Cryptococcal meningitis is the most common form of meningitis in human immunodeficiency virus (HIV) infected persons, responsible for over 1 million cases each year resulting in approximately 625, 000 deaths worldwide. Current optimal treatments still result in high mortality rates and more effective antifungal agents are needed urgently. Despite the threat posed by fungal pathogens, there is a shortage of new drugs successfully reaching the market, emphasising the need for more effective drug development strategies. Phenotypic screening using drug repositioning (or repurposing), is now becoming an attractive approach for antimicrobial discovery programmes, with apparent benefits compared to target-based strategies. This was demonstrated in previous work in the Charles Laboratory at the ithree Institute, with the discovery of novel compounds with antimicrobial activity.

Drug repositioning has been explored for Cryptococcus neoformans but not for Cryptococcus gattii, which is responsible for the majority of cryptococcal infections in immunocompetent individuals and has caused outbreaks with a high level of mortality and morbidity. This project aims to: 1) develop a screening protocol to test the FDA-approved Enzo library against C. gattii; 2) identify compounds in the library with significant antifungal activity; and 3) investigate the spectrum of activity of hit compounds against other pathogenic strains and genotypes of Cryptococcus.