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Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG)
Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.;Scripps Res Inst, Skaggs Inst Chem Biol, Dept Immunol, WIRM, 10550 North Torrey, La Jolla, CA 92037 USA..
Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.;Scripps Res Inst, Skaggs Inst Chem Biol, Dept Immunol, WIRM, 10550 North Torrey, La Jolla, CA 92037 USA..
Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.;Scripps Res Inst, Skaggs Inst Chem Biol, Dept Immunol, WIRM, 10550 North Torrey, La Jolla, CA 92037 USA..
Univ Hosp Bonn, IMMIP, Sigmund Freud Str 25, D-53105 Bonn, Germany..
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2017 (English)In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 27, no 15, 3436-3440 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD , 2017. Vol. 27, no 15, 3436-3440 p.
Keyword [en]
Onchocerciasis, Biomarker, Mass spectrometry, Metabolomics, Nematode
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-331210DOI: 10.1016/j.bmcl.2017.05.082ISI: 000405106500043PubMedID: 28600214OAI: oai:DiVA.org:uu-331210DiVA: diva2:1152254
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2017-10-24Bibliographically approved

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