PhD (Doctor of Philosophy)
Date of Award
Committee Chair or Co-Chairs
James Russell Hayman
Patrick Bradshaw, Jennifer Vanover Hall, Christopher L. Pritchett, Antonio E. Rusinol
Microsporidia are a distant fungal pathogen that have severe clinical consequences for the immunocompromised. Previous work identified a microsporidian pathogen protein termed Microsporidian ADAM or MADAM. This protein has close sequence homology to other ADAM proteins (A Disintegrin and Metalloproteinase) in two microsporidian species, Encephalitozoon intestinalis and E. cuniculi. ADAM proteins have a wide range of functions, including binding to integrins and host signaling. It is known that many pathogens manipulate integrins to invade host cells, and it is predicted that microsporidia are also exploiting this host target. Previous work with the MADAM protein demonstrated that this protein has a role in adherence to host cells. Separate work showed integrin inhibitors can also decrease spore adherence to cells. Experiments in this project complement previous research and further characterize the binding of microsporidia to host integrins and the intracellular consequences of that binding. This work found the integrin binding sequence of MADAM (MADAM peptide) is important for spore binding to host cells. Separate work shows that the host β1 integrin is also involved in spore adherence. Additional work demonstrated that spores and the MADAM peptide elicited an increase in host integrin signaling in Western blotting experiments. And finally, preliminary acellular interferometry experiments suggest the MADAM protein binds specifically to α5β1 and α6β4 integrins. Together, these results suggest microsporidia spores rely, in part, on host integrins to bind to host cells before infection.
Dissertation - embargo
Barrett, Cindy L., "Microsporidian Spores and the Integrin Binding Loop of the MADAM Protein Are Important for Integrin Signaling and Attachment to Host Cells" (2023). Electronic Theses and Dissertations. Paper 4264. https://dc.etsu.edu/etd/4264
Copyright by the authors.
Available for download on Sunday, September 15, 2024