Molecular mechanisms of fungal pathogenesis

Our lab investigates the mechanisms that promote the pathogenesis of Candida albicans.  This human fungal pathogen can infect a broad range of sites in including skin, mucosa and internal organs.  Lethal systemic infections caused by C. albicans are on the rise as new medical treatments are increasing the pool of susceptible individuals.  Therefore, our studies are aimed at identifying the genes that promote virulence.

The lethal effects of C. albicans are due to its ability to grow in the host and disseminate to internal organs.  Two of the major underlying factors are the ability of C. albicans to resist stress and to undergo invasive hyphal growth.  Our recent research has focused on the roles of the plasma membrane in these processes.  This essential barrier mediates secretion of virulence factors, morphogenesis, cell wall synthesis, interfaces with the extracellular environment, and is the first line of attack by the immune system.  As part of our work, we examined the role in virulence of specialized plasma membrane subdomains known as eisosomes.  These ~200 nm domains contain a special set of proteins that regulate stress resistance and invasive hyphal growth.

Our studies have identified Sur7 as one of the key proteins present in eisosomes.  Sur7 promotes virulence by acting as a novel regulator of membrane lipids.  Its functions include regulating the levels of the key signaling lipid PI4,5P2 that is important for proper cell wall morphogenesis and invasive growth.  Sur7 also indirectly regulates plasma membrane lipid asymmetry between the inner and outer leaflets, which is important for resisting stress in the host.

We also discovered that eisosomes contain a family of four flavodoxin-like proteins that represent a new antioxidant pathway that protects the plasma membrane from oxidative attack by the host immune system.  Current studies are aimed at better defining the pathways that protect the plasma membrane from the stressful environments encountered in the host.

Altogether, the goal of our research is to identify new avenues for development of antifungal drugs and to provide a better understanding of the mechanisms of current antifungal drugs that will enable them to be used more effectively.