title: A novel mechanism for an old drug: amphotericin B in the treatment of visceral leishmaniasis.
abstract: Visceral leishmaniasis (VL) is caused by various species of the genus Leishmania. Internalization of Leishmania into host cells is facilitated by a large number of receptors, and therefore no panacea is available for the treatment of leishmaniasis. We previously demonstrated the requirement of host membrane cholesterol in the entry of Leishmania into macrophages by cholesterol depletion using methyl-β-cyclodextrin (MβCD). We recently showed that leishmanial infection is inhibited upon sequestration of host membrane cholesterol using amphotericin B (AmB), considered as the best existing drug against VL. The reason for the antileishmanial activity of AmB is generally believed to be its ability to bind ergosterol in parasite membranes. Our recent results offer the opportunity to reexamine the mechanism behind the effectiveness of current AmB-based therapeutic strategies to treat leishmaniasis. We propose here a novel mechanism in which the effectiveness of AmB treatment could be partly based on its ability to sequester cholesterol in the host membrane, thereby abrogating macrophage-parasite interaction.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad 500 007, India. amit@ccmb.res.in
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Md
authors.initials: M
authors.lastname: Jafurulla
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002462:Cell Membrane / Q000737:chemistry / Q000469:parasitology; D002784:Cholesterol / Q000737:chemistry; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology / Q000635:transmission; D008264:Macrophages / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D000666:Amphotericin B; D002784:Cholesterol