TOLEDO, Max Jean de Ornelas

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Cadernos Espinosanos (E-Journal)

		%%$ !""*This thesis is available at the Library of the Instituto de Medicina Tropical de São PauloSUMMARY OF THESISTOLEDO, Max Jean de Ornelas – Comportamento biológico em camundongos de clones de Trypanosoma cruzi  pertencentes a diferentesgenótipos. Belo Horizonte, 2001. (Tese de Doutorado – Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais).BIOLOGICAL BEHAVIOR IN MICE OF DIFFERENT Trypanosoma cruzi CLONAL GENOTYPESTwenty Trypanosoma cruzi laboratory-cloned stocks attributed tothe 19 and 20 clonal genotypes included in T. cruzi I (Satellite Meeting,Rio de Janeiro, 1999) and to the 39 and 32 clonal genotypes included inT. cruzi II were comparatively studied in BALB/c mice during the acuteand chronic phases of the infection to test the working hypothesis that T.cruzi clonal evolution has a major impact on its biological properties.Twenty two parameters were assayed: (i) infectivity, pre patent period,patent period, maximum of parasitemia, day of maximum of parasitemiaand area under the curve of parasitemia, during the acute phase of theinfection; (ii) mortality, % of positive hemoculture, tissue parasitism,inflammatory process, % of positive ELISA, % of positive anti-livetrypomastigotes antibody (ALTA), susceptibility to benznidazole (BZ)and susceptibility to itraconazole (ITZ), during both acute and chronicphases of the infection.The stocks pertaining to the clonal genotype 19, phylogeneticallyvery close to the clonal genotype 20 and distinct from it by only oneenzyme locus (6-phosphogluconate dehydrogenase - 6Pgdh) out of 22loci analyzed, were similar in the majority (16 out of 22) of the biologicalparameters studied. They were significantly different in six importantbiological variables related to parasitemia pattern and BZ susceptibility.The clonal genotype 19 was considered of intermediate resistance to BZand totally resistant to ITZ.Mice infected with stocks attributed to the clonal genotype 20displayed the highest values for 8 parameters and the lowest values in 2parameters out of 22 analyzed from all genotypes. Stocks attributed tothe clonal genotype 20 displayed values significantly higher forinfectivity, area under the curve of parasitemia, maximum of parasitemia,tissue parasitism and inflammatory process in the acute phase. Thus,they were considered as more virulent and pathogenic during the acutephase of the infection and totally resistant to both chemotherapeuticagents in both phases of the infection.Stocks attributed to the clonal genotype 39 exhibited the mostcontrasting parasitemia levels. Mice infected with this genotype werethe only ones in which tissular parasitism was not detected in the acutephase and in which tissular parasitism was detected in the chronic phaseof the infection. Only mice infected with stocks of this clonal genotypeshowed no association between the levels of tissular parasitism andinflammatory process. This genotype was considered the most susceptibleto host immune response and of intermediate resistance to the drugsunder study, since it showed sensitive, partially resistant and totallyresistant stocks.Mice infected with stocks attributed to the clonal genotype 32exhibited the lowest values for in 8 out of 18 parameters related tovirulence, pathogenicity and humoral immune response from allgenotypes. Thus, this genotype was considered the less virulent amongall the genotypes studied and induces low antibodies production. Thisgenotype was considered sensitive to both chemotherapeutic agents.Statistical analysis showed that the results are overall consistent withthe working hypothesis: biological differences are proportional to theevolutionary divergence among the genotypes. Thus, closely relatedgenotypes (19 vs 20 and 32 vs 39) show fewer differences than distantlyrelated genotypes (19 or 20 vs 32 or 39). The working hypothesis isfurther supported by the result of the nonparametric Mantel test, whichshowed a highly significant correlation (r = 0.4233, p = 10-4) betweenbiological differences and genetic distances among all pairs of stocks.However, although this correlation is highly significant, some stocksshow non-typical biological behaviors, and tend to be similar to stocksfrom other genetic groups, as shown by cluster analysis of the 22 geneticmarkers and from the 17 biological parameters. Interestingly, it wasobserved that genotypes 19 and 20 were different in six importantbiological variables out of 22 although they are genetically very close.Our results confirm the statistical link between genetic divergenceand biological behavior and strongly suggest that the 2 major subdivisionsT. cruzi I and II are too broad for biological studies and that it is relevantto take into account also the lesser genetic groups, in all applied studiesdealing with diagnosis, drug and vaccine design, epidemiological surveysand clinical diversity of Chagas’ disease.Max Jean de Ornelas Toledomjotoledo@uem.br

Biological behavior in mice of different Trypanosoma cruzi clonal genotypes

Scientific Electronic Library Online - Brazil

Comportamento biológico em camundongos de clones de Trypanosoma cruzi pertencentes a diferentes genótipos

https://www.revistas.usp.br/rimtsp/article/download/30618/32502

Comportamento biológico em camundongos de clones de Trypanosoma cruzi pertencentes a diferentes genótipos

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Cadernos Espinosanos (E-Journal)

Scientific Electronic Library Online - Brazil