Rational design of a novel rapid diagnostic tool for coccidioidomycosis

粗球孢子菌和粗球孢子菌。Posadasii是引起球孢子菌病的两种土壤真菌， (or山谷热），其发病率在过去20年中增加了587%，现在造成超过15万人死亡。 美国每年新增感染病例疾病控制和预防中心（CDC）报告说， 治疗山谷热的平均费用超过每名患者50，000美元， 导致平均590，000美元的额外医疗费用，包括长期住院和终身 治疗目前的山谷热诊断测试是基于专有的抗体或抗原，这可能不 容易获得。我们认为，这些真菌病原体的先进基因组分析可以支持 确定新的生物标志物，并体现发展生物标志物所必需的基础框架。 新的诊断工具我们的目标是改进用于检测球孢子菌属的诊断方法。通过分析 现有的基因组数据，并使用计算机预测来鉴定几种高度 在宿主感染期间表达，并且可能与宿主相互作用。我们将表达这些新的抗原 沿着来自模式生物（大肠杆菌）中球孢子菌属的标准对照CF和TP抗原， 利用蛋白质产物制造电化学传感器分子印迹聚合物（MIP）诊断 比色法分子印迹聚合物是一种聚合物，使用分子印迹技术进行处理， 在聚合物基质中对所选择的“模板”分子具有高亲和力（在我们的情况下， E. coli）。当与电化学生物传感器配对时，MIP可以成为低成本诊断工具的基础 因为它们很好地模拟了生物识别，被称为“合成抗体”。总的来说，这项提案 代表了先进的基因组数据分析和新的诊断发展的独特配对， 重要但尚未充分研究的真菌病原体。

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.