Isolation of a taxol-resistant Leishmania donovani promastigote mutant that exhibits a multidrug-resistant phenotype

FEMS Microbiol Lett. 1999 Jul 15;176(2):437-41. doi: 10.1111/j.1574-6968.1999.tb13694.x.

Abstract

We raised a strain of Leishmania donovani in the laboratory that was resistant to 500 nM taxol. The IC50 of the wild-type strain for taxol was 35 nM and that of the taxol-resistant strain (T-500) was 1 microM. The T-500 strain exhibited a Mdr phenotype; it was also resistant to other unrelated drugs like vinblastine, adriamycin and the commonly used antimonial drugs pentostam and glucantime. Verapamil (20 nM), a calcium channel blocker, was found to reverse the resistance of T-500 to taxol. Acquired resistance to taxol has been reported to be mediated by alterations involving tubulin in cancer cells. Thus polymerisation assays with tubulin fractions in wild-type versus taxol-resistant cells (T-500) were performed in vitro. The tubulin fraction from T-500 was more resistant to in vitro polymerisation than the tubulin isolated from the wild-type, suggesting that this is one means by which the parasite may acquire resistance to taxol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / pharmacology*
  • Calcium Channel Blockers / pharmacology
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / genetics
  • Leishmania donovani / drug effects*
  • Leishmania donovani / genetics
  • Mutation
  • Paclitaxel / pharmacology*
  • Phenotype
  • Tubulin / drug effects
  • Tubulin / metabolism
  • Verapamil / pharmacology

Substances

  • Antiprotozoal Agents
  • Calcium Channel Blockers
  • Tubulin
  • Doxorubicin
  • Verapamil
  • Paclitaxel