RESUMO

DNA topoisomerase II (topo II), an enzyme essential for cellular replication, is an eminent target for antimicrobial therapy against Leishmania chagasi, the major cause of visceral leishmaniasis in Latin America. The complete L. chagasi (Lch) TOP2 gene, encoding L. chagasi topo II, was isolated from genomic DNA using the polymerase chain reaction. The LchTOP2 gene revealed an open reading frame (ORF) of 3,711 base pairs predicting a protein with 1,236 amino acids and an estimated molecular weight of 140 kDA. The L. chagasi topo II sequence had high identity with the L. donovani topo II (98.8%) and L. infantum topo II (98.7%), followed by Crithidia fasciculata topo II (84.4%), Trypanosoma cruzi topo II (67.6%) and Trypanosoma brucei topo II (66.6%). Lch topo II had low identity with the human homologs htopo II alpha (26.3%) and htopo II beta (26.4%). Differences between L. chagasi TOP2 and human TOP2 genes suggest that leishmanial topo II is a potential target for the development of new antileishmanial agents.

Assuntos

Antiprotozoários/farmacologia , DNA Topoisomerases Tipo II/genética , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/genética , Animais , Sequência de Bases , Southern Blotting , Clonagem Molecular , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/genética , Dados de Sequência Molecular , Farmacogenética , Reação em Cadeia da Polimerase/métodos , Estudos de Amostragem , Sensibilidade e Especificidade , Análise de Sequência de DNA