Date of Award
Master of Science (MS)
Robert L. McFeeters
Antifungal agents--Research., Cryptococcus neoformans., Lectins.
The pathogenic encapsulated yeast Cryptococcus neoformans causes a majority of fungal disease related deaths worldwide from pulmonary infections, meningitis, or meningoencephalitis. Loss of efficacy in current treatment options against C. neoformans and the emergence of antifungal drug resistance call for the development of new therapeutics. High mannose binding lectins such as Scytovirin have been shown to be promising anticryptococcal drug candidates. In this work, a homologous antifungal lectin, Myxovirin, was structurally engineered in an effort to improve both its carbohydrate binding affinity and its anticryptococcal activity. Carbohydrate binding was studied using both isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. The efficacy of a Myxovirin/synthetic antifungal peptide chimera was investigated by a microdilution antifungal assay. The carbohydrate binding affinity of Myxovirin was characterized, yet no significant changes in affinity were observed among the engineered mutants. Further optimization of the chimeric protein construct is necessary to produce a more potent antifungal agent. Overall, these findings provide a better understanding of using high mannose binding lectins as anticryptococcal therapeutics.
Osier, Jessica L., "Structural engineering of the antifungal high mannose binding lectin myxovirin" (2019). Theses. 285.