Dr. Catherine Brissette, Ph.D.
University of North Dakota
Study (2021): “Cerebrospinal Immune Response in a Tractable Murine Model of Lyme Neuroborreliosis”
Study (2021): “Cerebrospinal Immune Response in a Tractable Murine Model of Lyme Neuroborreliosis”
Lyme neuroborreliosis (LNB) occurs in 10–15% of Lyme disease cases. Although much progress has been made in diagnostic LNB research using clinical specimens, there is still an urgent need for a tractable animal model that can be utilized to study the pathobiology of LNB. Dr. Brissette’s team has developed a model of LNB using C3H mice, and their long-term goal is to utilize this model to identify pathogen, host, and environmental factors that trigger central nervous system involvement in order to develop new prophylactic and therapeutic treatments for LNB. Additionally, this study will determine markers of infection and/or inflammation in the cerebrospinal fluid (CSF) of infected mice, which could serve as inflammatory signals to the brain. Such biomarkers, if present in human CSF, might be indicative of continued infection.
Study (2021): “Lyme iDS: An Innovative Point-of-Care System for Reliable Diagnosis of Lyme Disease”
Accurate and rapid diagnosis of Lyme disease is currently one of the greatest obstacles to the clinical management of the disease. The majority of current diagnostic assays rely on two separate and sequential (2-tier) tests for anti-Borrelia burgdorferi antibodies (ELISA followed by immunoblot), which can routinely take multiple days to complete, lack standardization across different testing laboratories, require advanced technical expertise and be prone to subjectivity leading to potential misinterpretation and misdiagnosis. Dr. Jewett’s team seeks to develop a novel point-of-care (POC) test that would overcome the deficiencies associated with current testing approaches. Their strategy for rapid and accurate in-clinic diagnosis of patients relies on use of Immuno-PCR (iPCR), which combines the robust specificity of antibody-antigen interactions with the sensitivity of exponential DNA amplification. Perhaps the most exciting aspect of the project is the application of a battery-operated quantitative PCR device, approximately the size of a coffee mug, that will literally put a rapid and accurate means of detecting a B. burgdorferi infection in a physician’ hands.
Study (2021) “Impact of Borreliella burgdorferi infection, immunity & antibiotics on the host’s microbiome in a nonhuman primate model of Lyme disease”
Post-treatment Lyme Disease (PTLD) has been attributed to persistence of either viable bacteria or cellular remnants, such as bacterial proteins, that may incite aberrant host responses long after resolution of the initial infection with a recommended antibiotic therapy. An alternative or complementary explanation for PTLD is that Borreliella burgdorferi (Bb) infection alone or in combination with antibiotic treatment results in long-term dysbiosis of the gut microbiota, resulting in the development of the aberrant inflammatory state. Dr. Messaoudi’s team will use an innovative approach to address this knowledge gap by investigating the role of (a) Bb infection and subsequent antibiotic treatment on the gut microbiome, and (b) defining the systemic immune responses, as manifested in the blood and skin, to an on-going, established Bb infection and its subsequent treatment. Completion of the proposed studies will generate the data needed to fully utilize the NHP primate model to interrogate the role of microbial dysbiosis triggered by acute Bb infection and associated antibiotic treatments on the development of PTLD.
Study (2021): "Breaking down the wall: Targeting peptidoglycan to treat and diagnose Lyme disease"
Late-stage manifestations of Lyme disease are complex and poorly understood. Unlike other bacterial pathogens, the causative agent of Lyme disease, Borrelia burgdorferi, is not known to produce any toxins, however, the team at Virginia Tech has discovered that unique fragments of B. burgdorferi peptidoglycan (PG), an essential component of the bacterial cell wall, are released during growth. Similar molecules, produced by several important human pathogens, act as toxins, while others play essential roles in host immune modulation. They, too, hypothesize that during B. burgdorferi infection, excreted PG fragments drive patient inflammation in the absence of an active infection, and that we can intervene. They postulate that continual excretion of PG as the bacterium grows is a unique biomarker that can be exploited to diagnose both acute and late-stage disease states. The study aims to find the determinants of PG persistence and target PG to diagnose and treat chronic Lyme disease. The study will provide a fundamental understanding of how released PG fragments impact all aspects of Lyme disease pathology, including neuroborreliosis and carditis. They may also be the next generation of Lyme disease diagnostics.
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