Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring
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Date
2011-07-19
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PLoS Neglected Tropical Diseases
Abstract
Background: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its
capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target
for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples
and is modulated by antibiotic therapy remained to be established.
Methodology/Principal Finding: Peripheral blood and ulcer exudates were sampled from patients at various stages of
antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates
with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, fieldfriendly
method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect
mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously
established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we
could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic
treatment on the concentration of mycolactone.
Conclusions/Significance: Our study provides the proof of concept that assays based on mycolactone detection in serum
and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a
technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be
worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that
the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may
reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal
studies.
Description
An article published by PLoS Neglected Tropical Diseases and is available at doi:10.1371/journal.pntd.0001237
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Citation
PLoS Negl Trop Dis (7): e1237. doi:10.1371/journal.pntd.0001237