Open AccessIsolation of a taxol‐resistant Leishmania donovani promastigote mutant that exhibits a multidrug‐resistant phenotype
Author(s) -
Kapoor P,
Ghosh A,
Madhubala R
Publication year - 1999
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1999.tb13694.x
Subject(s) - leishmania donovani , in vitro , biology , multiple drug resistance , paclitaxel , vinblastine , leishmania , leishmania major , mutant , tubulin , verapamil , strain (injury) , microbiology and biotechnology , drug resistance , chemistry , leishmaniasis , cancer , microtubule , biochemistry , chemotherapy , immunology , parasite hosting , calcium , gene , genetics , visceral leishmaniasis , anatomy , world wide web , computer science , organic chemistry
We raised a strain of Leishmania donovani in the laboratory that was resistant to 500 nM taxol. The IC 50 of the wild‐type strain for taxol was 35 nM and that of the taxol‐resistant strain (T‐500) was 1 μM. 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.