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Metabolic profiling framework for discovery of candidate diagnostic markers of malaria

Tritten, Lucienne and Keiser, Jennifer and Godejohann, Markus and Utzinger, Jürg and Vargas, Mireille and Beckonert, Olaf and Holmes, Elaine and Saric, Jasmina. (2013) Metabolic profiling framework for discovery of candidate diagnostic markers of malaria. Scientific Reports, 3. p. 2769.

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Official URL: http://edoc.unibas.ch/dok/A6183883

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Abstract

Despite immense efforts to combat malaria in tropical and sub-tropical regions, the potency of this vector-borne disease and its status as a major driver of morbidity and mortality remain undisputed. We develop an analytical pipeline for characterizing Plasmodium infection in a mouse model and identify candidate urinary biomarkers that may present alternatives to immune-based diagnostic tools. We employ (1)H nuclear magnetic resonance (NMR) profiling followed by multivariate modeling to discover diagnostic spectral regions. Identification of chemical structures is then made on the basis of statistical spectroscopy, multinuclear NMR, and entrapment of candidates by iterative liquid chromatography (LC) and mass spectrometry (MS). We identify two urinary metabolites (i) 4-amino-1-[3-hydroxy-5-(hydroxymethyl)-2,3-dihydrofuran-2-yl]pyrimidin-2(1H)-one, (ii) 2-amino-4-({[5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-hydroxy-4,5-dihydrofuran-2-yl]methyl}sulfanyl)butanoic acid that were detected only in Plasmodium berghei-infected mice. These metabolites have not been described in the mammalian or parasite metabolism to date. This analytical pipeline could be employed in prospecting for infection biomarkers in human populations.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Eco System Health Sciences > Health Impact Assessment (Utzinger)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Keiser, Jennifer and Utzinger, Jürg and Vargas, Mireille
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
e-ISSN:2045-2322
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:12 Oct 2017 09:56
Deposited On:27 Mar 2014 13:13

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