Polymorphic secreted kinases are key virulence factors in toxoplasmosis.
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.
Saeij
J P J
JP
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Boyle
J P
JP
Coller
S
S
Taylor
S
S
Sibley
L D
LD
Brooke-Powell
E T
ET
Ajioka
J W
JW
Boothroyd
J C
JC
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D017125:Genes, Protozoan; D005816:Genetic Complementation Test; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D040641:Quantitative Trait Loci; D014122:Toxoplasma / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000469:parasitology*; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D015800:Protozoan Proteins; D037521:Virulence Factors