title: Role of NleH, a type III secreted effector from attaching and effacing pathogens, in colonization of the bovine, ovine, and murine gut.
abstract: The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 colonizes human and animal gut via formation of attaching and effacing lesions. EHEC strains use a type III secretion system to translocate a battery of effector proteins into the mammalian host cell, which subvert diverse signal transduction pathways implicated in actin dynamics, phagocytosis, and innate immunity. The genomes of sequenced EHEC O157:H7 strains contain two copies of the effector protein gene nleH, which share 49% sequence similarity with the gene for the Shigella effector OspG, recently implicated in inhibition of migration of the transcriptional regulator NF-kappaB to the nucleus. In this study we investigated the role of NleH during EHEC O157:H7 infection of calves and lambs. We found that while EHEC DeltanleH colonized the bovine gut more efficiently than the wild-type strain, in lambs the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. Using the mouse pathogen Citrobacter rodentium, which shares many virulence factors with EHEC O157:H7, including NleH, we observed that the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. We found no measurable differences in T-cell infiltration or hyperplasia in colons of mice inoculated with the wild-type or the nleH mutant strain. Using NF-kappaB reporter mice carrying a transgene containing a luciferase reporter driven by three NF-kappaB response elements, we found that NleH causes an increase in NF-kappaB activity in the colonic mucosa. Consistent with this, we found that the nleH mutant triggered a significantly lower tumor necrosis factor alpha response than the wild-type strain.
authors: Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
authors: Cordula
authors: C
authors: Hemrajani
authors: Olivier
authors: O
authors: Marches
authors: Siouxsie
authors: S
authors: Wiles
authors: Francis
authors: F
authors: Girard
authors: Alison
authors: A
authors: Dennis
authors: Francis
authors: F
authors: Dziva
authors: Angus
authors: A
authors: Best
authors: Alan D
authors: AD
authors: Phillips
authors: Cedric N
authors: CN
authors: Berger
authors: Aurelie
authors: A
authors: Mousnier
authors: Valerie F
authors: VF
authors: Crepin
authors: Laurens
authors: L
authors: Kruidenier
authors: Martin J
authors: MJ
authors: Woodward
authors: Mark P
authors: MP
authors: Stevens
authors: Roberto M
authors: RM
authors: La Ragione
authors: Thomas T
authors: TT
authors: MacDonald
authors: Gad
authors: G
authors: Frankel
mesh_terms: D000818:Animals; D002417:Cattle; D044082:Citrobacter rodentium / Q000472:pathogenicity*; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D037521:Virulence Factors