Attenuation of quorum sensing-mediated virulence in Gram-negative pathogenic bacteria: implications for the post-antibiotic era?

MedChemComm Pub Date: 2014-09-30 DOI: 10.1039/C4MD00363B

Abstract

Quorum sensing is a cell-density dependent regulatory system, which orchestrates that quorum-sensing (QS) systems use extracellular signals to modulate the expression of a particular gene(s) in a bacterial cell, which results in virulence gene expression or biofilm formation and occasionally causes deadly plant and animal diseases. The frequent use of antibiotics to treat deadly diseases has led to the development of multiple drug-resistant bacterial strains. The increasing presence of pathogenic bacteria has thus forced us to develop alternative methods for controlling pathogen virulence. One such possible method, quorum quenching (QQ), has emerged as an interesting approach. A variety of bioactive molecules or drugs from prokaryotic or eukaryotic sources have been identified as QQ molecules, some of which are chemically synthesized, and the agonist or antagonist of their cognate receptor or metabolic intermediate was determined. Current strategies to attenuate the virulence of gene expression can be grouped into the following categories: (a) blockage of AHL–Lux-R-type binding sites, (b) inhibition of AHL–Lux-R- and Lux-I-type interactions, (c) inhibition of transporters, (d) degradation of existing AHLs by QQ enzymes and (e) inhibition of enzymes involved in the metabolic synthesis of QS molecules. This review summarises several potential QQ molecules that have been reported to attenuate QS-based virulence gene expression in serious Gram-negative pathogenic bacteria. These QQ molecules suggest possible ways of controlling the virulence effects of pathogenic bacteria in the post-antibiotic era.

Graphical abstract: Attenuation of quorum sensing-mediated virulence in Gram-negative pathogenic bacteria: implications for the post-antibiotic era
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