# SHIGELLA EXOTOXIN--CELL RECEPTORS AND MODE OF ACTION

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 1992 · $200,570

## Abstract

This research represents an effort to understand the molecular
pathogenesis of intestinal diseases due to cytotoxin producing
bacteria such as Shigella, cause of bacillary dysentery, and
certain E. coli that causae watery diarrhea in infants (EPEC) and
hemorrhagic colitis in children and adults (0157:H7).  These
organisms results in considerable morbidity in the U.S. and
especially in the third world, and they are responsible for he
majority of cases of enteric infection-related hemolytic-uremic
syndrome, an often lethal complication, and also for most of the
ORT-unresponsive diarrheal disease deaths in the third world.  It
is the goal of this research to understand how the toxin interacts
with intestinal cells and its role in pathogenesis.  Based on these
data, we hope to develop better prophylactic, diagnostic and
therapeutic approaches.  These are three aims to the research:  1)
to find out how many different distinct but biologically related
toxins are produced, 2) to determine how many different tissue
receptors there are, to characterize them, and to identify the
biological process affected, and 3) to study the importance of the
ability of toxin to inhibit protein synthesis in mediating the
various toxin effects.  Studies under Aim 1 will utilize physical,
immunological, and functional criteria to assess the relatedness
of purified toxins obtained from different organisms.  Aim 2
encompasses a variety of chemical, metabolic, and immunologic
studies to define the fine structure and function of a glycolipid
receptor we have described on rabbit intestinal cells, and to
investigate whether or not a second glycoprotein receptor with
different carbohydrate specificity exists for the cytotoxic
activity of the toxin.  Aim 3 intends to produce of shigella:ricin
hybrid A:B and B:A molecules, to determine whether or not the
inactivation of 60S ribosomal subunits by the two toxins plays a
role in enterotoxicity and whether or not B subunit targeting to
a glycolipid receptor we have define (Gb3) is involved.  We will
also produce purified toxin for use in a  collaboration with Dr.
J. Robertus, University of Texas/San Antonio, to crystallize
shigella toxin, determine its three dimensional X-ray structure,
and compare it to ricin and attempt to define a common active site.

## Key facts

- **NIH application ID:** 3126611
- **Project number:** 5R01AI016242-11
- **Recipient organization:** TUFTS MEDICAL CENTER
- **SAM.gov UEI:** MY2ERHGDV956
- **Principal Investigator:** Gerald T. Keusch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $200,570
- **Award type:** 5
- **Project period:** 1987-04-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126611

## Citation

> US National Institutes of Health, RePORTER application 3126611, SHIGELLA EXOTOXIN--CELL RECEPTORS AND MODE OF ACTION (5R01AI016242-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126611. Licensed CC0.

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