Covalent Inhibition of Bacterial Quorum Sensing
| Autor: | Neri Amara, Roi Mashiach, Dotan Amar, Pnina Krief, Stéphane A. H. Spieser, Matthew J. Bottomley, Amir Aharoni, Michael M. Meijler |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Alkylation 010402 general chemistry 01 natural sciences Biochemistry Catalysis Substrate Specificity 03 medical and health sciences chemistry.chemical_compound Colloid and Surface Chemistry Protein structure Bacterial Proteins Isothiocyanates Pseudomonas Cysteine Binding site Cysteine metabolism 030304 developmental biology 0303 health sciences Binding Sites Chemistry Quorum Sensing General Chemistry Protein Structure Tertiary 0104 chemical sciences 3. Good health Quorum sensing Covalent bond Trans-Activators Substrate specificity |
| Zdroj: | Journal of the American Chemical Society. 131:10610-10619 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Chemical coordination of gene expression among bacteria as a function of population density is regulated by a mechanism known as 'quorum sensing' (QS). QS in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in immunocompromised patients, is mediated by binding of the transcriptional activator, LasR, to its ligand, 3-oxo-C(12)-HSL, leading to population-wide secretion of virulence factors and biofilm formation. We have targeted QS in P. aeruginosa with a set of electrophilic probes designed to covalently bind Cys79 in the LasR binding pocket, leading to specific inhibition of QS-regulated gene expression and concomitant reduction of virulence factor secretion and biofilm formation. This first example of covalent modification of a QS receptor provides a new tool to study molecular mechanisms of bacterial group behavior and could lead to new strategies for targeting bacterial virulence. |
| Databáze: | OpenAIRE |
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