Defining how cell wall changes during infection affect Cryptococcus neoformans virulence

Cryptococcal meningitis is a disease caused by the pathogen Cryptococcus neoformans (C. neoformans), which targets patients with weakened immunity, such as those with cancer, organ transplant and HIV/AIDS. It kills over 112,000 people living with HIV each year as antifungal drug treatments are currently inadequate. To develop more effective drugs, we need a better understanding of how Cryptococcus causes this terrible disease. The C. neoformans external surface consists of a bi-layered outer shield made of sugars. The outermost layer is gelatinous and called the capsule. The inner layer, the cell wall, is rigid and confers structure and physical strength. Previous research has focussed on the outermost layer, as it protects Cryptococcus from the immune system. However, my research shows the inner cell wall layer, on which the capsule depends, undergoes dynamic changes during infection that are not see in standard laboratory conditions. This project aims to characterise cell wall changes occurring during Cryptococcus infection, and how these changes influence disease progression. As the cell wall is absent in human cells, this project will provide crucial new information that will be required for future antifungal drug development.