ArticleBiochimica et biophysica acta. General subjects2020
Discovery of multidrug efflux pump inhibitors with a novel chemical scaffold.
Article in Biochimica et biophysica acta. General subjects, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- TolCV1 inhibition by NPPB rendersAntimicrobial agents and chemotherapy · 2025Article
- Synergistic Effects and Mechanisms of Action of Rutin with Conventional Antibiotics AgainstInternational journal of molecular sciences · 2024Article
- Structure-Based Identification of Novel Histone Deacetylase 4 (HDAC4) Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.ACS infectious diseases · 2024Review
- Predicting permeation of compounds across the outer membrane of P. aeruginosa using molecular descriptors.Communications chemistry · 2024Article
- Breaking membrane barriers to neutralize E. coli and K. pneumoniae virulence with PEGylated branched polyethylenimine.Biochimica et biophysica acta. Biomembranes · 2023Article
- Efflux Pump-Binding 4(3-Aminocyclobutyl)Pyrimidin-2-Amines Are Colloidal Aggregators.Biomolecules · 2023Article
- Identification and structure-activity relationships for a series of N, N-disubstituted 2-aminobenzothiazoles as potent inhibitors of S. aureus.Bioorganic & medicinal chemistry letters · 2023Article
- Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?Microbiology (Reading, England) · 2023Review
- Analysis of Orthogonal Efflux and Permeation Properties of Compounds Leads to the Discovery of New Efflux Pump Inhibitors.ACS infectious diseases · 2022Article
- Molecular rationale for the impairment of the MexAB-OprM efflux pump by a single mutation in MexA.Computational and structural biotechnology journal · 2022Article
- Mechanistic Duality of Bacterial Efflux Substrates and Inhibitors: Example of Simple Substituted Cinnamoyl and Naphthyl Amides.ACS infectious diseases · 2021Article
- Bacterial efflux transporters' polyspecificity - a gift and a curse?Current opinion in microbiology · 2021Review
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
- The Whole Is Bigger than the Sum of Its Parts: Drug Transport in the Context of Two Membranes with Active Efflux.Chemical reviews · 2021Article
- Multidrug Efflux Pumps and the Two-Faced Janus of Substrates and Inhibitors.Accounts of chemical research · 2021Article
- Efflux pump inhibitors: new updates.Pharmacological reports : PR · 2021Review
- Defining new chemical space for drug penetration into Gram-negative bacteria.Nature chemical biology · 2020Review
- Periplasmic Targets for the Development of Effective Antimicrobials against Gram-Negative Bacteria.ACS infectious diseases · 2020Review
- Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump.mBio · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Multidrug efflux is a major contributor to antibiotic resistance in Gram-negative bacterial pathogens. Inhibition of multidrug efflux pumps is a promising approach for reviving the efficacy of existing antibiotics. Previously, inhibitors targeting both the efflux transporter AcrB and the membrane fusion protein AcrA in the Escherichia coli AcrAB-TolC efflux pump were identified. Here we use existing physicochemical property guidelines to generate a filtered library of compounds for computational docking. We then experimentally test the top candidate coumpounds using in vitro binding assays and in vivo potentiation assays in bacterial strains with controllable permeability barriers. We thus identify a new class of inhibitors of E. coli AcrAB-TolC. Six molecules with a shared scaffold were found to potentiate the antimicrobial activity of erythromycin and novobiocin in hyperporinated E. coli cells. Importantly, these six molecules were also active in wild-type strains of both Acinetobacter baumannii and Klebsiella pneumoniae, potentiating the activity of erythromycin and novobiocin up to 8-fold.
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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.