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Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing.
- Source :
-
Chembiochem : a European journal of chemical biology [Chembiochem] 2016 May 03; Vol. 17 (9), pp. 825-35. Date of Electronic Publication: 2016 Mar 15. - Publication Year :
- 2016
-
Abstract
- Emerging antibiotic resistance among human pathogens has galvanized efforts to find alternative routes to combat bacterial virulence. One new approach entails interfering with the ability of bacteria to coordinate population-wide gene expression, or quorum sensing (QS), thus inhibiting the production of virulence factors and biofilm formation. We have recently developed such a strategy by targeting LasR, the master regulator of QS in the opportunistic human pathogen Pseudomonas aeruginosa, through the rational design of covalent inhibitors closely based on the core structure of the native ligand. We now report several groups of new inhibitors, one of which, fluoro-substituted ITC-12, displayed complete covalent modification of LasR, as well as effective QS inhibition in vitro and promising in vivo results. In addition to their potential clinical relevance, this series of synthetic QS modulators can be used as a tool to further unravel the complicated QS regulation in P. aeruginosa.<br /> (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- 4-Butyrolactone analogs & derivatives
4-Butyrolactone chemistry
4-Butyrolactone metabolism
Anti-Bacterial Agents chemistry
Bacterial Proteins agonists
Bacterial Proteins antagonists & inhibitors
Bacterial Proteins metabolism
Binding Sites
Biofilms drug effects
Catalytic Domain
Circular Dichroism
Isothiocyanates chemistry
Isothiocyanates metabolism
Kinetics
Molecular Docking Simulation
Oxidative Stress drug effects
Trans-Activators agonists
Trans-Activators antagonists & inhibitors
Trans-Activators metabolism
Virulence Factors metabolism
Anti-Bacterial Agents pharmacology
Pseudomonas aeruginosa physiology
Quorum Sensing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1439-7633
- Volume :
- 17
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Chembiochem : a European journal of chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 26840534
- Full Text :
- https://doi.org/10.1002/cbic.201500676