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Title: Hammondia hammondi harbors functional orthologs of the host-modulating effectors GRA15 and ROP16 but is distinguished from toxoplasma gondii by a unique transcriptional profile

item WALZER, KATELYN - University Of Pittsburgh
item DAM, RACHEL - University Of Pittsburgh
item SRINIVASAN, ANANTH - University Of Pittsburgh
item BORGES, ADAIR - University Of Pittsburgh
item HERMANN, DALAND - Wusterhausen
item SCHARES, GEREON - Wusterhausen
item Dubey, Jitender
item BOYLE, JON - University Of Pittsburgh

Submitted to: Eukaryotic Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/23/2014
Publication Date: 10/3/2014
Citation: Walzer, K., Dam, R., Srinivasan, A., Borges, A., Hermann, D., Schares, G., Dubey, J.P., Boyle, J. 2014. Hammondia hammondi harbors functional orthologs of the host-modulating effectors GRA15 and ROP16 but is distinguished from toxoplasma gondii by a unique transcriptional profile. Eukaryotic Cell. 13(12):1507-1518.

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 oocysts. Hammondia hammondi is the closest relative of T. gondii but does not cause disease. In the present study the secretions from certain organelles of H. hammondi were examined to better understand pathogenesis. These were found to be similar structure and physiology, and could be useful in studying pathogenesis of toxoplasmosis. The results will be of interest to biologists and parasitologists.

Technical Abstract: The mechanisms underlying the phenotypic differences between the human pathogen Toxoplasma gondii and its nearest extant relative, Hammondia hammondi are unknown, but they are likely to be due to both gene content and gene expression differences. To address thisfurther we tested whether two known host-interacting proteins, dense granule protein 15 (GRA15) and rhoptry protein 16 (ROP16) were functionally conserved in H. hammondi, and performed the first comparative transcriptional analysis of H. hammondi and T. gondii sporulated oocysts. We found that both GRA15 and ROP16 from H. hammondi (HhGRA15; HhROP16) modulate the host NF-'B andSTAT6 pathways, respectively, similar to their T. gondii orthologs. We also identified a 16 bp sequence that is deleted in the putative promoter of HhROP16 as a potential core promoter for TgROP16. In contrast to this functional conservation we found the transcriptomes of H. hammondi and T. gondii to be distinct. Twelve percent of the genes queried were at least 4-fold different between the two species, andsome of these were uniquely-expressed in H. hammondi. Moreover, consistent with the rapid conversion of H. hammondi to bradyzoite(e.g., cyst) stages during in vitro growth, a subset of the transcripts that were of higher abundance in H. hammondi T. gondii are upregulated during the tachyzoite to bradyzoite transition in T. gondii, suggesting that H. hammondi sporozoites may be more “cyst-like” in their expression profile than T. gondii. These data provide support for the hypothesis that gene deployment may play a more significant role in determining the phenotypic differences between these species than gene content.