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PMID: 3053452 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of Shiga toxin in the pathogenesis of bacillary dysentery, studied by using a Tox- mutant of Shigella dysenteriae 1.

Infection and immunity ·Vol. 56 ·No. 12 ·1988-12-00 ·Pages 3099-109

Fontaine A, Arondel J, Sansonetti PJ

Abstract

A Tox- mutant of Shigella dysenteriae 1, SC501, was genetically engineered by cloning the Shiga toxin operon, inserting a cassette into the A subunit gene, and exchanging this in vitro-mutagenized sequence with the wild-type gene. SC501 produced a low amount of residual cytotoxicity which was not neutralized by a rabbit immune serum directed against Shiga toxin. Invasion of cultured cells demonstrated that Shiga toxin had no effect on the rate of intracellular growth of bacteria or on the rapid killing of invaded host cells. On the other hand, several significant differences were observed in macaque monkeys infected intragastrically with either the wild-type strain or its mutant. The production of Shiga toxin by the invading strain was correlated with the presence of blood within stools, a sharp drop in blood polymorphonuclear cells, and histopathological alterations, such as the destruction of capillary vessels within the connective tissue of the colonic mucosa, severe inflammatory vasculitis of the peritoneal mesothelium, and major efflux of inflammatory cells to the intestinal lumen. It is proposed that Shiga toxin influences the severity of bacillary dysentery by inducing colonic vascular damage, which accounts for bloody stools, intestinal ischemia, and inflation of a polymorphonuclear intestinal compartment during the infectious process.

MeSH Terms
Animals Bacterial Toxins/genetics,toxicity Biological Assay Cell Survival/drug effects Cloning, Molecular DNA Mutational Analysis Dysentery, Bacillary/etiology In Vitro Techniques Leukocyte Count/drug effects Macrophages/drug effects Operon Shiga Toxins Shigella dysenteriae/genetics,growth & development Water-Electrolyte Balance/drug effects
Chemicals
Bacterial Toxins Shiga Toxins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Fontaine A
Service des Entérobactéries, Institut National de la Santé et de la Recherche Medicale-Unité 199, Institut Pasteur, Paris, France.
Arondel J
Sansonetti P J
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.56.12.3099-3109.1988
Published
1988-12-00
Pages
3099-109
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC259708
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.56.12.3099-3109.1988 PMC Full Text View journal details
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