Effect of the anti-microtubule drug oryzalin on growth and differentiation of the parasitic protozoan Leishmania mexicana

Marion Man Ying Chan, Richard E. Triemer, Dunne Fong

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The parasitic protozoan Leishmania mexicana differentiates from a non-motile intracellular amastigote in the mammalian macrophage phagolysosome into a motile, extracellular promastigote in the insect vector gut. This development program has been accomplished in vitro, thus providing a useful model for studying changes in the cytoskeleton during cell differentiation. The role of microtubules in leishmania differentiation was demonstrated by using the dinitroaniline herbicide oryzalin, which inhibited both leishmania proliferation and differentiation; 25 μM oryzalin reduced promastigote division by over 95%. Interestingly, at a sublethal dose (5 μM), promastigotes became round and multifla-gellated but remained motile. At 50 μM oryzalin, the number of intracellular amastigotes decreased by 50%. However, leishmania differentiation seemed to be the most drug-sensitive stage: there was a 60% reduction in amastigote-to-promastigote differentiation at 0.5 μM oryzalin. The specific action of oryzalin on leishmania microtubules was verified by its inhibition of in vitro polymerization of leishmania microtubules, but not control mammalian microtubules (from rat brain). These findings indicate that microtubules play a major role in leishmania proliferation, maintenance of cell shape, and cytodifferentiation.

Original languageEnglish (US)
Pages (from-to)15-21
Number of pages7
JournalDifferentiation
Volume46
Issue number1
DOIs
StatePublished - 1991

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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