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EnteropathogenicEscherichia coli(EPEC) has been shown to disrupt the barrier function of host intestinal epithelial tissues through entering tight junctions. However, the mechanism by which this occurs remains poorly understood. In this study, we determined that EPEC invades host cells through tight junctions as it initiates infection. | Invasion of enteropathogenic Escherichia coli into host cells through epithelial tight junctions Qiurong Li1 2 Qiang Zhang1 2 Chenyang Wang1 Ning Li1 and Jieshou Li1 1 Institute of GeneralSurgery Jinling Hospital Nanjing China 2 Schoolof Medicine Nanjing University Nanjing China Keywords enteropathogenic Escherichia coli lipid raft TER tight junction tight junction protein Correspondence J. Li Institute of GeneralSurgery Jinling Hospital 305 East Zhongshan Road Nanjing 210002 China Fax 86 25 84803956 Tel 86 25 80860064 E-mail liqiurong@yahoo.com Received 22 July 2008 revised 28 September 2008 accepted 6 October 2008 doi 10.1111 j.1742-4658.2008.06731.x Enteropathogenic Escherichia coli EPEC has been shown to disrupt the barrier function of host intestinal epithelial tissues through entering tight junctions. However the mechanism by which this occurs remains poorly understood. In this study we determined that EPEC invades host cells through tight junctions as it initiates infection. Immunofluorescence microscopy revealed redistribution of the tight-junction proteins occludin and ZO-1 from an intercellular to a cytoplasmic location after EPEC invasion. Flotillin-1 was recruited to sites of EPEC entry. EPEC entered host cells through tight-junction membrane microdomains. Tight-junction ultrastructure was disrupted following EPEC infection accompanied by loss of barrier function. EPEC infection caused a time-dependent decrease in trans-epithelial electrical resistance. Subcellular fractionation using discontinuous sucrose density gradients demonstrated a decline in raft-associated occludin following exposure to EPEC. These results indicate the important role of host membrane tight-junction microdomains in EPEC invasion. As pathogens invade the gastrointestinal tracts they must overcome epithelial barriers to initiate infection. An intact epithelial barrier is essential for physiological homeostasis and defense against extrinsic antigens. The intestinal barrier .
