Quorum Sensing Inhibitors as Pathoblockers for Pseudomonas aeruginosa Infections: A New Concept in Anti-Infective Drug Discovery

Abstract

Decades after the Golden Age of antibiotics, it is evident that antibiotic resistance is rapidly evolving and spreading among clinically relevant pathogens. The medical need for alternative anti-infective treatments is tremendously high today. A novel concept has emerged focusing on “pathoblockers” disarming a pathogen of its virulence weaponries instead of directly killing it. As such compounds should not instigate selection pressure – in contrast to conventional antibiotics – treated bacteria ought to be less prone to resistance development. The discovery of anti-pathogenic compounds necessitates a profound understanding of the respective pathogenic mechanisms and modern medicinal chemistry strategies in order to develop highly effective therapies. Interference with the bacterial cell-to-cell communication that globally regulates the production of various virulence factors and biofilm formation is a very promising approach. As an example, we herein review recent advances and forward-looking concepts in the development of quorum sensing inhibitors selectively targeting the ESKAPE pathogen Pseudomonas aeruginosa.