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Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG)
The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, p...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510726/ https://www.ncbi.nlm.nih.gov/pubmed/28600214 http://dx.doi.org/10.1016/j.bmcl.2017.05.082 |
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author | Globisch, Daniel Eubanks, Lisa M. Shirey, Ryan J. Pfarr, Kenneth M. Wanji, Samuel Debrah, Alexander Y. Hoerauf, Achim Janda, Kim D. |
author_facet | Globisch, Daniel Eubanks, Lisa M. Shirey, Ryan J. Pfarr, Kenneth M. Wanji, Samuel Debrah, Alexander Y. Hoerauf, Achim Janda, Kim D. |
author_sort | Globisch, Daniel |
collection | PubMed |
description | The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG’s biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development. |
format | Online Article Text |
id | pubmed-5510726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier Science Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55107262017-08-01 Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) Globisch, Daniel Eubanks, Lisa M. Shirey, Ryan J. Pfarr, Kenneth M. Wanji, Samuel Debrah, Alexander Y. Hoerauf, Achim Janda, Kim D. Bioorg Med Chem Lett Article The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG’s biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development. Elsevier Science Ltd 2017-08-01 /pmc/articles/PMC5510726/ /pubmed/28600214 http://dx.doi.org/10.1016/j.bmcl.2017.05.082 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Globisch, Daniel Eubanks, Lisa M. Shirey, Ryan J. Pfarr, Kenneth M. Wanji, Samuel Debrah, Alexander Y. Hoerauf, Achim Janda, Kim D. Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
title | Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
title_full | Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
title_fullStr | Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
title_full_unstemmed | Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
title_short | Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
title_sort | validation of onchocerciasis biomarker n-acetyltyramine-o-glucuronide (natog) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510726/ https://www.ncbi.nlm.nih.gov/pubmed/28600214 http://dx.doi.org/10.1016/j.bmcl.2017.05.082 |
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