DRUG-RESISTANT EPIMASTIGOTES OF TRYPANOSO MA-CRUZI AND PERSISTENCE OFTHIS PHENOTYPE AFTER DIFFERENTIATION INTO AMASTIGOTES

In vitro benznidazole resistance was induced in cloned T. cruzi epimas tigotes using a continuous drug pressure protocol Stocks were selected according to their previous genetic characterization by multilocus en zyme electrophoresis. All the resistant clones were able to grow in lo ng term cultivation in the presence of at least 50 mu M benznidazole, which is the drug plasma level during chemotherapy in man. The highest level of resistance achieved was 220 mu M. After differentiation of t he epimastigote into the amastigote forms, the drug-resistance level w as not affected. In both, the resistant epimastigotes and the resistan t amastigotes, growth curves exhibited a lower growth rate than the se nsitive counterparts without affecting the viability of the parasites. These data could be significant in basic research, to study the drug- resistance phenotype on relevant chemoresistant clones of T. cruzi, an d to follow this phenotype after in vivo cycles.