Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review

Eur J Med Chem. 2019 Jun 15:172:26-35. doi: 10.1016/j.ejmech.2019.03.049. Epub 2019 Mar 25.

Abstract

Nowadays, due to spreading antibiotic resistance among clinically relevant pathogens, the requirement of novel therapeutic approaches is felt more than ever. One of the alternative strategies is anti-virulence therapy without affecting bacterial growth or viability. In Pseudomonas aeruginosa, an opportunistic human pathogen that exhibits intrinsic multi-drug resistance, both virulence factors' production and biofilm formation depends on its quorum sensing (QS) network. Therefore, targeting the key proteins involved in QS system is an attractive method to overcome P. aeruginosa pathogenicity and resistance. The transcriptional regulator PqsR, also called MvfR, is one of these major proteins which employs 3,4-dihydroxy-2-heptylquinoline (PQS) and 4-hydroxy-2-heptylquinoline (HHQ) as signaling molecules. Reviewing the advances in development of small molecules inhibit this protein, assist to open a new window to smart molecule design that may revolutionize treatment of P. aeruginosa infections.

Keywords: Antibacterial resistance; HHQ; PQS; PqsR; Pseudomonas aeruginosa; Quorum sensing.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects*
  • Quinazolinones / chemical synthesis
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Quinolones / chemical synthesis
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Quorum Sensing / drug effects
  • Trans-Activators

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • LasR protein, Pseudomonas aeruginosa
  • Quinazolinones
  • Quinolones
  • Trans-Activators