Computational Studies on the Truncation of N-terminal Fragment of OspA Antigen of Borrelia burgdorferi: Towards Designing a Second- Generation Vaccine Against Lyme Disease

ABSTRACT Lyme disease, a global health concern, is caused by infection with Borrelia burgdorferi, B. afzelii, or B. garinii. The spirochete responsible for the disease in the United States is B. burgdorferi and is spread by the bite of an infected Ixodes tick. We utilized multiple two-dimensional gel techniques combined with proteomics to reveal the full humoral immune response of mice and Lyme patients to membrane-associated proteins isolated from Borrelia burgdorferi. Our studies indicated that a subset of immunogenic membrane-associated proteins (some new and some previously identified) was recognized by mice experimentally infected with Borrelia burgdorferi either by low-dose needle inoculation or by tick infestation. Moreover, the majority of these immunogenic membrane-associated proteins were recognized by sera from patients diagnosed with early-disseminated Lyme disease. These included RevA, ErpA, ErpP, DbpA, BmpA, FtsZ, ErpB, LA7, OppA I, OppA II, OppA IV, FlhF, BBA64, BBA66, and BB0323. Some immunogens (i.e., BBI36/38) were more reactive with sera from mice than Lyme patients, while additional membrane proteins (i.e., FlaB, P66, LA7, and Hsp90) were recognized more strongly with sera from patients diagnosed with early-localized, early-disseminated, or late (chronic)-stage Lyme disease. We were able to examine the humoral response in Lyme patients in a temporal fashion and to identify the majority of immunoreactive proteins as the disease progresses from early to late stages. This serologic proteome analysis enabled the identification of novel membrane-associated proteins that may serve as new diagnostic markers and, more importantly, as second-generation vaccine candidates for protection against Lyme disease.

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New ultrastructural findings about Borrelia burgdorferi by cryofixation, negative staining, thin sectioning and scanning techniques

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160467 ◽

1990 ◽

Vol 48 (3) ◽

pp. 582-583

Author(s):

S. F. Hayes ◽

M. D. Corwin ◽

T. G. Schwan ◽

D. W. Dorward ◽

W. Burgdorfer

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Structural Characterization ◽

Negative Staining ◽

Low Speed ◽

Thin Sectioning ◽

Ultrastructural Findings

Characterization of Borrelia burgdorferi strains by means of negative staining EM has become an integral part of many studies related to the biology of the Lyme disease organism. However, relying solely upon negative staining to compare new isolates with prototype B31 or other borreliae is often unsatisfactory. To obtain more satisfactory results, we have relied upon a correlative approach encompassing a variety EM techniques, i.e., scanning for topographical features and cryotomy, negative staining and thin sectioning to provide a more complete structural characterization of B. burgdorferi.For characterization, isolates of B. burgdorferi were cultured in BSK II media from which they were removed by low speed centrifugation. The sedimented borrelia were carefully resuspended in stabilizing buffer so as to preserve their features for scanning and negative staining. Alternatively, others were prepared for conventional thin sectioning and for cryotomy using modified procedures. For thin sectioning, the fixative described by Ito, et al.

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Surveillance of Ticks and Tick-Borne Pathogens in Suburban Natural Habitats of Central Maryland

Journal of Medical Entomology ◽

10.1093/jme/tjaa291 ◽

2021 ◽

Author(s):

Matthew T Milholland ◽

Lars Eisen ◽

Robyn M Nadolny ◽

Andrias Hojgaard ◽

Erika T Machtinger ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Spotted Fever ◽

Babesia Microti ◽

Borrelia Burgdorferi Sensu Lato ◽

Spotted Fever Group ◽

Borrelia Miyamotoi ◽

Natural Habitats ◽

Questing Ticks ◽

Tick Vectors

Abstract Lyme and other tick-borne diseases are increasing in the eastern United States and there is a lack of research on integrated strategies to control tick vectors. Here we present results of a study on tick-borne pathogens detected from tick vectors and rodent reservoirs from an ongoing 5-yr tick suppression study in the Lyme disease-endemic state of Maryland, where human-biting tick species, including Ixodes scapularis Say (Acari: Ixodidae) (the primary vector of Lyme disease spirochetes), are abundant. During the 2017 tick season, we collected 207 questing ticks and 602 ticks recovered from 327 mice (Peromyscus spp. (Rodentia: Cricetidae)), together with blood and ear tissue from the mice, at seven suburban parks in Howard County. Ticks were selectively tested for the presence of the causative agents of Lyme disease (Borrelia burgdorferi sensu lato [s.l.]), anaplasmosis (Anaplasma phagocytophilum), babesiosis (Babesia microti), ehrlichiosis (Ehrlichia ewingii, Ehrlichia chaffeensis, and ‘Panola Mountain’ Ehrlichia) and spotted fever group rickettsiosis (Rickettsia spp.). Peromyscus ear tissue and blood samples were tested for Bo. burgdorferi sensu stricto (s.s), A. phagocytophilum, Ba. microti, and Borrelia miyamotoi. We found 13.6% (15/110) of questing I. scapularis nymphs to be Bo. burgdorferi s.l. positive and 1.8% (2/110) were A. phagocytophilum positive among all sites. Borrelia burgdorferi s.s. was found in 71.1% (54/76) of I. scapularis nymphs removed from mice and 58.8% (194/330) of captured mice. Results from study on tick abundance and pathogen infection status in questing ticks, rodent reservoirs, and ticks feeding on Peromyscus spp. will aid efficacy evaluation of the integrated tick management measures being implemented.

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Arthritis and Diagnostics in Lyme Disease

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010018 ◽

2021 ◽

Vol 6 (1) ◽

pp. 18

Author(s):

Javier A. Quintero ◽

Raluchukwu Attah ◽

Reena Khianey ◽

Eugenio Capitle ◽

Steven E. Schutzer

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Diagnostic Tests ◽

Laboratory Tests ◽

Diagnostic Methods ◽

Lyme Arthritis ◽

Differential Diagnoses ◽

Antibody Testing ◽

Active Infection ◽

Indirect Measure

The diagnosis of Lyme disease, caused by Borrelia burgdorferi, is clinical but frequently supported by laboratory tests. Lyme arthritis is now less frequently seen than at the time of its discovery. However, it still occurs, and it is important to recognize this, the differential diagnoses, and how laboratory tests can be useful and their limitations. The most frequently used diagnostic tests are antibody based. However, antibody testing still suffers from many drawbacks and is only an indirect measure of exposure. In contrast, evolving direct diagnostic methods can indicate active infection.

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Populations of Human T Lymphocytes That Traverse the Vascular Endothelium Stimulated by Borrelia burgdorferi Are Enriched with Cells That Secrete Gamma Interferon

Infection and Immunity ◽

10.1128/iai.72.3.1530-1536.2004 ◽

2004 ◽

Vol 72 (3) ◽

pp. 1530-1536 ◽

Cited By ~ 11

Author(s):

Edna I. Gergel ◽

Martha B. Furie

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Vascular Endothelium ◽

Human Peripheral Blood ◽

Gamma Interferon ◽

Interleukin 4 ◽

Ifn Γ

ABSTRACT Some diseases are characterized by prevalence in the affected tissues of type 1 T lymphocytes, which secrete gamma interferon (IFN-γ) and other proinflammatory cytokines. For example, type 1 T cells predominate in the lesions of patients with Lyme disease, which is caused by the bacterium Borrelia burgdorferi. We used an in vitro model of the blood vessel wall to test the premise that the vascular endothelium actively recruits circulating type 1 T cells to such lesions. When T lymphocytes isolated from human peripheral blood were examined, the populations that traversed monolayers of resting human umbilical vein endothelial cells (HUVEC) or HUVEC stimulated by interleukin-1β or B. burgdorferi were markedly enriched for T cells that produced IFN-γ compared to the initially added population of T cells. No enrichment was seen for cells that produced interleukin-4, a marker for type 2 T lymphocytes. Very late antigen-4 and CD11/CD18 integrins mediated passage of the T cells across both resting and stimulated HUVEC, and the endothelium-derived chemokine CCL2 (monocyte chemoattractant protein 1) was responsible for the enhanced migration of T cells across stimulated HUVEC. These results suggest that the vascular endothelium may contribute to the selective accumulation of type 1 T cells in certain pathological lesions, including those of Lyme disease.

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