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. 2008 May;45(9):2710-4.
doi: 10.1016/j.molimm.2008.01.010. Epub 2008 Mar 4.

The Quorum Quenching Antibody RS2-1G9 Protects Macrophages From the Cytotoxic Effects of the Pseudomonas Aeruginosa Quorum Sensing Signalling Molecule N-3-oxo-dodecanoyl-homoserine Lactone

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Free PMC article

The Quorum Quenching Antibody RS2-1G9 Protects Macrophages From the Cytotoxic Effects of the Pseudomonas Aeruginosa Quorum Sensing Signalling Molecule N-3-oxo-dodecanoyl-homoserine Lactone

Gunnar F Kaufmann et al. Mol Immunol. .
Free PMC article

Abstract

The Gram-negative bacterium Pseudomonas aeruginosa, an opportunistic human pathogen, uses acyl-homoserine lactone-based quorum sensing systems to control its pathogenicity. One of its quorum sensing factors, N-3-oxo-dodecanoyl-homoserine lactone, has been shown not only to mediate bacterial quorum sensing but also to exert cytotoxic effects on mammalian cells. The monoclonal antibody RS2-1G9 generated against a 3-oxo-dodecanoyl-homoserine lactone analogue hapten was able to protect murine bone marrow-derived macrophages from the cytotoxic effects and also prevented the activation of the mitogen-activated protein kinase p38. These data demonstrate that an immunopharmacotherapeutic approach to combat P. aeruginosa infections might be a viable therapeutic option as the monoclonal antibody RS2-1G9 can readily sequester bacterial N-3-oxo-dodecanoyl-homoserine lactone molecules, thus interfering with their biological effects in prokaryotic and eukaryotic systems.

Figures

Figure 1
Figure 1
Chemical structures of the AHLs used by Pseudomonas aeruginosa and the AHL analogue hapten used to generate the mAb RS2-1G9.
Figure 2
Figure 2
Protection of RAW cells (A) and BMDM (B) from the cytotoxic effects of 3-oxo-C12-HSL. Results are expressed as percentages of cells still viable relative to non-treated control cells.
Figure 3
Figure 3
Western blot analysis of BMDM protection from cytotoxic effects of 3-oxo-C12-HSL by mAb RS2-1G9

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