title: The inhibition of COPII trafficking is important for intestinal epithelial tight junction disruption during enteropathogenic Escherichia coli and Citrobacter rodentium infection.
abstract: Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are bacterial pathogens that cause severe illnesses in humans. Citrobacter rodentium is a related mouse pathogen that serves as a small animal model for EPEC and EHEC infections. EPEC, EHEC and C. rodentium translocate bacterial virulence proteins directly into host intestinal cells via a type III secretion system (T3SS). Non-LEE-encoded effector A (NleA) is a T3SS effector that is common to EPEC, EHEC and C. rodentium. NleA interacts with and inhibits the mammalian COPII complex, impairing cellular secretion; this interaction is required for bacterial virulence. Although diarrhea is a hallmark of EPEC, EHEC and C. rodentium infections, the underlying mechanisms are not well characterized. One of the essential functions of the intestine is to maintain a barrier between the lumen and submucosa. Tight junctions seal the space between adjacent epithelial cells creating this barrier. Consequently, it is thought that the disruption of intestinal epithelial tight junctions by EPEC, EHEC, and C. rodentium could result in a loss of barrier function. In this study, we demonstrate that NleA mediated COPII inhibition is required for EPEC- and C. rodentium-mediated disruption of tight junction proteins and increases in fecal water content.
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec H3G 0B1, Canada.
authors.forename: Ajitha
authors.initials: A
authors.lastname: Thanabalasuriar
authors.forename: Jinoh
authors.initials: J
authors.lastname: Kim
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
mesh_terms: D000818:Animals; D022181:COP-Coated Vesicles / Q000378:metabolism*; D044082:Citrobacter rodentium / Q000502:physiology*; D003967:Diarrhea / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D051379:Mice; D008809:Mice, Inbred C3H; D019108:Tight Junctions; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C488216:NleA protein, E coli; D037521:Virulence Factors
keywords: COPII; Citrobacter rodentium; EPEC; NleA; Tight junctions