ArticleNature communications2022
Activating alternative transport modes in a multidrug resistance efflux pump to confer chemical susceptibility.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Proton hopping and secondary gating reveal a universal transport mechanism in a minimal bacterial transporter EmrE.Biophysical journal · 2026Article
- Diversity of Pharmaceuticals Enhances Antibiotic Resistance in the Invertebrate Gut via Biofilm-Mediated Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protonated Structure of EmrE Reveals C-terminal Tail Gating Mechanism.bioRxiv : the preprint server for biology · 2026Article
- Collateral effects of antibiotic resistance in Campylobacter jejuni.FEMS microbiology letters · 2026Article
- Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Backbone and sidechainBiomolecular NMR assignments · 2025Article
- 18-Crown-6-ether Utilizes Distinct Allosteric Interactions to Uncouple Transport by the Multidrug Efflux Pump EmrE.Biochemistry · 2025Article
- The C-terminus of the multi-drug efflux pump EmrE prevents proton leak by gating transport.eLife · 2025Article
- Enhancing Spectrometer Performance with Unsupervised Machine Learning.The journal of physical chemistry. B · 2024Article
- Substrate dependence of transport coupling and phenotype of a small multidrug resistance transporter inJournal of bacteriology · 2024Article
- Cross polarization stability in multidimensional NMR spectroscopy of biological solids.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2024Article
- Peripheral positions encode transport specificity in the small multidrug resistance exporters.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Small Multidrug Resistance Transporter inbioRxiv : the preprint server for biology · 2024Article
- Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus, Pseudomonas aeruginosa, and Francisella tularensis.Molecular microbiology · 2024Article
- Review
- Microsecond Motion of the Bacterial Transporter EmrE in Lipid Bilayers.Journal of the American Chemical Society · 2023Article
- Still rocking in the structural era: A molecular overview of the small multidrug resistance (SMR) transporter family.The Journal of biological chemistry · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Small multidrug resistance (SMR) transporters contribute to antibiotic resistance through proton-coupled efflux of toxic compounds. Previous biophysical studies of the E. coli SMR transporter EmrE suggest that it should also be able to perform proton/toxin symport or uniport, leading to toxin susceptibility rather than resistance in vivo. Here we show EmrE does confer susceptibility to several previously uncharacterized small-molecule substrates in E. coli, including harmane. In vitro electrophysiology assays demonstrate that harmane binding triggers uncoupled proton flux through EmrE. Assays in E. coli are consistent with EmrE-mediated dissipation of the transmembrane pH gradient as the mechanism underlying the in vivo phenotype of harmane susceptibility. Furthermore, checkerboard assays show this alternative EmrE transport mode can synergize with some existing antibiotics, such as kanamycin. These results demonstrate that it is possible to not just inhibit multidrug efflux, but to activate alternative transport modes detrimental to bacteria, suggesting a strategy to address antibiotic resistance.
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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.