Virulence factors and resistance genes in the ecological relationship between Toxoplasma gondii and Mus musculus

Professor Dr. Jonathan C. Howard

PhD students:

• Jingtao Li

• Urs Benedikt Müller

This project is devoted to analysis of the complex evolutionary relationship between wild house mice and an important protozoal pathogen, Toxoplasma gondii. Mice survive T. gondii infection through the action of a newly discovered resistance mechanism based on GTPases of a dedicated family, the IRG proteins. The parasites, however, possess a virulence mechanism based on a dedicated family of kinases, whose function is to inactivate the IRG proteins by phosphorylating them at critical residues. To escape from this, certain strains of mice carry IRG proteins that are not susceptible to phosphorylation by the T. gondii virulence kinases. Both the virulence kinases of the parasite and the resistance GTPases of the mouse are extremely polymorphic. Our goal is to understand the essential features of this complex, novel dynamic host-pathogen nexus. The field is particularly suitable for detailed functional analysis since both participants are standard genetic model species with several sequenced genomes and are suitable for detailed experimentation at cellular and molecular levels. The house mouse reached Brazil about 500 years ago on the ships of the European conquests. There they will have confronted many novel and highly virulent T. gondii strains unknown in Eurasia. We will examine the IRG proteins of house mice captured in Brazil for evidence of recent selection and match the IRG alleles of individual mice with the virulence alleles of T.gondii that have established stable infections in the same individuals. Mice caught around Lisbon will be used for comparison.