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Rational design of a novel rapid diagnostic tool for coccidioidomycosis

合理设计新型球孢子菌病快速诊断工具

基本信息

批准号：
10668184
负责人：
Bridget Marie Barker
金额：
$ 25.6万
依托单位：
NORTHERN ARIZONA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-23 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10668184
关键词：
Affinity Animals Anti-Bacterial Agents Antibodies Antifungal Agents Antigens Area Bioinformatics Biological Biological Assay Biological Markers Biosensor Blood Centers for Disease Control and Prevention (U.S.)Central America Clinical Clinical Trials Coccidioides Coccidioides immitis Coccidioides posadasii Coccidioidomycosis Coupled Data Data Analyses Dependence Detection Development Diagnosis Diagnostic Diagnostic tests Disease Engineering Escherichia coli Evaluation Filtration Future Gene Proteins Genes Genomics Goals Harvest Health Care Costs Human Hydrocortisone Imagery Immune response In Vitro Incidence Industry Infection Intellectual Property Laboratories Length of Stay Marketing Methodology Methods Molecular Mus Mycoses Outcome Study Patient-Focused Outcomes Patients Performance Phase Polymers Process Protein Secretion Proteins Provider Rapid diagnostics Recombinant Proteins Recombinants Reporting Reproducibility Research Resource-limited setting Sampling Serodiagnoses Serum Soil South America Southwestern United States Specificity Structure of parenchyma of lung Symptoms System Techniques Testing Transcript United States Up-Regulation Validation accurate diagnosis antibody test antigen diagnostic antigen test bacterial community bioelectronics biomarker validation candidate selection community acquired pneumonia cost desert fever design detection limit diagnostic assay diagnostic tool effective therapy experimental study fungus genomic data imprint improved in silico in vivo innovation interdisciplinary approach manufacture model organism novel novel diagnostics novel strategies pathogenic fungus peripheral blood radiological imaging rapid diagnosis rational design reagent testing screening sensor statistics synthetic antibodies synthetic biology time use transcriptome sequencing

项目摘要

Coccidioides immitis and C. posadasii are two species of soil fungi that cause the disease coccidioidomycosis, (or Valley fever), whose incidence has increased 587% over the last 20 years and now causes over 150,000 new infections in the United States annually. The Centers for Disease Control and Prevention (CDC) report that average cost for treating Valley fever is over $50,000 per patient and delays or misdiagnosis of Valley fever result in an average of $590,000 in extra healthcare costs, including extensive hospital stays and a lifetime of treatment. Current Valley fever diagnostic tests are based on proprietary antibodies or antigens, which may not be easily accessed. We propose that advanced genomic analyses of these fungal pathogens can support the identification of new biomarkers and embody the foundational framework that is necessary for development of new diagnostic tools. We aim to improve the diagnostics available for detection of Coccidioides spp. by analyzing existing genomic data and using in silico predictions to identify several putative antigens that are highly expressed during host infection and would likely interact with the host. We will express these novel antigens along with standard control CF and TP antigens from Coccidioides in a model organism (Escherichia coli) and use the protein products to create an electrochemical sensor Molecularly Imprinted Polymer (MIP) diagnostic assay. MIPs are a polymer that has been processed using a molecular imprinting technique which leaves cavities in the polymer matrix with high affinity for a chosen ‘template’ molecule (in our case the antigens expressed by E. coli). When paired with an electrochemical biosensor, MIPs can be the basis for a low-cost diagnostic tool because they mimic biological recognition well enough to be called ‘synthetic antibodies.’ In total, this proposal represents a unique pairing of advanced genomic data analysis and novel diagnostic development in an important, yet understudied, fungal pathogen.

球孢子菌病是引起球孢子菌病的两种土壤真菌。