Leishmania donovani: Isolation and characterization of sodium stibogluconate (Pentostam)-resistant cell lines

Buddy Ullman, Elvira Carrero-Valenzuela, Terry Coons

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Leishmania donovani promastigotes were generated by virtue of their reistance to incrementing concentrations of sodium stibogluconate (Pentostam) under completely defined growth conditions. The PENT0400 and PENT03200 cell lines were isolated after prolonged exposure to 0.4 mg/ml and 3.2 mg/ml Pentostam (Sb concentration), respectively. Whereas the effective concentration of Pentostam which inhibited the growth of wild type cells by 50% (EC50 value) was 0.1-0.15 mg/ml, the EC50 values for the PENT0400 and PENT03200 cells were approximately 1 and 4 mg/ml, respectively. The decreased sensitivities of both PENT0400 and PENT03200 cells to Pentostam were maintained after 6 months of continuous culture in the absence of selective pressure, indicating that the Pentostam resistance in the mutant organisms was a stable genetic trait. Interestingly, wild type and PENT03200 cells were equally sensitive to growth inhibition and cytotoxicity caused by SbCl5 and SbCl3, as well as to a variety of other cations such as Cd, Zn, and As. Wild type and PENT03200 cells also displayed equivalent growth sensitivities to a spectrum of other antiprotozoal agents, including antimony potassium tartrate, melarsoprol, pyrimethamine, pentamidine, formycin B, and difluoromethylornithine. These results illustrate a potentially useful model system to study Pentostam resistance in Leishmania and suggest that Pentostam resistance in vitro may be independent of antimony toxicity.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalExperimental Parasitology
Volume69
Issue number1
DOIs
StatePublished - Jul 1989

Keywords

  • Drug resistance
  • Leishmania donovani
  • Pentostam
  • Protozoa

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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