Escherichia coli ?-haemolysin induces focal leaks in colonic epithelium: a novel mechanism of bacterial translocation

• Published in: Cellular microbiology Vol. 9; no. 10; pp. 2530 - 2540
• Main Authors: Troeger, Hanno, Richter, Jan F., Beutin, Lothar, Günzel, Dorothee, Dobrindt, Ulrich, Epple, Hans-Jörg, Gitter, Alfred H., Zeitz, Martin, Fromm, Michael, Schulzke, Jörg-Dieter
• Format: Journal Article
• Language: English
• Published: Oxford Hindawi Limited 01.10.2007
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2007.00978.x

Extraintestinal pathogenic Escherichia coli (ExPEC) are usually harmless colonizer of the intestinal microflora. However, they are capable to translocate and cause life-threatening disease. Translocation of ExPEC isolates was quantified in colonic monolayers. Transepithelial resistance (Rt) was monitored and local changes in conductivity analysed with conductance scanning. Confocal microscopy visualized the translocation route. Corroboratory experiments were performed on native rat colon. One translocating strain E. coli O4 was identified. This translocation process was associated with an Rt decrease (36 ± 1% of initial resistance) beginning only 2 h after inoculation. The sites of translocation were small defects in epithelial integrity (focal leaks ) exhibiting highly increased local ion permeability. Translocation was enhanced by preincubation of monolayers with tumour necrosis factor-[alpha] or interleukin-13. Mutant strains lacking alpha-haemolysin lost the ability to induce focal leaks , while this effect could be restored by re-introducing the haemolysin determinant. Filtrate of a laboratory strain carrying the alpha-haemolysin operon was sufficient for focal leak induction. In native rat colon, E. coli O4 decreased Rt and immunohistology demonstrated focal leaks resembling those in cell monolayers. E. coli [alpha]-haemolysin is able to induce focal leaks in colonic cell cultures as well as in native colon. This process represents a novel route of bacterial translocation facilitated by pro-inflammatory cytokines.