Cryptococcus neoformans is a saprophytic fungal pathogen that predominantly causes disease in Acquired Immuno Deficiency Syndrome (AIDS) patients and cryptococcosis is consequently classified as an AIDS-defining illness (Perfect 2014). Although AIDS treatments have improved over the years the drug therapy against C. neoformans has not. The three currently recommended drugs have long been off patent and require long-term use to avoid relapse (Loyse, Thangaraj et al. 2013). However prolonged use of antifungals runs the risk of toxicity, development of resistance and is expensive. Because of this new antifungals are urgently needed to improve survival rates and availability in developing countries where they are often needed most.

De novo GTP biosynthesis has been previously identified as being essential in C. neoformans and subsequently this project aims to solve the structure of the second committed enzyme in this pathway, GMP synthase, in order to identify regions that may be exploited for drug design. Low homology with the human enzyme indicates that drugs may be developed to select against C. neoformans. Deletion of the gene encoding the enzyme results in guanine auotrophy, growth defects and loss of virulence in a mammalian model. To further investigate enzyme function and structural analyze where performed. Combining these studies have allowed insights into possible differences exploitable in antifungal development.