Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa

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.Keywords: Metformin, Pseudomonas aeruginosa, quorum sensing, virulence inhibitio

Glyceryl trinitrate blocks staphyloxanthin and biofilm formation in Staphylococcus aureus

Background: Staphylococcus aureus is an important nosocomial bacterium that is responsible for a number of infections that may be fatal. The treatment of such infections is limited by emergence of antibiotic resistance. Targeting virulence of Staphylococcus aureus may provide an alternative option to antibiotic that may bypass the emergence of resistant strains due to lack of stress on viability. Objectives: Investigation of the ability of glyceryl trinitrate (GTN) to inhibit staphyloxanthin, biofilm and tolerance to oxidative stress. Methods: The disk sensitivity method was used to detect the methicillin resistance of Staphylococcus aureus. The effect of sub-inhibitory concentration of GTN on biofilm formation, staphyloxanthin production and tolerance to oxidative stress was evaluated. Molecular docking study was used to investigate the ability of GTN to bind to dehydrosqualene synthase enzyme. Results: GTN showed a significant inhibition of biofilm, staphyloxanthin and tolerance to oxidative stress. In the molecular docking study, it was found that GTN could bind to dehydrosqualene synthase enzyme by hydrogen bonding,electrostatic interaction and pi-cation interaction. Conclusion: The present study revealed the ability of GTN to serve as a potential anti-virulence candidate for attenuation of S. aureus pathogenicity. DOI: https://dx.doi.org/10.4314/ahs.v19i1.10 Cite as: Abbas HA, Elsherbini AM, MA S. Glyceryl trinitrate blocks staphyloxanthin and biofilm formation in Staphylococcus aureus. Afri Health Sci. 2019;19(1). 1376-1384. https://dx.doi.org/10.4314/ahs.v19i1.1

Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa

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