Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters

<i>Leishmania</i> is an intracellular parasite with different species pathogenic to humans and causing the disease leishmaniasis. <i>Leishmania donovani</i> causes visceral leishmaniasis (VL) that manifests as hepatosplenomegaly, fever, pancytopenia and hypergammaglobulinemia...

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Main Authors: Mahbobeh Lesani, Camil Gosmanov, Andrea Paun, Michael D. Lewis, Laura-Isobel McCall
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/12/9/802
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author Mahbobeh Lesani
Camil Gosmanov
Andrea Paun
Michael D. Lewis
Laura-Isobel McCall
author_facet Mahbobeh Lesani
Camil Gosmanov
Andrea Paun
Michael D. Lewis
Laura-Isobel McCall
author_sort Mahbobeh Lesani
collection DOAJ
description <i>Leishmania</i> is an intracellular parasite with different species pathogenic to humans and causing the disease leishmaniasis. <i>Leishmania donovani</i> causes visceral leishmaniasis (VL) that manifests as hepatosplenomegaly, fever, pancytopenia and hypergammaglobulinemia. If left without treatment, VL can cause death, especially in immunocompromised people. Current treatments have often significant adverse effects, and resistance has been reported in some countries. Determining the metabolites perturbed during VL can lead us to find new treatments targeting disease pathogenesis. We therefore compared metabolic perturbation between <i>L. donovani</i>-infected and uninfected hamsters across organs (spleen, liver, and gut). Metabolites were extracted, analyzed by liquid chromatography-mass spectrometry, and processed with MZmine and molecular networking to annotate metabolites. We found few metabolites commonly impacted by infection across all three sites, including glycerophospholipids, ceramides, acylcarnitines, peptides, purines and amino acids. In accordance with VL symptoms and parasite tropism, we found a greater overlap of perturbed metabolites between spleen and liver compared to spleen and gut, or liver and gut. Targeting pathways related to these metabolite families would be the next focus that can lead us to find more effective treatments for VL.
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spelling doaj.art-dd428336682a4fcaa36ce9bd4eb94fca2023-11-23T17:43:52ZengMDPI AGMetabolites2218-19892022-08-0112980210.3390/metabo12090802Impact of Visceral Leishmaniasis on Local Organ Metabolism in HamstersMahbobeh Lesani0Camil Gosmanov1Andrea Paun2Michael D. Lewis3Laura-Isobel McCall4Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK 73019, USADepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USALaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USADepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKDepartment of Microbiology and Plant Biology, University of Oklahoma, Norman, OK 73019, USA<i>Leishmania</i> is an intracellular parasite with different species pathogenic to humans and causing the disease leishmaniasis. <i>Leishmania donovani</i> causes visceral leishmaniasis (VL) that manifests as hepatosplenomegaly, fever, pancytopenia and hypergammaglobulinemia. If left without treatment, VL can cause death, especially in immunocompromised people. Current treatments have often significant adverse effects, and resistance has been reported in some countries. Determining the metabolites perturbed during VL can lead us to find new treatments targeting disease pathogenesis. We therefore compared metabolic perturbation between <i>L. donovani</i>-infected and uninfected hamsters across organs (spleen, liver, and gut). Metabolites were extracted, analyzed by liquid chromatography-mass spectrometry, and processed with MZmine and molecular networking to annotate metabolites. We found few metabolites commonly impacted by infection across all three sites, including glycerophospholipids, ceramides, acylcarnitines, peptides, purines and amino acids. In accordance with VL symptoms and parasite tropism, we found a greater overlap of perturbed metabolites between spleen and liver compared to spleen and gut, or liver and gut. Targeting pathways related to these metabolite families would be the next focus that can lead us to find more effective treatments for VL.https://www.mdpi.com/2218-1989/12/9/802visceral leishmaniasis<i>Leishmania donovani</i>metabolitesliverspleengut
spellingShingle Mahbobeh Lesani
Camil Gosmanov
Andrea Paun
Michael D. Lewis
Laura-Isobel McCall
Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
Metabolites
visceral leishmaniasis
<i>Leishmania donovani</i>
metabolites
liver
spleen
gut
title Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
title_full Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
title_fullStr Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
title_full_unstemmed Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
title_short Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
title_sort impact of visceral leishmaniasis on local organ metabolism in hamsters
topic visceral leishmaniasis
<i>Leishmania donovani</i>
metabolites
liver
spleen
gut
url https://www.mdpi.com/2218-1989/12/9/802
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