ArticleAntibiotics (Basel, Switzerland)2022
Activation of a Bacterial Mechanosensitive Channel, MscL, Underlies the Membrane Permeabilization of Dual-Targeting Antibacterial Compounds.
Article in Antibiotics (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Review
- Structural basis of the gating mechanism of the large-conductance mechanosensitive channel from Escherichia coli.Nature communications · 2026Article
- A Pyrroloquinazoline Analogue Regulated Streptococcus mutans and Streptococcus sanguinis Dual-Species Biofilms.International dental journal · 2025Article
- Expanding the Landscape of Dual Action Antifolate Antibacterials through 2,4-Diamino-1,6-dihydro-1,3,5-triazines.ACS infectious diseases · 2025Article
- Exploring the principles behind antibiotics with limited resistance.Nature communications · 2025Article
- Biological characteristics of mechanosensitive channels MscS and MscL inJournal of bacteriology · 2024Article
- The efficacy of the food-grade antimicrobial xanthorrhizol againstFrontiers in microbiology · 2024Article
- A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance.Archives of microbiology · 2023Review
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Resistance to antibiotics is a serious and worsening threat to human health worldwide, and there is an urgent need to develop new antibiotics that can avert it. One possible solution is the development of compounds that possess multiple modes of action, requiring at least two mutations to acquire resistance. Compound SCH-79797 both avoids resistance and has two mechanisms of action: one inhibiting the folate pathway, and a second described as "membrane permeabilization"; however, the mechanism by which membranes from bacterial cells, but not the host, are disrupted has remained mysterious. The opening of the bacterial mechanosensitive channel of large conductance, MscL, which ordinarily serves the physiological role of osmotic emergency release valves gated by hypoosmotic shock, has been previously demonstrated to affect bacterial membrane permeabilization. MscL allows the rapid permeabilization of both ions and solutes through the opening of the largest known gated pore, which has a diameter of 30 Å. We found that SCH-79797 and IRS-16, a more potent derivative, directly bind to the MscL channel and produce membrane permeabilization as a result of its activation. These findings suggest that possessing or adding an MscL-activating component to an antibiotic compound could help to lower toxicity and evade 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.