Alexander Ballesteros
Pronouns: He/Him
Research Mentor(s): Michal Olszewski
Research Mentor School/College/Department: Internal Medicine, Pulmonary and Critical Care Medicine / Medicine
Program:
Authors: Kristie Goughenour, Rylan Hissong, Michal Olszewski
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 56
Abstract
Fungal infections have become a prominent issue among immunocompromised individuals and limited options are available for the treatment of fungal pathogens. Cryptococcus neformans is a pathogenic fungus for which HIV/AIDS, SCID, and secondary immunocompromised patients are all at high risk of infection. The mortality in this population is quite high, and this can be solved through urgently needed novel drugs targeting unique pathways in fungal pathogens. A pathway that has proven to be required for virulence in several pathogenic fungi is Trehalose-6 Phosphate Synthase or TPS. TPS is linked to polysaccharide capsule formation around cryptococcus cells, allowing its survival and immune evasion in the host environment. Trehalose allows for an increased cellular resistance to osmotic pressures and bypass of the thermal restriction zone. Neutrophils are the most numerous inflammatory cells in the human body and are key components of the immune system, with an important role against fungal pathogens. In this study, we would ask when Trehalose is required for virulence and how it would alter the immune response, specifically in response to neutrophils. In a pulmonary infection model, mice cleared tps-1-deficient C. neformans reducing it 10,000-fold within 72 hours post-infection. Tps1-deficient C. neo triggered improved neutrophil recruitment into infected lungs within this window of time and Tps1-deficient C. neo cell were prone to neutrophil killing in vitro as well. These results suggest that the TPS pathway is required for fungal evasion of neutrophil responses and its blocking with a drug compound may arm these cells against the fungus.
