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Antimicrobial Agents and Chemotherapy, October 2003, p. 3073-3079, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3073-3079.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antimony Uptake Systems in the Protozoan Parasite Leishmania and Accumulation Differences in Antimony-Resistant Parasites

Christian Brochu,1 Jingyu Wang,2 Gaétan Roy,1 Nadine Messier,1 Xiao-Yan Wang,2 Nancy G. Saravia,3 and Marc Ouellette1*

Centre de Recherche en Infectiologie du Centre de Recherche du CHUL and Division de Microbiologie, Faculté de Médecine, Université Laval, Québec, Canada,1 Central Laboratory School of Public Health, Peking University, Beijing, China,2 Centro Internacional de Entreamiento e Investigaciones Médicas, Cali, Colombia3

Received 12 May 2003/ Returned for modification 18 June 2003/ Accepted 7 July 2003

The first line drug against leishmaniasis consists of pentavalent antimony [Sb(V)], but there is general belief that the active form of the metal is the trivalent form [Sb(III)]. In this study, we have quantified the accumulation of Sb(V) and Sb(III) in Leishmania by using inductively coupled plasma mass spectrometry. The accumulation was studied in three Leishmania species at various life stages, sensitive or resistant to antimony. Both Sb(III) and Sb(V) are accumulated in promastigote and amastigote parasites, but through competition experiments with arsenite, we found that the routes of entry of Sb(V) and Sb(III) are likely to differ in Leishmania. The level of accumulation of either Sb(III) or Sb(V), however, was not correlated with the susceptibility of wild-type Leishmania cells to antimony. This suggests that other factors may also be implicated in the mode of action of the drugs. In contrast to metal susceptibility, resistance to Sb(III) correlated well with decreased antimony accumulation. This phenotype was energy dependent and highlights the importance of transport systems in drug resistance of this protozoan parasite.

* Corresponding author. Mailing address: Centre de Recherche en Infectiologie CHUQ, Pavillon CHUL, 2705 Boul. Laurier Sainte-Foy, Québec G1V 4G2, Canada. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail: Marc.Ouellette{at}crchul.ulaval.ca.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3073-3079, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3073-3079.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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