Characterizing Candida auris skin colonization and high-burden biofilm formation

项目总结 新出现的真菌病原体金黄色念珠菌驻留在皮肤上，在人与人之间迅速传播 医疗保健环境，这是该物种独有的特征。C.Auris皮肤定植使患者面临侵袭性风险 感染，这一诊断伴随着高达60%的死亡率。对金龟子皮肤的再认识 迫切需要殖民，以开发创新的方法来防止这种药物的传播-- 抗药性和致命性的病原体。我们的研究表明，金黄色葡萄球菌在皮肤中形成贴壁的生物膜结构 在体外和猪皮上的条件。对触发这一过程或真菌的因素知之甚少 参与生物膜形成的成分。这个应用程序的第一个目标是识别皮肤状况和 促进金黄色葡萄球菌生物膜生长和皮肤定植的因素。这些数据对于发现真菌是必不可少的 在这一进程中所涉及的途径，并找出防止或减少殖民的新办法。 此外，我们令人信服的初步数据显示，皮肤生态位生物膜显示出更强的能力 产生具有凝聚力的细胞外基质材料。我们的第二个目标是描述 这种细胞外物质。了解基质组成对于识别破坏C。 奥里斯生物膜与皮肤定植有关。这些研究将提供对皮肤机制的第一次洞察 对这一新的全球公共卫生威胁的殖民。我们预计这些研究的结果将会有 设计预防这种耐药性的皮肤定植和传播的方法具有广泛的意义 真菌病原体。

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.