Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG) |
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Authors: | Daniel Globisch Lisa M. Eubanks Ryan J. Shirey Kenneth M. Pfarr Samuel Wanji Alexander Y. Debrah Achim Hoerauf Kim D. Janda |
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Affiliation: | 1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States;2. Department of Immunology, The Skaggs Institute for Chemical Biology, The Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey, La Jolla, CA 92037, United States;3. Institute of Medical Microbiology, Immunology, and Parasitology (IMMIP), University Hospital Bonn, Sigmund Freud Straße 25, 53105 Bonn, Germany;4. Research Foundation in Tropical Diseases and Environment (REFOTDE), P.O Box 474, Buea, Cameroon;5. Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;6. Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana |
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Abstract: | 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. |
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Keywords: | Onchocerciasis Biomarker Mass spectrometry Metabolomics Nematode |
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