Trypanosoma cruzi is the agent of Chagas'disease, a major health problem in Latin America. By an extensive population genetics approach, our team has demonstrated that populations of Trypanosoma cruzi are subdivided into natural clones, stable in space and time, that represent the operational taxonomic unit to be taken into account in all applied studies (clinical surveys, epidemiology, immunology, pharmacology, etc). Moreover, we have shown that a limited number of these natural clones are dominant and widespread ("major-clones") : their medical and epidemiological significance might be considerable. With the help of a former EEC grant, we have designed PCR kDNA epidemiological and experimental studies involving these major clones.
The purpose of the present project is to compare some relevant medical and biological properties of 3 of these major clones with an experimental approach : the experiments will involve (i) in vitro models (Fibroblastes/ parasites, macrophages/parasites, growth in LIT and differentiation in TOP culture mediums) . (ii) in vivo models (various parameters studied with murine model) . (iii) drug sensitivity experiments, both in vitro and in vivo. In every case, the properties of the major clones will be studied (i) each clone considered isolately ; (ii) with experiments dealing with mixtures of natural clones, which probably represent a frequent situation in natural cycles. In a second time, other major clones, as evidenced by our population genetics analyses, will be included in the present project. This model, settled on a rigorous population genetics basis, aims to directly answer the long-opened question of the biological and medical consequences of T. cruzi genetic variability.
Funding SchemeCSC - Cost-sharing contracts