While many studies have explored the growth of Pseudomonas aeruginosa, comparatively few have focused on its survival. Previously, we reported that endogenous phenazines support the anaerobic survival of P. aeruginosa, yet the physiological mechanism underpinning survival was unknown. Here, we demonstrate that phenazine redox cycling enables P. aeruginosa to oxidize glucose and pyruvate into acetate, which promotes survival by coupling acetate and ATP synthesis through the activity of acetate kinase. By measuring intracellular NAD(H) and ATP concentrations, we show that survival is correlated with ATP synthesis, which is tightly coupled to redox homeostasis during pyruvate fermentation but not during arginine fermentation. We also show that ATP hydrolysis is required to generate a proton-motive force using the ATP synthase complex during fermentation. Together, our results suggest that phenazines enable maintenance of the proton-motive force by promoting redox homeostasis and ATP synthesis. This work demonstrates the more general principle that extracellular redox-active molecules, such as phenazines, can broaden the metabolic versatility of microorganisms by facilitating energy generation.
Interaction of the Pseudomonas aeruginosa secretory products pyocyanin and pyochelin generates hydroxyl radical and causes synergistic damage to endothelial cells. Implications for Pseudomonas-associated tissue injury
Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium.
Protonic conductance across phospholipid bilayer membranes induced by uncoupling agents for oxidative phosphorylation
Genetic and biochemical analyses of Escherichia coli strains having a mutation in the structural gene (poxB) for pyruvate oxidase.
Comparison of denitrification by Pseudomonas stutzeri, Pseudomonas aeruginosa, and Paracoccus denitrificans.
Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway.
N,N'-dicyclohexylcarbodiimide binds specifically to a single glutamyl residue of the proteolipid subunit of the mitochondrial adenosinetriphosphatases from Neurospora crassa and Saccharomyces cerevisiae
Transcription of the stationary-phase-associated hspX gene of Mycobacterium tuberculosis is inversely related to synthesis of the 16-kilodalton protein
Acetate metabolism in a pta mutant of Escherichia coli W3110: importance of maintaining acetyl coenzyme A flux for growth and survival
Accurate flow cytometric membrane potential measurement in bacteria using diethyloxacarbocyanine and a ratiometric technique
Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1
Metabolic engineering through cofactor manipulation and its effects on metabolic flux redistribution in Escherichia coli
Long-term anaerobic survival of the opportunistic pathogen Pseudomonas aeruginosa via pyruvate fermentation
Anaerobic survival of Pseudomonas aeruginosa by pyruvate fermentation requires an Usp-type stress protein
Saccharomyces cerevisiae-based molecular tool kit for manipulation of genes from gram-negative bacteria
The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa
Pyocyanin alters redox homeostasis and carbon flux through central metabolic pathways in Pseudomonas aeruginosa PA14
The intracellular concentration of acetyl phosphate in Escherichia coli is sufficient for direct phosphorylation of two-component response regulators
Responses of Pseudomonas aeruginosa to low oxygen indicate that growth in the cystic fibrosis lung is by aerobic respiration
Endogenous phenazine antibiotics promote anaerobic survival of Pseudomonas aeruginosa via extracellular electron transfer.
Compensatory periplasmic nitrate reductase activity supports anaerobic growth of Pseudomonas aeruginosa PAO1 in the absence of membrane nitrate reductase.
Pseudomonas aeruginosa increases formation of multidrug-tolerant persister cells in response to quorum-sensing signaling molecules.
The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide
Heterogeneity in Pseudomonas aeruginosa biofilms includes expression of ribosome hibernation factors in the antibiotic-tolerant subpopulation and hypoxia-induced stress response in the metabolically active population.
Isolation of phenazine 1,6-di-carboxylic acid from Pseudomonas aeruginosa strain HRW.1-S3 and its role in biofilm-mediated crude oil degradation and cytotoxicity against bacterial and cancer cells
Engineering mediator-based electroactivity in the obligate aerobic bacterium Pseudomonas putida KT2440
Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum
The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development
BEEP: An assay to detect bio-energetic and envelope permeability alterations in Pseudomonas aeruginosa
Generation of Reactive Oxygen Species Mediated by 1‑Hydroxyphenazine, a Virulence Factor of Pseudomonas aeruginosa
Recent developments in the isolation, biological function, biosynthesis, and synthesis of phenazine natural products
Virulence genes fliC, toxA and phzS are common among Pseudomonas aeruginosa isolates from diabetic foot infections
Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa
An orphan cbb3 -type cytochrome oxidase subunit supports Pseudomonas aeruginosa biofilm growth and virulence
Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP
Identification of Fitness Determinants during Energy-Limited Growth Arrest in Pseudomonas aeruginosa
Enzymatic Degradation of Phenazines Can Generate Energy and Protect Sensitive Organisms from Toxicity
Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation
Both toxic and beneficial effects of pyocyanin contribute to the lifecycle of Pseudomonas aeruginosa
The human innate immune protein calprotectin induces iron starvation responses in Pseudomonas aeruginosa
Interdependency of Respiratory Metabolism and Phenazine-Associated Physiology in Pseudomonas aeruginosa PA14
Pseudomonad reverse carbon catabolite repression, interspecies metabolite exchange, and consortial division of labor.
The Potential for Redox-Active Metabolites To Enhance or Unlock Anaerobic Survival Metabolisms in Aerobes.
Conditional antagonism in co-cultures of Pseudomonas aeruginosa and Candida albicans: An intersection of ethanol and phosphate signaling distilled from dual-seq transcriptomics
The Pyruvate and α-Ketoglutarate Dehydrogenase Complexes of Pseudomonas aeruginosa Catalyze Pyocyanin and Phenazine-1-carboxylic Acid Reduction via the Subunit Dihydrolipoamide Dehydrogenase.
Assessing biosynthetic potential of agricultural groundwater through metagenomic sequencing: A diverse anammox community dominates nitrate-rich groundwater
Pseudomonas aeruginosa gshA Mutant Is Defective in Biofilm Formation, Swarming, and Pyocyanin Production
Chlorate Specifically Targets Oxidant-Starved, Antibiotic-Tolerant Populations of Pseudomonas aeruginosa Biofilms
The Pseudomonas aeruginosa Complement of Lactate Dehydrogenases Enables Use of d- and l-Lactate and Metabolic Cross-Feeding
Harnessing Metabolic Regulation to Increase Hfq-Dependent Antibiotic Susceptibility in Pseudomonas aeruginosa
Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms
The transcription factors ActR and SoxR differentially affect the phenazine tolerance of Agrobacterium tumefaciens
Extracellular electron uptake by autotrophic microbes: physiological, ecological, and evolutionary implications.
Exposure to Bile Leads to the Emergence of Adaptive Signaling Variants in the Opportunistic Pathogen Pseudomonas aeruginosa
Synthesis of novel ligands targeting phenazine biosynthesis proteins as a strategy for antibiotic intervention
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