Role of the ABC transporter PRP1 in pentamidine resistance in Leishmania spp. / Papel do transportador ABC PRP1 na resistência à pentamidina em Leishmania spp.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Little it is known about the mechanism of action of pentamidine, an compound used for leishmaniases chemotherapy. To understand the mechanism of action and resistance of pentamidine, it was isolated a gene that codifies a member of ABC transporter family, named as PRP1 able to confer pentamidine resistance in promastigotes and amastigotes of Leishmania spp. Treatment of transfectants overexpressing PRP1 with pentamidine in presence of non toxic concentration of verapamil, an inhibitor of ABC transporters, was able to reverse the drug resistance mediated by this transporter. Two lines of L. amazonensis resistant to pentamidine were selected. Molecular analysis of parasites indicated that these mutants do not contain amplified DNA, including the PRP1 gene either not associated with overexpression in both lines. The two lines resistant to pentamidine had their resistance reversed when treated with verapamil, indicating that the mechanism of resistance may be associated to an ABC transporter. The results of this work lead to new insights for a better understanding of the mechanism of of resistance suggesting a probably potencial of pentamidine and verapamil association in the chemotherapy.

ASSUNTO(S)

leishmania leishmania abc transporter transfecção gene transportador abc resistance to drugs pentamidina resistência à drogas pentamidine transfecção gênica

ACESSO AO ARTIGO

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