Parasitology Research

, Volume 83, Issue 5, pp 413–418

Altered transport properties of pentamidine-resistant Leishmania donovani and L. amazonensis promastigotes

  • Mireille Basselin
  • Françoise Lawrence
  • M. Robert-Gero
REVIEW ARTICLE

DOI: 10.1007/s004360050274

Cite this article as:
Basselin, M., Lawrence, F. & Robert-Gero, M. Parasitol Res (1997) 83: 413. doi:10.1007/s004360050274

Abstract

Pentamidine-resistant clones of Leishmania donovani and L. amazonensis promastigotes were developed by increase of the drug pressure in the culture medium and characterized. The resistant clones could grow in 40 and 20 μM pentamidine as determined for L.␣donovani and L. amazonensis, respectively, with 50% inhibitory concentrations (IC50 values) being 140 and 60 μM, which were 18 and 75 times higher than those recorded for the parental clones, respectively. Biochemical analysis of the clones showed that the acquired pentamidine resistance was specific (no cross-resistance to unrelated drugs and no reversibility with verapamil) and stable in vitro and in vivo. Pentamidine resistance is related to decreased drug uptake and highly increased efflux in both clones of Leishmania spp., accompanied by an alteration in polyamine carriers. Furthermore, a modification of the uptake of pyrimidine nucleosides and several amino acids by these resistant clones indicates alterations in the surface membrane.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Mireille Basselin
    • 1
  • Françoise Lawrence
    • 1
  • M. Robert-Gero
    • 1
  1. 1.Institut de Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, F-91198 Gif-sur Yvette Cedex, France Tel: (1) 69 82 30 77; Fax: (1) 69 07 72 47FR