Bacterial translocation of intestinal apathogenic E. coli in a colon model system

Bacterial translocation is critical in various clinical conditions, e.g. during multiple organ failure, sepsis, systemic inflammatory response syndrome and it is possibly connected to chronic inflammatory bowel disease. Together with these clinical conditions, changes in barrier properties of the mucosal epithelium through increases in paracellular conductance have been described. Measurement of the transepithelial resistance and flux measurements using various macro-molecules demonstrate the importance of these changes in barrier properties with respect to a translocation of luminal content. Although bacterial translocation has been well described in an animal model, tissue culture models are not readily available. It is therefore planned to test translocation properties of extra-intestinally pathogenic E. coli isolates in a model epithelium. Possible translocations will be detected fluorescence optically (confocal laser scanning microscope) and described functionally (quantitative translocation, electrophysiologic parameters) and it will be attempted to identify the underlying molecular mechanisms. The human colon carcinoma cell lines Caco-2 and HT-29/B6 will serve as barrier model. The latter is particularly suitable as a barrier model simulating inflammatory conditions because of its sensitivity to cytokines.
Head of Project:

Jan Richter
Charité - Universitätsmedizin Berlin
Institute of Clinical Physiology CBF
Begin/End of Project:

01/2005- 12/2005
Funded by:

Universitäre Forschungsförderung Charité

Richter JF, Troeger H, Beutin H, Epple HJ, Florian P, Schulzke JD, Fromm M (2004) Bacterial translocation across colonic epithelial cells. Pflügers Arch. 447: S41, Clark EC, Patel SD, Chadwick PR, Warhurst G, Curry A, Carlson GL. Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate. Gut. 2003 Feb;52(2):224-30