Glyceryl trinitrate is a novel inhibitor of quorum sensing in Pseudomonas aeruginosa.

Hisham A Abbas1, Moutaz A Shaldam
1. Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
2. Department of Medicinal Chemistry, Faculty of Pharmacy, Delta University for Science and Technology,
Gamasa, Egypt

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 im-  mune system can easily eradicate bacteria.

Objectives: Investigation of the possible inhibition of quorum sensing-regulated virulence of Pseudomonas aeruginosaby glyceryltrinitrate.

Methods:The quorum sensing inhibiting activity of glyceryl trinitrate was assessed by inhibition of violacein production in Chromobacterium violaceumATCC 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.

Keywords: Glyceryl trinitrate,Pseudomonas aeruginosa, quorum sensing, virulence inhibition