Publikationsdatenbank

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

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

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

Quelle

Gut : the journal of the British Society of Gastroenterology

Bandzählung: 63

Heftzählung: 12

Seiten: 1893 – 1901

ISSN: 0017-5749

Sprache

Englisch

Verweise

DOI: 10.1136/gutjnl-2013-306099

Pubmed: 24534723

Kontakt

Institut für Mikrobiologie und Tierseuchen

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de

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.