Lyme Disease in Humans

Radolf, Justin D.; Strle, Klemen; Lemieux, Jacob E.; Strle, Franc

doi:10.21775/cimb.042.333

Cited by 84 publications

(138 citation statements)

References 598 publications

(956 reference statements)

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“…1 Wild-type and ΔplzA strains were compared to plzA-R145D and plzAcomp strains in separate experiments. 2 Serology is based on immunoreactivity of serum from individual mice against whole cell lysates of wild-type B. burgdorferi strain B31 cultivated at 37˚C in vitro (S4B Fig)…”

Section: Production Of C-di-gmp Antagonizes the Rpon/rpos Pathway Through Plzamentioning

confidence: 99%

“…Lyme disease, a multisystem disorder characterized by cutaneous, neurologic, cardiac, and rheumatologic manifestations [1,2], is caused by the spirochete Borrelia burgdorferi [3]. With 35,000 confirmed cases reported to the Centers for Disease Control and Prevention annually [4,5], Lyme disease is the most prevalent arthropod-borne infection in the United States [6].…”

Section: Introductionmentioning

confidence: 99%

“…Serology is based on immunoreactivity of serum from individual mice against whole cell lysates of wild-type B. burgdorferi strain B31 cultivated at 37˚C in vitro.Immunoblot data for individual mice are presented in S2 Fig 2. Wild-type and ΔplzA strains were compared to plzA-R145D and plzAcomp strains in separate experiments (5 mice per strain, per experiment) 3.…”

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confidence: 99%

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PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi

et al. 2021

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In this study, we examined the relationship between c-di-GMP and its only known effector protein, PlzA, in Borrelia burgdorferi during the arthropod and mammalian phases of the enzootic cycle. Using a B. burgdorferi strain expressing a plzA point mutant (plzA-R145D) unable to bind c-di-GMP, we confirmed that the protective function of PlzA in ticks is c-di-GMP-dependent. Unlike ΔplzA spirochetes, which are severely attenuated in mice, the plzA-R145D strain was fully infectious, firmly establishing that PlzA serves a c-di-GMP-independent function in mammals. Contrary to prior reports, loss of PlzA did not affect expression of RpoS or RpoS-dependent genes, which are essential for transmission, mammalian host-adaptation and murine infection. To ascertain the nature of PlzA’s c-di-GMP-independent function(s), we employed infection models using (i) host-adapted mutant spirochetes for needle inoculation of immunocompetent mice and (ii) infection of scid mice with in vitro-grown organisms. Both approaches substantially restored ΔplzA infectivity, suggesting that PlzA enables B. burgdorferi to overcome an early bottleneck to infection. Furthermore, using a Borrelia strain expressing a heterologous, constitutively active diguanylate cyclase, we demonstrate that ‘ectopic’ production of c-di-GMP in mammals abrogates spirochete virulence and interferes with RpoS function at the post-translational level in a PlzA-dependent manner. Structural modeling and SAXS analysis of liganded- and unliganded-PlzA revealed marked conformational changes that underlie its biphasic functionality. This structural plasticity likely enables PlzA to serve as a c-di-GMP biosensor that in its respective liganded and unliganded states promote vector- and host-adaptation by the Lyme disease spirochete.

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Section: Production Of C-di-gmp Antagonizes the Rpon/rpos Pathway Through Plzamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi

et al. 2021

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“…Wild Peromyscus leucopus mice are the main murine reservoir in north-east America and Apodemus flavicollis mice in Europe. 6,[97][98][99] To interrupt the vector-reservoir-host life cycle of Borrelia spirochaetes, several research groups have focused on reservoir-targeted vaccination of the murine reservoir. Reservoir-targeted vaccines are especially attractive for the control of tick-borne diseases as multi-host life cycle ticks will interact with wild life as well as pets, livestock and humans, and pathogens can be passed through tick generations using a wild life reservoir.…”

Section: Re S Ervoir-targ E Ted Vaccine Smentioning

confidence: 99%

Anti‐tick and pathogen transmission blocking vaccines

Oosterwijk

2021

Parasite Immunology

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Ticks and tick-borne diseases are a challenge for medical and veterinary public health and often controlled through the use of repellents and acaricides. Research on vaccination strategies to protect humans, companion animals, and livestock from ticks and tick-transmitted pathogens has accelerated through the use of proteomic and transcriptomic analyses. Comparative analyses of unfed versus engorged and uninfected versus infected ticks have provided valuable insights into candidates for antitick and pathogen transmission blocking vaccines. An intricate interplay between tick saliva and the host's immune system has revealed potential antigens to be used in vaccination strategies. Immunization of hosts with targeted anti-tick vaccines would ideally lead to a reduction in tick numbers and prevent transmission of tick-borne pathogens. Comprehensive control of tick-borne diseases would come from successful anti-tick vaccination, vaccination preventing transmission of tick-borne diseases or a combination. Due to the close interaction with wildlife and ticks, with wildlife reservoirs enabling propagation of pathogens between ticks, the vaccination of these reservoirs is an attractive target to reduce human contact with ticks and tick-borne diseases through a one-health approach. Wildlife vaccination presents formulation and regulatory challenges which should be considered early in the development of reservoir-targeted vaccines.

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“…LNB reflects the capacity of B. burgdorferi sensu lato to invade diverse targets within the peripheral and central nervous system and to cause neurological complications weeks to months after infection [10]. Early nervous system involvement is usually manifested by the involvement of cranial and/or peripheral nerves or nerve roots typically associated with lymphocytic meningitis [11], (Table 1). LNB may affect the abducens nerve, and very rarely the vestibulocochlear nerve, the optic nerve (optic neuritis, papilloedema), the oculomotor system (NN III, IV), the trigeminal nerve and the caudal cranial nerves (NN IX-XII) [12,13].…”

Section: Introductionmentioning

confidence: 99%

Vertigo as One of the Symptoms of Lyme Disease

Sowula

Szaleniec

Dworak

et al. 2021

JCM

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Objectives: The aim of the study was to evaluate the frequency of vertigo symptoms and potential labyrinth damage in patients with diagnosed Lyme disease (LD). LD can affect the vestibulocochlear nerve, leading to hearing loss and vertigo/dizziness. Material and Methods: The study included a group of 38 patients between the ages of 20 and 77, who were hospitalized due to vertigo/dizziness between 2018 and 2019. All of the patients underwent a detailed medical interview and an otolaryngological and neurological examination, including video electronystagmography (VENG), in addition to audiological and diagnostic tests. Additionally, ELISA and Western blot tests were performed to confirm the diagnosis of LD. Results: In 20 patients (53%), the Romberg trial was positive (p < 0.001). The degree of vestibular dysfunction as shown by the VENG test was associated with the rate of hearing loss as confirmed by the Auditory Brainstem Response (ABR) test (p = 0.011), and it mainly concerned high-frequency sounds (p = 0.014). Conclusion: Vertigo can be a symptom of LD. It is often associated with labyrinth and hearing-organ damage, which can imply that the inner ear or nerve VIII is dysfunctional in the course of this disease. Antibiotic therapy is effective in reducing otoneurological symptoms.

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Lyme Disease in Humans

Cited by 84 publications

References 598 publications

PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi

PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi

Anti‐tick and pathogen transmission blocking vaccines

Vertigo as One of the Symptoms of Lyme Disease

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