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Identification, expression and characterisation of a Babesia bovis hexose transporter

Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an estimated 500 million at risk worldwide. Here, two predicted hexose transporters (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1, having 40% and 47% amino acid sequence similarity compared w...

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Detalles Bibliográficos
Autores principales: Derbyshire, Elvira T., Franssen, Frits J., de Vries, Erik, Morin, Christophe, Woodrow, Charles J., Krishna, Sanjeev, Staines, Henry M.
Formato: Texto
Lenguaje:English
Publicado: Elsevier/North-Holland Biomedical Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688680/
https://www.ncbi.nlm.nih.gov/pubmed/18638508
http://dx.doi.org/10.1016/j.molbiopara.2008.06.010
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author Derbyshire, Elvira T.
Franssen, Frits J.
de Vries, Erik
Morin, Christophe
Woodrow, Charles J.
Krishna, Sanjeev
Staines, Henry M.
author_facet Derbyshire, Elvira T.
Franssen, Frits J.
de Vries, Erik
Morin, Christophe
Woodrow, Charles J.
Krishna, Sanjeev
Staines, Henry M.
author_sort Derbyshire, Elvira T.
collection PubMed
description Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an estimated 500 million at risk worldwide. Here, two predicted hexose transporters (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1, having 40% and 47% amino acid sequence similarity compared with the human (GLUT1) and Plasmodium falciparum (PfHT) hexose transporters, respectively, is the only one that could be characterised functionally after expression in Xenopus laevis oocytes. Radiotracer studies on BboHT1 showed that it is a saturable, Na(+)-independent, stereo-specific hexose transporter, with a K(m) value for glucose of 0.84 ± 0.54 mM (mean ± SEM). Using d-glucose analogues, hydroxyl positions at O-4 and O-6 have been identified as important for ligand binding to BboHT1. d-Glucose transport was inhibited maximally by cytochalasin B (50 μM). A long-chain O-3 hexose derivative (compound 3361) that selectively inhibits PfHT also inhibited relatively potently BboHT1, with an apparent K(i) value of 4.1 ± 0.9 μM (mean ± SEM). Compound 3361 did not inhibit B. bovis proliferation in in vitro growth assays but inhibited invasion of glucose-depleted bovine erythrocytes. Taken together with results of inhibition studies with cytochalasin B and β-glucogallin, these data provide new insights into glucose metabolism of erythrocytic-stage Babesia infections.
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spelling pubmed-26886802009-06-11 Identification, expression and characterisation of a Babesia bovis hexose transporter Derbyshire, Elvira T. Franssen, Frits J. de Vries, Erik Morin, Christophe Woodrow, Charles J. Krishna, Sanjeev Staines, Henry M. Mol Biochem Parasitol Article Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an estimated 500 million at risk worldwide. Here, two predicted hexose transporters (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1, having 40% and 47% amino acid sequence similarity compared with the human (GLUT1) and Plasmodium falciparum (PfHT) hexose transporters, respectively, is the only one that could be characterised functionally after expression in Xenopus laevis oocytes. Radiotracer studies on BboHT1 showed that it is a saturable, Na(+)-independent, stereo-specific hexose transporter, with a K(m) value for glucose of 0.84 ± 0.54 mM (mean ± SEM). Using d-glucose analogues, hydroxyl positions at O-4 and O-6 have been identified as important for ligand binding to BboHT1. d-Glucose transport was inhibited maximally by cytochalasin B (50 μM). A long-chain O-3 hexose derivative (compound 3361) that selectively inhibits PfHT also inhibited relatively potently BboHT1, with an apparent K(i) value of 4.1 ± 0.9 μM (mean ± SEM). Compound 3361 did not inhibit B. bovis proliferation in in vitro growth assays but inhibited invasion of glucose-depleted bovine erythrocytes. Taken together with results of inhibition studies with cytochalasin B and β-glucogallin, these data provide new insights into glucose metabolism of erythrocytic-stage Babesia infections. Elsevier/North-Holland Biomedical Press 2008-10 /pmc/articles/PMC2688680/ /pubmed/18638508 http://dx.doi.org/10.1016/j.molbiopara.2008.06.010 Text en © 2008 Elsevier B.V. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Derbyshire, Elvira T.
Franssen, Frits J.
de Vries, Erik
Morin, Christophe
Woodrow, Charles J.
Krishna, Sanjeev
Staines, Henry M.
Identification, expression and characterisation of a Babesia bovis hexose transporter
title Identification, expression and characterisation of a Babesia bovis hexose transporter
title_full Identification, expression and characterisation of a Babesia bovis hexose transporter
title_fullStr Identification, expression and characterisation of a Babesia bovis hexose transporter
title_full_unstemmed Identification, expression and characterisation of a Babesia bovis hexose transporter
title_short Identification, expression and characterisation of a Babesia bovis hexose transporter
title_sort identification, expression and characterisation of a babesia bovis hexose transporter
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688680/
https://www.ncbi.nlm.nih.gov/pubmed/18638508
http://dx.doi.org/10.1016/j.molbiopara.2008.06.010
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