Fachbereich Veterinärmedizin



    α-Haemolysin of Escherichia coli in IBD:
    a potentiator of inflammatory activity in the colon (2014)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Bücker, Roland
    Schulz, Emanuel
    Günzel, Dorothee
    Bojarski, Christian
    Lee, In-Fah M
    John, Lena J
    Wiegand, Stephanie
    Janßen, Traute (WE 7)
    Wieler, Lothar H (WE 7)
    Dobrindt, Ulrich
    Beutin, Lothar
    Ewers, Christa (WE 7)
    Fromm, Michael
    Siegmund, Britta
    Troeger, Hanno
    Schulzke, Jörg-Dieter
    Gut : the journal of the British Society of Gastroenterology; 63(12) — S. 1893–1901
    ISSN: 0017-5749
    DOI: 10.1136/gutjnl-2013-306099
    Pubmed: 24534723
    Institut für Mikrobiologie und Tierseuchen

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    Abstract / Zusammenfassung

    α-Haemolysin (HlyA) influences host cell ionic homeostasis and causes concentration-dependent cell lysis. As a consequence, HlyA-producing Escherichia coli is capable of inducing 'focal leaks' in colon epithelia, through which bacteria and antigens translocate. This study addressed the role of HlyA as a virulence factor in the pathogenesis of colitis according to the 'leaky gut' concept.

    To study the action of HlyA in the colon, we performed oral administration of HlyA-expressing E coli-536 and its isogenic α-haemolysin-deficient mutant (HDM) in three mouse models: wild type, interleukin-10 knockout mice (IL-10(-/-)) and monoassociated mice. Electrophysiological properties of the colonised colon were characterised in Ussing experiments. Inflammation scores were evaluated and focal leaks in the colon were assessed by confocal laser-scanning microscopy. HlyA quantity in human colon biopsies was measured by quantitative PCR.

    All three experimental mouse models infected with HlyA-producing E coli-536 showed an increase in focal leak area compared with HDM. This was associated with a decrease in transepithelial electrical resistance and an increase in macromolecule uptake. As a consequence, inflammatory activity index was increased to a higher degree in inflammation-prone mice. Mucosal samples from human colon were E coli HlyA-positive in 19 of 22 patients with ulcerative colitis, 9 of 9 patients with Crohn's disease and 9 of 12 healthy controls. Moreover, focal leaks were found together with 10-fold increased levels of HlyA in active ulcerative colitis.

    E coli HlyA impairs intestinal barrier function via focal leak induction in the epithelium, thereby intensifying antigen uptake and triggering intestinal inflammation in vulnerable mouse models. Therefore, HlyA-expressing E coli strains should be considered as potential cofactors in the pathogenesis of intestinal inflammation.