Author(s)

Hisham Abdel Monem Abbas¹, Wafaa Ezz Elarab Soliman^2*, Moutaz Ahamed Shaldam³

¹Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
²Department of Microbiology and Biotechnology, Faculty of Pharmacy, Delta University for Science and Technology, Mansoura, Egypt.
³Department of Medicinal Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Mansoura, Egypt.

Quorum sensing is a signal-based communication system in bacteria. It is an attractive target because it regulates the production of virulence factors in Pseudomonas aeruginosa. As a result, interference with quorum sensing could result in inhibition of virulence of Pseudomonas aeruginosa with the merit of lack of selective pressure on growth that leads to development of resistance. This study investigated the anti-quorum sensing and anti-virulence activities of febuxostat in Pseudomonas aeruginosa PAO1 strain. At 1/8 MIC of febuxostat, the production of the quorum-sensing regulated violacein pigment of Chromobacterium violaceum CV026 was significantly reduced. Moreover, it markedly reduced pyocyanin, hemolysin, protease and elastase production. Significant inhibitory activities were also found against biofilm, swimming, twitching and swarming motilities. Molecular docking showed the ability of febuxostat to inhibit quorum sensing by competing with the autoinducers to bind with LasR and RhlR receptors. Febuxostat could bind to both receptors by hydrogen bonding and hydrophobic interaction. From the Molecular docking scores, febuxostat is a very promising quorum sensing inhibitor. Febuxostat could also significantly decrease the level of expression of all QS genes LasI, LasR, RhlI, RhlR, PqsA and PqsR that regulate the production of virulene factors as confirmed by qRT-PCR.

Febuxostat, Pseudomonas aeruginosa, Quorum Sensing, Virulence Inhibition, Molecular Docking

Abbas, H. , Soliman, W. and Shaldam, M. (2018) Perturbation of Quorum Sensing in Pseudomonas aeruginosa by Febuxostat. Advances in Microbiology, 8, 650-664. doi: 10.4236/aim.2018.88044.