Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Catalytic Domain
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Chromosome Mapping
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Chromosomes / genetics
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Cloning, Molecular
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Genes, Protozoan
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Mice
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Molecular Sequence Data
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Movement
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Point Mutation
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protozoan Proteins / chemistry
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Protozoan Proteins / genetics
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Protozoan Proteins / metabolism*
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Quantitative Trait Loci
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Toxoplasma / enzymology*
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Toxoplasma / genetics
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Toxoplasma / growth & development
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Toxoplasma / pathogenicity*
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Toxoplasmosis, Animal / mortality
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Toxoplasmosis, Animal / parasitology
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Transfection
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Virulence / genetics
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Virulence Factors / chemistry
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Virulence Factors / genetics
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Virulence Factors / metabolism*
Substances
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Protozoan Proteins
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Virulence Factors
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Protein Serine-Threonine Kinases