MOLECULAR CHARACTERIZATION OF SUSCEPTIBLE AND NATURALLY RESISTANT STRAINS OF TRYPANOSOMA-CRUZI TO BENZNIDAZOLE AND NIFURTIMOX

Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resis tant to the nitroderivatives benznidazole and nifurtimox, were analyze d using the following molecular markers: (i) isoenzyme patterns of six enzymes; (ii) genetic variability assayed by randomly amplified polym orphic DNA (RAPD) with two different primers; and (iii) gene probes fo r P-glycoprotein (TcPGP), hypoxanthine-guanine phosphoribosyltransfera se (HGPRT), the ribosomal RNA gene (rDNA) and the mini-exon gene (MEX) . RAPD and isoenzyme profiles divided the T. cruzi strains into three groups, whereas the gene probes divided the T. cruzi strains in two gr oups. Strains classified as group I or II by RAPD or zymodemes Z1 or Z 2 by isoenzyme analysis were either susceptible or naturally resistant to the nitroderivatives. In contrast, strains classified as group III by RAPD and zymodeme ZB by isoenzyme analysis were only drug suscepti ble and showed polymorphisms for HGPRT and TcPGP. No correlation was o bserved between drug susceptibility and polymorphisms of rDNA and MEX. Eighteen T. cruzi strains isolated from different geographic regions were included in this study. Thus, from a total of 45 T. cruzi strains analyzed, all 19 of zymodeme B were susceptible to the experimental t reatment independent of their geographic origin. (C) 1998 Elsevier Sci ence B.V. All rights reserved.