In vivo, in vitro and molecular docking studies reveal the anti-virulence property of hispidulin against Pseudomonas aeruginosa through the modulation of quorum sensing

Abstract

Pseudomonas aeruginosa is an audacious infectious agent involved in multiple persistent and incurable diseases in hosts through quorum sensing mediated pathways. Thus, compounds targeting quorum sensing (QS) can reduce the pathogenesis and virulence. The present study attempts to elucidate the QS inhibition properties of hispidulin against P. aeruginosa PAO1. Hispidulin (HPD) at its sub-inhibitory concentration (75 μg/ml) decreased violacein and pyocyanin pigment production of reporter bacteria and test bacteria to 81.92 ± 1.90 and 71.69 ± 3.46%, respectively. HPD supressed the virulence and biofilm development as similar to the positive control, baicalein. The pathogenesis of P. aeruginosa was effectively reduced in the infected worm model. The infected C. elegans showed 80.43% survival on the 6th day in presence of sub-MIC of HPD. In addition, HPD reduced the transcription of genes regulated by Las and Rhl networks including the receptor proteins and autoinducer producing genes which validated the anti-QS potential of the flavonoid. Computational studies revealed competitive binding of HPD with LasR protein and a weak interaction with RhlR. The results suggested the ability of HPD to block QS regulatory networks of P. aeruginosa. The potential lead obtained through this study can be utilized in the near future to design and develop anti-pathogenic agents to treat pseudomonal infections.