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 journalArticle

100 Citations (Scopus)

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

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Acyl-Butyrolactones
Quorum Sensing
Pseudomonas aeruginosa
Biotechnology
Computer Simulation
Virulence
Transcription Factors
Binding Sites
Bacteria
Gene Expression
Genes

Keywords

  • Autoinduction
  • Bacterial communication
  • LasR
  • Sociomicrobiology

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. / Müh, Ute; Hare, Brian J.; Duerkop, Breck A.; Schuster, Martin; Hanzelka, Brian L.; Heim, Roger; Olson, Eric R.; Greenberg, E. Peter.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 45, 07.11.2006, p. 16948-16952.

Research output: Contribution to journalArticle

Müh, Ute ; Hare, Brian J. ; Duerkop, Breck A. ; Schuster, Martin ; Hanzelka, Brian L. ; Heim, Roger ; Olson, Eric R. ; Greenberg, E. Peter. / A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 45. pp. 16948-16952.
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