Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring.
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...
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ftdoajarticles:oai:doaj.org/article:2d998ecef65346a7ae77ed2dd58d0674 2023-05-15T15:16:53+02:00 Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. Fred S Sarfo Fabien Le Chevalier N'Guetta Aka Richard O Phillips Yaw Amoako Ivo G Boneca Pascal Lenormand Mireille Dosso Mark Wansbrough-Jones Romain Veyron-Churlet Laure Guenin-Macé Caroline Demangel 2011-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001237 https://doaj.org/article/2d998ecef65346a7ae77ed2dd58d0674 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3139662?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001237 https://doaj.org/article/2d998ecef65346a7ae77ed2dd58d0674 PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1237 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001237 2022-12-31T14:03:43Z 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.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, field-friendly 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.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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 7 e1237 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Fred S Sarfo Fabien Le Chevalier N'Guetta Aka Richard O Phillips Yaw Amoako Ivo G Boneca Pascal Lenormand Mireille Dosso Mark Wansbrough-Jones Romain Veyron-Churlet Laure Guenin-Macé Caroline Demangel Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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.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, field-friendly 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.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. |
format |
Article in Journal/Newspaper |
author |
Fred S Sarfo Fabien Le Chevalier N'Guetta Aka Richard O Phillips Yaw Amoako Ivo G Boneca Pascal Lenormand Mireille Dosso Mark Wansbrough-Jones Romain Veyron-Churlet Laure Guenin-Macé Caroline Demangel |
author_facet |
Fred S Sarfo Fabien Le Chevalier N'Guetta Aka Richard O Phillips Yaw Amoako Ivo G Boneca Pascal Lenormand Mireille Dosso Mark Wansbrough-Jones Romain Veyron-Churlet Laure Guenin-Macé Caroline Demangel |
author_sort |
Fred S Sarfo |
title |
Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. |
title_short |
Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. |
title_full |
Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. |
title_fullStr |
Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. |
title_full_unstemmed |
Mycolactone diffuses into the peripheral blood of Buruli ulcer patients--implications for diagnosis and disease monitoring. |
title_sort |
mycolactone diffuses into the peripheral blood of buruli ulcer patients--implications for diagnosis and disease monitoring. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001237 https://doaj.org/article/2d998ecef65346a7ae77ed2dd58d0674 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1237 (2011) |
op_relation |
http://europepmc.org/articles/PMC3139662?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001237 https://doaj.org/article/2d998ecef65346a7ae77ed2dd58d0674 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001237 |
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PLoS Neglected Tropical Diseases |
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5 |
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7 |
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e1237 |
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