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N-acetyl D-glucosamine stimulates growth in procyclic forms of Trypanosoma brucei by inducing a metabolic shift

Published online by Cambridge University Press:  27 March 2008

C. E. EBIKEME ,
L. PEACOCK ,
V. COUSTOU ,
L. RIVIERE ,
F. BRINGAUD ,
W. C. GIBSON  and
M. P. BARRETT
C. E. EBIKEME
Affiliation:
Division of Infection and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA
L. PEACOCK
Affiliation:
School of Biological Sciences, University of Bristol, Bristol BS8 1UG
V. COUSTOU
Affiliation:
Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, Université Victor Segalen Bordeaux 2, UMR-5234 CNRS, 146 rue Léo Saignat, 33076 Bordeaux cedex, France
L. RIVIERE
Affiliation:
Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, Université Victor Segalen Bordeaux 2, UMR-5234 CNRS, 146 rue Léo Saignat, 33076 Bordeaux cedex, France
F. BRINGAUD
Affiliation:
Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, Université Victor Segalen Bordeaux 2, UMR-5234 CNRS, 146 rue Léo Saignat, 33076 Bordeaux cedex, France
W. C. GIBSON
Affiliation:
School of Biological Sciences, University of Bristol, Bristol BS8 1UG
M. P. BARRETT*
Affiliation:
Division of Infection and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA
*
*Corresponding author. Division of Infection and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA. Tel/Fax: +44 141 330 6904. E-mail: [email protected]
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Summary

The lectin-inhibitory sugars D-glucosamine (GlcN) and N-acetyl D-glucosamine (GlcNAc) are known to enhance susceptibility of the tsetse fly vector to infection with Trypanosoma brucei. GlcNAc also stimulates trypanosome growth in vitro in the absence of any factor derived from the fly. Here, we show that GlcNAc cannot be used as a direct energy source, nor is it internalized by trypanosomes. It does, however, inhibit glucose uptake by binding to the hexose transporter. Deprivation of D-glucose leads to a switch from a metabolism based predominantly on substrate level phosphorylation of D-glucose to a more efficient one based mainly on oxidative phosphorylation using L-proline. Procyclic form trypanosomes grow faster and to higher density in D-glucose-depleted medium than in D-glucose-rich medium. The ability of trypanosomes to use L-proline as an energy source can be regulated depending upon the availability of D-glucose and here we show that this regulation is a graded response to D-glucose availability and determined by the overall metabolic state of the cell. It appears, therefore, that the growth stimulatory effect of GlcNAc in vitro relates to the switch from D-glucose to L-proline metabolism. In tsetse flies, however, it seems probable that the effect of GlcNAc is independent of this switch as pre-adaptation to growth in proline had no effect on tsetse infection rate.

Keywords

N-acetylglucosaminetrypanosomeprocyclicTrypanosoma bruceimetabolismmetabolic shift
Type
Original Articles
Information
Parasitology , Volume 135 , Issue 5 , May 2008 , pp. 585 - 594
Copyright
Copyright © Cambridge University Press 2008

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