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Author Notes:

Correspondence: Youngja H Park yjhwang@korea.ac.kr, Dean Jones dpjones@emory.edu 1

The authors acknowledged Jae Ho Cho, Korea University in making figures.

We also thank Dr. S. Patrick Kachur, Malaria Branch, DPDM, CGH, CDC for his critical review of this manuscript and valuable suggestions.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Subjects:

Research Funding:

This research was supported in part by the Center for Health Discovery and Well-being of Emory University, grant # NRF-2014R1A4A1007304 (Y.H.J) and grant# NRF-2014R1A1A2053787 of Korea University, and by Malaria Branch, Division of Parasitic Diseases and Malaria (DPDM), Center for Global Health, Centers for Disease Control and Prevention (CDC).

DPJ is supported in part by NIH grants HL113451, ES009047, ES019776 and AG038746 and NIAID Contract HHSN272201200031C.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Infectious Diseases
  • Parasitology
  • Tropical Medicine
  • Malaria
  • Plasmodium falciparum
  • Mass spectrometry
  • High-resolution metabolomics (HRM)
  • Biomarkers
  • Diagnostic tool
  • N-ARACHIDONOYL GLYCINE
  • ACID
  • MALARIA
  • DIAGNOSTICS
  • INHIBITION
  • INFECTION
  • PATHWAYS
  • DATABASE
  • KEGG

High-resolution metabolomics to discover potential parasite-specific biomarkers in a Plasmodium falciparum erythrocytic stage culture system

Journal Title:

Malaria Journal

Volume:

Volume 14, Number 1

Publisher:

, Pages 122-122

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Current available malaria diagnostic methods each have some limitations to meet the need for real-time and large-scale screening of asymptomatic and low density malaria infection at community level. It was proposed that malaria parasite-specific low molecular-weight metabolites could be used as biomarkers for the development of a malaria diagnostic tool aimed to address this diagnostic challenge. In this study, high resolution metabolomics (HRM) was employed to identify malaria parasite-specific metabolites in Plasmodium falciparum in vitro culture samples. Methods: Supernatants were collected at 12 hours interval from 3% haematocrit in vitro 48-hour time-course asynchronized culture system of P. falciparum. Liquid chromatography coupled with high resolution mass spectrometry was applied to discover potential parasite-specific metabolites in the cell culture supernatant. A metabolome-wide association study was performed to extract metabolites using Manhattan plot with false discovery rate (FDR) and hierarchical cluster analysis. The significant metabolites based on FDR cutoff were annotated using Metlin database. Standard curves were created using corresponding chemical compounds to accurately quantify potential Plasmodium-specific metabolites in culture supernatants. Results: The number of significant metabolite features was 1025 in the supernatant of the Plasmodium infected culture based on Manhattan plot with FDR q=0.05. A two way hierarchical cluster analysis showed a clear segregation of the metabolic profile of parasite infected supernatant from non-infected supernatant at four time points during the 48 hour culture. Among the 1025 annotated metabolites, the intensities of four molecules were significantly increased with culture time suggesting a positive association between the quantity of these molecules and level of parasitaemia: i) 3-methylindole, a mosquito attractant, ii) succinylacetone, a haem biosynthesis inhibitor, iii) S-methyl-L-thiocitrulline, a nitric oxide synthase inhibitor, and iv) O-arachidonoyl glycidol, a fatty acid amide hydrolase inhibitor, The highest concentrations of 3-methylindole and succinylacetone were 178 ± 18.7 pmoles at 36 hours and 157±30.5 pmoles at 48 hours respectively in parasite infected supernatant. Conclusion: HRM with bioinformatics identified four potential parasite-specific metabolite biomarkers using in vitro culture supernatants. Further study in malaria infected human is needed to determine presence of the molecules and its relationship with parasite densities.

Copyright information:

© 2015 Park et al.; licensee BioMed Central.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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