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Trypanosoma cruzi: sequence polymorphism of the gene encoding the Tc52 immunoregulatory-released factor in relation to the phylogenetic diversity of the species
Authors:Oury Bruno  Tarrieu Frédérique  Monte-Alegre Adriano  Ouaissi Ali
Affiliation:Institut de Recherche pour le Développement (IRD), Unité de Recherche no 8 Pathogénie des Trypanosomatidae, Montpellier, France. Bruno.Oury@mpl.ird.fr
Abstract:We have previously identified a Trypanosoma cruzi gene encoding a protein named Tc52 sharing structural and functional properties with the thioredoxin and glutaredoxin family involved in thiol-disulfide redox reactions. Gene targeting strategy and immunological studies allowed showing that Tc52 is among T. cruzi virulence factors. Taking into account that T. cruzi has a genetic variability that might be important determinant that governs the different behaviour of T. cruzi clones in vitro and in vivo, we thought it was of interest to analyse the sequence polymorphism of Tc52 gene in several reference clones. The DNA sequences of 12 clones which represent the whole genetic diversity of T. cruzi allowed showing that 40 amino-acid positions over 400 analysed are targets for mutations. A number of residues corresponding to putative amino-acids playing a role in GSH binding and/or enzymatic function and others located nearby are subject to mutations. Although the immunological analysis showed that Tc52 is present in parasite extracts from different clones, it is possible that the amino-acid differences could affect the enzymatic and/or the immunomodulatory function of Tc52 variants and therefore the parasite phenotype.
Keywords:Trypanosoma cruzi   Tc52   Immunomodulatory factor   Sequence polymorphism   aa, amino-acid(s)   Ala, alanine   Arg, arginine   bp, base pair(s)   kbp, kilobase pair(s)   cDNA, DNA complementary to RNA   dNTP, dinucleotide tri-phosphate   DTU, discrete typing unit   FCS, foetal calf serum   Gln, glutamine   Glu, glutamic acid   Gly, glycine   GSH, reduced tripeptide glutathione   GST, glutathione-S-transferase   Ile, isoleucine   kDa, kilodalton(s)   L. infantum, Leishmania infantum   L. lainsoni, Leishmania lainsoni   L. major, Leishmania major   LIT, liver infusion tryptose   Lys, lysine   Met, methionine   PBS, phosphate buffer saline   PCR, polymerase chain reaction   P. discolor, Phyllostomum discolor   Pro, proline   RPMI 1640, culture medium no 1640 developed at Roswell Park Memorial Institute   SDS, sodium dodecyl sulphate   Ser, serine   T. infestans, Triatoma infestans   T. brucei gambiense, Trypanosoma brucei gambiense   T. cruzi, Trypanosoma cruzi   T. marinkellei, Trypanosoma marinkellei   T. rangeli, Trypanosoma rangeli
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