Inhibiting N-acyl-homoserine lactone synthesis and quenching Pseudomonas quinolone quorum sensing to attenuate virulence.

Kok-Gan Chan,Chien-Yi Chang,Yi-Chia Liu

doi:10.3389/fmicb.2015.01173

Kok-Gan Chan, Chien-Yi Chang + Show 1 more

Open Access

https://doi.org/10.3389/fmicb.2015.01173

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Abstract

Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed.

Highlights

Quorum sensing (QS) is an intercellular communication mechanism of bacteria used to coordinate the activities of individual cells in population level in response to surroundings through production and perception of diffusible signal molecules
Mutants on AQ–quorum sensing (QS) showed reduced P. aeruginosa virulence in infection models (Cao et al, 2001; Diggle et al, 2003; Déziel et al, 2004). These results suggest that PQS or HHQ signaling pathway could be a novel target against P. aeruginosa infecyions
Besides targeting on PQS molecules production or modification, a group of compounds with a benzamidebenzimidazole backbone targeting on MvfR (PqsR)-regulated pathways have been identified by using a whole-cell highthroughput screen (HTS) and structure–activity relationship (SAR) analysis

Summary

INTRODUCTION

Quorum sensing (QS) is an intercellular communication mechanism of bacteria used to coordinate the activities of individual cells in population level in response to surroundings through production and perception of diffusible signal molecules. By reducing concentration of signals or interrupting the interactions of signal on receptor protein, the expression of QS-regulated genes can be disturbed and bacterial virulence can be subsequently attenuated (Dong et al, 2000, 2001). These approaches coined as quorum quenching (QQ) were considered as alternatives against bacterial infections (Cámara et al, 2002; Zhang and Dong, 2004; González and Keshavan, 2006). The recent QQ studies on AQ–QS are discussed

AHL SYNTHESIS AND INHIBITION

Mechanism of inhibition

Decreasing the level of pqsA expression

Findings

CONCLUSION