title: The bacterial virulence factor NleA is required for the disruption of intestinal tight junctions by enteropathogenic Escherichia coli.
abstract: Enteropathogenic Escherichia coli (EPEC) is a diarrhoeal pathogen that adheres to epithelial cells of the small intestine and uses a type III secretion system to inject effector proteins into host cells. EPEC infection leads to disruption of host intestinal tight junctions that are important for maintaining intestinal barrier function. This disruption is dependent on the bacterial type III secretion system, as well as the translocated effectors EspF and Map. Here we show that a third type III translocated bacterial effector protein, NleA, is also involved in tight junction disruption during EPEC infection. Using the drug Brefeldin A, we demonstrate that the effect of NleA on tight junction integrity is related to its inhibition of host cell protein trafficking through COPII-dependent pathways. These results suggest that NleA's striking effect on virulence is mediated, at least in part, via its role in disruption of intestinal barrier function.
authors.affiliation: Department of Microbiology and Immunology, The McGill Life Sciences Complex, Montreal, Quebec, Canada.
authors.forename: Ajitha
authors.initials: A
authors.lastname: Thanabalasuriar
authors.forename: Athanasia
authors.initials: A
authors.lastname: Koutsouris
authors.forename: Andrew
authors.initials: A
authors.lastname: Weflen
authors.forename: Mark
authors.initials: M
authors.lastname: Mimee
authors.forename: Gail
authors.initials: G
authors.lastname: Hecht
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
mesh_terms: D020126:Brefeldin A / Q000494:pharmacology; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity* / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005816:Genetic Complementation Test; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D047908:Intracellular Signaling Peptides and Proteins; D008856:Microscopy, Fluorescence; D019108:Tight Junctions / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014774:Virulence / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; D047908:Intracellular Signaling Peptides and Proteins; C512346:Map protein, E coli; C488216:NleA protein, E coli; D037521:Virulence Factors; D020126:Brefeldin A