RESUMEN

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.

Asunto(s)

Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Protozoarias/metabolismo , Toxoplasma/enzimología , Toxoplasma/patogenicidad , Factores de Virulencia/metabolismo , Alelos , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Dominio Catalítico , Mapeo Cromosómico , Cromosomas/genética , Clonación Molecular , Genes Protozoarios , Ratones , Datos de Secuencia Molecular , Movimiento , Mutación Puntual , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Sitios de Carácter Cuantitativo , Toxoplasma/genética , Toxoplasma/crecimiento & desarrollo , Toxoplasmosis Animal/mortalidad , Toxoplasmosis Animal/parasitología , Transfección , Virulencia/genética , Factores de Virulencia/química , Factores de Virulencia/genética