Characterization of a Putative Acid Phosphatase in Toxoplasma Gondii and Its Role in Parasite Propagation

dc.contributor.advisorArrizabalaga, Gustavo
dc.contributor.authorBlakely, William James
dc.contributor.otherGilk, Stacey
dc.contributor.otherMeroueh, Samy
dc.contributor.otherWek, Ronald
dc.date.accessioned2020-12-14T18:46:21Z
dc.date.available2020-12-14T18:46:21Z
dc.date.issued2020-11
dc.degree.date2020en_US
dc.degree.discipline
dc.degree.grantorIndiana Universityen_US
dc.degree.levelPh.D.en_US
dc.descriptionIndiana University-Purdue University Indianapolis (IUPUI)en_US
dc.description.abstractThe parasite Toxoplasma gondii infects approximately one-third of people worldwide. Infection can lead to severe disease in those with a compromised immune system and primary infection during pregnancy can lead to severe birth defects or miscarriage. Treatment options are limited, have significant side effects, and are ineffective for all infection stages. Imperative to the discovery of novel therapeutic targets is a thorough understanding of how Toxoplasma propagates within a host. To replicate, the parasite must enter the cells of an infected organism where, during the invasion process, it surrounds itself with host cell membrane to form a parasitophorous vacuole (PV), within which it freely divides. To endure the intracellular environment of a host cell, Toxoplasma secretes a large repertoire of proteins beyond the PV to manipulate important host cellular functions. How these Toxoplasma proteins transit from parasites to host cell is not well understood. Protein translocation into the host cell is mediated by three proteins hypothesized to function as a putative translocon complex inside the PV, but whether other proteins are involved in the structure or regulation of this putative translocon remains unknown. The secreted protein GRA44, which contains a putative acid phosphatase domain, has been discovered to interact with members of this translocon and is required for downstream alteration of host cells. GRA44 was found to be post-translationally cleaved in a region homologous to sequences targeted by protozoan proteases of the secretory pathway with both major cleavage products secreted to the PV. Conditional knockdown of GRA44 resulted in loss of host cell cMyc upregulation, a phenotype also seen in translocon member disruption. Therefore, the putative acid phosphatase GRA44, in association with the translocon complex, is critical for host cell manipulation during infection, a process Toxoplasma relies upon for successful propagation as an intracellular pathogen.en_US
dc.identifier.urihttps://hdl.handle.net/1805/24617
dc.identifier.urihttp://dx.doi.org/10.7912/C2/1918
dc.language.isoen_USen_US
dc.titleCharacterization of a Putative Acid Phosphatase in Toxoplasma Gondii and Its Role in Parasite Propagationen_US
dc.typeThesis
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