About this Research Topic
Lyme disease is the most common tick-borne disease with an estimated 300,000 cases per year in the United States. It has long been known that Lyme disease is caused by certain species of spirochetes from the Borrelia burgdorferi (sensu lato) complex. Despite recent advances in understanding the molecular pathogenesis of the Lyme disease though, infection with these pathogens remains difficult to diagnose and treat. Lyme disease is further complicated by the presence of other related Borrelia species and co-infection pathogens that may complicate diagnosis and treatment or even exacerbate the disease.
Signals that Borrelia spirochetes receive from hostile environments evoke morphological alterations to round bodies, tiny granular forms, and microcolonies, that keep the pathogen alive and induce the production of antibiotic-tolerant persister cells, which are refractory to antibiotic elimination. These metamorphoses could contribute significantly to treatment failures, as Borrelia is able to modulate and suppress host immune system which can further affect serodiagnosis and treatment outcome.
While the current two-tier serology tests can detect Lyme disease in stage 2 (early-disseminated disease) and stage 3 (Lyme arthritis) with high sensitivity, they are not so reliable in detecting Stage 1 early Lyme disease (within 4-6 weeks of tick bite) and persistent Lyme disease. Therefore, more sensitive diagnostic tests are needed to effectively diagnose and heal this zoonotic disease.
Although the current standard 2-4 week antibiotic treatment cures the majority of the patients, about 5-50% of Lyme disease patients continue to suffer from persistent symptoms of fatigue, musculoskeletal pain, and neurocognitive symptoms that last 6 months or greater, a condition called “Post-Treatment Lyme Disease Syndrome” or PTLDS. The pathobiology of PTLDS is poorly understood, and its therapy remains a contentious issue, as there is currently no FDA-approved treatment. Prolonged treatment of persistent Lyme disease with
the current Lyme antibiotics have limited effect and could have potential side effects. More effective therapies and new therapeutic approaches are urgently needed.
The recent identification of FDA-approved drug candidates that are active against Borrelia persister cells and their combination with existing Lyme antibiotics, could completely eradicate Borrelia persister cells in vitro and in animal models and may provide a more effective treatment of persistent Lyme disease. In addition to antibiotic compounds, natural products including herbal medicines which have a long history of medical use may also play a role in more effective management and treatment of persistent Lyme disease that is not cured by the standard 2-4 week antibiotic therapy. For example, a recent study has shown that some herbal products such as cryptolepis, black walnut, Japanese knotweed, and Cat’s claw have more activity than the first-line antibiotic for Lyme diseases. Thus, further exploration of natural products and herbal medicines for more effective treatment of
persistent Lyme disease seems warranted.
Overall in this Research Topic, we aim to better understand the role of microbial persisters and the host immune responses, and to identify biomarkers associated with PTLDS. We also welcome manuscripts that refer to molecular pathogenesis and pathophysiology of Lyme disease and further address the role of co-infection microbes. Finally, we are interested in studies of natural herbal products with potential activity against Borrelia burgdorferi and studies that suggest better diagnostics and more effective treatments for persistent Lyme disease and its co-infections.
Signals that Borrelia spirochetes receive from hostile environments evoke morphological alterations to round bodies, tiny granular forms, and microcolonies, that keep the pathogen alive and induce the production of antibiotic-tolerant persister cells, which are refractory to antibiotic elimination. These metamorphoses could contribute significantly to treatment failures, as Borrelia is able to modulate and suppress host immune system which can further affect serodiagnosis and treatment outcome.
While the current two-tier serology tests can detect Lyme disease in stage 2 (early-disseminated disease) and stage 3 (Lyme arthritis) with high sensitivity, they are not so reliable in detecting Stage 1 early Lyme disease (within 4-6 weeks of tick bite) and persistent Lyme disease. Therefore, more sensitive diagnostic tests are needed to effectively diagnose and heal this zoonotic disease.
Although the current standard 2-4 week antibiotic treatment cures the majority of the patients, about 5-50% of Lyme disease patients continue to suffer from persistent symptoms of fatigue, musculoskeletal pain, and neurocognitive symptoms that last 6 months or greater, a condition called “Post-Treatment Lyme Disease Syndrome” or PTLDS. The pathobiology of PTLDS is poorly understood, and its therapy remains a contentious issue, as there is currently no FDA-approved treatment. Prolonged treatment of persistent Lyme disease with
the current Lyme antibiotics have limited effect and could have potential side effects. More effective therapies and new therapeutic approaches are urgently needed.
The recent identification of FDA-approved drug candidates that are active against Borrelia persister cells and their combination with existing Lyme antibiotics, could completely eradicate Borrelia persister cells in vitro and in animal models and may provide a more effective treatment of persistent Lyme disease. In addition to antibiotic compounds, natural products including herbal medicines which have a long history of medical use may also play a role in more effective management and treatment of persistent Lyme disease that is not cured by the standard 2-4 week antibiotic therapy. For example, a recent study has shown that some herbal products such as cryptolepis, black walnut, Japanese knotweed, and Cat’s claw have more activity than the first-line antibiotic for Lyme diseases. Thus, further exploration of natural products and herbal medicines for more effective treatment of
persistent Lyme disease seems warranted.
Overall in this Research Topic, we aim to better understand the role of microbial persisters and the host immune responses, and to identify biomarkers associated with PTLDS. We also welcome manuscripts that refer to molecular pathogenesis and pathophysiology of Lyme disease and further address the role of co-infection microbes. Finally, we are interested in studies of natural herbal products with potential activity against Borrelia burgdorferi and studies that suggest better diagnostics and more effective treatments for persistent Lyme disease and its co-infections.
Keywords: Lyme Disease, Co-Infections, Pathogenesis, tick-borne disease, Post-Treatment Lyme Disease Syndrome, Borrelia burgdorferi
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