The Vibrio cholerae colonization factor GbpA possesses a modular structure that governs binding to different host surfaces
Resumen: 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.
Author Summary:
Vibrio cholerae is the bacterium that causes cholera, a disease endemic in developing countries with poor sanitation. The bacterium colonizes aquatic organisms that serve as a reservoir of transmission to humans. Our work has focused on GbpA, a protein that is secreted by V. cholerae and appears to facilitate growth of the bacteria both in the human intestine and on the exoskeletons of marine organisms. We show that the protein possesses an unusual three-dimensional structure consisting of four separate domains. Two of the domains are similar to proteins that are known to bind chitin, an exoskeleton biopolymer, and our data show that these domains indeed harbour the chitin binding properties of GbpA. One of these domains is also capable of binding intestinal mucus. The two remaining domains are required for interacting with the bacterium itself, creating a stable interface between the bacterium and the human/marine host, facilitating colonization. Finally, work with a cholera mouse model shows that only the first three domains of GbpA are required for colonization. These results show how GbpA provides structural/functional modular interactions between V. cholerae, the intestinal epithelium and chitinous exoskeletons.

Idioma: Inglés
DOI: 10.1371/journal.ppat.1002373
Año: 2012
Publicado en: PLoS Pathogens 8, 1 (2012)
ISSN: 1553-7366

Factor impacto JCR: 8.136 (2012)
Categ. JCR: MICROBIOLOGY rank: 11 / 116 = 0.095 (2012) - Q1 - T1
Categ. JCR: VIROLOGY rank: 2 / 34 = 0.059 (2012) - Q1 - T1
Categ. JCR: PARASITOLOGY rank: 2 / 34 = 0.059 (2012) - Q1 - T1

Tipo y forma: Article (Published version)

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