Coordinated responses to host-derived stresses in C. neoformans

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SUMMARY Although potent antifungal agents are currently available, invasive fungal infections remain highly prevalent causes of disease and death, especially in our most vulnerable patients with defective immune systems. AIDS, organ transplantation, and more aggressive cancer treatments all contribute to ever-expanding patient groups who are at risk for these serious infections. Future directions in the treatment of infectious diseases will increasingly involve identifying microbe-specific cellular processes that can be targeted for intervention. In this proposal, we will study central signaling pathways in the human fungal pathogen Cryptococcus neoformans (Cn) that are induced in the setting of infection. We began studying the fungal-specific Rim signaling pathway in Cn as a regulator of surface capsule expression and fungal cell fitness. Using complementary transcriptomic, proteomic, and microbial genetic techniques, we have defined Rim-dependent cellular events in this fungal pathogen that allow rapid microbial adaptation to the host environment. Many of these adaptations occur specifically in response to the pH of the infected host. Therefore, our studies not only address microbial pathogenesis, but they also explore central ways in which eukaryotic cells sense and respond to this important environmental condition.