Defining Molecular Mechanism of Egress in Cryptosporidium

Recent studies have identified Cryptosporidium as a major contributor to childhood disease in endemic areas. Current interventions are not ideal where only few have demonstrated anti-cryptosporidial activity and are often associated with relapses in infection. A vaccine to protect or reduce severity of infection would be ideal to protect young children who are most susceptible to complications associated with disease. Obstacles in vaccine development stem from limited understanding of gene function in the parasite. Merozoite egress is a crucial event in the life cycle of Cryptosporidium that contributes to parasite propagation. However, the molecular mechanisms behind egress remain unknown. We propose to study the genes upregulated in the intracellular stages of infection using a novel silencing method developed in our lab. Our aim was to analyze the C. parvum orthologues of molecules that mediate egress for other apicomplexans. Here we tested the hypothesis that calcium-dependent protein kinase 5 (CDPK5), subtilisin-like serine protease (SUB1), and cGMP-dependent protein kinase G (PKG) are essential for egress of Cryptosporidium parvum merozoites from host cells. Our results demonstrated that PKG and SUB1 are crucial mediators of merozoite egress, while CDPK5 did not seem to play a role. Cryptosporidiosis affects millions of people worldwide with no licensed vaccine available. Results from this study could contribute to the development of an attenuated vaccine for Cryptosporidium. Development of a vaccine that could prevent establishment of infection in young children would be a major advance in preventing the detrimental effects from infection.

Name thesis:degree_name

Microbiology and Immunology (Doctoral)

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Nava, Samantha

• Cryptosporidium, egress

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/11310

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/11310