Quorum sensing interference by phenolic compounds - A matter of bacterial misunderstanding

Abstract

Over the past decade, numerous publications have emerged in the literature focusing on the inhibition of quorum sensing (QS) by plant extracts and phenolic compounds. However, there is still a scarcity of studies that delve into the specific mechanisms by which these compounds inhibit QS. Thus, our question is whether phenolic compounds can inhibit QS in a specific or indirect manner and to elucidate the underlying mechanisms involved. This study is focused on the most studied QS system, namely, autoinducer type 1 (AI-1), represented by N-acyl-homoserine lactone (AHL) signals and the AHL-mediated QS responses. Here, we analyzed the recent literature in order to understand how phenolic compounds act at the cellular level, at sub-inhibitory concentrations, and evaluated by which QS inhibition mechanisms they may act. The biotechnological application of QS inhibitors holds promising prospects for the pharmaceutical and food industries, serving as adjunct therapies and in the prevention of biofilms on various surfaces.

Keywords: Acyl homoserine lactones; Cell-cell communication; Flavonoids; Mechanism; Quorum quenching.

Fig. 1

A typical Gram-negative QS system. A: general structure of an acyl homoserine lactone molecule (AHL). R can vary from 1 to 15 carbons. B: Activation of QS occurs at high concentration of signaling molecules, usually at high cell densities. In light beige cells (on the left), a complete QS system: AHLs, synthesized by a LuxI-type enzyme, passively diffuse through the bacterial cell membrane and when a threshold level is reached, they activate the intracellular LuxR-type transcription factor which subsequently activate target gene expression in a coordinated way. Some bacteria (dark gray, on the right) may possess a so-called LuxR solo protein, lacking a LuxI-type protein and the ability to synthesize their own AHL molecule, but still being able to respond to AHLs produced by other bacteria.

Fig. 2

Quorum sensing by two-component systems. A) Mechanism of QS in Gram-positive bacteria, particularly in Staphylococcus aureus. B) QS circuits in Vibrio harveyi. AIP, autoinducer peptides; RR, response regulator; H and D denote histidine and aspartate residues, which are phosphorylated upon signaling.

Fig. 3

Possible QS inhibitory modes of action by phytochemicals.

Fig. 4

Main classes of phenolic compounds and examples with chemical structure. Based on several studies, including [4,114,115].