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Los parásitos resistentes al antipalúdico atovacuona no se transmiten por los mosquitos
Christopher D Goodman1, Josephine E Siregar2, Vanessa Mollard3
1School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. gim@unimelb.edu.au deang@unimelb.edu.au.
Science (New York, N.Y.)
|April 16, 2016
Resumen
La resistencia a los medicamentos antimaláricos en los parásitos de la malaria es limitada. Las mutaciones que confieren resistencia a la atovacuona son letales en los mosquitos, previniendo la transmisión del parásito y la propagación de la resistencia.
Área de la Ciencia:
- Malariología
- Parasitología
- Estudios de resistencia a las drogas
Sus antecedentes:
- La resistencia a los fármacos de los parásitos de la malaria amenaza los esfuerzos mundiales de control.
- Atovaquone es un medicamento antipalúdico muy importante.
- Comprender los mecanismos de resistencia es vital para la eliminación sostenida de la malaria.
Objetivo del estudio:
- Investigar la dinámica de transmisión de los parásitos de la malaria resistentes a la atovacuona.
- Identificar los factores que limitan la propagación de la resistencia a la atovaquina.
- Evaluar la utilidad a largo plazo de la atovacuona en el control de la malaria.
Principales métodos:
- Selección in vitro de parásitos Plasmodium falciparum resistentes a la atovacuna.
- Análisis genómico de mutaciones en el gen del citocromo b.
- Evaluación de la aptitud y el desarrollo de los parásitos tanto en mamíferos como en mosquitos.
- Experimentos de apareamiento entre cepas resistentes y de tipo salvaje.
Principales resultados:
- La resistencia a la atovaquina es conferida por mutaciones en el gen del citocromo b del parásito.
- Las mutaciones de resistencia afectan la respiración del parásito en la etapa de mosquito.
- Los parásitos resistentes no completan el desarrollo en el vector del mosquito.
- La herencia materna del gen mitocondrial que codifica el citocromo b impide la complementación de las mutaciones de resistencia.
Conclusiones:
- Es poco probable que la resistencia a la atovacuona se propague en el campo debido a un costo de aptitud letal en los mosquitos.
- La incapacidad de los parásitos resistentes para transmitir aumenta significativamente la eficacia a largo plazo de la atovacuona para el control de la malaria.
- Dirigirse a la respiración del parásito presenta una estrategia viable para desarrollar nuevos antipalúdicos.
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