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Quorum Sensing pp 299-311 | Cite as

Generation of Quorum Quenching Antibodies

  • Gunnar F. KaufmannEmail author
  • Junguk Park
  • Alexander V. Mayorov
  • Diane M. Kubitz
  • Kim D. Janda
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 692)

Abstract

The exchange of information within and among bacterial populations using small diffusible molecules has been termed “quorum sensing” (QS). Due to the extracellular distribution of the QS autoinducer molecules and the evolutionary highly conserved nature of signaling components, microbial QS systems represent an excellent target for anti-infective immunotherapy. Recently, we have described the generation of quorum quenching monoclonal antibodies (mAbs) against acyl homoserine lactones (AHL) used by Pseudomonas aeruginosa as well as Staphylococcal autoinducing peptides (AIP). These mAbs suppressed QS signaling in bacteria and neutralized AHL-mediated cytotoxic effects in vitro, as well as protected animals in Staphylococcus aureus infection models.

Key words

Quorum sensing Monoclonal antibodies Autoinducers Hybridoma Quorum quenching Pseudomonas aeruginosa Staphylococcus aureus 

Notes

Acknowledgments

This work was supported by the National Institutes of Health (AI080715 to G.F.K). This is manuscript number 20549 from The Scripps Research Institute.

References

  1. 1.
    Hjelmgaard, T., Persson, T., Rasmussen, T. B., Givskov, M., and Nielsen, J. (2003) Synthesis of furanone-based natural product analogues with quorum sensing antagonist activity, Bioorganic & Medicinal Chemistry 11, 3261–3271.CrossRefGoogle Scholar
  2. 2.
    Hentzer, M., Riedel, K., Rasmussen, T. B., Heydorn, A., Andersen, J. B., Parsek, M. R., Rice, S. A., Eberl, L., Molin, S., Hoiby, N., Kjelleberg, S., and Givskov, M. (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound, Microbiology 148, 87–102.PubMedGoogle Scholar
  3. 3.
    Smith, K. M., Bu, Y. G., and Suga, H. (2003) Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs, Chemistry & Biology 10, 81–89.CrossRefGoogle Scholar
  4. 4.
    Geske, G. D., O’Neill, J. C., Miller, D. M., Mattmann, M. E., and Blackwell, H. E. (2007) Modulation of bacterial quorum sensing with synthetic ligands: Systematic evaluation of N-acylated homoserine lactones in multiple species and new insights into their mechanisms of action, Journal of the American Chemical Society 129, 13613–13625.PubMedCrossRefGoogle Scholar
  5. 5.
    Muh, U., Schuster, M., Heim, R., Singh, A., Olson, E. R., and Greenberg, E. P. (2006) Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen, Antimicrobial agents and chemotherapy 50, 3674–3679.PubMedCrossRefGoogle Scholar
  6. 6.
    George, E. A., Novick, R. P., and Muir, T. W. (2008) Cyclic peptide inhibitors of staphylococcal virulence prepared by Fmoc-based thiolactone peptide synthesis, Journal of the American Chemical Society 130, 4914–4924.PubMedCrossRefGoogle Scholar
  7. 7.
    Lyon, G. J., Mayville, P., Muir, T. W., and Novick, R. P. (2000) Rational design of a global inhibitor of the virulence response in Staphylococcus aureus, based in part on localization of the site of inhibition to the receptor-histidine kinase, AgrC, Proceedings of the National Academy of Sciences of the United States of America 97, 13330–13335.PubMedCrossRefGoogle Scholar
  8. 8.
    Kravchenko, V. V., Kaufmann, G. F., Mathison, J. C., Scott, D. A., Katz, A. Z., Wood, M. R., Brogan, A. P., Lehmann, M., Mee, J. M., Iwata, K., Pan, Q., Fearns, C., Knaus, U. G., Meijler, M. M., Janda, K. D., and Ulevitch, R. J. (2006) N-(3-oxo-acyl)homoserine lactones signal cell activation through a mechanism distinct from the canonical pathogen-associated molecular pattern recognition receptor pathways, The Journal of biological chemistry 281, 28822–28830.PubMedCrossRefGoogle Scholar
  9. 9.
    Tateda, K., Ishii, Y., Horikawa, M., Matsumoto, T., Miyairi, S., Pechere, J. C., Standiford, T. J., Ishiguro, M., and Yamaguchi, K. (2003) The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils, Infection and immunity 71, 5785–5793.PubMedCrossRefGoogle Scholar
  10. 10.
    Shiner, E. K., Terentyev, D., Bryan, A., Sennoune, S., Martinez-Zaguilan, R., Li, G., Gyorke, S., Williams, S. C., and Rumbaugh, K. P. (2006) Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling, Cellular microbiology 8, 1601–1610.PubMedCrossRefGoogle Scholar
  11. 11.
    Kravchenko, V. V., Kaufmann, G. F., Mathison, J. C., Scott, D. A., Katz, A. Z., Grauer, D. C., Lehmann, M., Meijler, M. M., Janda, K. D., and Ulevitch, R. J. (2008) Modulation of gene expression via disruption of NF-kappaB signaling by a bacterial small molecule, Science (New York, N.Y.) 321, 259–263.CrossRefGoogle Scholar
  12. 12.
    Kaufmann, G. F., Sartorio, R., Lee, S. H., Mee, J. M., Altobell, L. J., 3rd, Kujawa, D. P., Jeffries, E., Clapham, B., Meijler, M. M., and Janda, K. D. (2006) Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing, Journal of the American Chemical Society 128, 2802–2803.PubMedCrossRefGoogle Scholar
  13. 13.
    Kaufmann, G. F., Sartorio, R., Lee, S. H., Rogers, C. J., Meijler, M. M., Moss, J. A., Clapham, B., Brogan, A. P., Dickerson, T. J., and Janda, K. D. (2005) Revisiting quorum sensing: Discovery of additional chemical and biological functions for 3-oxo-N-acylhomoserine lactones, Proceedings of the National Academy of Sciences of the United States of America 102, 309–314.PubMedCrossRefGoogle Scholar
  14. 14.
    Kaufmann, G. F., Park, J., Mee, J. M., Ulevitch, R. J., and Janda, K. D. (2008) 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, Molecular immunology 45, 2710–2714.PubMedCrossRefGoogle Scholar
  15. 15.
    Debler, E. W., Kaufmann, G. F., Kirchdoerfer, R. N., Mee, J. M., Janda, K. D., and Wilson, I. A. (2007) Crystal structures of a quorum-quenching antibody, Journal of molecular biology 368, 1392–1402.PubMedCrossRefGoogle Scholar
  16. 16.
    Park, J., Jagasia, R., Kaufmann, G. F., Mathison, J. C., Ruiz, D. I., Moss, J. A., Meijler, M. M., Ulevitch, R. J., and Janda, K. D. (2007) Infection control by antibody disruption of bacterial quorum sensing signaling, Chemistry & biology 14, 1119–1127.CrossRefGoogle Scholar
  17. 17.
    Novick, R. P. (1991) Genetic systems in staphylococci, Methods in enzymology 204, 587–636.PubMedCrossRefGoogle Scholar
  18. 18.
    Smith, K. M., Bu, Y., and Suga, H. (2003) Library screening for synthetic agonists and antagonists of a Pseudomonas aeruginosa autoinducer, Chemistry & biology 10, 563–571.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gunnar F. Kaufmann
    • 1
    Email author
  • Junguk Park
    • 1
  • Alexander V. Mayorov
    • 2
  • Diane M. Kubitz
    • 3
  • Kim D. Janda
    • 4
    • 1
  1. 1.Departments of Chemistry and Immunology & Microbial ScienceThe Scripps Research InstituteLa JollaUSA
  2. 2.The Skaggs Institute for Chemical Biology and Departments of Chemistry and Immunology & Microbial ScienceThe Scripps Research InstituteLa JollaUSA
  3. 3.Antibody Production Core FacilityThe Scripps Research InstituteLa JollaUSA
  4. 4.Worm Institute for Research and Medicine (WIRM)The Skaggs Institute for Chemical BiologyLa JollaUSA

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