The Vibrio cholerae colonization factor GbpA possesses a modular structure that governs binding to different host surfaces

Edmond Wong, Gustav Vaaje-Kolstad, Avishek Ghosh, Ramon Hurtado-Guerrero, Peter V. Konarev, Adel F. M. Ibrahim, Dmitri I. Svergun, Vincent G. H. Eijsink, Nabendu S. Chatterjee, Daan M. F. van Aalten

    Research output: Contribution to journalArticlepeer-review

    80 Citations (Scopus)

    Abstract

    Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons.
    Original languageEnglish
    Article numbere1002373
    JournalPLoS Pathogens
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2012

    Keywords

    • Carbohydrate binding protein
    • Chitin
    • GbpA protein
    • Glycan
    • Mucin
    • n acetylglucosamine
    • Oligosaccharides
    • Unclassified drug
    • Bacterial colonization
    • Bacterial virulence
    • Exoskeleton
    • In vitro study
    • In vivo study
    • Intestine epithelium
    • Microarray analysis
    • Molecular cloning
    • Nonhuman
    • Pathogenesis
    • Protein binding
    • Protein interactions
    • Protein purification
    • Protein structure
    • Sequence analysis
    • Structural homology
    • Vibrio cholerae

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