Plumbagin inhibits quorum sensing-regulated virulence and biofilms of Gram-negative bacteria: in vitro and in silico investigations

The global rise in antimicrobial resistance and lack of discovery of new antimicrobials have created serious concerns. Targeting quorum sensing (QS) and biofilms of pathogenic bacteria is considered a promising approach in antimicrobial drug discovery. This study explored the inhibitory effect of plumbagin against biofilms and QS of Chromobacterium violaceum, Serratia marcescens and Pseudomonas aeruginosa. Violacein production in C. violaceum 12472 was reduced by >80%. The virulent traits of P. aeruginosa PAO1 such as pyocyanin, rhamnolipid and proteases were also inhibited at sub-minimum inhibitory concentrations. Moreover, the biofilms of the test bacteria were reduced by 56-70%. Plumbagin reduced the bacterial adherence and colonization on solid surface. Computational studies gave closer insights regarding the possible modes of action. Molecular dynamics simulations revealed that the protein complexes were quite stable under physiological conditions. This study provides both experimental and computational evidence regarding the efficacy of plumbagin against biofilms and the QS-controlled virulence factors of Gram-negative bacteria.

Automated summary

The study found that plumbagin has inhibitory effects on the biofilms and quorum sensing of certain pathogenic bacteria, reducing their virulence traits. Specifically, it decreased violacein production in Chromobacterium violaceum, inhibited the virulent traits of Pseudomonas aeruginosa, and reduced bacterial adherence and colonization on solid surfaces. Computational studies provided insights into the possible modes of action, showing that the protein complexes remained stable under physiological conditions. This research offers both experimental and computational evidence of the efficacy of plumbagin against biofilms and QS-controlled virulence factors of Gram-negative bacteria.