Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes

Leishmania species are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example, Leishmania species utilise host sphingolipid for synthesis of complex sphingolipid. In...

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Main Authors: Hayder Z. Ali, Clare R. Harding, Paul W. Denny
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Biochemistry Research International
Online Access:http://dx.doi.org/10.1155/2012/691363
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author Hayder Z. Ali
Clare R. Harding
Paul W. Denny
author_facet Hayder Z. Ali
Clare R. Harding
Paul W. Denny
author_sort Hayder Z. Ali
collection DOAJ
description Leishmania species are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example, Leishmania species utilise host sphingolipid for synthesis of complex sphingolipid. In this study L. mexicana endocytosis was shown to be significantly upregulated in amastigotes, indicating that sphingolipid scavenging may be enhanced. However, inhibition of host sphingolipid biosynthesis had no significant effect on amastigote proliferation within a macrophage cell line. In addition, infection itself did not directly influence host biosynthesis. Notably, in contrast to L. major, L. mexicana amastigotes are indicated to possess a complete biosynthetic pathway suggesting that scavenged sphingolipids may be nonessential for proliferation. This suggested that Old and New World species differ in their interactions with the macrophage host. This will need to be considered when targeting the Leishmania sphingolipid biosynthetic pathway with novel therapeutics.
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spelling doaj-art-c8048dee17304afaab60ae43d7e2d7852025-08-20T03:19:29ZengWileyBiochemistry Research International2090-22472090-22552012-01-01201210.1155/2012/691363691363Endocytosis and Sphingolipid Scavenging in Leishmania mexicana AmastigotesHayder Z. Ali0Clare R. Harding1Paul W. Denny2Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UKBiophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UKBiophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UKLeishmania species are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example, Leishmania species utilise host sphingolipid for synthesis of complex sphingolipid. In this study L. mexicana endocytosis was shown to be significantly upregulated in amastigotes, indicating that sphingolipid scavenging may be enhanced. However, inhibition of host sphingolipid biosynthesis had no significant effect on amastigote proliferation within a macrophage cell line. In addition, infection itself did not directly influence host biosynthesis. Notably, in contrast to L. major, L. mexicana amastigotes are indicated to possess a complete biosynthetic pathway suggesting that scavenged sphingolipids may be nonessential for proliferation. This suggested that Old and New World species differ in their interactions with the macrophage host. This will need to be considered when targeting the Leishmania sphingolipid biosynthetic pathway with novel therapeutics.http://dx.doi.org/10.1155/2012/691363
spellingShingle Hayder Z. Ali
Clare R. Harding
Paul W. Denny
Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
Biochemistry Research International
title Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
title_full Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
title_fullStr Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
title_full_unstemmed Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
title_short Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
title_sort endocytosis and sphingolipid scavenging in leishmania mexicana amastigotes
url http://dx.doi.org/10.1155/2012/691363
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