Adhesion Mechanisms of Borrelia burgdorferi

Antonara, Styliani; Ristow, Laura C.; Coburn, Jenifer

doi:10.1007/978-94-007-0940-9_3

Cited by 41 publications

(39 citation statements)

References 87 publications

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“…Their respective ligands include decorin, fibronectin, various glycosaminoglycans, laminin, and ␣ IIb ␤ 3 integrin (1,2,3,4,5,6,7). This is by no means a completely inclusive list (8); for example, a yet-unidentified borrelial adhesion binds directly to native type I collagen (9), and thus far, ligands for BmpD and members of the OspF family have not been characterized (10). However, the interactions of adhesins and ligands, particularly DbpA and DbpB (DbpA/B) and decorin, appear to play an important role during all stages of infection.…”

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confidence: 99%

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

et al. 2013

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The laboratory mouse model of Lyme disease has revealed that Borrelia burgdorferi differentially expresses numerous outer surface proteins that influence different stages of infection (tick-borne transmission, tissue colonization, dissemination, persistence, and tick acquisition). Deletion of two such outer surface proteins, decorin-binding proteins A and B (DbpA/B), has been documented to decrease infectivity, impede early dissemination, and, possibly, prevent persistence. In this study, DbpA/B-deficient spirochetes were confirmed to exhibit an early dissemination defect in immunocompetent, but not immunodeficient, mice, and the defect was found to resolve with chronicity. Development of disease (arthritis and carditis) was attenuated only in the early stage of infection with DbpA/B-deficient spirochetes in both types of mice. Persistence of the DbpA/B-deficient spirochetes occurred in both immunocompetent and immunodeficient mice in a manner indistinguishable from that of wild-type spirochetes. Dissemination through the lymphatic system was evaluated as an underlying mechanism for the early dissemination defect. At 12 h, 3 days, 7 days, and 14 days postinoculation, DbpA/B-deficient spirochetes were significantly less prevalent and in lower numbers in lymph nodes than wild-type spirochetes. However, in immunodeficient mice, deficiency of DbpA/B did not significantly decrease the prevalence or spirochete numbers in lymph nodes. Complementation of DbpA/B restored a wild-type phenotype. Thus, the results indicated that deficiency of DbpA/B allows the acquired immune response to restrict early dissemination of spirochetes, which appears to be at least partially mediated through the lymphatic system.

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confidence: 99%

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

et al. 2013

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“…1), and we analyzed its binding to collagen type I, collagen type IV, laminin, and human fibronectin (BD BioCoat, Bedford, MA). All incubations were performed using HBS buffer (HEPES-buffered saline) containing 0.25 mM Ca 2ϩ , 1 mM Mn 2ϩ , 1 mM Mg 2ϩ , and 1% bovine serum albumin (BSA) (46,47). After blocking plates with 3% BSA in HBS containing 1% Tween 20 (HBS-T), we added 500 ng/well of rBB0172 T or rBBK32 (positive binding control) To evaluate the binding of rBB0172 T to a wider range of ECMs and integrins, and to prevent any interference of the anti-rBB0172 antibody with binding capabilities to the substrates, 96-well flat-bottom plates (Nunc) were coated with 500 ng/well of each of the recombinant proteins: rBB0172, rBBK32, and rP66.…”

Section: Site-directed Mutagenesis Of Dxsxs Metal-binding Domain Bb0mentioning

confidence: 99%

“…After blocking plates with 3% BSA in HBS containing 1% Tween 20 (HBS-T), we added 500 ng/well of rBB0172 T or rBBK32 (positive binding control) To evaluate the binding of rBB0172 T to a wider range of ECMs and integrins, and to prevent any interference of the anti-rBB0172 antibody with binding capabilities to the substrates, 96-well flat-bottom plates (Nunc) were coated with 500 ng/well of each of the recombinant proteins: rBB0172, rBBK32, and rP66. All incubations used HBS buffer containing 0.25 mM Ca 2ϩ , 1 mM Mn 2ϩ , and 1 mM Mg 2ϩ (46,47). After coating overnight at 4°C in carbonate buffer, pH 9.2, plates were washed and blocked using HBS-T with 3% BSA buffer for 2 h at RT.…”

Section: Site-directed Mutagenesis Of Dxsxs Metal-binding Domain Bb0mentioning

confidence: 99%

“…After coating overnight at 4°C in carbonate buffer, pH 9.2, plates were washed and blocked using HBS-T with 3% BSA buffer for 2 h at RT. Blocked plates were washed with HBS-T and incubated for 1 h at RT with 500 ng/well of each of the ECM components (human plasma fibronectin, human tissue fibronectin, aggrecan, decorin, vitronectin, elastin, and fibrinogen; Sigma-Aldrich, Co., LLC) and integrins (␣ 1 ␤ 1 , ␣ 3 ␤ 1 , ␣ V ␤ 3 , ␣ V ␤ 5 , and ␣ 5 ␤ 1 ; EMD Millipore Corporation) (46,47). After washing, plates were incubated for 1 h at RT with each respective anti-ECM component or antiintegrin antibody.…”

Section: Site-directed Mutagenesis Of Dxsxs Metal-binding Domain Bb0mentioning

confidence: 99%

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BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds Integrin α ₃ β ₁

et al. 2013

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Lyme disease is a multisystemic disorder caused by Borrelia burgdorferi infection. Upon infection, some B. burgdorferi genes are upregulated, including members of the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) protein family, which facilitate B. burgdorferi adherence to extracellular matrix components of the host. Comparative genome analysis has revealed a new family of B. burgdorferi proteins containing the von Willebrand factor A (vWFA) domain. In the present study, we characterized the expression and membrane association of the vWFA domain-containing protein BB0172 by using in vitro transcription/translation systems in the presence of microsomal membranes and with detergent phase separation assays. Our results showed evidence of BB0172 localization in the outer membrane, the orientation of the vWFA domain to the extracellular environment, and its function as a metal ion-dependent integrin-binding protein. This is the first report of a borrelial adhesin with a metal ion-dependent adhesion site (MIDAS) motif that is similar to those observed in eukaryotic integrins and has a similar function.

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“…Adhesins expressed by B. burgdorferi facilitate interactions with these tissues. B. burgdorferi expresses a plethora of outer surface proteins that interact with numerous components of the extracellular matrix (ECM), such as fibronectin, decorin, and integrins (19)(20)(21)(22)(23). The attachment of B. burgdorferi to the host ECM is likely critical for pathogenesis and persistence in mammals.…”

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confidence: 99%

Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease

et al. 2015

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The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, with increased fibrotic collagen deposition in tibiotarsal joints. The mutants also induced increased levels of the chemokine CCL2, a monocyte chemoattractant, in serum, and this increase was abolished in the complemented strain. Therefore, while revA is not absolutely essential for infection, deletion of revA had distinct effects on dissemination, arthritis severity, and host response. Borrelia burgdorferi, the causative agent of Lyme disease, is a vector-borne pathogen that successfully colonizes both ticks and a variety of vertebrate hosts. In mammals, B. burgdorferi is frequently found associated with connective tissues (1-13), and the bacterium is often detected in cartilaginous or collagen-rich tissues, such as skin and joints (6,7,9,(11)(12)(13)(14)(15)(16)(17)(18). Adhesins expressed by B. burgdorferi facilitate interactions with these tissues. B. burgdorferi expresses a plethora of outer surface proteins that interact with numerous components of the extracellular matrix (ECM), such as fibronectin, decorin, and integrins (19-23). The attachment of B. burgdorferi to the host ECM is likely critical for pathogenesis and persistence in mammals. Indeed, for many of these adhesins, deletion mutants have significant defects in infectivity, fail to disseminate widely in the host, or have other effects on disease, such as alterations in the severity of arthritis (24-27).The interactions of B. burgdorferi with fibronectin are facilitated by several distinct bacterial surface proteins, including BBK32, RevA, BB0347, and CspA (BbCRASP-1) (28-31). The redundancy in adhesins makes it difficult to dissect the role of each B. burgdorferi fibronectin binding protein in the pathogenesis of Lyme disease. For example, real-time microscopic imaging in live mice revealed a significant role for BBK32 in interactions with host vasculature, yet bbk32 mutants are still able to infect mammals (32).RevA is a 19-kDa surface protein encoded on the circular plasmid 32 (cp32) family of plasmids (33). RevA expression is elevated during mammalian infection over its expression in the tick vector, suggesting a role in pathogenesis (30,(34)(35)(36). RevA binds to fibronectin, and anti-RevA antibodies block the binding of whole B. burgdorferi bacteria to fibronectin (30). RevA is antigenic, as evidenced by the fact that both mice and human Lyme disease patients produce antibodies...

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Adhesion Mechanisms of Borrelia burgdorferi

Cited by 41 publications

References 87 publications

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds Integrin α ₃ β ₁

Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease

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Adhesion Mechanisms of Borrelia burgdorferi

Cited by 41 publications

References 87 publications

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds Integrin α 3 β 1

Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease

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BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds Integrin α ₃ β ₁