A chronic bioluminescent model of experimental visceral leishmaniasis for accelerating drug discovery
Visceral leishmaniasis is a neglected disease that poses a significant threat to impoverished human populations of low-income countries. Due to the unavailability of vaccines, pharmacological treatment is the only approach to control the disease that otherwise can be lethal. To date, drug management...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/715783 |
| Acceso en línea: | http://hdl.handle.net/10486/715783 https://dx.doi.org/10.1371/journal.pntd.0007133 |
| Access Level: | acceso abierto |
| Palabra clave: | Antiprotozoal agent leishmaniasis macrophage Biología y Biomedicina / Biología |
| Sumario: | Visceral leishmaniasis is a neglected disease that poses a significant threat to impoverished human populations of low-income countries. Due to the unavailability of vaccines, pharmacological treatment is the only approach to control the disease that otherwise can be lethal. To date, drug management in endemic regions is based on combinations of a handful of mostly unsafe drugs, where the emergence of resistant strains is an additional problem. To accelerate the discovery of new drug entities, several gaps from the early discovery of a compound to its public use, should be filled. One of these gaps is the need of a rapid go/no-go testing system for compounds based on robust preclinical models. Here, we propose a new long-term model of murine visceral leishmaniasis using in vivo bioluminescent imaging. For this purpose, a red-shifted bioluminescent Leishmania infantum strain was engineered. This strain has allowed the appraisal of the disease in individual animals and the monitoring of parasite colonization in liver, spleen and bone marrow. As proof of concept of this platform, mice were infected with the transgenic L. infantum strain treated with a standard schedule of miltefosine, the only oral drug available against Leishmania parasites. Bioluminescence and parasite load in the target organs were compared showing a good correlation. Our findings provide a robust and reproducible tool for drug discovery in a chronic model of murine visceral leishmaniasis |
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