Evidence for a Causal Role for Escherichia coli Strains Identified as Adherent-Invasive (AIEC) in Intestinal Inflammation

Authors

Hatem Kittana, University of Nebraska-Lincoln
Joao Carlos Gomes-Neto, University of Nebraska - LincolnFollow
Kari Heck, University of Nebraska-Lincoln
Anthony Juritsch, University of Nebraska-LincolnFollow
Jason Sughroue, University of Nebraska-Lincoln
Yibo Xian, University of Nebraska-Lincoln
Sara Mantz, University of Nebraska-Lincoln
Rafael R. Segura Muñoz, University of Nebraska-Lincoln
Liz Cody, University of Nebraska-Lincoln
Robert J. Schmaltz, University of Nebraska - LincolnFollow
Christopher L. Anderson, University of Nebraska - LincolnFollow
Rodney A. Moxley, University of Nebraska - LincolnFollow
Jesse M. Hostetter, Iowa State University, University of Georgia
Samodha C. Fernando, University of Nebraska-LincolnFollow
Jennifer Clarke, University of Nebraska-LincolnFollow
Stephen D. Kachman, University of Nebraska-LincolnFollow
Clayton E. Cressler, University of Nebraska-LincolnFollow
Andrew K. Benson, University of Nebraska - LincolnFollow
Jens Walter, University of Alberta, University College Cork-National University of Ireland

Document Type

Article

Date of this Version

3-8-2023

Citation

AIEC Contribution to Intestinal Inflammation. March/April 2023 Volume 8 Issue 2. 10.1128/msphere.00478-22

Comments

Open access.

Abstract

Enrichment of adherent-invasive Escherichia coli (AIEC) has been consistently detected in subsets of inflammatory bowel disease (IBD) patients. Although some AIEC strains cause colitis in animal models, these studies did not systematically compare AIEC with non-AIEC strains, and causal links between AIEC and disease are still disputed. Specifically, it remains unclear whether AIEC shows enhanced pathogenicity compared to that of commensal E. coli found in the same ecological microhabitat and if the in vitro phenotypes used to classify strains as AIEC are pathologically relevant. Here, we utilized in vitro phenotyping and a murine model of intestinal inflammation to systematically compare strains identified as AIEC with those identified as non-AIEC and relate AIEC phenotypes to pathogenicity. Strains identified as AIEC caused, on average, more severe intestinal inflammation. Intracellular survival/replication phenotypes routinely used to classify AIEC positively correlated with disease, while adherence to epithelial cells and tumor necrosis factor alpha production by macrophages did not. This knowledge was then applied to design and test a strategy to prevent inflammation by selecting E. coli strains that adhered to epithelial cells but poorly survived/replicated intracellularly. Two E. coli strains that ameliorated AIEC-mediated disease were subsequently identified. In summary, our results show a relationship between intracellular survival/replication in E. coli and pathology in murine colitis, suggesting that strains possessing these phenotypes might not only become enriched in human IBD but also contribute to disease. We provide new evidence that specific AIEC phenotypes are pathologically relevant and proof of principle that such mechanistic information can be therapeutically exploited to alleviate intestinal inflammation.