An Antigen Capture Assay for the Detection of Mycolactone, the Polyketide Toxin of .

Mycolactone is a cytotoxin responsible for most of the chronic necrotizing pathology of disease (Buruli ulcer). The polyketide toxin consists of a 12-membered lactone ring with a lower -linked polyunsaturated acyl side chain and an upper C-linked side chain. Mycolactone is unique to and an immunological Ag capture assay would represent an important tool for the study of Buruli ulcer pathogenesis and for laboratory diagnosis.

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

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.

Configurationally Stabilized Analogs of Exotoxins Mycolactones A and B Reveal the Importance of Side Chain Geometry for Mycolactone Virulence.

Mycolactones A/B () are exotoxins of that are the molecular cause of Buruli ulcer. represent a rapidly equilibrating mixture of isomers about the C4'═C5' double bond of the C5-side chain. Here, we describe the syntheses of mycolactone analogs with configurationally stable C5-side chains (, mimetic; , mimetics).

The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.

Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, is central to the pathogenesis of the chronic necrotizing skin disease Buruli ulcer (BU). Here we show that mycolactone acts as an inhibitor of the mechanistic Target of Rapamycin (mTOR) signaling pathway by interfering with the assembly of the two distinct mTOR protein complexes mTORC1 and mTORC2, which regulate different cellular processes. Inhibition of the assembly of the rictor containing mTORC2 complex by mycolactone prevents phosphorylation of the serine/threonine protein kinase Akt.

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

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.