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The Borrelia burgdorferi adhesin DbpA is bifunctional, binding to extracellular matrix to foster tissue colonization and to the host complement regulatory protein C4BP to promote bloodstream survival
Author(s) -
Lin YiPin,
Blevins Jon S.,
Leong John M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb496
Subject(s) - borrelia burgdorferi , microbiology and biotechnology , biology , bacterial adhesin , decorin , borrelia , binding protein , extracellular matrix , immunology , antibody , escherichia coli , biochemistry , gene , proteoglycan
Borrelia burgdorferi sensu lato, the causative agent of Lyme disease, can infect the skin at the site of the tick bite and may subsequently spread via the bloodstream to the heart, nervous system, and joints, leading to multisystemic disease. B. burgdorferi produces two surface lipoproteins, decorin binding protein A (DbpA) and B (DbpB), that promote spirochetal binding to the extracellular matrix (ECM) components decorin and dermatan sulfate. A B. burgdorferi dbpBA deficient mutant is unable to establish mammalian infection. In this study, we found that the expression of wild type DbpA, but not DbpAΔC11, which lacks the C‐terminal 11 amino acids of DbpA and is incapable of binding to either decorin or dermatan sulfate, promoted stable murine colonization by B. burgdorferi dbpBA , indicating that the binding activity of DbpA is critical for colonization. Interestingly, unlike the parental B. burgdorferi dbpBA mutant, derivatives that ectopically produce either DbpA or DbpAΔC11 were detected in the bloodstream at 3 days post infection and were resistant to human serum in vitro . Further, pull‐down assays of human serum and quantitative binding analyses using recombinant DbpA revealed that DbpA recognizes the complement regulatory protein C4BP (C4‐binding protein) with high affinity (K D =0.82 ±0.03μM). These findings suggest that DbpA is a bifunctional protein that binds ECM to promote tissue colonization and C4BP to protect the spirochete from immune clearance at early stages of infection.