Polymorphic Secreted Kinases Are Key Virulence Factors in Toxoplasmosis

• DOI: 10.1126/science.1133690
• Publication Date: 2006-12-15T00:55:55Z
• Authors: J. P. J. Saeij; J. P. Boyle; S. Coller; S. Taylor; L. D. Sibley; E. T. Brooke-Powell; J. W. Ajioka; J. C. Boothroyd
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Virulence; Genes, Protozoan; Genetic Complementation Test; Molecular Sequence Data; Quantitative Trait Loci; Protozoan Proteins; Chromosome Mapping; Polymorphism, Single Nucleotide; Chromosomes; 3. Good health; Mice; 03 medical and health sciences; Toxoplasmosis, Animal; Mice, Inbred CBA; Animals; Female; Amino Acid Sequence; Toxoplasma; Alleles; Crosses, Genetic; Oligonucleotide Array Sequence Analysis

The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the responsible genes, we mapped virulence in F 1 progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence ( VIR ) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.