Borrelia burgdorferi and its tropisms for adhesion molecules in the joint

Coburn, Jenifer; Medrano, Melisa S.; Cugini, Carla

doi:10.1097/00002281-200207000-00010

Cited by 23 publications

(13 citation statements)

References 44 publications

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“…However, this observation also raises a paradox since B. burgdorferi can persist in infected animals even in the presence of specific antibodies against all seven of these proteins. One possible explanation for this phenomenon is that B. burgdorferi colonizes immune-privileged niches during early infection (24,50) or localizes to tissues with a low penetration of antibody and/or immune effector cells, which would allow organisms to persist in the presence of a specific and robust immune response (11,24,47,50,59). Therefore, as long as B. burgdorferi can colonize immune-restricted tissue niches before an immune response develops, they are protected and can chronically persist in the mammalian host.…”

Section: Vol 74 2006 Identification Of B Burgdorferi Surface Protementioning

confidence: 99%

Identification ofBorrelia burgdorferiOuter Surface Proteins

et al. 2006

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Several Borrelia burgdorferi outer surface proteins have been identified over the past decade that are up-regulated by temperature-and/or mammalian host-specific signals as this spirochete is transmitted from ticks to mammals. Given the potential role(s) that these differentially up-regulated proteins may play in B. burgdorferi transmission and Lyme disease pathogenesis, much attention has recently been placed on identifying additional borrelial outer surface proteins. To identify uncharacterized B. burgdorferi outer surface proteins, we previously performed a comprehensive gene expression profiling analysis of temperature-shifted and mammalian host-adapted B. burgdorferi. The combined microarray analyses revealed that many genes encoding known and putative outer surface proteins are down-regulated in mammalian host-adapted B. burgdorferi. At the same time, however, several different genes encoding putative outer surface proteins were found to be up-regulated during the transmission and infection process. Among the putative outer surface proteins identified, biochemical and surface localization analyses confirmed that seven (Bb0405, Bb0689, BbA36, BbA64, BbA66, BbA69, and BbI42) are localized to the surface of B. burgdorferi. Furthermore, enzymelinked immunosorbent assay analysis using serum from tick-infested baboons indicated that all seven outer surface proteins identified are immunogenic and that antibodies are generated against all seven during a natural infection. Specific antibodies generated against all seven of these surface proteins were found to be bactericidal against B. burgdorferi, indicating that these newly identified outer surface proteins are prime candidates for analysis as second-generation Lyme disease vaccinogens.Lyme disease, caused by the pathogenic spirochete Borrelia burgdorferi, is a debilitating multisystem disease that can chronically affect patients for decades (58, 61). The disease is typically transmitted to humans by the bite of infected Ixodes ticks and is currently the most common arthropod-borne infection in the United States (8,49,60). B. burgdorferi is maintained in nature through a complex enzootic cycle involving the horizontal transmission of spirochetes between ticks and mammalian hosts (39). As a consequence of its unique life cycle, this organism must adapt to very distinct environmental niches as it migrates from the tick to the mammalian host. Given the extracellular lifestyle of this pathogen, the outer surface of this organism is the interface between B. burgdorferi and its tick and mammalian hosts during infection. Therefore, to better examine Lyme disease pathogenesis and identify possible vaccine candidates, many investigations have focused on identifying new B. burgdorferi outer surface proteins (Osps). Additionally, since it is now well recognized that many surface proteins, such as OspA, expressed by B. burgdorferi are down-regulated or completely turned off during tick transmission and mammalian infection (1, 25), the identification of surface proteins that ...

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Section: Vol 74 2006 Identification Of B Burgdorferi Surface Protementioning

confidence: 99%

Identification ofBorrelia burgdorferiOuter Surface Proteins

et al. 2006

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“…B. burgdorferi is frequently found associated with connective tissues (12,13,14,15) and is often detected in and isolated from infected cartilaginous or membranous tissues, such as skin and joints. This suggests specific interactions between the pathogen and host skin tissues (5,16,17,18).…”

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confidence: 99%

Evaluation of RevA, a Fibronectin-Binding Protein of Borrelia burgdorferi, as a Potential Vaccine Candidate for Lyme Disease

Floden

Gonzalez

Gaultney

et al. 2013

Clin Vaccine Immunol

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Previous studies indicated that the Lyme disease spirochete Borrelia burgdorferi expresses the RevA outer surface protein during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA appears to be a good target for preventive therapies. RevA proteins are highly conserved across all Lyme borreliae, and antibodies against RevA protein are cross-reactive among RevA proteins from diverse strains. Mice infected with B. burgdorferi mounted a rapid IgM response to RevA, followed by a strong IgG response that generally remained elevated for more than 12 months, suggesting continued exposure of RevA protein to the immune system. RevA antibodies were bactericidal in vitro. To evaluate the RevA antigen as a potential vaccine, mice were vaccinated with recombinant RevA and challenged with B. burgdorferi by inoculation with a needle or by a tick bite. Cultured tissues from all treatment groups were positive for B. burgdorferi. Vaccinated animals also appeared to have similar levels of B. burgdorferi DNA compared to nonvaccinated controls. Despite its antigenicity, surface expression, and the production of bactericidal antibodies against it, RevA does not protect against Borrelia burgdorferi infection in a mouse model. However, passive immunization with anti-RevA antibodies did prevent infection, suggesting the possible utility of RevA-based immunotherapeutics or vaccine.

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“…A vital part of connective tissue and endothelial lining, proteoglycans are ubiquitous adhesion substrates for spirochetes. Of note, all known binding substrates for the spirochete are present in synovium, perhaps also explaining tropism of the organism to the joint (Coburn et al, 2002). The organism's decorin binding proteins (DBP) are associated with the pathogenesis of Lyme arthritis (Coburn et al, 2005;Cabello et al, 2007).…”

Section: Pathophysiologymentioning

confidence: 99%