Decphering the network of genes involved in the emergence of drug resistance in the human fungal pathogen Candida glabrata

Life threatening infections are an increasing reality. Multi-drug resistant bacteria such as MRSA are present in nearly all hospitals, and community acquired TB is often recalcitrant to treatment. Less well known, but causing four to five times more deaths in the UK than MRSA, are fungi in the genus Candida. These are commonly associated with mucosal infections such as "thrush", but are responsible for > 400,000 life-threatening infections worldwide every year, especially in the immunosuppressed patient population. One of the principle pathogens is Candida glabrata. This fungus grows as a single celled haploid yeast, and is highly resistant to host innate defences and can acquire resistance to many clinically used antifungal drugs, including the frontline azoles and echinocandins. Even with the best possible medical care, infections with this yeast cause ~50% mortality and the incidence of C. glabrata infections is steadily climbing. This demands that novel antifungal therapies are developed that can target drug resistant fungal infections such as C. glabrata. To address this, this project leverages genetic insights into common antifungal resistance mechanisms to identify an achilles heel that can be targeted to prevent resistance. Such an approach could provide a powerful tool in developing treatments for drug resistant infections.