# SHIGA-LIKE TOXIN OF ESCHERICHIA COLI

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 1992 · $218,490

## Abstract

Escherichia coli can cause diarrhea by several distinct mechanisms.
A newly recognized group of E. coli cause hemorrhagic colitis and
the hemolytic uremic syndrome.  These enterohemorrhagic E. coli
(EHEC) produce elevated levels of Shiga-like toxin I (SLT-I) or
Shiga-like toxin II (SLT-II) or both cytotoxins.  SLT-I and SLT-II
are antigenically distinct members of a family of cytotoxins that
are related to the Shiga toxin of Shigella dysenteriae 1.  These
toxins inhibit protein synthesis in eucaryotic cells by a mechanism
identical to that of the plant toxin ricin; the toxins act as 28
S rRNA glycosidases.  Moreover, Shiga toxin, SLT-I, and SLT-II
appear to have the same eucaryotic cell receptor, a glycolipid
called GB3.  The genes for Shiga toxin, SLT-I, and SLT-II have been
cloned in this laboratory and their nucleotide and deduced amino
acid sequences determined.  The results of these studies indicate
that SLT-I and Shiga toxin are >99% homologous, whereas SLT-II
shares 55-60% amino acid homology with Shiga toxin/SLT-I.  The
long-term goals of this project are to analyze the synthesis and
biologic activity of the Shiga/SLT toxin family at the molecular
levels and to determine if these have essential or accessory roles
in the pathogenesis of bacillary dysentery, hemorrhagic colitis,
and the hemolytic uremic syndrome.  The specific aims designed to
achieve these objectives are to:  1) investigate the relationships
between the structure and biological activities of Shiga toxin/SLT-
I and SLT-II by using site-directed mutagenesis, monoclonal
antibodies, and synthetic peptides; 2) compare the regulation of
the Shiga toxin/SLT-I and SLT-II operons by characterizing SLT-II
transcripts, mapping and defining the relative strengths of the
promoters for the Shiga toxin/SLT-I and SLT-II operons, identifying
and mapping other Shiga toxin/SLT-I and SLT-II regulatory genes,
and locating the transcription termination sequences for the Shiga
toxin/SLT-I and SLT-II operons; 3) assess the role of Shiga toxin
in the virulence of S. dysenteriae 1 and of SLT-I and SLT-II in the
pathogenicity of EHEC by constructing non-toxinogenic mutants and
comparing them with isogenic toxinogenic strains in appropriate
animals models; 4) characterize the SLT operon in strains of E.
coli that produce low levels of SLT by cloning and sequencing the
low-level SLT genes, analyzing the regulation of the low-level SLT
operon, and investigating the function of low-level SLT in E. coli.

## Key facts

- **NIH application ID:** 3129628
- **Project number:** 5R01AI020148-10
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **SAM.gov UEI:** UYLKBRENAPG5
- **Principal Investigator:** Alison Davis O'Brien
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $218,490
- **Award type:** 5
- **Project period:** 1983-08-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129628

## Citation

> US National Institutes of Health, RePORTER application 3129628, SHIGA-LIKE TOXIN OF ESCHERICHIA COLI (5R01AI020148-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129628. Licensed CC0.

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