Exploring the Molecular Interactions Between Host Cells and Cryptosporidium parvum During Invasion
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Cryptosporidium parvum is a zoonotic protozoan parasite belonging to the Phylum Apicomplexa and a causative agent of mild to severe watery diarrhea in humans and animals. The infection starts with the ingestion of oocysts, often from contaminated water, followed by the release of four sporozoites from individual oocysts in the small intestine and the invasion of sporozoites into intestinal epithelial cells. A unique, host cell-derived parasitophorous vacuole membrane (PVM) will be formed during the parasite invasion to contain the intracellular developing parasites. However, the essential molecular interactions between the parasite and host cells during infection and the mechanism of PVM formation are poorly understood. The study employed two approaches to study the molecular mechanisms of invasion by the C. parvum sporozoites. The first approach focused on identifying host cell factors, in which three host cell mutants generated with UV-irradiation-based mutagenesis have significantly increased resistance to the invasion by C. parvum sporozoites. One of the mutants was significantly resistant to the attachment of sporozoites onto host cells, and can be used to identify genes and pathways responsible for the parasite attachment by forward genetics. The second approach focused on a multifunctional parasite protein, which is discharged to the host cell surface during the parasite invasion. There was strong evidence indicating that this parasite protein participated in the aggregation of host cell filamentous actin (F-actin) and was associated with the formation of PVM. This study has not only generated new knowledge towards understanding the mechanisms of C. parvum infection, but also identified new directions to further explore the molecular pathways in the host cells and the parasites responsible for the parasite invasion.
Yu, Xue (2018). Exploring the Molecular Interactions Between Host Cells and Cryptosporidium parvum During Invasion. Doctoral dissertation, Texas A & M University. Available electronically from