# SHIGELLA TOXIN, STRUCTURE & FUNCTION RELATIONSHIPS

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 1993 · $160,084

## Abstract

Shigellosis is a world wide disease producing significant morbidity and in
developing countries, a leading cause of diarrheal disease mortality.  The
Shigella species which causes the severest disease, dysenteriae, produces a
potent toxin molecule which inhibits protein synthesis.  The toxin consists
of one A chain and 5 B chains.  A functional role of the B chain is to
mediate toxin binding to the eukaryotic cell surface.  The toxin receptors
are glycolipids containing terminal Gal-alpha1->4Gal disaccharide.  Shiga
toxin is now considered to be the prototype of a family of toxins which
have been called Shiga-like.  Shiga and Shiga-like toxins are associated
with many clinical manifestations including diarrhea, dysentery,
hemorrhagic colitis, and the hemolytic uremic syndrome.

This proposal is designed to study basic structure-function relationship of
the toxin B chain.  A monoclonal antibody which cross-reacts with the B
chain of Shiga and Shiga-like toxin II will be characterized.  Since these
two toxins are thought to be immunologically distinct and since the two
bind to an identical set of receptors, particular attention will be focused
on whether this antibody is directed against the binding domain.  A
monoclonal antibody and a glycoprotein with Gal-alpha1->4Gal terminal
disaccharide, P1-glycoprotein, will be used as tools to select bacterial
strains which produce B subunits with binding domain alterations.  The
characterization of these mutants will provide an understanding of the
regions of the B chain involved in receptor recognition.  This information
will be useful for the future design of safe and effective vaccines and for
the potential design of therapeutic intervention regimens.  Additionally
the biochemical and genetic characterization of a material which cross-
reacts with antibody against Shiga toxin will be undertaken with particular
emphasis on revealing the role this material may play in pathogenesis.
Finally, the uncharacterized cytotoxins produced by other Gram-negative
organisms will be analyzed for their Shiga-like properties.  Information as
to whether other pathogenic bacteria produce Shiga-like toxins will aid in
our understanding of the spectrum of disease associated with toxin.

## Key facts

- **NIH application ID:** 3129927
- **Project number:** 7R01AI020325-11
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **SAM.gov UEI:** C1F5LNUF7W86
- **Principal Investigator:** ARTHUR M. DONOHUE-ROLFE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $160,084
- **Award type:** 7
- **Project period:** 1984-04-01 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129927

## Citation

> US National Institutes of Health, RePORTER application 3129927, SHIGELLA TOXIN, STRUCTURE & FUNCTION RELATIONSHIPS (7R01AI020325-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129927. Licensed CC0.

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