Abstract
The human pathogenic bacterium Aeromonas hydrophila causes gastroenteritis and wound infections. Pathogenesis by its pore forming toxin aerolysin (AerA) has been described, but the effects on the epithelial barrier are poorly understood. Epithelial barrier function was determined in Ussing chambers with infected human HT 29/B6 colon cells. Para- and transcellular resistance were measured by two-path impedance spectroscopy (2PI). The subcellular distribution of tight junction (TJ) and cytoskeleton (CS) proteins was analyzed by confocal microscopy. Wound repair was investigated by induction of single cell lesions and measuring of recovery time. Permeability for a 4 kDa paracellular marker was doubled in treated HT-29/B6 cells. In parallel, 2PI revealed a rapid and permanent decrease in paracellular resistance. As structural correlate, TJ proteins were retracted from the TJ by CS constriction via Ca2+ signaling and MLCK activation. Moreover, epithelial wound repair was defective, which was caused by disturbance of TJ and CS. All effects could be assigned to AerA and were prevented by zinc. In conclusion, AerA induces intestinal epithelial barrier dysfunction along the paracellular route (leak flux) and concomitantly disturbs primary epithelial wound repair. Blockage of AerA by zinc corresponds to the efficacy of zinc therapy against epithelial lesions and diarrhea. (Supported by DFG Schu 559/11-1)
Published Version
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