title: Metabolite profiling of infection-associated metabolic markers of onchocerciasis.
abstract: The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20). We identified 286 known metabolites (167 in the cation mode and 119 in the anion mode). In addition, putative metabolites were identified based on KEGG (51), HMDB (37) and HMT (6) databases. One hundred ten of these putative metabolites were quantified based on peak areas of internal standards and their ability to be mapped to known pathways (primary-, carbon-, lipid-, amino acid-, nucleotide and coenzyme-metabolism). Multivariate analysis demonstrated clustering and segregation of some of these metabolites to either the infected or control groups. The levels of serotonin, hypoxanthine, pipecolic acid and inosine were significantly elevated in those with onchocerciasis, whereas the levels of glycerophosphocholine, choline and adenine were significantly lower. This non-targeted metabolomic approach provides a global view of the metabolic variations that occur during Ov infection and thus allow the discovery of key metabolites (and associated pathways) that may serve as useful biomarkers in human onchocerciasis.
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD, USA. Electronic address: bennurus@niaid.nih.gov.
authors.forename: Sasisekhar
authors.initials: S
authors.lastname: Bennuru
authors.affiliation: New York Blood Center, New York, NY, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Abraham
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D001685:Biological Factors / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis*; D019075:Electrophoresis, Capillary; D006801:Humans; D055442:Metabolome; D009855:Onchocerciasis / Q000175:diagnosis* / Q000473:pathology*; D044967:Serum / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001685:Biological Factors; D015415:Biomarkers
keywords: Biomarker; Metabolome; Onchocerca volvulus