Dataset Information

Comparative Analysis of Host Metabolic Alterations in Murine Malaria Models with Uncomplicated or Severe Malaria

ABSTRACT:

Malaria varies in severity, with complications ranging from uncomplicated to severe malaria. Severe malaria could be attributed to peripheral hyperparasitemia or cerebral malaria. The metabolic interactions between the host and Plasmodium species are yet to be understood during these infections of varied pathology and severity. An untargeted metabolomics approach utilizing the liquid chromatography-mass spectrometry platform has been used to identify the affected host metabolic pathways and associated metabolites in the serum of murine malaria models with uncomplicated malaria, hyperparasitemia and experimental cerebral malaria. We report that mice with malaria share similar metabolic attributes like higher levels of bile acids, bile pigments, and steroid hormones that have been reported for human malaria infections. Moreover, in severe malaria, upregulated levels of metabolites like phenylalanine, histidine, valine, pipecolate, ornithine and pantothenate, with decreased levels of arginine and hippurate, were observed. Metabolites of sphingolipid metabolism were upregulated in experimental cerebral malaria. Higher levels of 20-hydroxy-leukotriene B4 and epoxyoctadecamonoenoic acids were found in uncomplicated malaria, with lower levels observed for experimental cerebral malaria. Our study provides insights into host biology during different pathological stages of malaria disease and would be useful for the selection of animal models for evaluating diagnostic and therapeutic interventions against malaria.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - positive - reverse phase, Liquid Chromatography MS - negative - hilic

SUBMITTER: ALEENA DAS

PROVIDER: MTBLS4387 | MetaboLights | 2022-09-14

REPOSITORIES: MetaboLights

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Dataset's files

Source:

			Action	DRS
	MTBLS4387	Other
	FILES	Other
	a_MTBLS4387_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS4387_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS4387_LC-MS_positive_hilic_metabolite_profiling.txt	Txt

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Publications

Comparative Analysis of Host Metabolic Alterations in Murine Malaria Models with Uncomplicated or Severe Malaria.

Das Aleena A Sahu Welka W Ojha Deepak Kumar DK Reddy K Sony KS Suar Mrutyunjay M

Journal of proteome research 20220928 10

PMID: 36169658

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Project description:We aimed at finding differently expressed genes in whole blood cells of African children with asymptomatic Plasmodium falciparum infection (A), uncomplicated malaria (U), severe malarial anemia (A) and cerebral malaria (Ce) compared one to another and to healthy children (Co). Understanding malarial immunopathology in the human host represents and enormous challenge for transcriptomic research. In this work, we used microarray and real-time RT-PCR technology to pursue deeper knowledge about the mechanisms underlying this disease in African children. To this end, we investigated the genomic transcriptional profiles in whole blood of healthy children and children with asymptomatic infection, uncomplicated malaria, malaria associated with severe anemia and cerebral malaria and compared them with previously published microarray results. We were able to discriminate between the different presentations of P. falciparum infection using supervised and unsupervised clustering of microarray data and unsupervised double-hierarchical clustering of real-time RT-PCR results of a set of 22 genes known to be expressed in at least one of the principal blood cell lineages. We further found considerable overlap between genes regulated in Kenyan and Gabonese children with symptomatic malaria, in contrast to adults with acute malaria from Cameroon. Different signatures for transcription factor binding sites in promoters of genes either up-regulated in symptomatic disease, specifically up-regulated in uncomplicated malaria or specifically down-regulated in cerebral malaria point out that similar gene expression in each of these clinical presentations is probably a result of common regulation at the transcriptional level. Immunoglobulin production, complement regulation and IFN beta signalling emerged as most discrepant features between uncomplicated malaria and all other investigated presentations, correlating with IRF7 and ISRE binding signatures in the corresponding genes. Down-regulation of several genes in cerebral malaria seems instead to be a response to hypoxia orchestrated by AhRF, GABP and HIF1 transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia and inversely with hemoglobin concentration and should be evaluated as prognostic markers to direct early therapeutic measures and prevent malarial disease evolution and death.