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

• Published in: Science (American Association for the Advancement of Science) Vol. 314; no. 5806; pp. 1776 - 1780
• Main Authors: Taylor, S, Barragan, A, Su, C, Fux, B, Fentress, S.J, Tang, K, Beatty, W.L, Hajj, H. El, Jerome, M, Behnke, M.S, White, M, Wootton, J.C, Sibley, L.D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.12.2006; The American Association for the Advancement of Science
• Subjects: Alleles; Amino Acid Sequence; Animals; Animals, Genetically Modified; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Catalytic Domain; Chromosome Mapping; Chromosomes - genetics; Cloning, Molecular; Eukaryotes; Fundamental and applied biological sciences. Psychology; Genes; Genes, Protozoan; Genomes; Infections; Kinases; Life cycle. Host-agent relationship. Pathogenesis; Medical genetics; Medicin och hälsovetenskap; Mice; Molecular Sequence Data; Mortality; Movement; Parasite hosts; Parasites; Pathogens; Phenotypes; Point Mutation; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Protozoa; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Quantitative Trait Loci; Toxoplasma - enzymology; Toxoplasma - genetics; Toxoplasma - growth & development; Toxoplasma - pathogenicity; Toxoplasma gondii; Toxoplasmosis, Animal - mortality; Toxoplasmosis, Animal - parasitology; Transfection; Vacuoles; Virulence; Virulence - genetics; Virulence Factors - chemistry; Virulence Factors - genetics; Virulence Factors - metabolism; Pathogenicity; Protozoa; Host parasite relation; Apicomplexa; Toxoplasma gondii; Enzyme; Protein kinase; Transferases; Pathogenic; Parasite
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1133643

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.