Resistance to arsenite modulates levels of α-tubulin and sensitivity to paclitaxel in Leishmania donovani

Abstract

Tubulin expression is known to alter due to drug resistance. Differentiation of Leishmania promastigotes into infectious amastigotes has been reported to be accompanied by differential tubulin gene expression. In this study, alpha-tubulin expression under various stages of differentiation was measured in an in vitro generated arsenite-resistant L. donovani strain. While levels of expression of alpha-tubulin were similar in wild type and resistant promastigotes, during conversion into axenic amastigotes the changes in the expression levels of alpha-tubulin varied widely between the two strains. Sensitivity of the two strains to paclitaxel (known to promote tubulin assembly) differed, with the resistant strain being two-fold more sensitive than the wild type strain. Paclitaxel was also seen to cause differential effects on alpha-tubulin levels in the two strains.