|WALZER, KATELYN - University Of Pittsburgh|
|ADOMAKO-ANKOMAH, YAW - University Of Pittsburgh|
|DAM, RACHEL - University Of Pittsburgh|
|HERRMANN, DALAND - Federal Research Institute|
|SCHARES, GEREON - Federal Research Institute|
|BOYLE, JON - University Of Pittsburgh|
Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/20/2013
Publication Date: 4/30/2013
Citation: Walzer, K., Adomako-Ankomah, Y., Dam, R., Herrmann, D., Schares, G., Dubey, J.P., Boyle, J. 2013. Hammondia hammondi, an avirulent relative of Toxoplasma gondii, has functional orthologs of known T. gondii virulence genes. Proceedings of the National Academy of Sciences. 110:7446-7451.
Interpretive Summary: Toxoplasma gondii is a single-celled parasite of all warm-blooded hosts worldwide. It causesmental 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 oocysts. Why some people become sick whereas most hosts remain symptomless after contracting toxoplasmosis is unknown. Biologically, some strains of Toxoplasma are more pathogenic to mice whereas others do not cause clinical signs. In the present study, authors explore genetic basis of virulence in mice using pathogenic strains of Toxoplasma and a non pathogenic related organism, Hammondia. The results will be of interest to biologists, and parasitologists.
Technical Abstract: Toxoplasma gondii is a ubiquitous protozoan parasite capable of infecting all warm-blooded animals, including humans. Its closest extant relative, Hammondia hammondi, has never been found to infect humans and in contrast to T. gondii is highly attenuated in mice. To better understand the genetic bases for these phenotypic differences we sequenced the genome of a H. hammondi isolate (HhCatGer041) and found the genomic synteny between H. hammondi and T. gondii to be >95%. We used this genome to determine the H. hammondi primary sequence of two major T. gondii mouse virulence genes, TgROP5 and TgROP18. When we expressed these genes in T. gondii, we found that H. hammondi orthologs of TgROP5and TgROP18 were functional. Similar to T. gondii, the HhROP5 locus is expanded, and two distinct HhROP5 paralogs increased the virulence of a T. gondii TgROP5 knockout strain. We also identified a 107 base pair promoter region, absent only in Type III TgROP18, which is necessary for TgROP18 expression. This indicates that the ROP18 promoter was active in the most recent common ancestor of these two species, and that it was subsequently inactivated in progenitors of the Type III lineage. Overall these data suggest that the virulence differences between these species are not solely due to the functionality of these key virulence factors. This study provides evidence that other mechanisms, such as differences in gene expression or the lack of currently uncharacterized virulence factors, may underlie the phenotypic differences between these species.