Detecting released peptidoglycan fragments as a biomarker for direct diagnosis of acute and chronic Lyme disease

检测释放的肽聚糖片段作为直接诊断急性和慢性莱姆病的生物标志物

• 批准号: 10195072
• 负责人: Brandon Lyon Jutras
• 金额: $ 24.81万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-11 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10195072
• 关键词: Acute; Antibiotic Therapy; Antibiotics; Antibodies; Antibody Response; Arthritis; Bacteria; Biological Assay; Biological Markers; Borrelia; Borrelia burgdorferi; Carditis; Cell Wall; Cells; Cerebrospinal Fluid; Chemicals; Chronic; Clinical; Common Epitope; Country; Coupled; Cutaneous; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dose; Early Diagnosis; Environment; Enzyme-Linked Immunosorbent Assay; Epidemic; Growth; Heart; Human; Immune response; Immunoglobulin G; Infection; Insurance; Intravenous; Joints; Lead; Liquid substance; Lyme Arthritis; Lyme Disease; Measures; Mediating; Methods; Mus; Neurologic; Oral; Patient-Focused Outcomes; Patients; Peptidoglycan; Physicians; Proxy; Publishing; Radiolabeled; Reporting; Research Personnel; Residual state; Sampling; Sensitivity and Specificity; Serum; Specificity; Symptoms; Synovial Fluid; Synovial Membrane; System; Test Result; Testing; Tick-Borne Infections; Ticks; Tissues; United States; United States National Institutes of Health; Urine; Vector-transmitted infectious disease; acute infection; biobank; cross reactivity; detection method; detection test; disease diagnosis; experience; flu; improved; men; mouse model; next generation; novel; novel diagnostics; transmission process; virtual

ABSTRACT. Lyme disease is caused by the bacterium Borrelia burgdorferi, and several closely related genospecies. Over the past 25 years, the number of Lyme disease cases have increased ~ 1500% making it the number one reported vector-borne disease in the United States. Upon infection, patients have mild, flu-like symptoms that can go on to be more severe. In later stages, even after antibiotic therapy, patients can experience heart, joint, and neurological problems. Despite the dramatic increase, and potentially devastating consequences, diagnosing Lyme disease is still a major challenge. Current diagnostic testing for Lyme disease is indirect— measuring an antibody response to the most common epitope(s). Indirect testing reports on exposure, not active infection. Furthermore, producing detectable titers can take weeks, and even still, the false negative rate is estimated to be high. The lead investigator of this proposal discovered that B. burgdorferi sheds ~45% of its peptidoglycan (PG)—the essential component of the bacterial cell-wall—from inside the cell, into its environment. B. burgdorferi PG can be detected in the synovial fluid of Lyme arthritis patients’ months after oral and/or intravenous antibiotics. Virtually all bacteria possess PG, but, as it turns out, the PG of B. burgdorferi is extremely unique, but conserved among Lyme Borreliae. These findings led us to hypothesize that the detection of shed B. burgdorferi PG fragments can act as a biomarker for both acute and late stages of the disease. Using previously developed methods, in conjunction with a novel Immuno-PCR approach, we will test the sensitivity and specificity of our assays, in experimentally infected mice and in human samples, at different stages of disease and treatment. Our studies promise to provide the first direct diagnostic test for Lyme disease.

抽象的。 莱姆病是由伯氏伯氏菌和几种密切相关的基因种引起的。超过 过去25年，莱姆病病例的数量增加了约1500％，使其成为第一 报道了美国的载体传播疾病。感染后，患者患有轻度流感样症状 可以继续变得更加严重。在以后的阶段，即使经过抗生素治疗，患者也可以体验心脏，关节， 和神经问题。尽管有巨大的增长和潜在的毁灭性后果，但 诊断莱姆病仍然是一个主要挑战。当前对莱姆病的诊断测试是间接的 测量对最常见表位的抗体反应。间接测试有关暴露的报告，不活动 感染。此外，产生可检测的滴度可能需要数周的时间，即使是，假负率仍然是 估计为高。该提案的主要研究人员发现，B。Burgdorferi占用了约45％ 肽聚糖（PG）（PG）（细菌细胞壁的重要成分）从细胞内到其环境。 在口服后几个月和/或 静脉注射抗生素。几乎所有广播都有PG，但是事实证明，B。Brgdorferi的PG非常 独特，但在莱姆疏螺旋体中配置。这些发现使我们假设棚屋的检测 B. burgdorferi pg碎片可以充当该疾病的急性和晚期的生物标志物。使用 先前开发的方法，以及一种新型的免疫PCR方法，我们将测试灵敏度 在我们的评估，实验感染的小鼠和人类样品中的特异性和在不同阶段 疾病和治疗。我们的研究有望为莱姆病提供首次直接诊断测试。