Role of NleH, a type III secreted effector from attaching and effacing pathogens, in colonization of the bovine, ovine, and murine gut.
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.
Hemrajani
Cordula
C
Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
Marches
Olivier
O
Wiles
Siouxsie
S
Girard
Francis
F
Dennis
Alison
A
Dziva
Francis
F
Best
Angus
A
Phillips
Alan D
AD
Berger
Cedric N
CN
Mousnier
Aurelie
A
Crepin
Valerie F
VF
Kruidenier
Laurens
L
Woodward
Martin J
MJ
Stevens
Mark P
MP
La Ragione
Roberto M
RM
MacDonald
Thomas T
TT
Frankel
Gad
G
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*
D016328:NF-kappa B; D037521:Virulence Factors