Trypanosoma cruzi proliferation and differentiation are blocked by topoisomerase II inhibitors.

AUTOR(ES)

Gonzales-Perdomo, M

RESUMO

Bacterial topoisomerase II inhibitors (ofloxacin and its commercial derivative Tarivid, nalidixic acid, and novobiocin) were tested as blockers of Trypanosoma cruzi differentiation and proliferation. The transformation of either epimastigotes into metacyclic trypomastigotes or amastigotes into trypomastigotes was inhibited by the drugs in a dose-dependent manner. The inhibition of epimastigote differentiation was also dependent on the time of drug addition to the medium. Proliferation of T. cruzi was also blocked in a dose-dependent manner by the drugs, with the exception of novobiocin, which did not inhibit epimastigote replication and resulted in cell lysis when it was used at high concentrations. On the other hand, the transformation of amastigotes into epimastigotes in axenic culture was not inhibited; this process did not require either kinetoplast (mitochondrial) DNA replication or changes in the DNA network organization. Electron microscopy of cells treated with Tarivid (ofloxacin) showed damage to the kinetoplast, suggesting that this organelle might be the target of the drug. These results indicate that a bacterial-like topoisomerase II plays an important role in T. cruzi proliferation and differentiation.

Documentos Relacionados

• Mutational analysis of a type II topoisomerase cleavage site: distinct requirements for enzyme and inhibitors.
• Inhibition of muscle differentiation by trypanosoma cruzi.
• Differentiation of Pasteurella haemolytica biotypes A and T with growth inhibitors.
• Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors
• Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi