The African trypanosome cyclophilin A homologue contains unusual conserved central and N-terminal domains and is developmentally regulated

We have cloned and characterized the homologue of cyclophilin A (CypA) from Trypanosoma brucei brucei, Trypanosoma congolense, Trypanosoma evansi and Trypanosoma vivax. The 1-kilobase African trypanosome CypA complementary DNA contains an open reading frame of 531 base pairs, corresponding to 177 amino acids with a calculated molecular weight of 18,700. The CypA gene is present at one copy/haploid genome in T. brucei, T. congolense and T. vivax and is located on large chromosomes (>3 Mb) in T. brucei. CypA is differentially transcribed in African trypanosomes and is localized in the cytosol as well as in the flagellum. It is also detected in the supernatant of in vitro cultivated parasites. The African trypanosome CypA is unique due to a ten amino acid residue N-terminus extension and a block that includes a three amino acid insertion around position 100 that might result in a differently structured surface. Wild-type recombinant CypA and several mutants were over-expressed in Escherichia coli and purified to >98% homogeneity. Antisera from cattle immunized with a trypanosome fraction containing immunosuppressive activity react strongly against CypA. These data indicate that trypanosome CypA might play an important role in the establishment and maintenance of infections in susceptible animals.