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Trypanosoma brucei brucei oligopeptidase B null mutants display increased prolyl oligopeptidase-like activity

Kangethe R.T., Boulangé A., Coustou V., Baltz T., Goetzer T.H.T.. 2012. Molecular and Biochemical Parasitology, 182 (1) : p. 7-16.

African trypanosomosis is a parasitic disease in man and animals caused by protozoan parasites of the genus Trypanosoma. Nagana, the cattle form of the disease, is caused by Trypanosoma congolense, Trypanosoma vivax and Trypanosoma brucei brucei. An option for developing vaccines and chemotherapeutic agents against trypanosomosis is to target pathogenic factors released by the parasite during infection, namely an "anti-disease" approach. One such pathogenic factor is oligopeptidase B (TbOPB), a trypanosome peptidase that hydrolyses Arg/Lys containing peptides smaller than 30 amino acid residues and is suspected to be involved in the hormonal deregulation associated with the disease. To better understand the role TbOPB plays in parasite physiology and host pathogenesis, oligopeptidase B null mutant parasites (?opb) were generated in the T. b. brucei Lister 427 strain. ?opb Trypanosoma brucei parasites grew at a significantly faster rate in vitro, and were as virulent as wild type strains during infection in mice. Immunohistopatholgy of infected mouse testes revealed ?opb parasites in extra vascular regions showing that TbOPB is not involved in assisting T. brucei parasites to cross microvascular endothelial cells. Gelatine gel analysis of ?opb null mutants showed an increase in discrete cysteine peptidase activities when compared to wild type strains. Enzymatic activity assays were carried out to identify how closely related oligopeptidases are affected by TbOPB gene deletion. A significant increase of T. brucei prolyl oligopeptidase (TbPOP) activity was observed, but no concomitant increase in TbPOP protein levels, suggesting that a POP-like enzyme might compensate for a loss in OPB activity in ?opb null mutants. (Résumé d'auteur)

Mots-clés : parasite; mutant; peptidase; trypanosoma brucei; trypanosoma brucei brucei

Thématique : Maladies des animaux

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