Mechanisms of Candida auris Colonization in the Skin

项目摘要 耳念珠菌（CA）是一种主要在皮肤中定植的新型多药耐药真菌病原体 最近被美国疾病控制和预防中心（CDC）列为紧急威胁 抗生素威胁报告。CA无症状地长时间定殖于皮肤并迅速传播 在住院病人和疗养院居民之间通过医院传播， 全身感染CA在需要留置器械的患者中获得血液，导致侵入性 感染导致CA感染患者的死亡率为40%至60%。大多数CA分离株 对所有三类FDA批准的抗真菌药物（包括唑类、多烯类和 棘白菌素对治疗这种真菌病原体构成了重大挑战。因此，了解这些因素 调节CA皮肤定殖对于控制CA爆发和预防侵袭性CA感染是重要的。 最近，我们发现皮肤微生物群调节CA皮肤定植。基于我们令人信服的 数据，我们将定义控制CA皮肤定殖的微生物群和宿主介导的机制。在目标1中， 我们将定义皮肤微生物群如何直接抑制CA生长和皮肤定植，在目标2中，我们将定义 宿主介导的皮肤微生物群调节CA皮肤定植的机制。了解 微生物群和宿主因素在CA的调节，预计将导致更全面的了解， 控制CA皮肤定植的因素，长期目标是确定新的抗真菌治疗方法 战略布局

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.