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Antibacterials pp 185-210 | Cite as

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

  • Ahmed A. M. Kamal
  • Christine K. Maurer
  • Giuseppe Allegretta
  • Jörg Haupenthal
  • Martin Empting
  • Rolf W. HartmannEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 26)

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.

Keywords

Biofilm Fragment-based drug discovery High-throughput screening Ligand-based design PQS PqsR (MvfR) QS inhibitors Quorum sensing (QS) Signal molecules Structure-based design Virulence factors 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Ahmed A. M. Kamal
    • 1
  • Christine K. Maurer
    • 1
  • Giuseppe Allegretta
    • 1
  • Jörg Haupenthal
    • 1
  • Martin Empting
    • 1
  • Rolf W. Hartmann
    • 1
    • 2
    Email author
  1. 1.Department of Drug Design and OptimizationHelmholtz-Institute for Pharmaceutical Research SaarlandSaarbrückenGermany
  2. 2.Department of Pharmacy, Pharmaceutical and Medicinal ChemistrySaarland UniversitySaarbrückenGermany

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