DETERMINING AN APPROPRIATE MURINE MODEL FOR STUDYING THE PATHOLOGICAL RESPONSE TO BORRELIA BURGDORFERI IN DEVELOPING LYME CARDITIS

ABSTRACT The MICs of evernimicin at which 90% of Borrelia burgdorferi patient isolates were inhibited ranged from 0.1 to 0.5 μg/ml. Evernimicin was as effective as ceftriaxone againstB. burgdorferi in a murine model of experimental Lyme disease. As assessed by culturing the urinary bladders of infected C3H mice, no live Borrelia isolates were recoverable following antibiotic treatment.

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Analysis of Mechanisms Associated with Loss of Infectivity of Clonal Populations of Borrelia burgdorferi B31MI

Infection and Immunity ◽

10.1128/iai.69.6.3670-3677.2001 ◽

2001 ◽

Vol 69 (6) ◽

pp. 3670-3677 ◽

Cited By ~ 50

Author(s):

John V. McDowell ◽

Shian Ying Sung ◽

Maria Labandeira-Rey ◽

Jon T. Skare ◽

Richard T. Marconi

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Murine Model ◽

Southern Hybridization ◽

Clonal Population ◽

Suggestive Evidence

ABSTRACT Numerous studies have provided suggestive evidence that the loss of plasmids correlates with the loss of infectivity of the Lyme disease spirochetes. In this study we have further investigated this correlation. Clonal populations were obtained from the skin of a mouse infected for 3 months with a clonal population of Borrelia burgdorferi B31MI. The complete plasmid compositions of these populations were determined using a combination of PCR and Southern hybridization. The infectivities of clones differing in plasmid composition were tested using the C3H-HeJ murine model for Lyme disease. While several clones were found to be noninfectious, a correlation between the loss of a specific plasmid and loss of infectivity in the clones analyzed in this report was not observed. While it is clear from recent studies that the loss of some specific plasmids results in attenuated virulence, this study demonstrates that additional mechanisms also contribute to the loss of infectivity.

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A Case of Lyme Carditis Presenting with Atrial Fibrillation

Case Reports in Cardiology ◽

10.1155/2018/5265298 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Peter J. Kennel ◽

Melvin Parasram ◽

Daniel Lu ◽

Diane Zisa ◽

Samuel Chung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Borrelia Burgdorferi ◽

Antibiotic Therapy ◽

Unusual Presentation ◽

Type I ◽

Atrial Arrhythmias ◽

Av Block ◽

Lyme Carditis ◽

Second Degree

We report a case of a 20-year-old man who presented to our institution with a new arrhythmia on a routine EKG. Serial EKG tracings revealed various abnormal rhythms such as episodes of atrial fibrillation, profound first degree AV block, and type I second degree AV block. He was found to have positive serologies for Borrelia burgdorferi. After initiation of antibiotic therapy, the atrial arrhythmias and AV block resolved. Here, we present a case of Lyme carditis presenting with atrial fibrillation, a highly unusual presentation of Lyme carditis.

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An rfuABCD -like operon and its relationship to riboflavin utilization and mammalian

Infection and Immunity ◽

10.1128/iai.00307-21 ◽

2021 ◽

Author(s):

Matthew K. Muramatsu ◽

Jianli Zhou ◽

Bryna L. Fitzgerald ◽

Ranjit K. Deka ◽

John T. Belisle ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Lyme Borreliosis ◽

Murine Model ◽

Flavin Adenine Dinucleotide ◽

Antimicrobial Effect ◽

Flavin Mononucleotide

Riboflavin is an essential micronutrient, but its transport and utilization has remained largely understudied among pathogenic spirochetes. Here we show that Borrelia burgdorferi , the zoonotic spirochete that causes Lyme disease, is able to import riboflavin via products of its rfuABCD -like operon as well as synthesize flavin mononucleotide and flavin adenine dinucleotide despite lacking canonical genes for their synthesis. Additionally, a mutant deficient in the rfuABCD -like operon is resistant to the antimicrobial effect of roseoflavin, a natural riboflavin analog, and is attenuated in a murine model of Lyme borreliosis. Our combined results indicate that not only are riboflavin and the maintenance of flavin pools essential for B. burgdorferi growth, but that flavin utilization and its downstream products (e.g., flavoproteins) may play a more prominent role in B. burgdorferi pathogenesis than previously appreciated.

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Decorin-Binding Protein A (DbpA) of Borrelia burgdorferi Is Not Protective When Immunized Mice Are Challenged via Tick Infestation and Correlates with the Lack of DbpA Expression by B. burgdorferi in Ticks

Infection and Immunity ◽

10.1128/iai.68.8.4759-4764.2000 ◽

2000 ◽

Vol 68 (8) ◽

pp. 4759-4764 ◽

Cited By ~ 79

Author(s):

Kayla E. Hagman ◽

Xiaofeng Yang ◽

Stephen K. Wikel ◽

George B. Schoeler ◽

Melissa J. Caimano ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Murine Model ◽

Blood Meal ◽

Tick Infestation ◽

Ixodes Scapularis ◽

Binding Protein ◽

Protein A ◽

Lyme Disease Vaccine

ABSTRACT Previous studies showed that decorin-binding protein A (DbpA) ofBorrelia burgdorferi was a protective immunogen in the murine model of Lyme borreliosis when mice were challenged (needle inoculated) intradermally with in vitro-cultivated spirochetes. In the present study, DbpA-immunized C3H/HeJ mice were not protected from infection when infested with Ixodes scapularis nymphs harboring virulent B. burgdorferi 297. This lack of protection correlated with the failure to detect DbpA on B. burgdorferi in ticks, suggesting that DbpA is not available as a target for bactericidal antibodies in serum when B. burgdorferi-infected ticks take their blood meal from an immunized host. The failure of DbpA immunization to protect tick-challenged mice contradicts the results of earlier needle inoculation vaccination experiments and suggests that DbpA may not be suitable as a Lyme disease vaccine.

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Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00399-15 ◽

2015 ◽

Vol 22 (11) ◽

pp. 1176-1186 ◽

Cited By ~ 6

Author(s):

Zachary P. Weiner ◽

Rebecca M. Crew ◽

Kevin S. Brandt ◽

Amy J. Ullmann ◽

Martin E. Schriefer ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Recombinant Proteins ◽

Erythema Migrans ◽

Disease Patient ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Early Stages ◽

Lyme Carditis ◽

Mammalian Infection

ABSTRACTLaboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series ofBorrelia burgdorferiproteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additionalin vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing.

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Borrelia burgdorferi bbk13Is Critical for Spirochete Population Expansion in the Skin during Early Infection

Infection and Immunity ◽

10.1128/iai.00887-18 ◽

2019 ◽

Vol 87 (5) ◽

Cited By ~ 2

Author(s):

George F. Aranjuez ◽

Hunter W. Kuhn ◽

Philip P. Adams ◽

Mollie W. Jewett

Keyword(s):

Borrelia Burgdorferi ◽

Population Expansion ◽

Targeted Mutagenesis ◽

Lyme Arthritis ◽

Content Type ◽

Lyme Carditis ◽

Inoculation Site ◽

Full Complement ◽

Mammalian Infection ◽

Mouse Model Of Infection

ABSTRACTLyme disease is caused by the spirocheteBorrelia burgdorferiand is transmitted via the bite of an infected tick.B. burgdorferienters the skin, disseminates via the bloodstream, and infects various distal tissues, leading to inflammatory sequelae, such as Lyme arthritis and Lyme carditis.B. burgdorferilinear plasmid 36 (lp36) is critical for mammalian infectivity; however, the full complement of genes on lp36 that contribute to this process remains unknown. Through a targeted mutagenesis screen of the genes on lp36, we identified a novel infectivity gene of unknown function,bbk13, which encodes an immunogenic, non-surface-exposed membrane protein that is important for efficient mammalian infection. Loss ofbbk13resulted in reduced spirochete loads in distal tissues in a mouse model of infection. Through a detailed analysis ofB. burgdorferiinfection kinetics, we discovered thatbbk13is important for promoting spirochete proliferation in the skin inoculation site. The attenuated ability of Δbbk13spirochetes to proliferate in the inoculation site was followed by reduced numbers ofB. burgdorferispirochetes in the bloodstream and, ultimately, consistently reduced spirochete loads in distal tissues. Together, our data indicate thatbbk13contributes to disseminated infection by promoting spirochete proliferation in the early phase of infection in the skin. This work not only increases the understanding of the contribution of the genes on lp36 toB. burgdorferiinfection but also begins to define the genetic basis forB. burgdorferiexpansion in the skin during localized infection and highlights the influence of the early expansion of spirochetes in the skin on the outcome of infection.

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Variations in Barbour-Stoenner-Kelly Culture Medium Modulate Infectivity and Pathogenicity of Borrelia burgdorferi Clinical Isolates

Infection and Immunity ◽

10.1128/iai.72.11.6702-6706.2004 ◽

2004 ◽

Vol 72 (11) ◽

pp. 6702-6706 ◽

Cited By ~ 28

Author(s):

Guiqing Wang ◽

Radha Iyer ◽

Susan Bittker ◽

Denise Cooper ◽

Jennifer Small ◽

...

Keyword(s):

Borrelia Burgdorferi ◽

Prospective Study ◽

Clinical Isolate ◽

Murine Model ◽

Prospective Studies ◽

Culture Medium ◽

Clinical Isolates ◽

In Vitro Cultivation ◽

A Prospective Study

ABSTRACT The effects of variations in Barbour-Stoenner-Kelly (BSK) medium on the infectivity and pathogenicity of Borrelia burgdorferi clinical isolates were assessed by retrospective and prospective studies using a murine model of Lyme borreliosis. Thirty of 35 (86%) mice infected with any of six virulent B. burgdorferi clinical isolates grown in a BSK-H medium developed clinically apparent arthritis. By contrast, arthritis was observed in only 25 of 60 (42%) mice inoculated with two of these B. burgdorferi strains grown in a different lot of BSK-H medium (P < 0.001). In a prospective study, mice inoculated with a B. burgdorferi clinical isolate grown in a BSK medium prepared in-house produced significantly greater disease than those injected with the same isolate cultured in BSK-H medium (P < 0.05). The attenuated pathogenicity is not due to the loss of plasmids during in vitro cultivation. The data suggest that variations in BSK medium have a significant impact on the infectivity and pathogenicity of B. burgdorferi clinical isolates.

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