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

• Published in: Parasitology 2008-04, Vol.135 (5), p.585-594
• Main Authors: EBIKEME, C. E., PEACOCK, L., COUSTOU, V., RIVIERE, L., BRINGAUD, F., GIBSON, W. C., BARRETT, M. P.
• Format: Article
• Language: English
• Subjects: Acetylglucosamine; Acetylglucosamine - pharmacology; Animals; Biological and medical sciences; Culture Media; Energy sources; Enzymes; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; General aspects; General aspects and techniques. Study of several systematic groups. Models; Glossina; Glucose; Glucose - metabolism; Host-Parasite Interactions; Invertebrates; Life Sciences; metabolic shift; Metabolism; Microbiology and Parasitology; N-acetylglucosamine; Parasitic diseases; procyclic; Proline; Proline - metabolism; Trypanosoma brucei; Trypanosoma brucei brucei; Trypanosoma brucei brucei - drug effects; Trypanosoma brucei brucei - growth & development; Trypanosoma brucei brucei - metabolism; Trypanosoma brucei brucei - physiology; trypanosome; Tsetse Flies; Tsetse Flies - parasitology
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S0031182008004241

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.