Abstract
African trypanosomes are protozoan parasites, most species of which are transmitted by tsetse flies. They reside in the mammalian bloodstream and evade the immune system by periodically switching the major protein on their surface — a phenomenon called antigenic variation, mediated by gene rearrangements in the trypanosome genome. The trypanosomes eventually enter the central nervous system and cause a fatal disease, commonly called ngana in domestic cattle and sleeping sickness in humans. Two sub-species of Trypanosoma brucei infect humans (T. b. rhodesiense and T. b. gambiense) and one sub-species does not survive in humans (T. b. brucei) because it is lysed by the human-specific serum protein, apolipoprotein L-I. Wild animals in Africa have other (less well understood) molecular mechanisms of suppressing the number of African trypanosomes in the blood, and some indigenous breeds of African cattle also display a partial “trypanotolerance” whose genetic loci have recently been mapped.
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References
Babour, A.G. & Restrepo, B.I. 2000. Antigenic variation in vector-borne pathogens. Emerging Infectious Diseases, 6: 449–457.
Baltz, T., Baltz, D., Giroud, C. & Crockett, J. 1985. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. EMBO Journal, 4: 1273–1277.
Baltz, T., Giroud, C., Baltz, D., Roth, C., Raibaud, A. & Eisen, H. 1986. Stable expression of two variable surface glycoproteins by cloned Trypanosoma equiperdum. Nature, 319: 602–604.
Bellofatto, V. & Cross, G.A. 1989. Expression of a bacterial gene in a trypanosomatid protozoan. Science, 244: 1167–1169.
Berriman, M., Hall, N., Sheader, K., Bringaud, F., Tiwari, B., Isobe, T., Bowman, S., Corton, C., Clark, L., Cross, G.A., Hoek, M., Zanders, T., Berberof, M., Borst, P. & Rudenko, G. 2002. The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei. Molecular and Biochemical Parasitology, 122: 131–140.
Bitter, W., Gerrits, H., Kieft, R. & Borst, P. 1998. The role of transferrin-receptor variation in the host range of Trypanosoma brucei. Nature, 391: 499–502.
Black, S.J., Sicard, E.L., Murphy, N. & Nolan, D. 2001. Innate and acquired control of trypanosome parasitaemia in Cape buffalo. International Journal of Parasitology, 31: 561–564.
Blum, M.L., Down, J.A., Gurnett, A.M., Carrington, M., Turner, M.J. & Wiley, D.C. 1993. A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature, 362: 603–609.
Borst, P. & Ulbert, S. 2001. Control of VSG gene expression sites. Molecular and Biochemical Parasitology, 114: 17–27.
Bridgen, P.J., Cross, G.A. & Bridgen, J. 1976. N-terminal amino acid sequences of variant-specific surface antigens from Trypanosoma brucei. Nature, 263: 613–614.
Carruthers, V.B. & Cross, G.A. 1992. High-efficiency clonal growth of bloodstream-and insect-form Trypanosoma brucei on agarose plates. Proceedings of the National Academy of Sciences, USA, 89: 8818–8821.
Cross, G.A.M., Wirtz, L.E. & Navarro, M. 1998. Regulation of vsg expression site transcription and switching in Trypanosoma brucei. Molecular and Biochemical Parasitology, 91: 77–91.
d’Ieteren, G.D., Authie, E., Wissocq, N. & Murray, M. 1998. Trypanotolerance, an option for sustainable livestock production in areas at risk from trypanosomosis. Revue scientifique et technique de L’Office International des Epizooties, 17: 154–175.
Davies, K.P., Carruthers, V.B. & Cross, G.A. 1997. Manipulation of the vsg cotransposed region increases expression-site switching in Trypanosoma brucei. Molecular and Biochemical Parasitology, 86: 163–177.
De Greef, C. & Hamers, R. 1994. The serum-resistance associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a VSG-like protein. Molecular and Biochemical Parasitology, 68: 277–284.
Donelson, J.E. 2003. Antigenic variation and the African trypanosome genome. Acta Tropica, 85: 391–404.
El-Sayed, N.M., Ghedin, E., Song, J., MacLeod, A., Bringaud, F., Larkin, C., Wanless, D., Peterson, J., Hou, L., Taylor, S., Tweedie, A., Biteau, N., Khalak, H.G., Lin, X., Mason, T., Hannick, L., Caler, E., Blandin, G., Bartholomeu, D., Simpson, A.J., Kaul, S., Zhao, H., Pai, G., Van Aken, S., Utterback, T., Haas, B., Koo, H.L., Umayam, L., Suh, B., Gerrard, C., Leech, V., Qi, R., Zhou, S., Schwartz, D., Feldblyum, T., Salzberg, S., Tait, A., Turner, C.M., Ullu, E., White, O., Melville, S., Adams, M.D., Fraser, C.M. & Donelson, J.E. 2003. The sequence and analysis of Trypanosoma brucei chromosome II. Nucleic Acids Research, 31: 4856–4863.
Esser, K.M. & Schoenbechler, M.J. 1985. Expression of two variant surface glycoproteins on individual African trypanosomes during antigen switching. Science, 229: 190–193.
Gerrits, H., Mußmann, R., Bitter, W., Kieft, R. & Borst, P. 2002. The physiological significance of transferrin receptor variations in Trypanosoma brucei. Molecular and Biochemical Parasitology, 119: 237–247.
Hager, K.M. & Hajduk, S.L. 1997. Mechanism of resistance of African trypanosomes to cytotoxic human HDL. Nature, 385: 823–826.
Hanotte, O., Ronin, Y., Agaba, M., Nilsson, P., Gelhaus, A., Horstmann, R., Sugimoto, Y., Kemp, S., Gibson, J., Korol, A., Soller, M. & Teal, A. 2003. Mapping of quantitative trait loci controlling trypanotolerance in a cross of tolerant West African N’Dama and susceptible East African Boran cattle. Proceedings of the National Academy of Sciences, USA, 100: 7443–7448.
Hide, G. 1999. History of sleeping sickness in East Africa. Clinical Microbiology Reviews, 2: 112–125.
Iraqi, F., Clapcott, S.J., Kumari, P., Haley, C.S., Kemp, S.J. & Teale, A. 2000. Fine mapping of trypanosomiasis resistance loci in murine advanced intercross lines. Mammalian Genome, 11: 645–648.
Jordt, T., Mahon, G.D., Touray, B.N., Ngulo, W.K., Morrison, W.I., Rawle, J. & Murray, M. 1986. Successful transfer of frozen N’Dama embryos from the Gambia to Kenya. Tropical Animal Health and Production, 18: 65–75.
LaCount, D.J., El-Sayed, N.M., Kaul, S., Wanless, D., Turner, C.M.R. & Donelson, J.E. 2001. Analysis of a donor gene region for a variant surface glycoprotein and its expression site in African trypanosomes. Nucleic Acids Research, 29: 2012–2019.
Lu, Y., Hall, T., Gay, L.S. & Donelson, J.E. 1993. Point mutations are associated with a gene duplication leading to the bloodstream re-expression of a trypanosome metacyclic VSG. Cell, 72: 397–406.
Melville, S.E., Leech, V., Gerrard, C.S., Tait, A. & Blackwell, J.M. 1998. The molecular karyotype of the megabase chromosomes of Trypanosoma brucei and the assignment of chromosome markers. Molecular and Biochemical Parasitology, 94: 155–173.
Muñoz-Jordń, J.L., Davies, K.P. & Cross, G.A.M. 1996. Stable expression of mosaic coats of variant surface glycoproteins in Trypanosoma brucei. Science, 272: 1791–1794.
Muranjan, M., Wang, Q., Li, Y.L., Hamilton, E., Otieno-Omondi, F.P., Wang, J., Van Praagh, A., Grootenhuis, J.G. & Black, S.J. 1997. The trypanocidal Cape buffalo serum protein is xanthine oxidase. Infection and Immunity, 65: 3806–3814.
Naessens, J., Teale, A.J. & Sileghem, M. 2002. Identification of mechanisms of natural resistance to African trypanosomiasis in cattle. Veterinary Immunology and Immunopathology, 87: 187–194.
Opperdoes, F.R. & Michels, P.A. 1993. The glycosomes of the Kinetoplastida. Biochimie, 75: 231–234.
Pays, E. & Nolan, D.P. 1998. Expression and function of surface proteins in Trypanosoma brucei. Molecular and Biochemical Parasitology, 91: 3–36.
Pays, E., Lips, S., Nolan, D., Vanhamme, L. & Perez-Morga, D. 2001. The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts. Molecular and Biochemical Parasitology, 114: 1–16.
Reduth, D., Grootenhuis, J.G., Olubayo, R.O., Muranjan, M., Otieno-Omondi, F.P., Morgan, G.A., Brun, R., Williams D.J.L. & Black, S.J. 1994. African buffalo serum contains novel trypanocidal protein. Journal of Eukaryotic Microbiology, 41: 95–103.
Rifkin, M.R. 1978. Identification of the trypanocidal factor in normal human serum: high density lipoprotein. Proceedings of the National Academy of Sciences, USA, 75: 3450–3454.
Rifkin, M.R., De Greef, C., Jiwa, A., Landsberger, F.R. & Shapiro, S.Z. 1994. Human serum-sensitive Trypanosoma brucei rhodesiense: a comparison with serologically identical human serum-resistant clones. Molecular and Biochemical Parasitology, 66: 211–220.
Ross, R. & Thompson, D. 1910. A case of sleeping sickness studied by precise enumerative methods: regular periodic increase of the parasites observed. Proceedings of the Royal Society of London, Series B, 82: 411–415.
Schmidt, A. & Krauth-Siegel, R.L. 2002. Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development. Current Topics in Medical Chemistry, 2: 1239–1259.
Thon, G., Baltz, T. & Eisen, H. 1989. Antigenic diversity by the recombination of pseudogenes. Genes Development, 3: 1247–1254.
Turner, C.M. 1997. The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei. FEMS Microbiology Letters, 153: 227–231.
Turner, C.M. & Barry, J.D. 1989. High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Parasitology, 99: 67–75.
Vanhamme, L., Paturiaux-Hanocq, F., Poelvoorde, P., Nolan, D.P., Lins, L., Van Den Abbeele, J., Pays, A., Tebabi, P., Van Xong, H., Jacquet, A., Moguilevsky, N., Dieu, M., Kane, J.P., De Baetselier, P., Brasseur, R. & Pays, E. 2003. Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature, 422: 83–87.
Wang, J., Bohme, U. & Cross, G.A. 2003. Structural features affecting variant surface glycoprotein expression in Trypanosoma brucei. Molecular and Biochemical Parasitology, 128: 135–145.
Wang, J., Van Praagh, A., Hamilton, E., Wang, Q., Zou, B., Muranjan, M., Murphy, N.B. & Black, S.J. 2002. Serum xanthine oxidase: origin, regulation, and contribution to control of trypanosome parasitemia. Antioxidants Redox Signaling, 4: 161–178.
Xong, H.V., Vanhamme, L., Chamekh, M., Chimfwembe, C.E., Van Den Abbeele, J., Pays, A., Van Meirvenne, N., Hamers, R., De Baetselier, P. & Pays, E. 1998. A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell, 95: 839–846.
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Donelson, J.E. (2005). The Molecular Basis of Livestock Disease as Illustrated by African Trypanosomiasis. In: Makkar, H.P., Viljoen, G.J. (eds) Applications of Gene-Based Technologies for Improving Animal Production and Health in Developing Countries. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3312-5_21
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DOI: https://doi.org/10.1007/1-4020-3312-5_21
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