title: Intestinal adherence of Vibrio cholerae involves a coordinated interaction between colonization factor GbpA and mucin.
abstract: The chitin-binding protein GbpA of Vibrio cholerae has been recently described as a common adherence factor for chitin and intestinal surface. Using an isogenic in-frame gbpA deletion mutant, we first show that V. cholerae O1 El Tor interacts with mouse intestinal mucus quickly, using GbpA in a specific manner. The gbpA mutant strain showed a significant decrease in intestinal adherence, leading to less colonization and fluid accumulation in a mouse in vivo model. Purified recombinant GbpA (rGbpA) specifically bound to N-acetyl-D-glucosamine residues of intestinal mucin in a dose-dependent, saturable manner with a dissociation constant of 11.2 microM. Histopathology results from infected mouse intestine indicated that GbpA binding resulted in a time-dependent increase in mucus secretion. We found that rGbpA increased the production of intestinal secretory mucins (MUC2, MUC3, and MUC5AC) in HT-29 cells through upregulation of corresponding genes. The upregulation of MUC2 and MUC5AC genes was dependent on NF-kappaB nuclear translocation. Interestingly, mucin could also increase GbpA expression in V. cholerae in a dose-dependent manner. Thus, we propose that there is a coordinated interaction between GbpA and mucin to upregulate each other in a cooperative manner, leading to increased levels of expression of both of these interactive factors and ultimately allowing successful intestinal colonization and pathogenesis by V. cholerae.
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Rudra
authors.initials: R
authors.lastname: Bhowmick
authors.forename: Abhisek
authors.initials: A
authors.lastname: Ghosal
authors.forename: Bhabatosh
authors.initials: B
authors.lastname: Das
authors.forename: Hemanta
authors.initials: H
authors.lastname: Koley
authors.forename: Dhira Rani
authors.initials: DR
authors.lastname: Saha
authors.forename: Sandipan
authors.initials: S
authors.lastname: Ganguly
authors.forename: Ranjan K
authors.initials: RK
authors.lastname: Nandy
authors.forename: Rupak K
authors.initials: RK
authors.lastname: Bhadra
authors.forename: Nabendu Sekhar
authors.initials: NS
authors.lastname: Chatterjee