# PATHOGENICITY OF SHIGA-LIKE TOXIN-PRODUCING E COLI

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 1993 · $248,874

## Abstract

Shiga-like toxins (SLTs) are produced by enterohemorrhagic Escherichia
coli (EHEC), a group of organisms that cause food-borne hemorrhagic
colitis and the hemolytic uremic syndrome.  SLTs are comprised of
pentamers of B subunits that bind to glycolipid receptors and monomers
of A subunits that act as 28S rRNA N-glycosidases.  In addition to
expression of one or more types of SLTs, prototypic EHEC E. coli 0157:H7
strains also carry an ~90 kb plasmid as well as a gene, designated eae,
that shares homology with the attach/efface eae gene of enteropathogenic
E. coli (EPEC The long-term objective of this project is to define at the
cellular and molecular levels the pathogenic mechanisms of SLT-producing
E. coli.  The SPECIFIC AIMS designed to achieve this goal are to: 1.)
evaluate the basis for the marked virulence of EHEC 091:H21 strain B2F1
in the orally-infected, streptomycin-treated mouse model by examining the
contribution to pathogenicity of slt-IIc operon copy number, the large
plasmid, the intestinal site and level of colonization, and any adhesions
identified by tnphoA mutagenesis; 2.) dissect the role of eae in EHEC
adherence by constructing an eae negative derivative of an EHEC 0157:H7
strain and comparing the mutant with wild-type for adherence to HEp-2
cells and for virulence in the mouse model; 3.) analyze the basis for the
differential Vero cell cytotoxicities of SLT-II and SLT-IIc by comparing
the toxins for functional receptor, affinity of receptor binding, and
influence of proteolytic cleavage on Vero cell cytotoxicity; 4.) define
any environmental conditions that regulate expression of slt-II and slt-
IIc in EHEC isolates by measuring chloramphenicol acetyltransferase (CAT)
activity in promoter-cat fusions in vitro and in vivo; and 5.)
investigate the reason(s) that E. coli strains that produce SLT-IIc or
SLT-II alone are more virulent in the mouse model than strains that
produce both SLT-I and SLT-II by assessing whether SLT-I interferes with
the toxicity of SLT-IIc or SLT-II.

## Key facts

- **NIH application ID:** 3129624
- **Project number:** 2R01AI020148-11
- **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:** 1993
- **Award amount:** $248,874
- **Award type:** 2
- **Project period:** 1983-08-01 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129624

## Citation

> US National Institutes of Health, RePORTER application 3129624, PATHOGENICITY OF SHIGA-LIKE TOXIN-PRODUCING E COLI (2R01AI020148-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129624. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*