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.
abstract: Toxoplasma gondii and its nearest extant relative, Hammondia hammondi, are phenotypically distinct despite their remarkable similarity in gene content, synteny, and functionality. To begin to identify genetic differences that might drive distinct infection phenotypes of T. gondii and H. hammondi, in the present study we (i) determined whether two known host-interacting proteins, dense granule protein 15 (GRA15) and rhoptry protein 16 (ROP16), were functionally conserved in H. hammondi and (ii) performed the first comparative transcriptional analysis of H. hammondi and T. gondii sporulated oocysts. We found that GRA15 and ROP16 from H. hammondi (HhGRA15 and HhROP16) modulate the host NF-κB and STAT6 pathways, respectively, when expressed heterologously in T. gondii. We also found the transcriptomes of H. hammondi and T. gondii to be highly distinct. Consistent with the spontaneous conversion of H. hammondi tachyzoites into bradyzoites both in vitro and in vivo, H. hammondi high-abundance transcripts are enriched for genes that are of greater abundance in T. gondii bradyzoites. We also identified genes that are of high transcript abundance in H. hammondi but are poorly expressed in multiple T. gondii life stages, suggesting that these genes are uniquely expressed in H. hammondi. Taken together, these data confirm the functional conservation of known T. gondii virulence effectors in H. hammondi and point to transcriptional differences as a potential source of the phenotypic differences between these species.
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Katelyn A
authors.initials: KA
authors.lastname: Walzer
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Wier
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Dam
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Ananth R
authors.initials: AR
authors.lastname: Srinivasan
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Adair L
authors.initials: AL
authors.lastname: Borges
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: English
authors.affiliation: Federal Research Institute for Animal Health, Institute of Epidemiology, Greifswald-Isle of Riems, Germany.
authors.forename: Daland C
authors.initials: DC
authors.lastname: Herrmann
authors.affiliation: Federal Research Institute for Animal Health, Institute of Epidemiology, Greifswald-Isle of Riems, Germany.
authors.forename: Gereon
authors.initials: G
authors.lastname: Schares
authors.affiliation: Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland, USA.
authors.forename: Jitender P
authors.initials: JP
authors.lastname: Dubey
authors.affiliation: Dietrich School of Arts and Sciences, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA boylej@pitt.edu.
authors.forename: Jon P
authors.initials: JP
authors.lastname: Boyle
mesh_terms: D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006790:Host-Parasite Interactions; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D014122:Toxoplasma / Q000235:genetics*; D059467:Transcriptome
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human