Quorum Quenching: A Drug Discovery Approach Against Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa, a ubiquitous opportunistic and nosocomial biofilm-forming pathogen with complex, interconnected and hierarchical nature of QS systems (Las, Rhl, PQS, and IQS), is posing the biggest challenge to the healthcare sector and have made current chemotherapies incapable. Conventional antibiotics designed to intercept the biochemical or physiological processes precisely of planktonic microorganisms exert extreme selective pressure and develop resistance against them thereby emphasizing the development of alternative therapeutic approaches. Additionally, quorum sensing induced pathogenic microbial biofilms and production of virulence factors have intensified the pathogenicity, drug resistance, recurrence of infections, hospital visits, morbidity, and mortality many-folds. In this regard, QS could be a potential druggable target and the discovery of QS inhibiting agents as an anti-virulent measure could serve as an alternative therapeutic approach to conventional antibiotics. Quorum quenching (QQ) is a preferred strategy to combat microbial infections since it attenuates the pathogenicity of microbes and enhances the microbial biofilm susceptibility to antibiotics, thus qualifying as a suitable target for drug discovery. This review discusses the QS-induced pathogenicity of P. aeruginosa, the hierarchical QS systems, and QS inhibition as a drug discovery approach to complement classical antibiotic strategy.

Keywords: Biofilm; Drug discovery; Pseudomonas aeruginosa; Quorum quenching; Quorum sensing.