Mechanisms of Candida auris Colonization in the Skin

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Project Summary Candida auris (CA), an emerging multi-drug resistant fungal pathogen that predominately colonizes in the skin has recently been classified as an urgent threat by the US Centers for Disease Control and Prevention (CDC) Antibiotic Threats Report. CA asymptomatically colonizes the skin for prolonged periods and rapidly spreads between hospitalized patients and nursing home residents via nosocomial transmission resulting in outbreaks of systemic infections. CA gains access to the blood in patients requiring indwelling devices leading to invasive infections resulting in mortality ranging from 40 to 60 percent among CA infected patients. Majority of CA isolates exhibit resistance to all three classes of FDA-approved antifungal drugs including azoles, polyenes, and echinocandins posing a significant challenge to treat this fungal pathogen. Therefore, understanding the factors regulating CA skin colonization is important to control CA outbreaks and prevent invasive CA infections. Recently, we have uncovered that skin microbiota regulate the CA skin colonization. Based on our compelling data, we will define the microbiota and host mediated mechanism(s) that control CA skin colonization. In Aim 1, we will define how skin microbiota directly inhibit CA growth and skin colonization and In Aim 2, we will define the host-mediated mechanisms through which skin microbiota regulate CA skin colonization. Understanding the microbiota and host factors in the regulation of CA is expected to lead to a more complete understanding of the factors that control CA skin colonization, with the long-term aim of identifying new antifungal therapeutic strategies.