Glycomics-driven diagnostics for Candida auris

糖组学驱动的耳念珠菌诊断

• 批准号: 10302987
• 负责人: VISHNU CHATURVEDI
• 金额: $ 25.32万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302987
• 关键词: Adherence; Adhesions; Admission activity; Alcohols; Area; Bathing; Binding; Biological Assay; Biophysics; Blood; Candida auris; Cell Wall; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemistry; Chlorhexidine; Clinical; Communicable Diseases; DNA; Decontamination; Detection; Development; Diagnostic; Diagnostic tests; Disease Outbreaks; Disinfectants; Ear; Early Diagnosis; Elements; Epidemiology; Genome; Glycobiology; Goals; Health; Health care facility; Healthcare; Hospital Nursing; Hospitals; Human; Immunoglobulin G; Infection; Institutes; Iodine; Knowledge; Laboratories; Long-Term Care; Mannans; Mass Spectrum Analysis; Methods; Mycoses; New Jersey; New York; Nursing Homes; Organism; Patient Isolation; Patients; Point of Care Technology; Polysaccharides; Prevalence Study; Principal Investigator; Property; Proteins; Public Health; Puncture procedure; Rapid diagnostics; Reporting; Residual state; Sampling; Site; Skin; Skin colonization; Soaps; Specimen; Structure; Surface Plasmon Resonance; Suspensions; Swab; Systemic infection; Testing; The science of Mycology; Time; Tissues; United States National Institutes of Health; Urine; Validation; Yeasts; base; biomarker discovery; design; design and construction; experience; hospital laboratories; innovation; insight; metropolitan; microbiome; pathogen; point of care testing; rapid detection; rapid test; response; screening; tool; whole genome; wound

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.

项目摘要/摘要 念珠菌引起与医疗相关的真菌感染。 C. Auris在皮肤上定居，耳朵（因此 名称“ Auris”）和其他身体部位。 C. Auris随后进入身体会导致全身感染和 可能的死亡。 C. c. auris殖民的人皮肤殖民地均很难放射性，尽管洗澡和 病原体在医院和护士房屋中无生命物体上的持久性需要使用漂白剂 和孢子系消毒剂。缺乏对C. auris的粘附特性的机械洞察力。自从 2013年，在美国，尤其是在纽约大都会 区域。纽约州卫生部（NYSDOH）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个医疗机构的病例，包括59家医院和92家护士房屋。 Nysdoh的Wadsworth Center Mycology实验室（WC）和流行病学的分工已经发展为 验证了对Auris的快速，高通量PCR测试以及创新的监视，入学筛查和 点患病率研究。新的PCR测试分发给了纽约医院实验室，也部署了 其他州和地方公共卫生实验室的疾病控制中心（CDC）。但是，可用性 PCR测试的限制仍然受到限制，结果仅在24-48 h后才获得。因此，有差距 早期检测到奥里斯的实验室能力。 Rensselaer理工学院的Linhardt实验室 Institute（RPI）以其在传染病的糖原中的创新而闻名，并设计出独特的诊断 工具。 Linhardt和Chaturvedi实验室合作发现了一个独特的C. Auris Mannan，其独特 1,2个链接，对于与人IgG的相互作用至关重要。这一发现将通过设计 基于聚糖的快速诊断测试。拟议的项目有两个目标：目标1是表征 C.来自不同进化枝的Auris细胞壁甘氨酸，并通过SPR/MS方法优化聚糖检测。目标2是 开发签名，尿液和血液残留的Auris免疫色谱法测定法（ICA）测试 人类标本，并执行符合实验室开发测试（LDT）要求的验证。 该NIH R21项目旨在满足NIH PA-阐明的真菌诊断创新目标 19-081。