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The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei

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The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei. / Kuettel, Sabine; Wadum, Majken C. T.; Guther, Maria Lucia S.; Marino, Karina; Riemer, Carolin; Ferguson, Michael A. J. (Lead / Corresponding author).

In: Molecular Microbiology, Vol. 84, No. 2, 04.2012, p. 340-351.

Research output: Contribution to journalArticle

Harvard

Kuettel, S, Wadum, MCT, Guther, MLS, Marino, K, Riemer, C & Ferguson, MAJ 2012, 'The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei' Molecular Microbiology, vol 84, no. 2, pp. 340-351.

APA

Kuettel, S., Wadum, M. C. T., Guther, M. L. S., Marino, K., Riemer, C., & Ferguson, M. A. J. (2012). The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei. Molecular Microbiology, 84(2), 340-351doi: 10.1111/j.1365-2958.2012.08026.x

Vancouver

Kuettel S, Wadum MCT, Guther MLS, Marino K, Riemer C, Ferguson MAJ. The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei. Molecular Microbiology. 2012 Apr;84(2):340-351.

Author

Kuettel, Sabine; Wadum, Majken C. T.; Guther, Maria Lucia S.; Marino, Karina; Riemer, Carolin; Ferguson, Michael A. J. (Lead / Corresponding author) / The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei.

In: Molecular Microbiology, Vol. 84, No. 2, 04.2012, p. 340-351.

Research output: Contribution to journalArticle

Bibtex - Download

@article{dbb29f0eb0dd49449ae3d7dc65abb448,
title = "The <em>de novo</em> and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form <em>Trypanosoma brucei</em>",
author = "Sabine Kuettel and Wadum, {Majken C. T.} and Guther, {Maria Lucia S.} and Karina Marino and Carolin Riemer and Ferguson, {Michael A. J.}",
year = "2012",
volume = "84",
number = "2",
pages = "340--351",
journal = "Molecular Microbiology",
issn = "0950-382X",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The <em>de novo</em> and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form <em>Trypanosoma brucei</em>

A1 - Kuettel,Sabine

A1 - Wadum,Majken C. T.

A1 - Guther,Maria Lucia S.

A1 - Marino,Karina

A1 - Riemer,Carolin

A1 - Ferguson,Michael A. J.

AU - Kuettel,Sabine

AU - Wadum,Majken C. T.

AU - Guther,Maria Lucia S.

AU - Marino,Karina

AU - Riemer,Carolin

AU - Ferguson,Michael A. J.

PY - 2012/4

Y1 - 2012/4

N2 - <p>The sugar nucleotide GDP-mannose is essential for Trypanosoma brucei. Phosphomannose isomerase occupies a key position on the de novo pathway to GDP-mannose from glucose, just before intersection with the salvage pathway from free mannose. We identified the parasite phosphomannose isomerase gene, confirmed that it encodes phosphomannose isomerase activity and localized the endogenous enzyme to the glycosome. We also created a bloodstream-form conditional null mutant of phosphomannose isomerase to assess the relative roles of the de novo and salvage pathways of GDP-mannose biosynthesis. Phosphomannose isomerase was found to be essential for parasite growth. However, supplementation of the medium with low concentrations of mannose, including that found in human plasma, relieved this dependence. Therefore, we do not consider phosphomannose isomerase to be a viable drug target. We further established culture conditions where we can control glucose and mannose concentrations and perform steady-state [U-13C]-d-glucose labelling. Analysis of the isotopic sugar composition of the parasites variant surface glycoprotein synthesized in cells incubated in 5 mM [U-13C]-d-glucose in the presence and absence of unlabelled mannose showed that, under physiological conditions, about 80% of GDP-mannose synthesis comes from the de novo pathway and 20% from the salvage pathway.</p>

AB - <p>The sugar nucleotide GDP-mannose is essential for Trypanosoma brucei. Phosphomannose isomerase occupies a key position on the de novo pathway to GDP-mannose from glucose, just before intersection with the salvage pathway from free mannose. We identified the parasite phosphomannose isomerase gene, confirmed that it encodes phosphomannose isomerase activity and localized the endogenous enzyme to the glycosome. We also created a bloodstream-form conditional null mutant of phosphomannose isomerase to assess the relative roles of the de novo and salvage pathways of GDP-mannose biosynthesis. Phosphomannose isomerase was found to be essential for parasite growth. However, supplementation of the medium with low concentrations of mannose, including that found in human plasma, relieved this dependence. Therefore, we do not consider phosphomannose isomerase to be a viable drug target. We further established culture conditions where we can control glucose and mannose concentrations and perform steady-state [U-13C]-d-glucose labelling. Analysis of the isotopic sugar composition of the parasites variant surface glycoprotein synthesized in cells incubated in 5 mM [U-13C]-d-glucose in the presence and absence of unlabelled mannose showed that, under physiological conditions, about 80% of GDP-mannose synthesis comes from the de novo pathway and 20% from the salvage pathway.</p>

U2 - 10.1111/j.1365-2958.2012.08026.x

DO - 10.1111/j.1365-2958.2012.08026.x

M1 - Article

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 2

VL - 84

SP - 340

EP - 351

ER -

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