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JAC Advance Access published online on January 22, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl518
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Inhibition of Leishmania (Leishmania) amazonensis growth and infectivity by aureobasidin A

Ameria K. Tanaka, Valderez B. Valero, Helio K. Takahashi and Anita H. Straus*

Department of Biochemistry, Universidade Federal de São Paulo/Escola Paulista de Medicina, Rua Botucatu 862, São Paulo, SP, 04023-900, Brazil

Received 17 July 2006; returned 27 August 2006; revised 6 October 2006; accepted 27 November 2006

* Corresponding author. Tel: +55-11-5549-4122; Fax: +55-11-5579-2509; E-mail: straus.bioq{at}epm.br

OBJECTIVES: To study the effect of aureobasidin A, an inhibitor of inositol phosphorylceramide (IPC) synthase, on Leishmania growth and infectivity.

METHODS: Effects of aureobasidin A were determined for: (i) promastigote growth in axenic culture; (ii) promastigote infectivity in macrophage monolayers; (iii) development of footpad lesions in BALB/c mice; (iv) differentiation of amastigotes into promastigotes.

RESULTS: Aureobasidin A (20 µM) inhibited 90% of Leishmania (Leishmania) amazonensis promastigote growth in axenic culture, but the parasites remained viable, i.e. growth curves returned to normal after aureobasidin A was removed from culture medium. The aureobasidin A IC50 was determined by MTT assay as 4.1 µM for L. (L.) amazonensis promastigotes, 12.6 µM for Leishmania (Leishmania) major and 13.7 µM for Leishmania (Viannia) braziliensis. There was a significant delay in infection when L. (L.) amazonensis promastigotes pre-treated with aureobasidin A were inoculated into BALB/c mouse footpads. When aureobasidin A was added to cultured macrophages infected with amastigotes, the number of infected macrophages was reduced by >90%.

CONCLUSIONS: Aureobasidin A is an interesting pharmacological tool to investigate the effect of lipid metabolism inhibition in Leishmania spp.

Key Words: anti-Leishmania , sphingolipids , amastigotes


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