Abstract
Introduction
Despite the advances in diagnosis and treatment, malaria has still not been eradicated. Metabolic interactions between the host and Plasmodium may present novel targets for malaria control, but such interactions are yet to be deciphered. An exploration of metabolic interactions between humans and two Plasmodium species by high-resolution metabolomics may provide fundamental insights that can aid the development of a new strategy for the control of malaria.
Objectives
This study aimed at exploring the metabolic changes in the sera of patients infected with Plasmodium falciparum and Plasmodium vivax.
Methods
Uni- and multivariate metabolomic analyses were performed on the sera of four groups of patients, namely normal control (N, n = 100), P. falciparum-infected patients (PF, n = 21), P. vivax-infected patients (PV, n = 74), and non-malarial pyretic patients (Pyr, n = 25).
Results
Univariate and multivariate analyses of N, PF, and PV groups showed differential metabolic phenotypes and subsequent comparisons in pairs revealed significant features. Pathway enrichment test with significant features showed the affected pathways, namely glycolysis/gluconeogenesis for PF and retinol metabolism for PV. The metabolites belonging to the affected pathways included significantly low 2,3-diphosphoglycerate and glyceraldehyde-3-phosphate in the sera of PF. The sera of PV had significantly low levels of retinol but high levels of retinoic acid.
Conclusion
Our study reveals metabolic alterations induced by Plasmodium spp. in human serum and would serve as a milestone in the development of novel anti-malarial strategies.
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Abbreviations
- ANOVA:
-
Analysis of variance
- HCA:
-
Hierarchical cluster analysis
- HRM:
-
High resolution metabolomics
- HRP:
-
Histidine-rich protein
- IQR:
-
Interquartile range
- LC–MS:
-
Liquid chromatography–mass spectrometry
- N:
-
Normal control
- PCA:
-
Principal component analysis
- PF:
-
Plasmodium falciparum-Infected patients
- PLS-DA:
-
Partial least square-discriminant analysis
- PV:
-
Plasmodium vivax-Infected patients
- RDT:
-
Rapid diagnostic test
- WHO:
-
World Health Organization
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Acknowledgements
The authors would like to thank Dr. Karan Uppal and Dr. Shuzhao Li from the Emory University School of Medicine (Atlanta, GA, USA) for providing the R-package used to run the MWAS.
Funding
This work was supported by the National Research Foundation of Korea (Grant Numbers NRF-2017M3A9F1031229 and NRF-2017R1A2B4003890); Rural Development Administration (Grant Number PJ01345402); a Grant of the Establish R&D Platform Project through the Korea University Medical Center and Korea University Guro Hospital, funded by the Korea University Guro Hospital (Grant Number O1903851).
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YHP and CSL designed the study. YHP, NJH, AK, and JKK carried out the metabolomics experiments and comprehensive data analysis. CSL and YLC collected the human samples. DPJ and DIW provided their interpretations on the results. YHP, NJH, AW, and AK prepared the manuscript. All the authors read and approved the final manuscript.
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This study was reviewed and approved by the Korea University Guro Hospital (Approval Number 2016GR0793) and was performed in accordance with the guidelines of the Ethical Committee of the Korea University Guro Hospital.
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All the patients included in this study provided informed consent.
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Na, J., Khan, A., Kim, J.K. et al. Discovery of metabolic alterations in the serum of patients infected with Plasmodium spp. by high-resolution metabolomics. Metabolomics 16, 9 (2020). https://doi.org/10.1007/s11306-019-1630-2
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DOI: https://doi.org/10.1007/s11306-019-1630-2