The search for inhibitors of the quorum sensing receptor of pseudomonas aeruginosa.

• Main Author: Chua, Jenna.
• Other Authors: School of Biological Sciences
• Format: Final Year Project
• Language: English
• Published: 2013
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/52746
• Institution: Nanyang Technological University

Imprudent use of antibiotics has led to antibiotic resistance development in human pathogens such as P. aeruginosa whose chronic infections are particularly widespread and severe among immunocompromised patients. Its persistence in disease can be linked to its readiness to form biofilms and release harmful virulence factors at the population level through inter-cell bacterial communication or quorum sensing (QS). Hence QS inhibitors (QSIs) against P. aeruginosa can increase its susceptibility to antibiotic treatment. In this study, structure-based virtual screening (SB-VS) was employed to identify QSIs against Pseudomonas quinolone signal receptor (PqsR), a QS receptor of P. aerugionsa. An automated docking system was used to run a collection of 10,000 diverse compounds against a computationally modeled PqsR structure, using cavity- and template- based docking methods. Twenty-seven compounds were selected based on docking scores and acquired to test for their efficacy as QSIs. Using a live cell reporter assay, one compound, named Cavity 3 (C3), was found to significantly inhibit PqsR-regulated gene expression. When tested using a known QS inhibition assay, it showed complete abolishment of QS-mediated virulence factor production. These results confirm C3 as a suitable candidate for drug development, and attest to the versatility of SB-VS in its application to drug discovery.