Derrisisoflavone-B interferes with AHL-mediated quorum sensing of Pseudomonas aeruginosa and decreased pathogenicity in Caenorhabditis elegans infection model

Abstract

The alarming situation of drug resistance demands novel antimicrobial strategies. Treatment of infections due to ESKAPE pathogens, especially by P. aeruginosa became challenging over the time. Acyl homoserine lactone (AHL) autoinducer based cell communication is one of the major mechanism contributing to this pathogen's virulence as well as biofilm formation. Derrisisoflavone- B (DIF-B) is an unexplored diprenylated isoflavonoid mostly isolated from Derris sp. Our study evaluated the anti-quorum sensing and anti-biofilm efficiency of DIF-B against the pathogen P. aeruginosa PAO1. In vitro tests revealed that compound DIF-B inhibited the quorum sensing associated virulence factors (Pyocyanin, LasA protease, LasB elastase, and total protease) to more than 60 %. Biofilm formation was also inhibited considerably. Significant inhibition of biofilm components including rhamnolipid, alginate and total exopolysaccharide was observed as well. Downregulation of AHL based quorum sensing transcriptional regulators, autoinducer synthase genes and virulence associated genes highlighted the anti-quorum sensing potential of DIF-B. In vivo experiments in C. elegans confirmed the non-toxicity of DIF-B, and their efficacy on survival of the infected worms. In silico studies evaluated the binding affinity of DIF-B to AHL based receptors, stability of receptor-ligand complex, chemical reactivity, pharmacokinetic properties and toxicity.

Keywords: Acyl homoserine lactone; Biofilm; Derrisisoflavone-B; Pseudomonas aeruginosa; Quorum sensing.