# SHIGELLA EXOTOXIN:  CELL RECEPTOR AND MODE OF ACTION

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 1987 · $140,775

## Abstract

Shigellosis is a world wide infection, particularly prevalent among the young in
developing countries, where it is associated with severe malnutrition, and in
certain groups in industrialized nations.  Effective vaccines are currently not
available.  Understanding pathogenesis of shigellosis may allow development of
specific and effective prophylactic and therapeutic measures.

We have demonstrated that an exotoxin produced by various shigella species is
undoubtedly a key virulence factor.  In fact, it may be the proximate cause of
both watery diarrhea and dysentery.  In studies using an in vitro cell culture
model measuring cytotoxicity, we have shown that a glycoprotein receptor
involving oligomeric beta 1 yields 4 linked N-acetyl glucosamine is a
determinant of sensitivity to toxin.  In some situations the receptor can be
blocked by a terminal, beta-galactosidase sensitive, galactose moiety.  Removal
of this galactose increases toxin binding.

This study aims at characterizing the recptors on intestinal epithelial cells,
both in proximal small bowel and colon,   In order to determine this we are
preparing purified toxin by affinity chromatography for isotope labeling and
binding studies with isolated brush borders or with intact small or large bowel
cells.  These binding assays will be compared with a toxin consumption assay
using cytotoxicity in HeLa cells as the measure, and with direct cytotoxic
effects on HeLa monolayers.

## Key facts

- **NIH application ID:** 3126612
- **Project number:** 7R01AI016242-07
- **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:** 1987
- **Award amount:** $140,775
- **Award type:** 7
- **Project period:** 1987-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126612

## Citation

> US National Institutes of Health, RePORTER application 3126612, SHIGELLA EXOTOXIN:  CELL RECEPTOR AND MODE OF ACTION (7R01AI016242-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126612. Licensed CC0.

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