Role of fibronectin-binding protein A in Clostridium difficile intestinal colonization
Open Access
- 1 August 2011
- journal article
- Published by Microbiology Society in Journal of Medical Microbiology
- Vol. 60 (8), 1155-1161
- https://doi.org/10.1099/jmm.0.029553-0
Abstract
Clostridium difficile is a frequent cause of severe, recurrent, post-antibiotic diarrhoea and pseudomembranous colitis. Its pathogenicity is mediated mainly by two toxins, TcdA and TcdB. However, different adhesins have also been described as important colonization factors which are implicated in the first step of the intestinal infection. In this study, we focused our interest on one of these adhesins, fibronectin-binding protein A (FbpA), and on its role in the intestinal colonization process. A mutant of FbpA (CDΔFbpA) was constructed in C. difficile strain 630Δerm by using ClosTron technology. This mutant was characterized in vitro and in vivo and compared to the isogenic wild-type strain. Adhesion of the CDΔFbpA mutant to the human colonic epithelial cell line Caco-2 and to mucus-secreting HT29-MTX cells was examined. Surprisingly, the CDΔFbpA mutant adhered more than the wild-type parental strain. The CDΔFbpA mutant was also analysed in three different mouse models by following the intestinal implantation kinetics (faecal shedding) and caecal colonization (7 days post-challenge). We showed that in monoxenic mice, CDΔFbpA shed C. difficile in faeces at the same rate as that of the isogenic wild-type strain but its colonization of the caecal wall was significantly reduced. In dixenic mice, the shedding rate was slower for the CDΔFbpA mutant than for the isogenic wild-type strain during the first days of infection, but no significant difference was observed in caecal colonization. Similar rates of intestinal implantation and caecal colonization were observed for both strains in assays performed in human microbiota-associated mice. Taken together, our data suggest that FbpA plays a role in intestinal colonization by C. difficile.Keywords
This publication has 20 references indexed in Scilit:
- The emergence of ‘hypervirulence’ in Clostridium difficileInternational Journal of Medical Microbiology, 2010
- Clostridium difficile toxins: More than mere inhibitors of Rho proteinsThe International Journal of Biochemistry & Cell Biology, 2008
- Cwp84, a Surface-Associated Protein of Clostridium difficile , Is a Cysteine Protease with Degrading Activity on Extracellular Matrix ProteinsJournal of Bacteriology, 2007
- The ClosTron: A universal gene knock-out system for the genus ClostridiumJournal of Microbiological Methods, 2007
- FbpA, a novel multifunctional Listeria monocytogenes virulence factorMolecular Microbiology, 2004
- Identification and characterization of a fibronectin-binding protein from Clostridium difficileMicrobiology, 2003
- Binding of Clostridium difficile Surface Layer Proteins to Gastrointestinal TissuesInfection and Immunity, 2002
- GroEL (Hsp60) of Clostridium difficile is involved in cell adherenceMicrobiology, 2001
- Characterization of surface layer proteins from different Clostridium difficile clinical isolatesMicrobial Pathogenesis, 2000
- Microbial adhesion to solvents: a novel method to determine the electron-donor/electron-acceptor or Lewis acid-base properties of microbial cellsColloids and Surfaces B: Biointerfaces, 1996