Renal injury is a consistent finding in Dutch Belted rabbits experimentally infected with enterohemorrhagic Escherichia coli.
Enterohemorrhagic Escherichia coli (EHEC) produces Shiga toxin (Stx) and causes renal disease in humans. Dutch Belted (DB) rabbits naturally infected with EHEC O153 develop hemolytic-uremic syndrome-like disease. The aims of this study were to experimentally reproduce O153-induced renal disease in DB rabbits and investigate bacterial and host factors involved in pathogenesis. The pathogenicity of E. coli O157:H7 was also investigated in rabbits. The stx1AB region of O153 was sequenced. By use of liquid chromatography-tandem mass spectrometry, we identified homologs of the Stx receptor, globotriaosylceramide (Gb3), in rabbit kidney extracts. Infected rabbits developed clinical signs and intestinal and kidney lesions. Renal pathological changes consisted of intimal swelling, perivascular edema, erythrocyte fragmentation, capillary thickening, luminal constriction, leukocytic infiltration, mesangial deposits, and changes in Bowman's capsule and space. Sequence analysis of a approximately 7-kb region of the O153 chromosome indicated homology to the Stx1-producing bacteriophage H19B. Our findings indicate that DB rabbits are suitable for the study of the renal manifestations of EHEC infection in humans.
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02139, USA. agarcia@mit.edu
Alexis
A
Garcia
Carlos J
CJ
Bosques
John S
JS
Wishnok
Yan
Y
Feng
Brad J
BJ
Karalius
Joan R
JR
Butterton
David B
DB
Schauer
Arlin B
AB
Rogers
James G
JG
Fox
D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D018938:Caco-2 Cells; D002432:Cecum / Q000473:pathology; D004269:DNA, Bacterial / Q000737:chemistry; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology*; D019453:Escherichia coli O157 / Q000235:genetics / Q000472:pathogenicity*; D005243:Feces / Q000382:microbiology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D011817:Rabbits; D017421:Sequence Analysis; D022621:Shiga Toxin / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D014281:Trihexosylceramides / Q000737:chemistry
D004269:DNA, Bacterial; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D022621:Shiga Toxin