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

作者：Dangy Jean Pierre; Scherr Nicole; Ger**ach Philipp; Hug Melanie N; Bieri Raphael; Bomio Claudio; Li Jun; Huber Sylwia; Altmann Karl Heinz; Pluschke Gerd^*

来源：PLoS Neglected Tropical Diseases, 2016, 10(6): e0004808.

DOI：10.1371/journal.pntd.0004808

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.

• 出版日期2016-6