Plant-Derived Inhibitors of AHL-Mediated Quorum Sensing in Bacteria: Modes of Action.

Dmitry Deryabin,Anna Galadzhieva,Galimjan Duskaev,Dianna Kosyan

doi:10.3390/ijms20225588

Abstract

Numerous gram-negative phytopathogenic and zoopathogenic bacteria utilise acylated homoserine lactone (AHL) in communication systems, referred to as quorum sensing (QS), for induction of virulence factors and biofilm development. This phenomenon positions AHL-mediated QS as an attractive target for anti-infective therapy. This review focused on the most significant groups of plant-derived QS inhibitors and well-studied individual compounds for which in silico, in vitro and in vivo studies provide substantial knowledge about their modes of anti-QS activity. The current data about sulfur-containing compounds, monoterpenes and monoterpenoids, phenylpropanoids, benzoic acid derivatives, diarylheptanoids, coumarins, flavonoids and tannins were summarized; their plant sources, anti-QS effects and bioactivity mechanisms have also been summarized and discussed. Three variants of plant-derived molecules anti-QS strategies are proposed: (i) specific, via binding with LuxI-type AHL synthases and/or LuxR-type AHL receptor proteins, which have been shown for terpenes (carvacrol and l-carvone), phenylpropanoids (cinnamaldehyde and eugenol), flavonoid quercetin and ellagitannins; (ii) non-specific, by affecting the QS-related intracellular regulatory pathways by lowering regulatory small RNA expression (sulphur-containing compounds ajoene and iberin) or c-di-GMP metabolism reduction (coumarin); and (iii) indirect, via alteration of metabolic pathways involved in QS-dependent processes (vanillic acid and curcumin).

Highlights

Quorum sensing (QS) is a cell–cell communication system that is ubiquitously used in microbial communities to monitor their population density and adapt to external environment
quorum sensing (QS) was named and discovered in the marine bacterium Vibrio fischeri ( Aliivibrio fischeri) [1], where it regulates bioluminescence development in symbiotic “light” organs of squids from the genera Euprymna and Sepiola. This phenomenon involves LuxI synthase, which produces small diffusible signal molecules—acylated homoserine lactones (AHLs)—that accumulate in the environment
This study revealed that the simple coumarin aesculetin (6,7-dihydroxycoumarin) and coumarin glucoside aesculin are structurally compatible with the TraR AHL-binding site

Summary

Introduction

Quorum sensing (QS) is a cell–cell communication system that is ubiquitously used in microbial communities to monitor their population density and adapt to external environment. QS was named and discovered in the marine bacterium Vibrio fischeri ( Aliivibrio fischeri) [1], where it regulates bioluminescence development in symbiotic “light” organs of squids from the genera Euprymna and Sepiola. This phenomenon involves LuxI synthase, which produces small diffusible signal molecules—acylated homoserine lactones (AHLs)—that accumulate in the environment. Many other Gram-negative proteobacteria that belong to α, β and γ subdivisions use similar LuxI-type synthases and LuxR-type activator proteins They utilise AHL-dependent gene expression mechanisms to perform processes that are not effective at low cell density but very useful for the microbial community at high cell density [2]

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