PROJECT SUMMARY The emerging fungal pathogen Candida auris resides on skin and spreads rapidly person-to-person in healthcare settings, a trait unique to this species. C. auris skin colonization places patients at risk for invasive infection, a diagnosis that accompanies a mortality rate as high as 60%. Further understanding of C. auris skin colonization is urgently needed for the development of innovative approaches to prevent spread of this drug- resistant and deadly pathogen. Our studies show that C. auris forms adherent biofilm structures in skin conditions in vitro and on porcine skin. Little is known about factors triggering this process or the fungal components involved in biofilm formation. The first objective of this application is to identify skin conditions and factors that promote C. auris biofilm growth and skin colonization. These data are essential to uncover fungal pathways involved in this process and to identify new approaches to prevent or reduce colonization. Furthermore, our compelling preliminary data show that skin niche biofilms exhibit a heightened capacity to produce a cohesive, extracellular matrix material. Our second objective is to characterize the components of this extracellular material. Knowledge of the matrix composition is critical to identify targets to disrupt the C. auris biofilms involved in skin colonization. These studies will provide the first insights into mechanisms of skin colonization for this emerging global public health threat. We anticipate the results of these studies will have broad implications for designing approaches to prevent skin colonization and transmission of this drug-resistant fungal pathogen.