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Genetic Manipulation in Δku80 Strains for Functional Genomic Analysis of Toxoplasma gondii
Published on: July 12, 2013
Una serina-treonina quinasa secretada determina la virulencia en el patógeno eucariota Toxoplasma gondii
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63130, USA.
Science (New York, N.Y.)
|December 16, 2006
Resumen
La virulencia de Toxoplasma gondii está controlada por el gen ROP18. Esta serina-treonina quinasa, secretada durante la invasión, aumenta significativamente el crecimiento del parásito y la mortalidad del huésped, destacando la secreción del efector como un factor de virulencia clave.
Área de la Ciencia:
- Parasitología Parasitología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- Toxoplasma gondii exhibe una variación significativa en la virulencia entre las diferentes cepas, a pesar de la alta similitud genética.
- Comprender la base genética de la virulencia de T. gondii es crucial para el control de la toxoplasmosis.
Objetivo del estudio:
- Identificar los factores genéticos responsables de la virulencia extrema de las cepas de Toxoplasma gondii tipo I.
- Aclarar el papel de genes específicos y proteínas efectoras en la virulencia de los parásitos.
Principales métodos:
- Se empleó mapeo genético para identificar loci de rasgos cuantitativos asociados con la virulencia en el cromosoma VIIa. del parásito.
- Se utilizó la clonación posicional para identificar el gen de virulencia candidato ROP18.
- Se evaluó la actividad de la cinasa y la secreción de ROP18, y su efecto sobre el crecimiento del parásito y la mortalidad del huésped se evaluó a través de experimentos de transfección.
Principales resultados:
- Dos loci de rasgos cuantitativos adyacentes en el cromosoma VIIa se vincularon con la virulencia del linaje tipo I.
- La serina-treonina quinasa ROP18 fue identificada como un gen de virulencia clave, polimórfico y secretado en las células huésped.
- La transfección del alelo ROP18 virulento en una cepa de tipo III aumentó dramáticamente el crecimiento del parásito y la mortalidad del huésped (4-5 registros).
- Los atributos asociados a la virulencia de ROP18 dependían de su actividad de la quinasa.
Conclusiones:
- ROP18 es un determinante importante de la virulencia de Toxoplasma gondii.
- La secreción de proteínas efectoras, como ROP18, es un mecanismo crítico que contribuye a la virulencia de los parásitos.
- La actividad de la cinasa ROP18 es esencial para su papel en la mejora del crecimiento de parásitos y la mortalidad del huésped.
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