Pathogenesis (studies performed in the human pathogen Cryptococcus neoformans)

• How does the human fungal pathogen C. neoformans avoid phagocytosis by host macrophages?
• What molecules does C. neoformans synthesize to communicate with the host?
• What are the molecular functions of C. neoformans virulence genes we have identified?

Why these questions interest us: The impact of human disease caused by fungal pathogens is high. One estimate suggests that the health care costs of systemic fungal infections in the US are $2.6 billion annually. Most human fungal pathogens are opportunists that produce the most severe outcomes in immunocompromised patients.  Thus, fungi are a major cause of death among premature infants, patients with hematopoietic malignancies, cancer chemotherapy patients, organ transplant recipients, diabetics, critical care patients, and HIV-infected individuals. The impact of fungal infections continues to grow as these patient populations increase in size.  Because of the comparatively close evolutionary kinship of fungi to humans, far fewer antifungal drugs exist than antibacterial antibiotics. 
            Cryptococcus neoformans is one of the leading causes of morbidity and mortality in AIDS patients, resulting in one million cases and 600,000 deaths annually worldwide. 1 Infection leads to a meningoencephalitis that is uniformly fatal if untreated. In addition to its high worldwide clinical impact, C. neoformans has become an excellent model system for the study of fungal pathogenesis mechanisms. In contrast to most other major human fungal pathogens, it is haploid, has a well-characterized sexual cycle and highly amenable to genetics. Both gene knockout and insertional mutagenesis strategies are available and excellent animal models for infection exist. Thus, in addition to being an important fungal pathogen, it is an outstanding model system for investigating mechanisms by which pathogenic fungi subvert host defenses.

Our progress in this area can be found in our publications on fungal pathogenesis mechanisms: click here.