期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 45, 页码 16948-16952出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0608348103
关键词
autoinduction; bacterial communication; LasR; sociomicrobiology
资金
- NIGMS NIH HHS [GM 59026, T32 GM 07270, T32 GM007270, R01 GM059026] Funding Source: Medline
The pathogenic bacterium Pseudomonas aeruginosa uses acylhomoserine 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 (30C12-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 30C12-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 30C12-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.
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