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|Title: ||Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG)|
|Authors: ||Globisch, Daniel|
Eubanks, Lisa M.
Shirey, Ryan J.
Pfarr, Kenneth M.
Debrah, Alexander Y.
Janda, Kim D.
|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|
|Appears in Collections:||College of Health Sciences|
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