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, 128 (9), 2802-3

Antibody Interference With N-acyl Homoserine Lactone-Mediated Bacterial Quorum Sensing

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Antibody Interference With N-acyl Homoserine Lactone-Mediated Bacterial Quorum Sensing

Gunnar F Kaufmann et al. J Am Chem Soc.

Abstract

Many bacterial pathogens coordinate their virulence factor expression in a cell density-dependent manner. This population-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). N-Acyl homoserine lactones (AHLs) are used by over 70 Gram-negative bacterial species as autoinducers. Inhibition of QS signaling might represent a new target for antimicrobial therapy. Here we report the hapten design, synthesis, generation of monoclonal antibodies (mAbs) against AHLs, and the evaluation of these mAbs for their ability to blunt QS signaling and inhibit virulence factor expression in P. aeruginosa. The mAbs can be envisioned as a tool for future investigations into AHL-based QS, which may aid in gaining new insights into the pathogenesis of P. aeruginosa and may ultimately lead to the development of new strategies to combat bacterial diseases.

Figures

Figure 1
Figure 1
Examples of N-acyl homoserine lactones employed by bacteria as quorum sensing molecules.
Figure 2
Figure 2
4-methoxyphenyl amide AHL analogs.
Figure 3
Figure 3
Inhibition of 3-oxo-C12-AHL mediated QS signaling by RS2 mAbs and control mAb in P. aeruginosa PAO (wildtype, filled columns) and in PAO-JM2 (open columns) in a GFP reporter assay (A); Inhibition of pyocyanin production in P. aeruginosa PAO (wildtype, filled columns) and in PAO-JM2 (open columns) by mAb RS2-1G9 (B). Anti-nicotine and anti-stilbene mAbs (NIC9D9 and EP2-19G2) and BSA were used as additional controls.
Scheme 1
Scheme 1
Synthesis of lactam containing haptens.

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