Identification and characterization of decorin binding proteins from Borrelia burgdorferi /
Borrelia burgdorferi, the spirochete that causes Lyme disease, is deposited by a tick into the host dermis where it associates with collagen fibers, replicates, and eventually disseminates to other tissues. In several tissues, the spirochetes are found primarily in the host extracellular matrix, pa...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1996.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=739667371&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Borrelia burgdorferi, the spirochete that causes Lyme disease, is deposited by a tick into the host dermis where it associates with collagen fibers, replicates, and eventually disseminates to other tissues. In several tissues, the spirochetes are found primarily in the host extracellular matrix, particularly in close association with collagen fibers. We examined the adherence of the spirochete to different components of the collagen fiber and demonstrated that decorin, a proteoglycan which "decorates" collagen fibers, can support the attachment of B. burgdorferi. B. burgdorferi adherence to decorin was shown to be a highly specific interaction. B. burgdorferi expresses two proteins of approximately 20 kDa that bind decorin. We hypothesize that these proteins are adhesins responsible for mediating spirochete attachment to collagen fibers. The genes encoding these decorin-binding proteins (DbpA and DbpB) were isolated by screening a []KZAPII genomic library with labeled decorin. dbpA and dbpB each consist of 561 bp arranged in tandem with separate promoters. Recombinant DbpA and DbpB appear to bind to the same or closely spaced binding sites within decorin. The deduced amino acid sequences of the two Dbps share 40% identity, however polyclonal antisera raised against the Dbps do not cross-react, suggesting a possible role in host evasion of immunologic recognition. As adhesins are important targets for vaccines, the effectiveness of DbpA as a Lyme disease vaccine was investigated. DbpA was confirmed to be surface exposed on intact spirochetes by growth inhibition assay and immuno-electron microscopy. Furthermore, Western blots and passive immunization studies indicate that DbpA is expressed in vivo. Passive administration of antibodies raised against recombinant DbpA protected mice from challenge with several strains of B. burgdorferi, even after a period of host-adaptation by the spirochetes. The target epitope(s) for these functional antibodies were also found to be well conserved among B. burgdorferi strains of diverse geographic, biological, and clinical origins. These findings support a role for DbpA in spirochetal pathogenesis and as a candidate vaccine for Lyme disease. |
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| Item Description: | Vita. "Major Subject: Biochemistry". |
| Physical Description: | xi, 112 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 98-107. |