Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug pentostam.

Pentostam activation and uptake in Leishmania major: Role of the Sb(V) reductase LmAcr2 and the aquaglyceroporin LmAqp1

Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentava...

A new ABC half-transporter in Leishmania major is involved in resistance to antimony.

The characterization of ABCI4, a new intracellular ATP-binding cassette (ABC) half-transporter in Leishmania major, is described. We show that ABCI4 is involved in heavy metal export, thereby conferring resistance to Pentostam, to Sb(III), and to As(III) and Cd(II). Parasites overexpressing ABCI4 showed a lower mitochondrial toxic effect of antimony by decreasing reactive oxygen species product...

Axenically cultured amastigote forms as an in vitro model for investigation of antileishmanial agents.

Using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide microassay, previously described as a means of quantifying Leishmania amazonensis in vitro at the amastigote stage (D. Sereno and J. L. Lemesre, Parisitol. Res., in press), we have compared the activities of seven drugs, including those currently used to treat leishmaniasis, against axenically grown amastigote and promastigote...

Pentostam induces resistance to antimony and the preservative chlorocresol in Leishmania donovani promastigotes and axenically grown amastigotes.

An axenic amastigote culture system was utilized to directly assess the stage-specific antileishmanial effects of antimony on amastigotes of Leishmania donovani devoid of the macrophage host cell. Pentostam, which contains antimony in the form of sodium stibogluconate and the preservative chlorocresol, was used. Cell density was quantified by measuring the activity of the stable enzyme ornithin...