Toxicity and immunogenicity of a verotoxin 1 mutant with reduced globotriaosylceramide receptor binding in rabbits.

Infection and Immunity
D J BastS E Richardson

Abstract

The verotoxins (VT1 and VT2), produced by strains of enterohemorrhagic Escherichia coli, have been implicated in the pathogenesis of hemorrhagic colitis and the hemolytic uremic syndrome. To better understand the role of globotriaosylceramide (Gb3) receptor binding by the verotoxins in disease production, we examined the clinicopathologic effects of an intravenously (i.v.) administered verotoxin 1 mutant holotoxin (Phe30Ala) in rabbits. The substitution of alanine for phenylalanine 30 in the VT1 B subunit has been shown previously to reduce both Gb3 binding affinity and capacity in vitro. This reduction in receptor binding corresponded to a 10(5)-fold reduction in the toxic activity of VT1 on a Vero cell monolayer. In this study, purified 125I-labeled Phe30Ala was administered i.v. to rabbits to determine its specific distribution in rabbit tissues. In contrast to the rapid elimination of i.v. administered 125I-VT1 from the bloodstream, 125I-Phe30Ala had a 52-fold-longer half-life in serum and failed to localize preferentially in the gastrointestinal tract and central nervous system (CNS). Rabbits challenged with Phe30Ala at a dose equivalent to 10 times the 50% lethal dose (LD50) of VT1 showed no visible clinical symptoms typi...Continue Reading

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Citations

Feb 18, 2003·British Journal of Haematology·Sarah L AllfordUNKNOWN Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology
Nov 16, 2007·The Journal of Biological Chemistry·María Fabiana De RosaClifford Lingwood
Dec 19, 2000·Infection and Immunity·V M WolskiJ L Brunton
Jul 8, 1999·The Journal of Nutrition·H VesperA H Merrill
Jul 27, 2011·Molecular Cancer Therapeutics·Matthias MaakKlaus-Peter Janssen
Jan 31, 2016·Molecular Cancer Therapeutics·Philipp Emanuel GeyerKlaus-Peter Janssen
Aug 8, 2002·Kidney International·Niels W P RutjesClifford A Lingwood
Jul 17, 1998·Clinical Microbiology Reviews·J C Paton, A W Paton
Mar 31, 1999·Baillière's Clinical Haematology·N C van de Kar, L A Monnens

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