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

基本信息

批准号：
10369673
负责人：
Brandon Lyon Jutras
金额：
$ 19.29万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-11 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369673
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 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 Lyme disease diagnosis Lyme disease diagnostic Measures Mediating Methods Mus Neurologic Oral Patient-Focused Outcomes Patients Peptidoglycan Persons 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 experience flu improved men mouse model next generation novel novel diagnostics transmission process virtual

项目摘要

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。莱姆病是由伯氏疏螺旋体和几个密切相关的基因种引起的。过去 25 年，莱姆病病例数增加了约 1500%，成为第一大疾病据报道，美国有媒介传播疾病，感染后患者会出现轻微的流感样症状。在后期，即使经过抗生素治疗，患者也会出现心脏、关节、尽管数量急剧增加，并可能带来毁灭性的后果，诊断莱姆病仍然是一个重大挑战，目前莱姆病的诊断测试是间接的。测量抗体对最常见表位的反应，间接检测报告的暴露情况，而非活性表位。此外，产生可检测的滴度可能需要数周时间，即使如此，假阴性率仍然很高该提案的首席研究员发现伯氏疏螺旋体的脱落量约为 45%。肽聚糖 (PG)——细菌细胞壁的重要组成部分——从细胞内部进入其环境。莱姆关节炎患者口服和/或口服后几个月的滑液中可以检测到伯氏疏螺旋体 PG 几乎所有细菌都具有 PG，但事实证明，伯氏疏螺旋体的 PG 极其严重。这些发现使我们认为，莱姆疏螺旋体的检测是独特的，但是保守的。伯氏疏螺旋体 PG 片段可以作为疾病急性期和晚期的生物标志物。先前开发的方法，结合新型免疫 PCR 方法，我们将测试灵敏度以及我们的检测的特异性，在实验感染的小鼠和人类样本中，在不同的阶段我们的研究有望为莱姆病提供第一个直接诊断测试。