A yeast-based high-throughput screen identifies inhibitors of trypanosomatid HRG heme transporters with potent leishmanicidal and trypanocidal activity

Objectives`] New drugs are required to treat neglected diseases caused by trypanosomatid parasites such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi. An Achilles' heel of these parasites is their heme auxotrophy; they have an absolute dependence on scavenging this molecule from the h...

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Detalles Bibliográficos
Autores: Cabello-Donayre, María, Cabello-Donayre, Irene, Guerra, Diego, Orrego, Lina M., Morales, Juan Carlos, Cautain, Bastien, Vicente, Francisca, Pérez-Victoria, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/362872
Acceso en línea:http://hdl.handle.net/10261/362872
Access Level:acceso abierto
Palabra clave:Leishmania
Trypanosoma
Trypanosomatid parasites
Heme
HTS Screening
HRG transporters
Descripción
Sumario:Objectives`] New drugs are required to treat neglected diseases caused by trypanosomatid parasites such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi. An Achilles' heel of these parasites is their heme auxotrophy; they have an absolute dependence on scavenging this molecule from the host, and trypanosomatid HRG heme transporters (TrypHRG) play an important role in this process. As these proteins are essential for the parasites and have low similarity with their human orthologue, they have been proposed as attractive therapeutic targets. Here, we have developed two yeast-based assays that allow an inexpensive high-throughput screening of TrypHRG inhibitors within a cellular context.