Trypanosoma cruzi: Induction of benznidazole resistance in vivo and its modulation by in vitro culturing and mice infection.
Through a continuous in vivo drug pressure protocol, using mice as experimental model, we induced benznidazole resistance in Trypanosoma cruzi stocks. Full resistance was obtained for four out of five T. cruzi stocks analyzed. However, the number of benznidazole doses (40-180), as well as the time (4-18 months) necessary to induce resistance varied among the different T. cruzi stocks. The resistance phenotype remained stable after T. cruzi stocks has been maintained by 12 passages in mice (six months) and in acellular culture for the same time. However, the maintenance of resistant parasite for 12 months in acellular culture induces a reduction in its level of benznidazole resistance, while no alteration was detected in parasite maintained for the same time in mice. The data showed the stability of the resistance acquired by drug pressure, but suggest the possibility of reversible changes in the resistance levels after maintenance for long time in acellular culture.
Dos Santos
Fabiane Matos
FM
Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil.
Caldas
Sérgio
S
de Assis Cáu
Stêfany Bruno
SB
Crepalde
Geovam Pereira
GP
de Lana
Marta
M
Machado-Coelho
George L L
GL
Veloso
Vanja Maria
VM
Bahia
Maria Terezinha
MT
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004285:Dogs; D004351:Drug Resistance; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
D007166:Immunosuppressive Agents; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D003520:Cyclophosphamide; C009999:benzonidazole