Arianna Creech
Pronouns: she, her
Research Mentor(s): Michal Olszewski
Research Mentor School/College/Department: /
Program: RS
Session: Session 1 (9:00am – 9:50am)
Authors: Arianna Creech, Kristie Goughenour, Jintao Xu, Michal Olszewski
Abstract
Cryptococcus neoformans is an opportunistic fungi found naturally in the environment and can cause severe meningoencephalitis in immunocompromised individuals. Cryptococcal infection causes about 200,000 deaths yearly worldwide. Current anti-fungal medications are limited to a few classes of drugs and often have significant toxicity for the patients. Thus, there is a significant need to direct attention to novel drug targets found in fungi and not mammals. In C. neoformans, there is a biosynthetic pathway that converts glucose-6-phosphate into the sugar trehalose, using the two-step pathway containing two trehalose phosphate synthase (TPS) genes, TPS1 and TPS2. Trehalose is found in fungi, bacteria, plants, and invertebrates, but not in mammals. This makes it an excellent potential therapeutic target. Our previous work has shown that trehalose is required for virulence early in C. neoformans infections in mice. Surfactant protein A (SPA) and Surfactant protein D (SPD) are major, well-characterized proteins found in the alveoli of the lungs and are involved in of the first lines of defense, when something foreign enters the lungs. Through in vitro co-culture, we determined that tps1-defiecent C. neo was more sensitive to these proteins, than wildtype fungi. To investigate this in vivo, we validated our model in the wildtype background of the SPA and SPD KO mice, C57BL/6. Having established that SPA and SPD have a critical role in in vitro control of tps1-deficient Cryptococcus, we now will move towards examining its role in in vivo models using the validated SPA and SPD KO mice model.
