A Secreted Serine-Threonine Kinase Determines Virulence in the Eukaryotic Pathogen Toxoplasma gondii

• DOI: 10.1126/science.1133643
• Publication Date: 2006-12-15T00:55:55Z
• Authors: S. Taylor; A. Barragan; C. Su; B. Fux; S. J. Fentress; K. Tang; W. L. Beatty; H. El Hajj; M. Jerome; M. S. Behnke; M. White; J. C. Wootton; L. D. Sibley
• Keywords: 0301 basic medicine; Virulence; Movement; Genes, Protozoan; Molecular Sequence Data; Quantitative Trait Loci; Protozoan Proteins; Chromosome Mapping; Protein Serine-Threonine Kinases; Transfection; Chromosomes; 3. Good health; Animals, Genetically Modified; Mice; 03 medical and health sciences; Toxoplasmosis, Animal; Catalytic Domain; Animals; Point Mutation; Amino Acid Sequence; Cloning, Molecular; Toxoplasma; Alleles

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.