devastating P. aeruginosa infections while reducing the overall use of antibiotics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.