Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers.

Christian Schütz,Martin Empting

doi:10.3762/bjoc.14.241

Abstract

The Gram-negative opportunistic pathogen Pseudomonas aeruginosa causes severe nosocomial infections. It uses quorum sensing (QS) to regulate and coordinate population-wide group behaviours in the infection process like concerted secretion of virulence factors. One very important signalling network is the Pseudomonas quinolone signal (PQS) QS. With the aim to devise novel and innovative anti-infectives, inhibitors have been designed to address the various potential drug targets present within pqs QS. These range from enzymes within the biosynthesis cascade of the signal molecules PqsABCDE to the receptor of these autoinducers PqsR (MvfR). This review shortly introduces P. aeruginosa and its pathogenicity traits regulated by the pqs system and highlights the published drug discovery efforts providing insights into the compound binding modes if available. Furthermore, suitability of the individual targets for pathoblocker design is discussed.

Highlights

In recent years, attempts to raise public awareness on antimicrobial resistance (AMR) and the large threat that it poses towards modern health standards have been made [1]
With the aim to devise novel and innovative anti-infectives, inhibitors have been designed to address the various potential drug targets present within pqs quorum sensing (QS). These range from enzymes within the biosynthesis cascade of the signal molecules PqsABCDE to the receptor of these autoinducers PqsR (MvfR)
This review shortly introduces P. aeruginosa and its pathogenicity traits regulated by the pqs system and highlights the published drug discovery efforts providing insights into the compound binding modes if available

Summary

Introduction

Attempts to raise public awareness on antimicrobial resistance (AMR) and the large threat that it poses towards modern health standards have been made [1]. Due to these important virulence mechanisms, which are under direct or indirect control of pqs QS, targeting this master regulatory system with small molecular compounds, thereby blocking P. aeruginosa pathogenicity, is very attractive.

Results

Conclusion