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Utpal Pal - One of the best experts on this subject based on the ideXlab platform.
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Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Disease Vaccine.
Frontiers in immunology, 2018Co-Authors: Ashley L. Marcinkiewicz, Utpal Pal, Xiuli Yang, Ilva Lieknina, Svetlana Kotelovica, Peter Kraiczy, Yi-pin Lin, Kaspars TarsAbstract:The Spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the U.S and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of Spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H. To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds factor H to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from Infection, which we speculate is because factor H-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating factor H binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared Spirochete Infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating factor H-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
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A surface enolase participates in Borrelia burgdorferi-plasminogen interaction and contributes to pathogen survival within feeding ticks.
Infection and immunity, 2011Co-Authors: Sarah Veloso Nogueira, Alexis A. Smith, Jinhong Qin, Utpal PalAbstract:ABSTRACT Borrelia burgdorferi, a tick-borne bacterial pathogen, causes a disseminated Infection involving multiple organs known as Lyme disease. Surface proteins can directly participate in microbial virulence by facilitating pathogen dissemination via interaction with host factors. We show here that a fraction of the B. burgdorferi chromosomal gene product BB0337, annotated as enolase or phosphopyruvate dehydratase, is associated with Spirochete outer membrane and is surface exposed. B. burgdorferi enolase, either in a recombinant form or as a membrane-bound native antigen, displays enzymatic activities intrinsic to the glycolytic pathway. However, the protein also interacts with host plasminogen, potentially leading to its activation and resulting in B. burgdorferi-induced fibrinolysis. As expected, enolase displayed consistent expression in vivo, however, with a variable temporal and spatial expression during Spirochete Infection in mice and ticks. Despite an extracellular exposure of the antigen and a potential role in host-pathogen interaction, active immunization of mice with recombinant enolase failed to evoke protective immunity against subsequent B. burgdorferi Infection. In contrast, enolase immunization of murine hosts significantly reduced the acquisition of Spirochetes by feeding ticks, suggesting that the protein could have a stage-specific role in B. burgdorferi survival in the feeding vector. Strategies to interfere with the function of surface enolase could contribute to the development of novel preventive measures to interrupt the Spirochete Infection cycle and reduce the incidences of Lyme disease.
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BB0323 Function Is Essential for Borrelia burgdorferi Virulence and Persistence through Tick-Rodent Transmission Cycle
The Journal of infectious diseases, 2009Co-Authors: Xinyue Zhang, Xiuli Yang, Manish Kumar, Utpal PalAbstract:Borrelia burgdorferi bb0323 encodes an immunogenic protein in mammalian hosts, including humans. An analysis of bb0323 expression in vivo showed variable transcription throughout the Spirochete Infection cycle, with elevated expression during tick-mouse transmission. Deletion of bb0323 in infectious B. burgdorferi did not affect microbial survival in vitro, despite considerable alterations in growth kinetics and cell morphology. The bb0323 mutants were unable to infect either mice or ticks and were quickly eliminated from immunocompetent and immunodeficient hosts and the vector within the first few days after inoculation. Chromosomal complementation of the mutant with native bb0323 and phenotypic analysis in vivo indicated the substantial restoration of Spirochete virulence and persistence throughout the mouse-tick Infection cycle. The BB0323 protein may serve an indispensable physiological function that is more pronounced during microbial persistence and transitions between the host and the vector in vivo. Strategies to interfere with BB0323 function may interrupt the infectious cycle of Spirochetes.
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Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks
The Journal of infectious diseases, 2009Co-Authors: Erol Fikrig, Utpal Pal, Sukanya Narasimhan, Girish Neelakanta, Manchuan Chen, Richard A. FlavellAbstract:Lyme disease, which is caused by Borrelia burgdorferi, is the most common tickborne infectious disease in the United States [1, 2]. Pathognomonic rash, arthritis, and carditis are common clinical manifestations [1, 2]. Murine models partially mimic the human illness, given that the animals develop a persistent Infection and tissue inflammation, and host immune responses are critical for controlling disease [3]. The surface of B. burgdorferi is unique and does not befit its apparently gram-negative cell wall [4]. The segmented genome of B. burgdorferi encodes ~130–150 lipoproteins [5, 6], many of which decorate the outer wall of the Spirochete. Surface proteins of the Spirochete present a critical interface between the bacterium and its diverse niches in the vertebrate and invertebrate host. The Spirochete apparently changes its transcriptome to successfully disseminate and survive in the different niches [7]. B. burgdorferi surface proteins possibly lead these changes via direct interactions with the microenvironment, as seen by signature changes in the makeup of the outer surface of the Spirochete that precede and succeed its migration to specific niches [7]. However, in their vantage position, the outer surface proteins of Borrelia also risk hostile interactions with host innate immune molecules. Toll-like receptors (TLRs) interact with a wide variety of microbial molecules and are critical for initiating host defenses [8–10]. The triacylated lipoproteins on the surface of the Lyme disease agent are recognized by TLR1/2 heterodimers, resulting in the activation of innate immune signaling pathways [11, 12]. This reduces Spirochete Infection in mice, because higher pathogen loads are evident in mice lacking either TLR1 or TLR2 when challenged with various B. burgdorferi isolates [11, 13–16]. Furthermore, myeloid differentiation primary response protein 88 (MyD88)–deficient mice have greater difficulty controlling Spirochetes than do TLR1- or TLR2-deficient animals [17–19]. MyD88 serves as the adapter molecule for several TLRs, suggesting that additional receptors are also involved in the identification of B. burgdorferi. The Spirochete uses several strategies to circumvent these immune responses. When it enters the host via a tick bite, B. burgdorferi begins its standoff with the host immune responses by exploiting tick salivary proteins spit into the bite site [20, 21]. Soon after entry into the host, the Spirochete transcriptome and proteome undergo further changes as they adapt in the host, using their own proteins (such as the complement regulator– acquiring surface proteins) to defuse [22] and extra-cellular matrix binding-proteins to escape [23] host immune reactions. Liang et al [24] have suggested that the expression profile of several Borrelia genes—including ospc, bbf01, and vlsE [25]—might be altered by host humoral responses. Crowley and Hubner [26] have shown that an in vivo inflammatory environment induces the expression of outer surface protein A by unknown molecular mechanisms. Work by Anguita et al [27] has indicated that the recombination of the vlsE locus, an important aspect of immune evasion, might be influenced by interferon γ–mediated inflammation in the host. Because the engagement of Spirochete lipoproteins with TLRs is a critical initiator of host immune responses to Borrelia [28], TLR-mediated signals might influence Spirochete gene expression. In the present study, we examined how gene expression in the Lyme disease agent is altered by TLR1/2-mediated signals, using TLR1/2 heterodimer recognition of B. burgdorferi as a model.
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BBK07, a Dominant In Vivo Antigen of Borrelia burgdorferi, Is a Potential Marker for Serodiagnosis of Lyme Disease
Clinical and vaccine immunology : CVI, 2009Co-Authors: Adam S. Coleman, Utpal PalAbstract:One of the recently identified Borrelia burgdorferi immunogens, BBK07, is characterized for its expression in the Spirochete Infection cycle and evaluated for its potential use as a serodiagnostic marker for Lyme disease. We show that the BBK07 gene is expressed at extremely low levels in vitro and in ticks but is dramatically induced by Spirochetes once introduced into the host and is highly expressed throughout mammalian Infection. In contrast, the expression of BBK12, a paralog of BBK07 with 87% amino acid identity, although expressed in vitro, remained undetectable in vivo throughout murine Infection and in ticks. BBK07 is localized in the outer membrane, and the amino-terminal domain of the antigen is exposed on the microbial surface. A truncated BBK07 protein representing the amino-terminal domain is able to effectively detect antibodies to B. burgdorferi, both in experimentally infected mice and in humans. Further characterization of the immunodominant antigens of B. burgdorferi, such as BBK07, could contribute to the development of novel serodiagnostic markers for detection of Lyme disease.
Erol Fikrig - One of the best experts on this subject based on the ideXlab platform.
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Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks
The Journal of infectious diseases, 2009Co-Authors: Erol Fikrig, Utpal Pal, Sukanya Narasimhan, Girish Neelakanta, Manchuan Chen, Richard A. FlavellAbstract:Lyme disease, which is caused by Borrelia burgdorferi, is the most common tickborne infectious disease in the United States [1, 2]. Pathognomonic rash, arthritis, and carditis are common clinical manifestations [1, 2]. Murine models partially mimic the human illness, given that the animals develop a persistent Infection and tissue inflammation, and host immune responses are critical for controlling disease [3]. The surface of B. burgdorferi is unique and does not befit its apparently gram-negative cell wall [4]. The segmented genome of B. burgdorferi encodes ~130–150 lipoproteins [5, 6], many of which decorate the outer wall of the Spirochete. Surface proteins of the Spirochete present a critical interface between the bacterium and its diverse niches in the vertebrate and invertebrate host. The Spirochete apparently changes its transcriptome to successfully disseminate and survive in the different niches [7]. B. burgdorferi surface proteins possibly lead these changes via direct interactions with the microenvironment, as seen by signature changes in the makeup of the outer surface of the Spirochete that precede and succeed its migration to specific niches [7]. However, in their vantage position, the outer surface proteins of Borrelia also risk hostile interactions with host innate immune molecules. Toll-like receptors (TLRs) interact with a wide variety of microbial molecules and are critical for initiating host defenses [8–10]. The triacylated lipoproteins on the surface of the Lyme disease agent are recognized by TLR1/2 heterodimers, resulting in the activation of innate immune signaling pathways [11, 12]. This reduces Spirochete Infection in mice, because higher pathogen loads are evident in mice lacking either TLR1 or TLR2 when challenged with various B. burgdorferi isolates [11, 13–16]. Furthermore, myeloid differentiation primary response protein 88 (MyD88)–deficient mice have greater difficulty controlling Spirochetes than do TLR1- or TLR2-deficient animals [17–19]. MyD88 serves as the adapter molecule for several TLRs, suggesting that additional receptors are also involved in the identification of B. burgdorferi. The Spirochete uses several strategies to circumvent these immune responses. When it enters the host via a tick bite, B. burgdorferi begins its standoff with the host immune responses by exploiting tick salivary proteins spit into the bite site [20, 21]. Soon after entry into the host, the Spirochete transcriptome and proteome undergo further changes as they adapt in the host, using their own proteins (such as the complement regulator– acquiring surface proteins) to defuse [22] and extra-cellular matrix binding-proteins to escape [23] host immune reactions. Liang et al [24] have suggested that the expression profile of several Borrelia genes—including ospc, bbf01, and vlsE [25]—might be altered by host humoral responses. Crowley and Hubner [26] have shown that an in vivo inflammatory environment induces the expression of outer surface protein A by unknown molecular mechanisms. Work by Anguita et al [27] has indicated that the recombination of the vlsE locus, an important aspect of immune evasion, might be influenced by interferon γ–mediated inflammation in the host. Because the engagement of Spirochete lipoproteins with TLRs is a critical initiator of host immune responses to Borrelia [28], TLR-mediated signals might influence Spirochete gene expression. In the present study, we examined how gene expression in the Lyme disease agent is altered by TLR1/2-mediated signals, using TLR1/2 heterodimer recognition of B. burgdorferi as a model.
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Borrelia burgdorferi enzyme-linked immunosorbent assay for discrimination of OspA vaccination from Spirochete Infection.
Journal of clinical microbiology, 1997Co-Authors: Y Q Zhang, Dane A. Mathiesen, C P Kolbert, John F. Anderson, R T Schoen, Erol Fikrig, David H. PersingAbstract:Recombinant Lyme disease vaccines based on purified preparations of outer surface protein A (OspA) have been shown to be effective in preventing transmission of Borrelia burgdorferi in experimental animal models and are now being tested in humans. Since the most widely used screening tests for Lyme disease are based on a whole-cell sonicate of B. burgdorferi, serologic false positivity in vaccinated persons could result from reactivity to OspA within the antigen preparation. In order to avoid serologic false positivity in vaccinated subjects, we developed an immunoassay based on a low-passage-number, naturally occurring variant of B. burgdorferi which lacks the plasmid encoding OspA and OspB. The use of an antigen preparation derived from this organism provided sensitive and specific detection of B. burgdorferi seropositivity in experimental animals and in human Lyme disease cases. The OspA-B-negative enzyme-linked immunosorbent assay (ELISA) also appeared to be capable of discriminating the vaccinated state from vaccine failure and natural Infection in experimental animals. Sera from human subjects participating in a vaccine trial gave false-positive results with an ELISA based on an OspA-containing strain, but no such reactivity was observed when the OspA-negative ELISA was used. We conclude that low-passage-number OspA-B-negative isolates in immunoassays may become useful for the immunologic discrimination of the vaccinated state, natural Infection, and vaccine failure.
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borrelia burgdorferi ospa is an arthropod specific transmission blocking lyme disease vaccine
Journal of Experimental Medicine, 1996Co-Authors: A M De Silva, Stephen W. Barthold, S R Telford, L R Brunet, Erol FikrigAbstract:Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A protects mice from Spirochete Infection. Here we report on the expression of OspA on Spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of Spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most Spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdorferi Infection. When OspA antibody was administered to mice 48 h after tick attachment, Spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing Spirochetes in the tick gut and block transmission from the vector to the host.
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Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice.
Infection and immunity, 1992Co-Authors: Erol Fikrig, Stephen W. Barthold, Nancy Marcantonio, K. Deponte, Fred S. Kantor, Richard A. FlavellAbstract:Vaccination with recombinant outer surface protein A (OspA) has been shown to protect mice from Infection with Borrelia burgdorferi, the Lyme disease agent. To determine whether antibodies to B. burgdorferi proteins other than OspA are involved in protective immunity, antibodies to OspA were removed from protective anti-B. burgdorferi serum; the residual serum was still protective. Absorption of OspA and OspB antibodies from anti-B. burgdorferi serum eliminated the protective effect. Therefore, active immunization experiments were performed to determine the roles of OspB and flagellin in protective immunity and to determine whether protective immunity induced by OspA is dose dependent. Active immunization with recombinant OspA protected mice from Infection with an inoculum of 10(4) Spirochetes, but this protection could be overcome with a challenge of 10(7) Spirochetes; OspB protected mice from Infection with an inoculum of 10(3) Spirochetes but was insufficient to fully protect against 10(4) organisms; and immunization with flagellin had no protective effect. These studies suggest that OspA and OspB, but not flagellin, play roles in protective immunity to Spirochete Infection.
Joseph Piesman - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of an Experimental Azithromycin Cream for Prophylaxis of Tick-Transmitted Lyme Disease Spirochete Infection in a Murine Model
Antimicrobial agents and chemotherapy, 2013Co-Authors: Joseph Piesman, Andrias Hojgaard, Amy J. Ullmann, Marc C. DolanAbstract:As an alternative to oral prophylaxis for the prevention of tick transmission of Borrelia burgdorferi, we tested antibiotic cream prophylactic formulations in a murine model of Spirochete Infection. A 4% preparation of doxycycline cream afforded no protection, but a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. Indeed, the azithromycin cream was 100% effective when applied at up to 3 days after tick removal and protected 74% of mice exposed to tick bite when applied at up to 2 weeks after tick removal. Azithromycin cream was also protective when applied at a site distal to the tick bite site, suggesting that it was having a systemic effect in addition to a local transdermal effect. Mice that were protected from tick-transmitted Infection did not seroconvert and did not infect larval ticks on xenodiagnosis. Azithromycin cream formulations appear to hold promise for Lyme disease prophylaxis.
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A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.
The American journal of tropical medicine and hygiene, 2008Co-Authors: Marc C. Dolan, Nordin S. Zeidner, Elizabeth Gabitzsch, Gabrielle Dietrich, Jeff N. Borchert, Rich M. Poché, Joseph PiesmanAbstract:The prophylactic and curative potential of doxycycline hyclate formulated in a rodent bait at concentrations of 250 and 500 mg/Kg was evaluated in a murine model of Lyme borreliosis. Both bait formulations prevented tick-transmitted Borrelia burgdorferi Infection in 100% of C3H/HeJ mice (N = 16), as well as cured acute, established Infection in mice (N = 8) exposed to bait for 14 days. Spirochete Infection was cleared in 88.9% to 100% of infected nymphs feeding on mice fed 250 and 500 mg/Kg antibiotic bait formulations, respectively. These data provide evidence for exploring alternative techniques to prevent transmission of Lyme disease Spirochetes.
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Distribution, density, and lyme disease Spirochete Infection in Ixodes dammini (Acari: Ixodidae) on white-tailed deer in Maryland
Journal of medical entomology, 1992Co-Authors: F. P. Amerasinghe, Joseph Piesman, N. L. Breisch, Abdu F. Azad, W. F. Gimpel, M. Greco, K. Neidhardt, B. Pagac, J. Sandt, Thomas W. ScottAbstract:A Statewide survey of ticks parasitizing white-tailed deer was carried out in Maryland during November 1989 to assess the status of the deer tick, Ixodes dammini Spielman, Clifford, Piesman & Corwin, the major vector of Lyme disease in the northeastern United States. Ticks were collected from deer carcasses brought in by hunters at 23 check stations (one per county). A total of 3,437 I. dammini were collected from 538 of 1,281 deer (42%), together with 2,013 Dermacentor albipictus (Packard) and 23 Amblyomma americanum (L.) from 34 and 0.5% of deer respectively. I. dammini prevalence ranged from 0 to 79% of deer and mean abundance from 0 to 7.3 ticks per deer at different check stations. Lyme Spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, Infection rates in ticks ranged from 0 to 21%, with a mean of 8%. Deer-tick density and Spirochete Infection rates varied with physiographic region and were low in the Appalachian, intermediate in the Piedmont, and high in the Western and Eastern Coastal Plains regions. County-based human case rates correlated positively with I. dammini abundance. We concluded that I. dammini was well established except in the mountainous western region of Maryland and was involved in Lyme disease transmission.
Zhe Ding - One of the best experts on this subject based on the ideXlab platform.
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Integrative Transcriptome and Proteome Analyses Provide New Insights Into the Interaction Between Live Borrelia burgdorferi and Frontal Cortex Explants of the Rhesus Brain
Journal of neuropathology and experimental neurology, 2020Co-Authors: Zhe Ding, Luyun Sun, Yu Zhang, Peng Yue, Wenjing Cao, Lisha Luo, Taigui ChenAbstract:Borrelia burgdorferi (Bb), which is neurotropic, can attack the central nervous system (CNS), leading to the development of various neurologic symptoms. The pathogenesis of Lyme neuroborreliosis (LNB) remains poorly understood. Presently, there is a lack of knowledge of the changes in mRNA and proteins in the CNS following early disseminated Lyme disease. Explants from the frontal cortex of 3 rhesus brains were incubated with medium alone or with medium containing live Bb for 6, 12, or 24 hours. Then, we analyzed identified mRNA and proteins in the frontal cortex tissues, allowing for an in-depth view of the transcriptome and proteome for a macroscopic and unbiased understanding of early disseminated Lyme disease in the brain. Through bioinformatics analysis, a complex network of enriched pathways that were mobilized during the progression of Lyme Spirochete Infection was described. Furthermore, based on the analysis of omics data, translational regulation, glycosaminoglycan/proteoglycan-binding activity in colonization and dissemination to tissues, disease-associated genes, and synaptic function were enriched, which potentially play a role in pathogenesis during the interaction between frontal cortex tissues and Spirochetes. These integrated omics results provide unbiased and comprehensive information for the further understanding of the molecular mechanisms of LNB.
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Rhesus Brain Transcriptomic Landscape in an ex vivo Model of the Interaction of Live Borrelia Burgdorferi With Frontal Cortex Tissue Explants.
Frontiers in neuroscience, 2019Co-Authors: Zhe Ding, Luyun Sun, Ma Mingbiao, Lvyan Tao, Peng Yun, Yuanyuan Han, Dai Xiting, Bai Ruolan, Miaomiao JianAbstract:Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease caused by the Spirochete Borrelia burgdorferi which can reach the central nervous system most commonly presenting with lymphocytic meningitis; however, the molecular basis for neuroborreliosis is still poorly understood. We incubated explants from the frontal cortex of three rhesus brains with medium alone or medium with added live Borrelia burgdorferi for 6, 12, and 24 h and isolated RNA from each group was used for RNA sequencing with further bioinformatic analysis. Transcriptomic differences between the ex vivo model of live Borrelia burgdorferi with rhesus frontal cortex tissue explants and the controls during the progression of the Infection were identified. A total of 2249, 1064, and 420 genes were significantly altered, of which 80.7, 52.9, and 19.8% were upregulated and 19.3, 47.1, 80.2% were downregulated at 6, 12, and 24 h, respectively. Gene ontology and KEGG pathway analyses revealed various pathways related to immune and inflammatory responses during the Spirochete Infection were enriched which is suggested to have a causal role in the pathogenesis of neurological Lyme disease. Moreover, we propose that the overexpressed FOLR2 which was demonstrated by the real-time PCR and western blotting could play a key role in neuroinflammation of the neuroborreliosis based on PPI analysis for the first time. To our knowledge, this is the first study to provide comprehensive information regarding the transcriptomic signatures that occur in the frontal cortex of the brain upon exposure to Borrelia burgdorferi, and suggest that FOLR2 is a promising target that is associated with neuroinflammation and may represent a new diagnostic or therapeutic marker in LNB.
Marc C. Dolan - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of an Experimental Azithromycin Cream for Prophylaxis of Tick-Transmitted Lyme Disease Spirochete Infection in a Murine Model
Antimicrobial agents and chemotherapy, 2013Co-Authors: Joseph Piesman, Andrias Hojgaard, Amy J. Ullmann, Marc C. DolanAbstract:As an alternative to oral prophylaxis for the prevention of tick transmission of Borrelia burgdorferi, we tested antibiotic cream prophylactic formulations in a murine model of Spirochete Infection. A 4% preparation of doxycycline cream afforded no protection, but a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. Indeed, the azithromycin cream was 100% effective when applied at up to 3 days after tick removal and protected 74% of mice exposed to tick bite when applied at up to 2 weeks after tick removal. Azithromycin cream was also protective when applied at a site distal to the tick bite site, suggesting that it was having a systemic effect in addition to a local transdermal effect. Mice that were protected from tick-transmitted Infection did not seroconvert and did not infect larval ticks on xenodiagnosis. Azithromycin cream formulations appear to hold promise for Lyme disease prophylaxis.
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A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.
The American journal of tropical medicine and hygiene, 2008Co-Authors: Marc C. Dolan, Nordin S. Zeidner, Elizabeth Gabitzsch, Gabrielle Dietrich, Jeff N. Borchert, Rich M. Poché, Joseph PiesmanAbstract:The prophylactic and curative potential of doxycycline hyclate formulated in a rodent bait at concentrations of 250 and 500 mg/Kg was evaluated in a murine model of Lyme borreliosis. Both bait formulations prevented tick-transmitted Borrelia burgdorferi Infection in 100% of C3H/HeJ mice (N = 16), as well as cured acute, established Infection in mice (N = 8) exposed to bait for 14 days. Spirochete Infection was cleared in 88.9% to 100% of infected nymphs feeding on mice fed 250 and 500 mg/Kg antibiotic bait formulations, respectively. These data provide evidence for exploring alternative techniques to prevent transmission of Lyme disease Spirochetes.