Luteolin, a promising quorum quencher mitigates virulence factors production in Pseudomonas aeruginosa - In vitro and In vivoapproach

Abstract

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes healthcare-associated infection and high mortality in immunocompromised patients. It produces several virulence factors through quorum sensing (QS) mechanisms that is essential for subverting host immune system. Even front-line antibiotics are unable to control PA pathogenicity due to the emergence of antibiotic resistance. Luteolin is a naturally derived compound that has proven to be the effective drug to annihilate pathogens through quorum quenching mechanism. In this study, the protective effect of luteolin against the PA-mediated inflammation was demonstrated using zebrafish model. Luteolin protects zebrafish from PA infection and increases their survival rate. It was found that PA-mediated ROS, lipid peroxidation, and apoptosis were also significantly reduced in luteolin-treated zebrafish larvae. Open field test (OFT) reveals that luteolin rescued PA-infected zebrafish from retarded swimming behavior. Furthermore, luteolin increases SOD and CAT levels and decreases LDH and NO levels in PA-infected zebrafish compare to control group. Histological and gene expression analysis reveals that luteolin protects PA-infected zebrafish by decreasing gut inflammation and altering the expression of inflammatory (TNF-α, IL-1β, IL-6) and antioxidant markers (iNOS, SOD, CAT). Thus, luteolin was found to have dual effect in protecting PA-infected zebrafish by decreasing virulence factors production in PA and stimulating host immune system. This is the first study demonstrating the protective effect of luteolin using animal model. Hence, luteolin could be used as a future therapeutic drug to control multi-drug resistant PA.