ArticleProceedings of the National Academy of Sciences of the United States of America2016
The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 167 citations in OpenAlex.
- Efflux modulation as an antimicrobial strategy: mechanisms and translational perspectives.npj drug discovery · 2026Review
- Genetic regulation of biosynthesis and resistance to redox-active phenazines inMicrobiology spectrum · 2026Article
- The Cyclic Di-GMP Receptor HpoR Modulates Mycobacterial Multidrug Susceptibility by Regulating IniBAC-Mediated Envelope Permeability.Microorganisms · 2026Article
- Environmental redox conditions and strain variation define phenazine-mediated antagonism in co-infecting bacteria.PLoS biology · 2026Article
- A farnesol-sensing triad inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Redox-dependent lipophilicity of phenazine metabolites is modulated by intramolecular hydrogen bonds and controls their biological distribution.bioRxiv : the preprint server for biology · 2026Article
- Chemical-mediated alteration of antibiotic susceptibility: mechanisms and potential new targets for antibiotic adjuvant discovery.Journal of bacteriology · 2026Review
- TheJournal of bacteriology · 2026Article
- Bioinformatics-Driven, Plant-Based Antibiotic Research Against Quorum Sensing and Biofilm Formation inBiomolecules · 2026Review
- Microbial phenazines: biosynthesis, structural diversity, evolution, regulation, and biological significance.Microbiology and molecular biology reviews : MMBR · 2025Review
- Roles of Pho regulon in bacterial pathogenicity.Virulence · 2025Review
- Sulfur starvation induces an Fe-replete response and attenuates virulence pathways in Pseudomonas aeruginosa PAO1.BMC microbiology · 2025Article
- A choline-sensing regulator coordinates metabolic adaptation and pathogenesis inScience advances · 2025Article
- Minimal gene signatures enable high-accuracy prediction of antibiotic resistance in Pseudomonas aeruginosa.NPJ systems biology and applications · 2025Article
- Synthetic Whole-Cell Bioelectronic Chemical Sensing withChem & bio engineering · 2025Article
- Species-Specific Stress Responses to Selenium Nanoparticles inNanomaterials (Basel, Switzerland) · 2025Article
- Article
- tRNA hydroxylation is an epitranscriptomic modulator of metabolic states affecting Pseudomonas aeruginosa pathogenicity.Nucleic acids research · 2025Article
- RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance.Biophysical reviews · 2025Review
- Fluorescence Lifetime Imaging Detects Long-Lifetime Signal Associated with Reduced Pyocyanin at the Surface ofACS infectious diseases · 2025Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI-OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We also show that 5-Me-PCA is sufficient to fully induce MexGHI-OpmD expression and that it is required for wild-type colony biofilm morphogenesis. These physiological effects are consistent with the high redox potential of 5-Me-PCA, which distinguishes it from other well-studied P. aeruginosa phenazines. Our observations highlight the importance of this compound, which was previously overlooked due to the challenges associated with its detection, in the context of P. aeruginosa gene expression and multicellular behavior. This study constitutes a unique demonstration of efflux-based self-resistance, controlled by a simple circuit, in a Gram-negative pathogen.
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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.