Grant: Operating Grant

Fungal infections can be extremely dangerous, especially for the elderly, infants and the critically ill. Even with our current collection of antifungal drugs, we are unable to effectively treat some infections, and as a consequence the mortality rate for fungal infections such as invasive candidiasis and aspergilosis is unacceptably high (e.g. up to 50% for patients with compromised immune systems). This implies that research on fungal infections is needed. In this proposal, we will examine how fungi make a major component of their cell wall known as mannan. Mannan is one of the main components of fungi that first interact with us (fungal-host interaction), and this interaction impacts how our immune system responds to the fungal infection. Moreover, the amount of mannan modulates how dangerous fungi are (virulence). Because of the importance of mannan for fungal-host interactions and virulence, we will study the enzymes that synthesize mannan, by elucidating their three-dimensional shape and how they facilitate chemical reactions. This information can be exploited for antifungal therapy development that reduces the virulence of fungal infections.