Gene Expression of Diverse Cryptococcus Isolates during Infection of the Human Central Nervous System
Chen-Hsin Yu, Poppy Sephton-Clark, Jennifer L. Tenor, Dena L. Toffaletti, Charles Giamberardino, Miriam Haverkamp, Christina A. Cuomo, John R. Perfect
Abstract
Cryptococcus is the most common fungus causing high-morbidity and -mortality human meningitis. This encapsulated yeast has a unique propensity to travel to the central nervous system to produce disease. In this study, we captured transcriptomes of yeasts directly out of the human cerebrospinal fluid, the most concerning site of infection. By comparing the RNA transcript levels with other conditions, we gained insights into how the basic machinery involved in metabolism and environmental responses enable this fungus to cause disease at this body site. This approach was applied to clinical isolates with diverse genotypes to begin to establish a genotype-agnostic understanding of how the yeast responds to stress. Based on these results, future studies can focus on how these genes and their pathways and networks can be targeted with new therapeutics and possibly classify yeasts with bad infection outcomes.