Location: Animal Parasitic Diseases LaboratoryTitle: Genetic approaches to defining pathogenesis of Toxoplasma gondii
|BEHINKE, MICHAEL - Washington University School Of Medicine|
|SIBLEY, L. - Washington University School Of Medicine|
Submitted to: Annual Review of Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/28/2017
Publication Date: 9/8/2016
Citation: Behinke, M., Dubey, J.P., Sibley, L.D. 2016. Genetic approaches to defining pathogenesis of Toxoplasma gondii. Annual Review of Microbiology. 70:63-81.
Interpretive Summary: Toxoplasma gondii is a single-celled parasite of all warm-blooded hosts worldwide. It causes mental retardation and loss of vision in children, and abortion in livestock. Cats are the main reservoir of T. gondii because they are the only hosts that can excrete the resistant stage (oocyst) of the parasite in the feces. Humans become infected by eating under cooked meat from infected animals and food and water contaminated with oocyst. Why some people become ill and even die from toxoplasmosis whereas others remain asymptomatic is largely unknown. The genetic characteristics of T. gondii strains are considered a factor in the pathogenesis on clinical disease. The underlying mechanism for the parasite virulence is also not fully understood. In the present study the authors discuss molecular basis of pathogenicity of T. gondii. This paper will be useful for parasitologists, biologists, and epidemiologists.
Technical Abstract: Toxoplasma gondii is a widespread parasite of warm-blooded vertebrates that also causes opportunistic infections in humans. Rodents are a natural host for transmission to cats, which serve as the definitive host for sexual development. The laboratory mouse provides a model to study pathogenesis. Strains of T. gondii are globally diverse with more than 16 distinct haplogroups clustered into 6 major clades. Forward genetic analysis of genetic crosses between different lineages has been used to define the molecular basis of acute virulence in the mouse. These studies have identified a family of secretory serine threonine rhoptry (ROP) kinases that target innate immune pathways to protect intracellular parasites from destruction. ROP kinases target immunity related GTPases, a family of immune effectors that is expanded in rodents. Similar forward genetic studies may be useful to define the basis of pathogenesis in other hosts, including humans where different strains present with different clinical severity.