Principal Investigator Jeroen Saeij
The majority of Toxoplasma isolates from Europe and North America belong to three distinct clonal lines, referred to as types I, II and III. The three types have been shown to differ widely in a number of phenotypes in mice such as virulence, persistence, migratory capacity, attraction of different cell-types and induction of cytokine expression. Recent data suggest that such differences may also exist in human infection. In South America many other Toxoplasma strains exist, some of which can cause severe disease even in healthy individuals. One of our long-term goals is to understand how distinct Toxoplasma strains differ in their ability to cause disease in humans. Determining how particular Toxoplasma genotypes differ in their capacity to induce pathology in a particular animal species could enable prediction of the outcome of infection based on the genotype of the infecting organism. For example, not all seropositive AIDS patients develop toxoplasmic encephalitis; the ones that do might be infected with a particular subset of parasite strains. Similarly, seroconversion during pregnancy does not always lead to infection of the fetus; this might be a result of variability in the ability of different strains to cross the placental barrier. We have sequenced whole genomes of strains with different phenotypes and compared the differences and commonalities. This approach allowed us to correlate genotype with phenotype and have led to the identification of Toxoplasma loci and genes that affect fitness, clonality, virulence and modulation of host signaling pathways.