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Antimicrobial Agents and Chemotherapy, April 2007, p. 1425-1430, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01123-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Miltefosine Affects Lipid Metabolism in Leishmania donovani Promastigotes{triangledown}

M. Rakotomanga,1 S. Blanc,1 K. Gaudin,2 P. Chaminade,2 and P. M. Loiseau1*

Chimiothérapie Antiparasitaire, UMR 8076 CNRS, and Groupe de Chimie Analytique Paris-Sud,1 EA 4041, Faculté de Pharmacie, Université Paris-Sud XI, F-92290 Châtenay-Malabry, France2

Received 5 September 2006/ Returned for modification 5 November 2006/ Accepted 18 December 2006

Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active antileishmanial drug. Transient HePC treatment of Leishmania donovani promastigotes at 10 µM significantly reduced the phosphatidylcholine content and enhanced the phosphatidylethanolamine (PE) content in parasite membranes, suggesting a partial inactivation of PE-N-methyltransferase. Phospholipase D activity did not seem to be affected by HePC. In addition, the enhancement of the lysophosphatidylcholine content could be ascribed to phospholipase A2 activation. Moreover, transient HePC treatment had no effect on the fatty acid alkyl chain length or the fatty acid unsaturation rate. Concerning sterols, we found a strong reduction of the C24 alkylated sterol content, and the enhancement of the cholesterol content could be the result of the HePC condensation effect with sterols. Because some of the effects observed after transient HePC treatment were different from those previously observed in HePC-resistant parasites, it could be hypothesized that continuous in vitro drug pressure induces the mechanisms of regulation in Leishmania lipid metabolism.

* Corresponding author. Mailing address: Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud XI, F-92290 Châtenay-Malabry, France. Phone: 33 1 46 83 55 53. Fax: 33 1 46 83 55 57. E-mail: philippe.loiseau{at}u-psud.fr

{triangledown} Published ahead of print on 22 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1425-1430, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01123-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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