Development and Characterization of Paromomycin-Resistant Leishmania Donovani Promastigotes

Parasite. 1998 Jun;5(2):167-73. doi: 10.1051/parasite/1998052167.

Abstract

Paromomycin is an antileishmanial chemotherapeutic agent. Leishmania donovani promastigotes resistant to 800 microM of paromomycin were selected by increasing drug pressure and cloned. These promastigotes did not acquire multidrug resistance. Paromomycin resistance was stable in the absence of the drug in the culture. It remained stable also in amastigotes isolated after a passage in mice. Furthermore the resistant parasites were still infective to macrophages in vitro and for mice in vivo. A sensitive method to detect and to quantify intracellular paromomycin by HPLC was developed and allowed to show that the main mechanism of resistance seems to be due to decreased drug uptake probably as a consequence of altered membrane composition.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Antiprotozoal Agents / analysis
  • Antiprotozoal Agents / metabolism
  • Antiprotozoal Agents / pharmacology*
  • Chromatography, High Pressure Liquid
  • Drug Resistance / genetics
  • Drug Resistance, Multiple / genetics
  • Leishmania donovani / drug effects*
  • Leishmania donovani / genetics
  • Leishmania donovani / metabolism
  • Mice
  • Mutation
  • Paromomycin / analysis
  • Paromomycin / metabolism
  • Paromomycin / pharmacology*
  • Phenotype
  • RNA, Protozoan / genetics
  • RNA, Ribosomal / genetics

Substances

  • Anti-Bacterial Agents
  • Antiprotozoal Agents
  • RNA, Protozoan
  • RNA, Ribosomal
  • Paromomycin