Abstract
Quorum sensing (QS) systems are bacterial cell-to-cell communication systems that use small molecules as signals. Since QS is involved in the regulation of virulence and biofilm formation in several pathogenic bacteria, it has been suggested as a new target for the development of novel antibacterial therapies. As such, interference with the signal receptors by using chemical compounds has been proposed as an alternative strategy for treatment of bacterial infections and has already shown promising results in combination with traditional antibiotic treatments. In Gram-negative bacteria, the best studied QS systems use N-acyl homoserine lactones (AHLs) as signal molecules. This review provides an overview of all new chemical structure types that inhibit AHL-mediated QS systems as reported during the last three years in scientific journals and in the patent literature. The compounds were classified into three main groups depending on their structure: AHL analogues, 2(5H)-furanones, and compounds that are not structurally related to AHLs. We discuss the biological assays used and the different strategies applied to discover these molecules, including new approaches such as molecular docking for in silico identification of lead structures and random high-throughput screening of large libraries of chemicals. Finally, we elaborate on structure-activity relationships and on the new insights in the mechanisms of action of the identified inhibitors, highlighting the potential of these small molecules in medicine.
Keywords: Quorum sensing, N-acyl homoserine lactone, inhibitor, furanone, mode of action, antagonist, superagonist, Pseudomonas aeruginosa
Current Medicinal Chemistry
Title: Small Molecules for Interference with Cell-Cell-Communication Systems in Gram-Negative Bacteria
Volume: 15 Issue: 21
Author(s): Joost C.A. Janssens, Sigrid C.J. De Keersmaecker, Dirk E. De Vos and Jos Vanderleyden
Affiliation:
Keywords: Quorum sensing, N-acyl homoserine lactone, inhibitor, furanone, mode of action, antagonist, superagonist, Pseudomonas aeruginosa
Abstract: Quorum sensing (QS) systems are bacterial cell-to-cell communication systems that use small molecules as signals. Since QS is involved in the regulation of virulence and biofilm formation in several pathogenic bacteria, it has been suggested as a new target for the development of novel antibacterial therapies. As such, interference with the signal receptors by using chemical compounds has been proposed as an alternative strategy for treatment of bacterial infections and has already shown promising results in combination with traditional antibiotic treatments. In Gram-negative bacteria, the best studied QS systems use N-acyl homoserine lactones (AHLs) as signal molecules. This review provides an overview of all new chemical structure types that inhibit AHL-mediated QS systems as reported during the last three years in scientific journals and in the patent literature. The compounds were classified into three main groups depending on their structure: AHL analogues, 2(5H)-furanones, and compounds that are not structurally related to AHLs. We discuss the biological assays used and the different strategies applied to discover these molecules, including new approaches such as molecular docking for in silico identification of lead structures and random high-throughput screening of large libraries of chemicals. Finally, we elaborate on structure-activity relationships and on the new insights in the mechanisms of action of the identified inhibitors, highlighting the potential of these small molecules in medicine.
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Cite this article as:
Janssens C.A. Joost, De Keersmaecker C.J. Sigrid, De Vos E. Dirk and Vanderleyden Jos, Small Molecules for Interference with Cell-Cell-Communication Systems in Gram-Negative Bacteria, Current Medicinal Chemistry 2008; 15 (21) . https://dx.doi.org/10.2174/092986708785747580
DOI https://dx.doi.org/10.2174/092986708785747580 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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