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Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

Warryn, Louisa and Dangy, Jean-Pierre and Gersbach, Philipp and Gehringer, Matthias and Schäfer, Anja and Ruf, Marie-Thérèse and Ruggli, Nicolas and Altmann, Karl-Heinz and Pluschke, Gerd. (2020) Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans. PLoS Neglected Tropical Diseases, 14 (6). e0008357.

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Official URL: https://edoc.unibas.ch/77661/

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Abstract

Mycolactones, macrolide cytotoxins, are key virulence factors of Mycobacterium ulcerans, the etiological agent of the chronic necrotizing skin disease Buruli ulcer. There is urgent need for a simple point-of-care laboratory test for Buruli ulcer and mycolactone represents a promising target for the development of an immunological assay. However, for a long time, all efforts to generate mycolactone-specific antibodies have failed. By using a protein conjugate of a truncated non-toxic synthetic mycolactone derivative, we recently described generation of a set of mycolactone-specific monoclonal antibodies. Using the first mycolactone-specific monoclonal antibodies that we have described before, we were able to develop an antigen competition assay that detects mycolactones. By the systematic selection of a capturing antibody and a reporter molecule, and the optimization of assay conditions, we developed an ELISA that detects common natural variants of mycolactone with a limit of detection in the low nanomolar range. The mycolactone-specific ELISA described here will be a very useful tool for research on the biology of this macrolide toxin. After conversion into a simple point-of-care test format, the competition assay may have great potential as laboratory assay for both the diagnosis of Buruli ulcer and for the monitoring of treatment efficacy.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Molecular Immunology (Pluschke)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medicine (MED) > Diagnostic (Poppert)
UniBasel Contributors:Pluschke, Gerd and Warryn, Louisa and Dangy, Jean-Pierre and Ruf, Marie-Therese and Schäfer, Anja
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1935-2727
e-ISSN:1935-2735
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:10 Jul 2020 08:14
Deposited On:10 Jul 2020 08:14

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