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Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa
Hisham A Abbas1, Ahmed M Elsherbini2, Moutaz A Shaldam3
1Department of Microbiology and Immunology-Faculty of Pharmacy-Zagazig University- Zagazig- Egypt.
Background:
Quorum sensing is a mechanism of intercellular communication that controls the production of virulence factors in Pseudomonas aeruginosa. Inhibition of quorum sensing can disarm the virulence factors without exerting stress on bacterial growth that leads to emergence of antibiotic resistance.
Objectives:
Finding a new quorum sensing inhibitor and determining its inhibitory activities against virulence factors of Pseudomonas aeruginosa PAO1 strain.
Methods:
Quorum sensing was evaluated by estimation of violacein production by Chromobacterium violaceum CV026. Molecular docking was used to investigate the possible binding of metformin to LasR and rhlR receptors. The inhibition of pyocyanin, hemolysin, protease, elastase in addition to swimming and twitching motilities, biofilm formation and resistance to oxidative stress by metformin was also assessed.
Results:
Metformin significantly reduced the production of violacein pigment. Significant inhibition of pyocyanin, hemolysin, protease and elastase was achieved. Metformin markedly decreased biofilm formation, swimming and twitching motilities and increased the sensitivity to oxidative stress. In the molecular docking study, metformin could bind to LasR by hydrogen bonding and electrostatic interaction and to rhlR by hydrogen bonding only.
Conclusion:
Metformin can act as a quorum sensing inhibitor and virulence inhibiting agent that may be useful in the treatment of Pseudomonas aeruginosa infection.
Insights
Metformin inhibits quorum sensing in Pseudomonas aeruginosa by targeting key receptors. This virulence inhibiting agent reduces bacterial virulence factors and biofilm formation, offering a potential treatment for infections.
Area of Science:
- Microbiology
- Pharmacology
- Bacterial Communication
Background:
- Quorum sensing regulates virulence factors in Pseudomonas aeruginosa.
- Inhibiting quorum sensing disarms bacteria without promoting antibiotic resistance.
Purpose of the Study:
- Identify a novel quorum sensing inhibitor.
- Evaluate inhibitory effects against Pseudomonas aeruginosa PAO1 virulence factors.
Main Methods:
- Assessed quorum sensing via violacein production in Chromobacterium violaceum.
- Utilized molecular docking to study metformin binding to LasR and rhlR receptors.
- Measured inhibition of pyocyanin, hemolysin, protease, elastase, motility, biofilm, and oxidative stress resistance.
Main Results:
- Metformin significantly reduced violacein production and inhibited key virulence factors (pyocyanin, hemolysin, protease, elastase).
- Metformin decreased biofilm formation, motility, and increased oxidative stress sensitivity.
- Molecular docking indicated metformin binds to LasR and rhlR receptors.
Conclusions:
- Metformin functions as a quorum sensing inhibitor.
- Metformin exhibits virulence-inhibiting properties against Pseudomonas aeruginosa.
- Metformin shows potential for treating Pseudomonas aeruginosa infections.
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