Characterisation of Leishmania donovani promastigotes resistant to hexadecylphosphocholine (miltefosine).
Leishmania donovani promastigote lines resistant to hexadecylphosphocholine (HePC, miltefosine) at 2.5, 5.0, 10.0, 20.0 and 40.0 microM were developed in vitro by continuous step-wise drug pressure. The 40 microM line was 15 times more resistant to HePC than the wild-type clone and showed cross-resistance to the ether lipid ET-18-OCH3 (edelfosine) but not to the standard anti-leishmanial drugs. Resistance was stable up to 12 weeks in drug-free culture medium. No amplification of specific genes, including the multidrug resistance P-glycoprotein gene, could be detected in the resistant parasites.
Seifert
Karin
K
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Matu
Sangeeta
S
Javier Pérez-Victoria
F
F
Castanys
Santiago
S
Gamarro
Francisco
F
Croft
Simon L
SL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D005784:Gene Amplification; D007893:Leishmania donovani / Q000187:drug effects* / Q000235:genetics; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000981:Antiprotozoal Agents; D016054:DNA, Protozoan; D010767:Phosphorylcholine; C039128:miltefosine