Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Enteropathogenic Escherichia coli (EPEC) disrupts intestinal barrier function.
• E. coli secreted protein F (EspF) is a key virulence factor responsible for these disruptions.
• The C57BL/6J mouse model effectively mimics EPEC infection in vivo.

Purpose of the Study:

• To investigate the impact of EPEC on mouse intestinal tight junction (TJ) structure and barrier function.
• To elucidate the specific role of EspF in EPEC-induced intestinal damage in vivo.

Main Methods:

• C57BL/6J mice were infected with wild-type EPEC or an EspF-deficient strain (delta espF).
• Intestinal barrier function was assessed using Ussing chambers to measure transepithelial resistance.
• Tight junction structure was analyzed via immunofluorescence microscopy, and cytokine levels were measured.

Main Results:

• Wild-type EPEC significantly impaired ileal and colonic barrier function and altered occludin distribution at both 1 and 5 days post-infection.
• EspF deficiency prevented barrier defects and TJ alterations at 1 day post-infection.
• At 5 days post-infection, both wild-type EPEC and delta espF induced similar barrier dysfunction and occludin redistribution, associated with increased TNF-alpha levels.

Conclusions:

• EPEC infection significantly compromises intestinal barrier function and TJ integrity in C57BL/6J mice.
• EspF is essential for EPEC to cause early-stage TJ defects, but not for late-stage effects.
• Late-stage EPEC-induced intestinal damage is associated with immune activation, irrespective of EspF presence.