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.
A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Publishing Authors By Initials
A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Journal Published:
PUBLICATION TYPE: Research Support, U.S. Gov't,
Journal: Proceedings of the National Academy of Sciences of
VOLUME: 103
Page Numbers: 16948-52
Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.
ISSN: 0027-8424
DAY: 30
MONTH: 10
YEAR: 2006
A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Information
Number of References:
LANGUAGE: eng
NlmUniqueID: 7505876
A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Keywords Mesh Terms:
KEYWORDS: Trans-Activators
MESH TERMS: metabolism
Chemical & Substance for Abstract: A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Information
Substance Name: 4-Butyrolactone
Registry Number: 96-48-0
Grant and Affiliation Information for A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal.
AFFILIATION: Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139, USA.
Country: United States
AGENCY: United States NIGMS
GRANT: T32 GM 07270
ACRONYM: GM
MEDLINETA: Proc Natl Acad Sci U S A
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