Grant: Project Grant

Fungal pathogens have a devastating impact on human health. They infect billions of people worldwide and kill more than 2.5 million per year. At greatest risk are people with reduced immune function, including individuals with HIV or undergoing immune-suppressing treatments for cancer or organ transplantation. One of the most alarming fungal pathogens of humans is Candida auris, which was discovered in 2009. It is now causing outbreaks around the globe with unprecedented resistance to the three major classes of antifungal drugs, and is classified as a critical priority fungal pathogen by the World Health Organization. To address the urgent need for new therapeutics that are effective against C. auris, it is critical to uncover the genes that are required for the pathogen to survive and cause disease, and to identify molecules that inhibit the products of these genes. We are building the first collection of C. auris mutants to allow us to identify and characterize essential genes. We will use sophisticated computational approaches to predict essential genes based on our work in other fungal pathogens, and will expand a genomic resource to cover all predicted essential genes. This resource will provide an unprecedented opportunity to identify which genes are essential to the pathogen, and to determine their molecular function. We will use this platform to characterize the impact of reducing the dosage of each gene on fungal growth, physiology, and traits associated with the capacity to cause disease. We will perform state-of-the-art screens to identify molecules that target essential gene products, and will evaluate their therapeutic potential. This research will reveal new approaches to cripple a deadly fungal pathogen, and will enable development of novel therapeutic strategies to improve clinical outcome for millions of people.