Binding and degradation of fibrinogen by Bacteroides fragilis and characterization of a 54 kDa fibrinogen-binding protein

S Houston, G. W. Blakely, L. Martin, S. Patrick

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    Bacteroides fragilis is a bacterium that resides in the normal human gastro-intestinal tract; however, it is also the most commonly isolated Gram-negative obligate anaerobe from human clinical infections, such as intra-abdominal abscesses, and the most common cause of anaerobic bacteraemia. Abscess formation is important in bacterial containment, limiting dissemination of infection and bacteraemia. In this study, we investigated B. fragilis binding and degradation of human fibrinogen, the major structural component involved in fibrin abscess formation. We have shown that B. fragilis NCTC9343 binds human fibrinogen. A putative Bacteroides fragilis fibrinogen-binding protein, designated BF-FBP, identified in the genome sequence of NCTC9343, was cloned and expressed in Escherichia coli. The purified recombinant BF-FBP bound primarily to the human fibrinogen Bβ-chain. In addition, we have identified fibrinogenolytic activity in B. fragilis exponential phase culture supernatants, associated with fibrinogenolytic metalloproteases in NCTC9343 and 638R, and cysteine protease activity in YCH46. All nine clinical isolates of B. fragilis examined degraded human fibrinogen; with eight isolates, initial Aα-chain degradation was observed, with varying Bβ-chain and γ-chain degradation. With one blood culture isolate, Bβ-chain and γ-chain degradation occurred first, followed by subsequent Aα-chain degradation. Our data raise the possibility that the fibrinogen-binding protein of B. fragilis, along with a variety of fibrinogenolytic proteases, may be an important virulence factor that facilitates dissemination of infection via reduction or inhibition of abscess formation.
    LanguageEnglish
    Pages2516-2526
    JournalMicrobiology
    Volume156
    Issue number8
    DOIs
    Publication statusPublished - May 2010

    Fingerprint

    Bacteroides fragilis
    Fibrinogen
    Carrier Proteins
    Abscess
    Bacteremia
    Infection
    Abdominal Abscess
    Cysteine Proteases
    Metalloproteases
    Virulence Factors
    Fibrin
    Peptide Hydrolases
    Genome
    Escherichia coli
    Bacteria

    Cite this

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    title = "Binding and degradation of fibrinogen by Bacteroides fragilis and characterization of a 54 kDa fibrinogen-binding protein",
    abstract = "Bacteroides fragilis is a bacterium that resides in the normal human gastro-intestinal tract; however, it is also the most commonly isolated Gram-negative obligate anaerobe from human clinical infections, such as intra-abdominal abscesses, and the most common cause of anaerobic bacteraemia. Abscess formation is important in bacterial containment, limiting dissemination of infection and bacteraemia. In this study, we investigated B. fragilis binding and degradation of human fibrinogen, the major structural component involved in fibrin abscess formation. We have shown that B. fragilis NCTC9343 binds human fibrinogen. A putative Bacteroides fragilis fibrinogen-binding protein, designated BF-FBP, identified in the genome sequence of NCTC9343, was cloned and expressed in Escherichia coli. The purified recombinant BF-FBP bound primarily to the human fibrinogen Bβ-chain. In addition, we have identified fibrinogenolytic activity in B. fragilis exponential phase culture supernatants, associated with fibrinogenolytic metalloproteases in NCTC9343 and 638R, and cysteine protease activity in YCH46. All nine clinical isolates of B. fragilis examined degraded human fibrinogen; with eight isolates, initial Aα-chain degradation was observed, with varying Bβ-chain and γ-chain degradation. With one blood culture isolate, Bβ-chain and γ-chain degradation occurred first, followed by subsequent Aα-chain degradation. Our data raise the possibility that the fibrinogen-binding protein of B. fragilis, along with a variety of fibrinogenolytic proteases, may be an important virulence factor that facilitates dissemination of infection via reduction or inhibition of abscess formation.",
    author = "S Houston and Blakely, {G. W.} and L. Martin and S. Patrick",
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    Binding and degradation of fibrinogen by Bacteroides fragilis and characterization of a 54 kDa fibrinogen-binding protein. / Houston, S; Blakely, G. W.; Martin, L.; Patrick, S.

    In: Microbiology, Vol. 156, No. 8, 05.2010, p. 2516-2526.

    Research output: Contribution to journalArticle

    TY - JOUR

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    AU - Houston, S

    AU - Blakely, G. W.

    AU - Martin, L.

    AU - Patrick, S.

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    N2 - Bacteroides fragilis is a bacterium that resides in the normal human gastro-intestinal tract; however, it is also the most commonly isolated Gram-negative obligate anaerobe from human clinical infections, such as intra-abdominal abscesses, and the most common cause of anaerobic bacteraemia. Abscess formation is important in bacterial containment, limiting dissemination of infection and bacteraemia. In this study, we investigated B. fragilis binding and degradation of human fibrinogen, the major structural component involved in fibrin abscess formation. We have shown that B. fragilis NCTC9343 binds human fibrinogen. A putative Bacteroides fragilis fibrinogen-binding protein, designated BF-FBP, identified in the genome sequence of NCTC9343, was cloned and expressed in Escherichia coli. The purified recombinant BF-FBP bound primarily to the human fibrinogen Bβ-chain. In addition, we have identified fibrinogenolytic activity in B. fragilis exponential phase culture supernatants, associated with fibrinogenolytic metalloproteases in NCTC9343 and 638R, and cysteine protease activity in YCH46. All nine clinical isolates of B. fragilis examined degraded human fibrinogen; with eight isolates, initial Aα-chain degradation was observed, with varying Bβ-chain and γ-chain degradation. With one blood culture isolate, Bβ-chain and γ-chain degradation occurred first, followed by subsequent Aα-chain degradation. Our data raise the possibility that the fibrinogen-binding protein of B. fragilis, along with a variety of fibrinogenolytic proteases, may be an important virulence factor that facilitates dissemination of infection via reduction or inhibition of abscess formation.

    AB - Bacteroides fragilis is a bacterium that resides in the normal human gastro-intestinal tract; however, it is also the most commonly isolated Gram-negative obligate anaerobe from human clinical infections, such as intra-abdominal abscesses, and the most common cause of anaerobic bacteraemia. Abscess formation is important in bacterial containment, limiting dissemination of infection and bacteraemia. In this study, we investigated B. fragilis binding and degradation of human fibrinogen, the major structural component involved in fibrin abscess formation. We have shown that B. fragilis NCTC9343 binds human fibrinogen. A putative Bacteroides fragilis fibrinogen-binding protein, designated BF-FBP, identified in the genome sequence of NCTC9343, was cloned and expressed in Escherichia coli. The purified recombinant BF-FBP bound primarily to the human fibrinogen Bβ-chain. In addition, we have identified fibrinogenolytic activity in B. fragilis exponential phase culture supernatants, associated with fibrinogenolytic metalloproteases in NCTC9343 and 638R, and cysteine protease activity in YCH46. All nine clinical isolates of B. fragilis examined degraded human fibrinogen; with eight isolates, initial Aα-chain degradation was observed, with varying Bβ-chain and γ-chain degradation. With one blood culture isolate, Bβ-chain and γ-chain degradation occurred first, followed by subsequent Aα-chain degradation. Our data raise the possibility that the fibrinogen-binding protein of B. fragilis, along with a variety of fibrinogenolytic proteases, may be an important virulence factor that facilitates dissemination of infection via reduction or inhibition of abscess formation.

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