Journal article

Publication year: 2011

Pages: 1283-1292

Journal: The Journal of Infectious Diseases

Volume number: 204

Issue number: 8

ISSN: 0022-1899

eISSN: 1537-6613

Open access status: Bronze

DOI Link: https://doi.org/10.1093/infdis/jir504

Publisher: Oxford University Press

Abstract: 

Background. Aeromonads cause a variety of infections, including gastroenteritis, sepsis, and wound necrosis. Pathogenesis of Aeromonas hydrophila and its hemolysin has been characterized, but the mechanism of the epithelial barrier dysfunction is currently poorly understood.

Methods. Human colon epithelial monolayers HT-29/B6 were apically inoculated with clinical isolates of A. hydrophila or with the secreted pore-forming toxin aerolysin. Epithelial resistance and permeability for several markers were determined in Ussing chambers, using 2-path impedance spectroscopy. The subcellular distribution of tight junction (TJ) and cytoskeleton proteins was analyzed by Western blotting and confocal laser-scanning microscopy.

Results. A. hydrophila infection induces chloride secretion with a small decrease in transcellular resistance. However, the major effect of A. hydrophila, mediated by its toxin aerolysin, was a sustained reduction of paracellular resistance by retracting sealing TJ proteins from the TJ strands. Aerolysin-treated monolayers showed increased paracellular permeability to FITC-dextran-4000 (0.104 +/- 0.014 vs 0.047 +/- 0.001 10(-6) cm/s in control; P < .05). Moreover, restitution of epithelial lesions was impaired. The effects were myosin light chain kinase (MLCK) dependent and mediated by intracellular Ca2+ signaling.

Conclusions. During Aeromonas infection, pore formation by aerolysin impairs epithelial integrity by promoting TJ protein redistribution and consequently affecting wound closure. Thus, Aeromonas-induced diarrhea is mediated by 2 mechanisms, transcellular secretion and paracellular leak flux.

Harvard Citation style: Buecker, R., Krug, S., Rosenthal, R., Guenzel, D., Fromm, A., Zeitz, M., et al. (2011) Aerolysin From Aeromonas hydrophila Perturbs Tight Junction Integrity and Cell Lesion Repair in Intestinal Epithelial HT-29/B6 Cells, The Journal of Infectious Diseases, 204(8), pp. 1283-1292. https://doi.org/10.1093/infdis/jir504

APA Citation style: Buecker, R., Krug, S., Rosenthal, R., Guenzel, D., Fromm, A., Zeitz, M., Chakraborty, T., Fromm, M., Epple, H., & Schulzke, J. (2011). Aerolysin From Aeromonas hydrophila Perturbs Tight Junction Integrity and Cell Lesion Repair in Intestinal Epithelial HT-29/B6 Cells. The Journal of Infectious Diseases. 204(8), 1283-1292. https://doi.org/10.1093/infdis/jir504