Abstract
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. Finding a new quorum sensing inhibitor and determining its inhibitory activities against virulence factors of Pseudomonas aeruginosa PAO1 strain. 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. 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. Metformin can act as a quorum sensing inhibitor and virulence inhibiting agent that may be useful in the treatment of Pseudomonas aeruginosa infection.
Highlights
Pseudomonas aeruginosa is an opportunistic pathogen that affects patients with suppressed immunity
This study aimed to investigate the possible anti-quorum sensing and anti-virulence activities of metformin in P. aeruginosa PAO1 strain
Bacterial strains Pseudomonas aeruginosa PAO1 strain was kindly provided by the Department of Microbiology, Faculty of Pharmacy, Mansoura University, while Chromobacterium violaceum CV026 was kindly gifted by the Department of Microbiology, Faculty of Pharmacy, Ain Shams University
Summary
Pseudomonas aeruginosa is an opportunistic pathogen that affects patients with suppressed immunity. It is extremely necessary to develop new therapeutic approaches to overcome antibiotic resistance[4] One of these promising approaches is the interference with the virulence of bacteria. 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. The inhibition of pyocyanin, hemolysin, protease, elastase in addition to swimming and twitching motilities, biofilm formation and resistance to oxidative stress by metformin was assessed. Conclusion: Metformin can act as a quorum sensing inhibitor and virulence inhibiting agent that may be useful in the treatment of Pseudomonas aeruginosa infection.
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