A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal

Ute Müh, Brian J. Hare, Breck A. Duerkop, Martin Schuster, Brian L. Hanzelka, Roger Heim, Eric R. Olson, E. Peter Greenberg

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

The pathogenic bacterium Pseudomonas aeruginosa uses acyl-homoserine lactone quorum-sensing signals to coordinate the expression of a battery of virulence genes in a cascade of regulatory events. The quorum-sensing signal that triggers the cascade is N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), which interacts with two signal receptor-transcription factors, LasR and QscR. This signal is base labile, and it is degraded by mammalian PON lactonases. We have identified a structurally unrelated triphenyl mimic of 3OC12-HSL that is base-insensitive and PON-resistant. The triphenyl mimic seems to interact specifically with LasR but not with QscR. In silico analysis suggests that the mimic fits into the 3OC12-HSL-binding site of LasR and makes key contacts with LasR. The triphenyl mimic is an excellent scaffold for developing quorum-sensing inhibitors, and its stability and potency make it ideal for biotechnology uses such as heterologous gene expression.

Original languageEnglish (US)
Pages (from-to)16948-16952
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number45
DOIs
StatePublished - Nov 7 2006

Keywords

  • Autoinduction
  • Bacterial communication
  • LasR
  • Sociomicrobiology

ASJC Scopus subject areas

  • General

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