ArticleMolecular microbiology2019
An agonist of the MscL channel affects multiple bacterial species and increases membrane permeability and potency of common antibiotics.
Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Review
- Non-Equilibrium Molecular Dynamics Simulation Captures Potential New Drug Target: Ec-MscL Gating Mechanism Explored with External Electric Field.Antibiotics (Basel, Switzerland) · 2026Article
- Biological characteristics of mechanosensitive channels MscS and MscL inJournal of bacteriology · 2024Article
- The efficacy of the food-grade antimicrobial xanthorrhizol againstFrontiers in microbiology · 2024Article
- The Effects of Airflow on the Mechanosensitive Channels ofMicroorganisms · 2023Article
- Approaches for the modulation of mechanosensitive MscL channel pores.Frontiers in chemistry · 2023Review
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
- Activation of a Bacterial Mechanosensitive Channel, MscL, Underlies the Membrane Permeabilization of Dual-Targeting Antibacterial Compounds.Antibiotics (Basel, Switzerland) · 2022Article
- Roles of Bacterial Mechanosensitive Channels in Infection and Antibiotic Susceptibility.Pharmaceuticals (Basel, Switzerland) · 2022Review
- In Silico Screen Identifies a New Family of Agonists for the Bacterial Mechanosensitive Channel MscL.Antibiotics (Basel, Switzerland) · 2022Article
- Mechanosensitive Channels Mediate Hypoionic Shock-Induced Aminoglycoside Potentiation against Bacterial Persisters by Enhancing Antibiotic Uptake.Antimicrobial agents and chemotherapy · 2022Article
- Curcumin activation of a bacterial mechanosensitive channel underlies its membrane permeability and adjuvant properties.PLoS pathogens · 2021Article
- Life with Bacterial Mechanosensitive Channels, from Discovery to Physiology to Pharmacological Target.Microbiology and molecular biology reviews : MMBR · 2020Review
- Article
- Novel MscL agonists that allow multiple antibiotics cytoplasmic access activate the channel through a common binding site.PloS one · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The bacterial MscL channel normally functions as an emergency release valve discharging cytoplasmic solutes upon osmotic stress. The channel opens and passes molecules up to 30 Å and its pore is the largest of any gated channel. Opening the MscL pore inappropriately is detrimental to the bacterial cell, suggesting MscL as a potential novel drug target. A small-molecule compound, 011A, has been shown to increase sensitivity of the Escherichia coli MscL channel, slow growth, and even decrease viability of quiescent cultures. The mscL gene is highly conserved and found in the vast majority of bacterial species, including pathogens. Here, we test the hypothesis that 011A can influence the growth and viability of other bacterial species, specifically Staphylococcus aureus and Mycobacterium smegmatis, in a MscL-dependent manner. Furthermore, we demonstrate that the 011A compound can increase potency of other antibiotics, presumably by permeabilizing the membrane and allowing easier access of the antibiotic into the cytoplasm. Thus, MscL activators have potential as novel broad-spectrum antibiotics or adjuvants that work with antibiotics to selectively allow passage across bacterial membranes.
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Registered trials
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