Glycomics-driven diagnostics for Candida auris

项目摘要/摘要 金黄色念珠菌会引起医疗保健相关的真菌感染。C.Auris在皮肤、耳朵上定居(因此 代号“Auris”)，以及其他身体部位。C.Auris随后进入人体会导致全身感染和 可能是死亡。C.Auris对人类皮肤的定植很难根除，尽管洗必泰洗澡和 要使病原体在医院和疗养院的无生命物体上持续存在，需要使用漂白剂 和杀孢子剂消毒剂。对金龟子的粘附性缺乏机械论的洞察。自.以来 2013年，美国的奥里斯感染病例激增1,200多例，特别是在纽约大都市 区域。纽约州卫生局记录了641例临床病例和849例筛查 截至2020年10月23日，来自151家医疗机构的病例，包括59家医院和92家疗养院。 Nysdoh的沃兹沃斯中心真菌实验室(WC)和流行病学部开发并 经过验证的快速、高通量的PCR检测金黄色葡萄球菌，并创新了监测、入院筛查和 时点流行率研究。新的聚合酶链式反应检测被分发给纽约医院的实验室，并由 疾病控制中心(CDC)在其他州和地方公共卫生实验室。然而，可用性 仍然受到限制，而且只有在24-48小时后才能得到结果。因此，在 早期检测金黄色葡萄球菌的实验室能力。伦斯勒理工学院的林哈特实验室 RPI研究所(RPI)以其在传染病的糖组学方面的创新和设计独特的诊断方法而闻名 工具。林哈特和查图尔维迪实验室合作发现了一种独特的具有独特的奥里斯甘露聚糖- 1，2连接，这是与人免疫球蛋白相互作用的关键。这一发现将通过设计一种 基于多糖的金黄色葡萄球菌快速诊断试验。拟议的项目有两个目标：目标1是描述 金合欢胞壁糖来源于不同支系，并优化了SPR/MS检测方法。目标2是 建立一种检测拭子、尿液和血液残留物的金黄色葡萄球菌免疫层析法(ICA) 人体样本，并执行符合实验室开发的测试(LDT)要求的验证。 NIH R21项目旨在满足NIH PA阐述的真菌诊断创新目标- 19-081.

Project Summary/Abstract Candida auris causes healthcare-associated fungal infections. C. auris colonizes the skin, ears (hence the designation ‘auris’), and other body sites. C. auris subsequent entry into the body leads to systemic infection and possible death. C. auris colonization of the human skin is difficult to eradicate despite chlorhexidine bathing and the persistence of the pathogen on inanimate objects in the hospitals and nursing homes requires use of bleach and sporicide disinfectants. There is a lack of mechanistic insight into the adherence properties of C. auris. Since 2013, there has been a surge of over 1,200 C. auris infections in the US, particularly in the New York metropolitan area. The New York State Department of Health (NYSDOH) documented 641 clinical cases and 849 screening cases from 151 healthcare facilities, including 59 hospitals and 92 nursing homes as of October 23, 2020. NYSDOH’s Wadsworth Center Mycology Laboratory (WC) and Division of Epidemiology developed and validated rapid, high-throughput PCR tests for C. auris, and innovated surveillance, admission screening, and point prevalence studies. The new PCR tests were distributed to NY hospital laboratories and also deployed by the Center for Disease Control (CDC) in other state and local public health laboratories. However, the availability of PCR tests remains restricted, and the results are available only after 24-48 h. Therefore, there is a gap in the laboratory capacity for the early detection of C. auris. The Linhardt Laboratory at the Rensselaer Polytechnic Institute (RPI) is known for its innovations in glycomics of infectious diseases and for devising unique diagnostic tools. The Linhardt and Chaturvedi Laboratories collaboratively found a unique C. auris mannan with distinct - 1,2 linkages, which are crucial for interactions with human IgG. This discovery will be expanded by devising a rapid glycan-based diagnostic test for C. auris. The proposed project has two aims: Aim 1 is to characterize the C. auris cell wall glycome from different clades and optimize glycan detection by SPR/MS methods. Aim 2 is to develop a C. auris immunochromatography assay (ICA) point-of-care test for swab, urine, and blood residual human specimens, and perform a validation compliant with the laboratory-developed test (LDT) requirements. This NIH R21 project has been designed to meet the fungal diagnostic innovation goals enunciated in NIH PA- 19-081.