Characterizing Candida auris skin colonization and high-burden biofilm formation

耳念珠菌皮肤定植和高负荷生物膜形成的特征

• 批准号: 10194141
• 负责人: Jeniel E Nett
• 金额: $ 19.41万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-03 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194141
• 关键词: Blood Circulation; Blood Vessels; Candida; Candida auris; Carbohydrates; Catheters; Critical Pathways; Data; Data Set; Development; Diagnosis; Digestion; Disease; Disease Outbreaks; Dissection; Drug resistance; Environmental Risk Factor; Epithelial; Exhibits; Extracellular Matrix; Family suidae; Foundations; Fungal Components; Future; Genes; Growth; Health care facility; Hospitals; Immunosuppression; In Vitro; Infection; Knowledge; Label; Light; Lipids; Medical Device; Microbial Biofilms; Modeling; Molecular; Nucleic Acids; Pathway interactions; Patients; Persons; Polysaccharides; Process; Production; Proliferating; Proteins; Public Health; Pyruvate; Risk; Skin; Skin colonization; Structure; Surface; Testing; Weight; Work; Yeasts; base; cohesion; design; drug resistant pathogen; experimental study; extracellular; fungus; gut colonization; health care settings; in vivo; innovation; insight; macromolecule; mortality; novel; novel strategies; pathogen; pathogenic fungus; porcine model; prevent; trait; transmission process

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.

项目摘要 新出现的真菌病原体耳念珠菌驻留在皮肤上，并在人与人之间迅速传播， 医疗机构，这是这个物种独有的特征。C.耳皮肤定植使患者面临侵入性 感染，诊断伴随死亡率高达60%。对C.耳皮肤 殖民化是迫切需要发展创新的方法，以防止这种药物的传播- 耐药且致命的病原体研究表明，C.耳在皮肤中形成粘附的生物膜结构 在体外和猪皮肤上的条件。关于触发这一过程的因素或真菌 参与生物膜形成的成分。本申请的第一个目的是识别皮肤状况， 促进C.耳生物膜生长和皮肤定植。这些数据对于揭示真菌 研究人员正在研究这一过程所涉及的途径，并确定防止或减少殖民化的新方法。 此外，我们令人信服的初步数据表明，皮肤生态位生物膜表现出更高的能力， 产生粘性的细胞外基质材料。我们的第二个目标是描述 这种细胞外物质。基质组成的知识对于确定破坏C的目标至关重要。 耳生物膜参与皮肤定植。这些研究将提供第一个深入了解皮肤的机制， 这一新兴的全球公共卫生威胁的殖民化。我们预计这些研究的结果将 广泛的影响，设计方法，以防止皮肤定植和传播这种耐药 真菌病原体