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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/11976

Title: Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG)
Authors: Globisch, Daniel
Eubanks, Lisa M.
Shirey, Ryan J.
Pfarr, Kenneth M.
Wanji, Samuel
Debrah, Alexander Y.
Hoerauf, Achim
Janda, Kim D.
Keywords: Onchocerciasis
Mass spectrometry
Issue Date: May-2017
Publisher: Bioorganic & Medicinal Chemistry Letters
Citation: Bioorganic & Medicinal Chemistry Letters 27(15)
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 noninvasive 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.
Description: This article was published in Bioorganic & Medicinal Chemistry Letters and also available at DOI: 10.1016/j.bmcl.2017.05.082
URI: 10.1016/j.bmcl.2017.05.082
Appears in Collections:College of Health Sciences

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