title: Inhibition of Leishmania (Leishmania) amazonensis growth and infectivity by aureobasidin A.
abstract: OBJECTIVE
  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 microM) 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 microM for L. (L.) amazonensis promastigotes, 12.6 microM for Leishmania (Leishmania) major and 13.7 microM 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.
authors.affiliation: Department of Biochemistry, Universidade Federal de São Paulo/Escola Paulista de Medicina, Rua Botucatu 862, São Paulo, SP, 04023-900, Brazil.
authors.forename: Ameria K
authors.initials: AK
authors.lastname: Tanaka
authors.forename: Valderez B
authors.initials: VB
authors.lastname: Valero
authors.forename: Helio K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Anita H
authors.initials: AH
authors.lastname: Straus
mesh_terms: D000818:Animals; D047630:Depsipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006028:Glycosphingolipids / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D047630:Depsipeptides; D004791:Enzyme Inhibitors; D006028:Glycosphingolipids; C477937:inositolphosphorylceramide; C071398:aureobasidin A