Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa.

Hisham A Abbas, Ahmed M Elsherbini, Moutaz A Shaldam
1. Department of Microbiology and Immunology-Faculty of Pharmacy-Zagazig University- Zagazig- Egypt
2. Health Sciences College-Umm Al Qura University, AlQunfudah, Saudi Arabia
3. Department of Medicinal Chemistry, Faculty of Pharmacy, Delta University for Science and Technology,
Gamasa, Egypt

Abstract
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 aeruginosaPAO1 strain.

Methods: Quorum sensing was evaluated by estimation of violacein production by Chromobacterium violaceumCV026. Moleculardocking 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 aeruginosainfection.

Keywords: Metformin, Pseudomonas aeruginosa, quorum sensing, virulence inhibition