Characterisation of Leishmania donovani promastigotes resistant to hexadecylphosphocholine (miltefosine)

• Published in: International journal of antimicrobial agents Vol. 22; no. 4; pp. 380 - 387
• Main Authors: Seifert, Karin, Matu, Sangeeta, Javier Pérez-Victoria, F., Castanys, Santiago, Gamarro, Francisco, Croft, Simon L.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 01-10-2003; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - pharmacology; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Biological and medical sciences; DNA, Protozoan - genetics; Drug Resistance; Gene Amplification; Hexadecylphosphocholine; Leishmania; Leishmania donovani - drug effects; Leishmania donovani - genetics; Medical sciences; Miltefosine; Pharmacology. Drug treatments; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacology; Miltefosine; Hexadecylphosphocholine; Drug resistance; Leishmania; Kinetoplastida; Protozoa; Leishmania donovani; Phospholipid; In vitro; Resistance; Lysophospholipid; Parasiticide; Promastigote
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/S0924-8579(03)00125-0

Leishmania donovani promastigote lines resistant to hexadecylphosphocholine (HePC, miltefosine) at 2.5, 5.0, 10.0, 20.0 and 40.0 μM were developed in vitro by continuous step-wise drug pressure. The 40 μM line was 15 times more resistant to HePC than the wild-type clone and showed cross-resistance to the ether lipid ET-18-OCH
3 (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.