Glyceryl trinitrate is a novel inhibitor of quorum sensing in <i>Pseudomonas aeruginosa</i>

Abstract

Background: Targeting quorum sensing is an alternative approach to antibiotics.Targeting quorum sensing-regulated virulence will disarm the pathogen without exerting pressure on its growth. As a result, emergence of resistance is avoided and the immune system can easily eradicate bacteria. Objectives: Investigation of the possible inhibition of quorum sensing-regulated virulence of Pseudomonas aeruginosa by glyceryltrinitrate. Methods: The quorum sensing inhibiting activity of glyceryl trinitrate was assessed by inhibition of violacein production in Chromobacterium violaceum ATCC 12472. Its ability to inhibit pyocyanin, protease, biofilm and tolerance to oxidative stress was evaluated. Docking study was performed to study the interference of glyceryl trinitrate with the binding of autoinducers with LasR and rhlR receptors. Results: Glyceryl trinitrate exerted a significant biofilm inhibiting and eradicating activities. It decreased the production of quorum-sensing dependent violacein production. It significantly inhibited the production of pyocyanin and protease and diminished the tolerance against oxidative stress. Molecular docking study showed that glyceryl trinitrate interferes with the binding of autoinducers to their receptors. It could bind to Las Rand rhlr receptors with binding energy of -93.47 and -77.23, respectively. Conclusion: Glyceryl trinitrate can be an antivirulence agent in the treatment of Pseudomonas aeruginosa topical infections such as burn infections.

Perturbation of Quorum Sensing in &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; by Febuxostat

“…As a result, many reports tested the possibility of finding QS inhibitors among FDA approved drugs to make their use possible on clinical background. This hypothesis was found to be true in our previous studies [32] [33].…”

Repurposing metformin as a quorum sensing inhibitor in <i>Pseudomonas aeruginosa</i>

“…To solve this problem, screening of FDA approved drugs for possible quorum sensing inhibition may be a useful alternative option that enables their clinical application for treatment of infections. This approach was found to be successful in our previous study on glyceryl trinitrate 34 . In the present study, the oral hypoglycemic drug metformin was tested for its potential quorum sensing inhibition.…”

Silencing the nosocomial pathogen Serratia marcescens by glyceryl trinitrate

“…Glyceryl trinitrate (GTN) is an anti-hypertensive that has anti-microbial properties 9 , 10 . It could inhibit the growth of Candida albicans and Pseudomonas aeruginosa planktonic growth 10 , 11 . Moreover, GTN exerted antibiofilm activity against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and candida albicans 12 .…”