ArticlePLoS pathogens2024
Pyrrole-based inhibitors of RND-type efflux pumps reverse antibiotic resistance and display anti-virulence potential.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Identification of oxyresveratrol, a food-as-medicine substrate, as a novel EPI that targets the RND efflux pumps ofMicrobiology spectrum · 2026Article
- Emerging host-directed strategies for overcoming drug resistance and immune evasion in Staphylococcus aureus infections.Journal of advanced research · 2026Review
- Design of Poly-Catechol Biodynamers for Potentiation of Antibiotic Efficacy against Drug-Resistant Bacteria.Biomacromolecules · 2026Article
- Dipiperazine-Phenyl Derivatives Based on Convergent Molecular Platforms Can Reverse Multidrug Resistance in Gram-Negative Bacteria by Inhibiting Efflux and Permeabilizing Cell Membranes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RND efflux pump inhibitor-like natural products as antibiotic adjuvants against multidrug-resistant gram-negative bacteria: a graded-evidence review.Frontiers in microbiology · 2026Review
- Respiratory syncytial virus (RSV) antibody and small-molecule drugs: current status of clinical translation and challenges.Frontiers in microbiology · 2026Review
- Probing Antibiotic Inhibition in Small Bacterial Populations With Combinatorial Droplet Microfluidics.Small science · 2026Article
- Broadly Defined Antibiotic Adjuvants forThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- Beyond antibiotic resistance: evidence for resistance-nodulation-division (RND) efflux pumps as virulence determinants.Microbiology and molecular biology reviews : MMBR · 2025Review
- Preclinical evaluation of tridecaptin M:Antimicrobial agents and chemotherapy · 2025Article
- A transcriptional plasticity-aware framework for RNA-seq differential expression analysis.Briefings in bioinformatics · 2025Article
- Bioinspired Nanoplatforms: Polydopamine and Exosomes for Targeted Antimicrobial Therapy.Polymers · 2025Review
- Mobile genetic elements inJournal of bacteriology · 2025Review
- Dihydromyricetin alleviates ETEC K88-induced intestinal inflammatory injury by inhibiting quorum sensing-related virulence factors.BMC microbiology · 2025Article
- Blue benzoquinone from scorpion venom shows bactericidal activity against drug-resistant strains of the priority pathogen Acinetobacter baumannii.The Journal of antibiotics · 2025Article
- Mechanisms of antimicrobial resistance: From genetic evolution to clinical manifestations.AIMS microbiology · 2025Review
- Review
- Mechanism-guided strategies for combating antibiotic resistance.World journal of microbiology & biotechnology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Efflux pumps of the resistance-nodulation-cell division (RND) superfamily, particularly the AcrAB-TolC, and MexAB-OprM, besides mediating intrinsic and acquired resistance, also intervene in bacterial pathogenicity. Inhibitors of such pumps could restore the activities of antibiotics and curb bacterial virulence. Here, we identify pyrrole-based compounds that boost antibiotic activity in Escherichia coli and Pseudomonas aeruginosa by inhibiting their archetype RND transporters. Molecular docking and biophysical studies revealed that the EPIs bind to AcrB. The identified efflux pump inhibitors (EPIs) inhibit the efflux of fluorescent probes, attenuate persister formation, extend post-antibiotic effect, and diminish resistant mutant development. The bacterial membranes remained intact upon exposure to the EPIs. EPIs also possess an anti-pathogenic potential and attenuate P. aeruginosa virulence in vivo. The intracellular invasion of E. coli and P. aeruginosa inside the macrophages was hampered upon treatment with the lead EPI. The excellent efficacy of the EPI-antibiotic combination was evidenced in animal lung infection and sepsis protection models. These findings indicate that EPIs discovered herein with negligible toxicity are potential antibiotic adjuvants to address life-threatening Gram-negative bacterial infections.
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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.