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Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases
Published on: January 1, 2016
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Interception of Epoxide ring to quorum sensing system in Enterococcus faecalis and Staphylococcus aureus
Mohammed Y Refai1, Ahmed M Elazzazy1, Said E Desouky2,3
1Department of Biological Science, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
AMB Express
|November 9, 2023
Summary
Quorum sensing inhibitors (QSIs) with an epoxide group show promise as anti-virulence agents against antibiotic-resistant bacteria like MRSA and VRE. These compounds effectively disarm pathogens by interfering with essential signaling pathways.
Area of Science:
- Microbiology
- Medicinal Chemistry
- Pharmacology
Background:
- Antibiotic resistance poses a significant global health threat, necessitating novel therapeutic strategies.
- Quorum sensing inhibitors (QSIs) offer an anti-virulence approach by disarming pathogens instead of killing them.
- Gram-positive bacteria utilize cyclic peptide-mediated quorum sensing (QS) systems, such as agr and fsr, which are crucial for virulence.
Purpose of the Study:
- To investigate the role of the epoxide group in the anti-virulence activity of QSIs.
- To evaluate the efficacy of known natural epoxide compounds as QSIs against Gram-positive bacterial QS systems.
- To explore structure-activity relationships (SAR) and in silico interactions of epoxide-containing compounds.
Main Methods:
- Screening of epoxide compounds for QSI activity against agr and fsr QS systems.
- In silico analysis and SAR studies of epoxide-containing molecules.
- Testing of natural epoxide compounds like Cerulenin and Fosfomycin for QSI properties.
Main Results:
- Two epoxide compounds, Ambuic acid and Synerazol, were identified as potent inhibitors of agr and fsr QS systems.
- Most tested epoxide-containing antibiotics demonstrated correlative interference with QSI activity at sublethal concentrations.
- The epoxide moiety appears to be involved in the mechanism of action for these QSIs.
Conclusions:
- Epoxide-containing compounds, including natural antibiotics, can function as effective QSIs against Gram-positive bacteria.
- This finding supports the development of epoxide-based QSIs as a viable strategy to combat antibiotic-resistant infections.
- QSIs represent a promising alternative or adjunct to traditional antibiotic chemotherapy.
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