Title: Yersiniabactin-Producing Adherent/Invasive Escherichia coli Promotes Inflammation-Associated Fibrosis in Gnotobiotic Il10-/- Mice.

Authors: Ellermann, Melissa; Gharaibeh, Raad Z; Fulbright, Laura; Dogan, Belgin; Moore, Lyndsey N; Broberg, Christopher A; Lopez, Lacey R; Rothemich, Aaron M; Herzog, Jeremy W; Rogala, Allison; Gordon, Ilyssa O; Rieder, Florian; Brouwer, Cory R; Simpson, Kenneth W; Jobin, Christian; Sartor, R Balfour; Arthur, Janelle C

Published In Infect Immun, (2019 11)

Abstract: Fibrosis is a significant complication of intestinal disorders associated with microbial dysbiosis and pathobiont expansion, notably Crohn's disease (CD). Mechanisms that favor fibrosis are not well understood, and therapeutic strategies are limited. Here we demonstrate that colitis-susceptible Il10-deficient mice develop inflammation-associated fibrosis when monoassociated with adherent/invasive Escherichia coli (AIEC) that harbors the yersiniabactin (Ybt) pathogenicity island. Inactivation of Ybt siderophore production in AIEC nearly abrogated fibrosis development in inflamed mice. In contrast, inactivation of Ybt import through its cognate receptor FyuA enhanced fibrosis severity. This corresponded with increased colonic expression of profibrogenic genes prior to the development of histological disease, therefore suggesting causality. fyuA-deficient AIEC also exhibited greater localization within subepithelial tissues and fibrotic lesions that was dependent on Ybt biosynthesis and corresponded with increased fibroblast activation in vitro Together, these findings suggest that Ybt establishes a profibrotic environment in the host in the absence of binding to its cognate receptor and indicate a direct link between intestinal AIEC and the induction of inflammation-associated fibrosis.

PubMed ID: 31481410

MeSH Terms: No MeSH terms associated with this publication