ArticleNature communications2020
Perturbed structural dynamics underlie inhibition and altered efflux of the multidrug resistance pump AcrB.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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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Who cites it
42 citing papers in PubMed, 57 citations in OpenAlex.
- Molecular mechanism of transition-state inhibitors of bacterial antibiotic efflux pumps.npj antimicrobials and resistance · 2026Article
- Chemical Characterization and Evaluation of Antimicrobial, Antioxidant, and Synergistic Activities ofPharmaceutics · 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
- Computer Simulations of Multidrug Efflux Pumps of the Resistance-Nodulation-Cell Division Superfamily.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- RND efflux pump inhibitor-like natural products as antibiotic adjuvants against multidrug-resistant gram-negative bacteria: a graded-evidence review.Frontiers in microbiology · 2026Review
- Unveiling structural dynamics and allosteric vulnerabilities in Klebsiella pneumoniae KPHS_11890: an integrated DRKG-MD study.Journal of computer-aided molecular design · 2025Article
- Molecular basis for multidrug efflux by an anaerobic-associated RND transporter.Nature communications · 2025Article
- A ternary switch model governing ERα ligand binding domain conformation.Nature communications · 2025Article
- Efflux-Mediated Resistance inAntibiotics (Basel, Switzerland) · 2025Review
- Small-molecule strategies to combat antibiotic resistance: mechanisms, modifications, and contemporary approaches.RSC advances · 2025Review
- Regulation, structure, and activity of theAntimicrobial agents and chemotherapy · 2025Review
- Drug delivery dynamics dictate evolution of bacterial antibiotic responses.The ISME journal · 2025Article
- Insights into substrate recognition and export tunnel preferences in the efflux transporter AcrB.Protein science : a publication of the Protein Society · 2025Article
- Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.Microbiology and molecular biology reviews : MMBR · 2024Review
- Dynamics of drug delivery determines course of evolution of antibiotic responses in bacteria.bioRxiv : the preprint server for biology · 2024Article
- Screening and Evaluation of Potential Efflux Pump Inhibitors with a Seaweed Compound Diphenylmethane-Scaffold against Drug-ResistantAntibiotics (Basel, Switzerland) · 2024Article
- [Applications of native mass spectrometry and ultraviolet photodissociation in protein structure and interaction analysis].Se pu = Chinese journal of chromatography · 2024Review
- Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024Review
- Mode of the Interaction of Efflux Inhibitor Phenylalanyl-arginyl-β-naphtylamide with Bacterial Cells.Biomedicines · 2024Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Resistance-nodulation-division efflux pumps play a key role in inherent and evolved multidrug resistance in bacteria. AcrB, a prototypical member of this protein family, extrudes a wide range of antimicrobial agents out of bacteria. Although high-resolution structures exist for AcrB, its conformational fluctuations and their putative role in function are largely unknown. Here, we determine these structural dynamics in the presence of substrates using hydrogen/deuterium exchange mass spectrometry, complemented by molecular dynamics simulations, and bacterial susceptibility studies. We show that an efflux pump inhibitor potentiates antibiotic activity by restraining drug-binding pocket dynamics, rather than preventing antibiotic binding. We also reveal that a drug-binding pocket substitution discovered within a multidrug resistant clinical isolate modifies the plasticity of the transport pathway, which could explain its altered substrate efflux. Our results provide insight into the molecular mechanism of drug export and inhibition of a major multidrug efflux pump and the directive role of its dynamics.
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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.