Elucidating the impact of chitin and chitin-like structures on C. neoformans virulence

Meningitis caused by the fungal pathogen Cryptococcus neoformans affect around 152,000 patients with HIV/AIDS and kills around 112,000 of those patients every year. The high mortality associated with this fungus indicates that current therapy against Cryptococcus is inadequate. There is, therefore, a need for new treatment strategies to improve the patient outcome. To develop new treatment, we need to understand how this fungus cause disease in humans. This proposal achieves this through an examining of key elements of the cell wall of this fungus that drive pathogenesis.
Cryptococcus has a two layered outer shield made of sugars. The outermost layer is called the capsule and is gelatinous in nature and inner one, the cell wall is rigid and confers structure and physical strength. This project focuses on understanding the link between components of the cell wall (chitin structures) and the ability of Cryptococcus to cause disease in humans. We will determine the structure and position of these components in the cell wall of Cryptococcus isolates collected from patients suffering from Cryptococcus meningitis. In addition, we will identify how differences in these cell wall structures impact the host immune responses against Cryptococcus.