Antibody-Mediated Neutralization of the Exotoxin Mycolactone, the Main Virulence Factor Produced by Mycobacterium ulcerans

PLoS Negl Trop Dis. 2016 Jun 28;10(6):e0004808. doi: 10.1371/journal.pntd.0004808. eCollection 2016 Jun.

Abstract

Background: Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, causes extensive tissue destruction by inducing apoptosis of host cells. In this study, we aimed at the production of antibodies that could neutralize the cytotoxic activities of mycolactone.

Methodology/principal findings: Using the B cell hybridoma technology, we generated a series of monoclonal antibodies with specificity for mycolactone from spleen cells of mice immunized with the protein conjugate of a truncated synthetic mycolactone derivative. L929 fibroblasts were used as a model system to investigate whether these antibodies can inhibit the biological effects of mycolactone. By measuring the metabolic activity of the fibroblasts, we found that anti-mycolactone mAbs can completely neutralize the cytotoxic activity of mycolactone.

Conclusions/significance: The toxin neutralizing capacity of anti-mycolactone mAbs supports the concept of evaluating the macrolide toxin as vaccine target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Exotoxins / immunology*
  • Exotoxins / metabolism
  • Macrolides / chemistry
  • Macrolides / immunology*
  • Macrolides / metabolism
  • Mice
  • Molecular Structure
  • Mycobacterium ulcerans / metabolism*
  • Virulence Factors / immunology*
  • Virulence Factors / metabolism

Substances

  • Antibodies, Monoclonal
  • Exotoxins
  • Macrolides
  • Virulence Factors
  • mycolactone

Grants and funding

This work was supported by the Stop Buruli consortium funded by the UBS Optimus Foundation and the Medicor Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.