Conserved lysine residues in decorin binding proteins of<i>Borrelia garinii</i>are critical in adhesion to human brain microvascular endothelial cells

Pietikäinen, Annukka; Åstrand, Mia; Cuellar, Julia; Glader, Otto; Elovaara, Heidi; Rouhiainen, Meri; Salo, Jemiina; Furihata, Tomomi; Salminen, Tiina A.; Hytönen, Jukka

doi:10.1111/mmi.14687

Cited by 5 publications

(7 citation statements)

References 55 publications

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“…Thus, we propose that the flexible loop between α-helix 1 and α-helix 2 (and certain flanking residues) constitutes an immunodominant epitope on DbpA recognized in LD patients. In this respect, it is interesting to note that that the core of the A7 peptide is a tripartite Thr-Gly-Ser motif that is conserved in DbpA and DbpB from B. burgdorferi and B. garinii , although the functional significance of this motif is unknown (44).…”

Section: Discussionmentioning

confidence: 99%

The Flexible Linker of Decorin Binding Protein A from Borrelia burgdorferi is a Target of Antibodies in Lyme disease

Movahed

Vance

Slyke

et al. 2022

Preprint

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Decorin binding protein A (DbpA) is a surface adhesin expressed by Borrelia burgdorferi, the causative agent of Lyme disease. While DbpA is one of the most immunogenic B. burgdorferi antigens in Lyme disease patients, the B cell epitopes recognized over the course of infection have not been defined. In this report we profiled ∼300 human serum samples from early, mid, and late-stage Lyme disease for IgM and IgG reactivity with DbpA and a tiled DbpA 18-mer peptide array derived from B.b. strains B31 and 297. Using ELISA and multiplex immunoassays (MIA), we identified 12 DbpA-derived peptides whose reactivity was elevated in Lyme disease patients as compared to healthy controls. The most reactive peptide (“A7”) corresponds to the flexible loop between DbpAB31 α-helix 1 and α-helix 2, implicated in influencing DbpA binding to heparin and dermatan sulfate. An A7-like peptide is also reportedly a target of antibodies in Lyme neuroborreliosis patients. The remaining peptides, while highly reactive in serum samples across disease stages, likely represent non-native epitopes, as antibody reactivity to a subset of peptides in competition assays was unaffected by the addition of soluble DbpA. Moreover, peptide reactivity of any given patient sample rarely correlated with overall DbpA antibody levels, suggesting the antibodies were raised against DbpA degradation products. Insights into B cell epitopes on DbpA elicited during Lyme disease have important implications for understanding how B.burgdorferi persists in the face of an overwhelming antibody response.IMPORTANCEThe bacterium, Borrelia burgdorferi, is the causative agent of Lyme disease, the most reported tick-borne illness in the United States. In humans, clinical manifestations of Lyme disease are complex and can persist for months, even in the face of a robust antibody response directed against numerous B. burgdorferi surface proteins, including decorin binding protein A (DbpA), which is involved in early stages of infection. In this study we employed ∼300 serum samples from Lyme disease patients to better understand antibody reactivity with specific regions (“epitopes”) of DbpA. We identified one epitope on DbpA recognized by antibodies from almost half of the serum samples tested and that, theoretically, should block DbpA’s ability to function in promoting B. burgdorferi colonization of human hosts.

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Section: Discussionmentioning

confidence: 99%

The Flexible Linker of Decorin Binding Protein A from Borrelia burgdorferi is a Target of Antibodies in Lyme disease

Movahed

Vance

Slyke

et al. 2022

Preprint

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“…Indeed, the same loop and flanking regions are predicted to contain conformational B cell epitopes, according to Discotope ( 39 ) and ElliPro ( 40 ). Finally, it is also noteworthy that the A7 peptide contains a tripartite motif (Thr-Gly-Ser) that is conserved in DbpA and DbpB from B. burgdorferi and B. garinii , although the functional significance of this motif is unknown ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Serological Analysis Identifies Consequential B Cell Epitopes on the Flexible Linker and C-Terminus of Decorin Binding Protein A (DbpA) from Borrelia burgdorferi

Movahed

Vance

Ehrbar

et al. 2022

mSphere

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The bacterium, Borrelia burgdorferi , is the causative agent of Lyme disease, the most reported tick-borne illness in the United States. In humans, clinical manifestations of Lyme disease are complex and can persist for months, even in the face of a robust antibody response directed against numerous B. burgdorferi surface proteins, including decorin binding protein A (DbpA), which is involved in the early stages of infection. In this study we employed ~270 serum samples from B. burgdorferi -seropositive individuals to better understand human antibody reactivity to specific regions (called epitopes) of DbpA and how such antibodies may function in limiting B. burgdorferi dissemination and tissue colonization.

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“…α2β1 integrin [184,185]; TN-X [194]; LDL [195,196] DbpA and DbpA [197][198][199][200][201][202][203][204][205][206]; vWF [208]; matrilin-1 [209];…”

Section: Classunclassified

“…Two surface lipoproteins, DbpA and DbpB of the Lyme disease spirochete Borrelia burgdorferi bind decorin and GAGs [197][198][199][200][201][202][203][204][205][206]. DbpA and DbpB also bind biglycan only under flow condition [207].…”

Section: Decorin -Binding Proteins a And B (Dbpa And Dbpb)mentioning

confidence: 99%

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Structural Insights into Protein-Ligand Interactions of Small Leucine Rich Repeat Proteoglycans with a Large Number of Binding Partners: An Overview

Matsushima

Miyashita²,

Batkhishig

et al. 2023

J Cell Signal

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Small leucine rich repeat proteoglycans (SLRPs) exist in the extracellular matrix. SLRPs contain tandem arrays of LRRs flanked by cysteine clusters at the both N- and C-termini. The extreme N- and/or C-termini contain low complexity sequences, glycosaminoglycan (GAG) chain and/or sulfated tyrosine residues in some members of SLRPs. The LRR solenoid structure may be divided into four parts consisting of a concave surface, an ascending surface, a convex surface, and a descending surface. SLRPs share many biological functions including collagen fibrillogenesis, signaling, innate immunity, and inflammation through the binding of various ligands. We undertake a comprehensive literature search of publications in order to make a list of ligands of SLRPs. We describe and discuss the interacting sites of SLRPs to binding partners. The protein-ligand interactions occur on not only the concave surface but also the ascending surface and the N- or C-terminal capping regions. In addition, the extreme N- and/or C-terminal regions with the GAG chains or sulfated tyrosine residues participate in ligand-interactions.

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Conserved lysine residues in decorin binding proteins ofBorrelia gariniiare critical in adhesion to human brain microvascular endothelial cells

Cited by 5 publications

References 55 publications

The Flexible Linker of Decorin Binding Protein A from Borrelia burgdorferi is a Target of Antibodies in Lyme disease

The Flexible Linker of Decorin Binding Protein A from Borrelia burgdorferi is a Target of Antibodies in Lyme disease

Serological Analysis Identifies Consequential B Cell Epitopes on the Flexible Linker and C-Terminus of Decorin Binding Protein A (DbpA) from Borrelia burgdorferi

Structural Insights into Protein-Ligand Interactions of Small Leucine Rich Repeat Proteoglycans with a Large Number of Binding Partners: An Overview

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