Advances and perspectives in Leishmania cell based drug-screening procedures.
Efforts for the development of new therapeutics, essential for the control of leishmaniasis rely mainly on screening of potentially effective compounds in pathogen growth/multiplication assays, both in vitro and in vivo. Screenings designed to closely reflect the situation in vivo are currently labor-intensive and expensive, since they require intracellular amastigotes and animal models. Screenings designed to facilitate rapid testing of a large number of drugs are not performed on the clinically relevant parasite stage, but the promastigotes. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent protein (GFP) or the luciferase, opened up new possibilities for the development of drug screening tests. In this review we will focus on available methodologies for direct drug screening purposes against the mammalian stage of the parasite, with emphasis on the future developments that could improve sensitivity, reliability, versatility and the throughput of the intracellular model screening.
Sereno
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IRD, UR008 Pathogénie des Trypanosomatidés, 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France. sereno@mpl.ird.fr
Cordeiro da Silva
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Mathieu-Daude
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Ouaissi
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D000818:Animals; D030801:Animals, Genetically Modified; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D008018:Life Cycle Stages; D021261:Parasitic Sensitivity Tests / Q000379:methods*
D000981:Antiprotozoal Agents