ArticleACS infectious diseases2019
Conformational Dynamics of AcrA Govern Multidrug Efflux Pump Assembly.
Article in ACS infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- High-level polymyxin B resistance and underlying mechanism in a multidrug-resistant Acinetobacter strain isolated from the marine plastisphere.The Journal of antibiotics · 2026Article
- Antibiotic resistance inFrontiers in microbiology · 2026Article
- MgbioRxiv : the preprint server for biology · 2024Article
- sRNA expression profile of KPC-2-producing carbapenem-resistant Klebsiella pneumoniae: Functional role of sRNA51.PLoS pathogens · 2024Article
- Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.bioRxiv : the preprint server for biology · 2024Article
- Uncovering the folding mechanism of pertactin: A comparative study of isolated and vectorial folding.Biophysical journal · 2023Article
- Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein.Nature communications · 2023Article
- Insights into substrate transport and water permeation in the mycobacterial transporter MmpL3.Biophysical journal · 2023Article
- Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?Microbiology (Reading, England) · 2023Review
- A genetic platform to investigate the functions of bacterial drug efflux pumps.Nature chemical biology · 2022Article
- What have molecular simulations contributed to understanding of Gram-negative bacterial cell envelopes?Microbiology (Reading, England) · 2022Review
- A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump.Antibiotics (Basel, Switzerland) · 2022Article
- Molecular rationale for the impairment of the MexAB-OprM efflux pump by a single mutation in MexA.Computational and structural biotechnology journal · 2022Article
- Lpp positions peptidoglycan at the AcrA-TolC interface in the AcrAB-TolC multidrug efflux pump.Biophysical journal · 2021Article
- Mechanistic Duality of Bacterial Efflux Substrates and Inhibitors: Example of Simple Substituted Cinnamoyl and Naphthyl Amides.ACS infectious diseases · 2021Article
- Insight into the AcrAB-TolC Complex Assembly Process Learned from Competition Studies.Antibiotics (Basel, Switzerland) · 2021Article
- MexAB-OprM Efflux Pump Interaction with the Peptidoglycan ofInternational journal of molecular sciences · 2021Article
- The Whole Is Bigger than the Sum of Its Parts: Drug Transport in the Context of Two Membranes with Active Efflux.Chemical reviews · 2021Article
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
- A "Drug Sweeping" State of the TriABC Triclosan Efflux Pump from Pseudomonas aeruginosa.Structure (London, England : 1993) · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Multidrug efflux pumps of pathogenic, Gram-negative bacteria comprise an innate resistance mechanism and are key contributors to the emerging global pandemic of antibiotic resistance. Several increasingly detailed cryo-electron microscopy maps have been resolved of an entire efflux pump complex, AcrAB-TolC, resulting in atomistic structural models. Using a recent model, we have carried out nearly 40 μs of molecular dynamics simulations to study one of the key components of the protein complex AcrA, the membrane fusion protein that connects the inner-membrane-bound AcrB to the outer-membrane-bound TolC. We determined a three-dimensional potential of mean force (PMF) for AcrA, which displays two main conformational basins representing assembly competent and incompetent states. Corresponding experiments show that stabilizing mutations at an interdomain interface shift the dynamic equilibrium between these states to the incompetent one, disrupting pump assembly and function and resensitizing bacteria to existing antibiotics. The modulation of AcrA dynamics through pharmacological intervention therefore presents a promising route for the development of new antibiotics.
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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.