Resistance to arsenite modulates expression of beta- and gamma-tubulin and sensitivity to paclitaxel during differentiation of Leishmania donovani.

Abstract

Differentiation of Leishmania donovani promastigotes into infectious amastigotes is accompanied by differential tubulin gene expression. Tubulin is one of the proposed targets of clinically useful antileishmanial agents and its expression is known to alter due to drug resistance. In this study, beta- and gamma-tubulin expression under various stages of differentiation was measured in an in vitro generated arsenite-resistant L. donovani strain. Results showed higher constitutive expression of beta-tubulin in the arsenite-resistant promastigotes and amastigotes compared with the wild-type. beta-Tubulin expression in the resistant promastigotes increased on paclitaxel treatment. Significant differences in gamma-tubulin expression were observed only between the amastigotes, but not between promastigotes, of wild-type and resistant strains. Paclitaxel did not produce any significant change in the expression profile of gamma-tubulin in either of the strains, neither before nor after differentiation. Data suggest that the beta- and gamma-tubulin expression and the response to paclitaxel is affected due to arsenite resistance.