Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania

Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is defi...

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Main Authors: Akpunarlieva, Snezhana, Weidt, Stefan, Lamasudin, Dhilia Udie, Naula, Christina, Henderson, David, Barrett, Michael, Burgess, Karl, Burchmore, Richard
Format: Article
Language:English
Published: Elsevier 2017
Online Access:http://psasir.upm.edu.my/id/eprint/62193/
http://psasir.upm.edu.my/id/eprint/62193/1/Integration%20of%20proteomics%20and%20metabolomics%20to%20elucidate%20metabolic%20adaptation%20in%20Leishmania.pdf
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author Akpunarlieva, Snezhana
Weidt, Stefan
Lamasudin, Dhilia Udie
Naula, Christina
Henderson, David
Barrett, Michael
Burgess, Karl
Burchmore, Richard
author_facet Akpunarlieva, Snezhana
Weidt, Stefan
Lamasudin, Dhilia Udie
Naula, Christina
Henderson, David
Barrett, Michael
Burgess, Karl
Burchmore, Richard
author_sort Akpunarlieva, Snezhana
building UPM Institutional Repository
collection Online Access
description Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells.Here we report the generation and integration of proteomic and metabolomic approaches to identify molecular changes that may explain these phenotypes. Our data suggest changes in pathways of glycoconjugate production and redox homeostasis, which likely represent adaptations to the loss of sugar uptake capacity and explain the reduced virulence of this mutant in sand flies and mammals. Our data contribute to understanding the mechanisms of metabolic adaptation in Leishmania and illustrate the power of integrated proteomic and metabolomic approaches to relate biochemistry to phenotype. Biological significance: This paper reports the application of comparative proteomic and metabolomic approaches to reveal the molecular basis for important phenotypic changes Leishmania parasites that are deficient in glucose uptake. Leishmania cause a very significant disease burden across the world and there are few effective drugs available for control. This work shows that proteomics and metabolomics can produce complementary data that advance understanding of parasite metabolism and highlight potential new targets for chemotherapy.
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spelling upm-621932019-04-22T02:13:52Z http://psasir.upm.edu.my/id/eprint/62193/ Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania Akpunarlieva, Snezhana Weidt, Stefan Lamasudin, Dhilia Udie Naula, Christina Henderson, David Barrett, Michael Burgess, Karl Burchmore, Richard Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells.Here we report the generation and integration of proteomic and metabolomic approaches to identify molecular changes that may explain these phenotypes. Our data suggest changes in pathways of glycoconjugate production and redox homeostasis, which likely represent adaptations to the loss of sugar uptake capacity and explain the reduced virulence of this mutant in sand flies and mammals. Our data contribute to understanding the mechanisms of metabolic adaptation in Leishmania and illustrate the power of integrated proteomic and metabolomic approaches to relate biochemistry to phenotype. Biological significance: This paper reports the application of comparative proteomic and metabolomic approaches to reveal the molecular basis for important phenotypic changes Leishmania parasites that are deficient in glucose uptake. Leishmania cause a very significant disease burden across the world and there are few effective drugs available for control. This work shows that proteomics and metabolomics can produce complementary data that advance understanding of parasite metabolism and highlight potential new targets for chemotherapy. Elsevier 2017-02 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/62193/1/Integration%20of%20proteomics%20and%20metabolomics%20to%20elucidate%20metabolic%20adaptation%20in%20Leishmania.pdf Akpunarlieva, Snezhana and Weidt, Stefan and Lamasudin, Dhilia Udie and Naula, Christina and Henderson, David and Barrett, Michael and Burgess, Karl and Burchmore, Richard (2017) Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania. Journal of Proteomics, 155. pp. 85-98. ISSN 1874-3919; ESSN: 1876-7737 https://www.sciencedirect.com/science/article/pii/S1874391916305267 10.1016/j.jprot.2016.12.009
spellingShingle Akpunarlieva, Snezhana
Weidt, Stefan
Lamasudin, Dhilia Udie
Naula, Christina
Henderson, David
Barrett, Michael
Burgess, Karl
Burchmore, Richard
Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
title Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
title_full Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
title_fullStr Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
title_full_unstemmed Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
title_short Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
title_sort integration of proteomics and metabolomics to elucidate metabolic adaptation in leishmania
url http://psasir.upm.edu.my/id/eprint/62193/
http://psasir.upm.edu.my/id/eprint/62193/
http://psasir.upm.edu.my/id/eprint/62193/
http://psasir.upm.edu.my/id/eprint/62193/1/Integration%20of%20proteomics%20and%20metabolomics%20to%20elucidate%20metabolic%20adaptation%20in%20Leishmania.pdf