Ilimaquinone as a novel marine sponge-derived antibacterial agent: mechanistic insights into its antibiofilm and quorum sensing inhibitory properties targeting bacterial virulence.

Abstract

This study evaluates the antibacterial, antibiofilm, and anti-quorum-sensing (QS) properties of ilimaquinone (IQ) against Gram-positive and Gram-negative pathogens. The agar cup diffusion method revealed significant bacterial inhibition, with minimum inhibitory (MIC) and bactericidal (MBC) concentrations ranging from 6.25 to 25 μM and 12.5 to 50 μM, respectively. IQ exhibited dose-dependent biofilm inhibition, demonstrating its potential as an anti-biofilm agent. QS inhibition was assessed by pigment suppression in Chromobacterium violaceum (violacein), Serratia marcescens (prodigiosin), and Pseudomonas aeruginosa (pyocyanin, pyoverdine), reducing their production by 73.33%, 53.68%, 57.13%, and 62.42%, respectively, at sub-MIC concentrations. IQ also inhibited QS-regulated virulence factors in P. aeruginosa, including LasA protease, elastase, rhamnolipid, and extracellular polymeric substance (EPS) production, disrupting biofilm formation. Molecular docking and dynamics analysis confirmed strong binding affinities of IQ to key QS and biofilm-associated proteins (EsaI, PilY1, LasA, PilT, LasR, RhlR, LasI, PqsR, CviR, and CviR'), highlighting its mechanistic role in QS inhibition. These findings suggest that IQ is a promising antibacterial and anti-QS compound with potential therapeutic applications for managing bacterial infections and biofilm-related complications.