An agonist of the MscL channel affects multiple bacterial species and increases membrane permeability and potency of common antibiotics.
Mol Microbiol
; 112(3): 896-905, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31177589
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcus aureus
/
Mycobacterium smegmatis
/
Escherichia coli Proteins
/
Escherichia coli
/
Small Molecule Libraries
/
Ion Channels
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Anti-Bacterial Agents
Language:
En
Journal:
Mol Microbiol
Journal subject:
BIOLOGIA MOLECULAR
/
MICROBIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
United States