The invasin IbeA and its role in Adherent-Invasive Escherichia coli (AIEC) pathogenesis

dc.contributor.advisorTorres, Alfredo G
dc.contributor.committeeMemberSoong, Lynn
dc.contributor.committeeMemberValbuena, Gustavo
dc.contributor.committeeMemberCong, Yingzi
dc.contributor.committeeMemberFarfan, Mauricio
dc.creatorCieza, Roberto Javier
dc.creator.orcid0000-0001-7400-722X 2015
dc.description.abstractIn this study, an Adherent-Invasive Escherichia coli (AIEC) ∆ibeA mutant was constructed and characterized, and its effect on AIEC adhesion and invasion of intestinal epithelial cells evaluated. The role that this outer membrane protein, IbeA, plays in intra-macrophage survival was also assessed. Compared to the wild-type, AIEC ∆ibeA presented reduced invasion to not only enterocytes but also M cells, which correlated with impaired transcytosis through a monolayer of M cells. The observed impairment in invasion was not a consequence of impaired adhesion to intestinal epithelial cells, since this process was not affected. Furthermore, the invasive properties that IbeA confers to AIEC seem to be specific for this pathotype, since complementation of a non-AIEC strain with a plasmid carrying IbeA did not render the recipient strain invasive. Besides intestinal epithelial cells, the other major host cells that are known to be a target for AIEC are macrophages; therefore, the effect of IbeA in intra-macrophage AIEC survival was evaluated, and it was observed that AIEC ∆ibeA had reduced intra-macrophage survival when compared to the wild-type, starting as early as 4 hours post infection. Finally, all of these components were integrated by evaluating the contribution of IbeA in an in vivo animal inflammation model, and it was found that AIEC ∆ibeA was recovered at the same levels observed for the wild-type from mouse intestines. Even though colonization levels were similar, differences were found at the level of the inflammatory response, reflected in lower pathology scores in the small intestine and the cecum for AIEC ∆ibeA when compared to the wild-type, and reduced IFN-γ secretion in the cecum. This study reports, for the first time, the role of the invasin IbeA in the AIEC pathotype, and shows that it plays a relevant role not only in the invasion of intestinal epithelial cells but also in AIEC-associated pathology. This finding opens the possibility of further work evaluating the intracellular mechanisms triggered by IbeA in intestinal epithelial cells in response to AIEC.
dc.subjectChron's disease
dc.subjectM cells.
dc.titleThe invasin IbeA and its role in Adherent-Invasive Escherichia coli (AIEC) pathogenesis
dc.type.materialtext and Immunology University of Texas Medical Branch at Galveston and Immunology (Doctoral)


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