Journal
INFECTION AND IMMUNITY
Volume 82, Issue 8, Pages 3383-3393Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.01888-14
Keywords
-
Categories
Funding
- Vertex-Crohn's and Colitis Canada partnership program
- Canadian Institutes of Health Research (CIHR)
- Canada Research Chairs program
- Michael G. DeGroote Postdoctoral Fellowship
- Ontario Graduate Scholarship
Ask authors/readers for more resources
Host defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associated Escherichia coli commonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasive E. coli (AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to alpha-helical cationic peptides and alpha- and beta-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6, arlA, which encodes a Mig-14 family protein implicated in defensin resistance, and arlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available