# MECHANISM OF ACTION OF C PERFRINGENS ENTEROTOXIN

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1991 · $148,267

## Abstract

Clostridium perfringens enterotoxin (CPE) is a single polypeptide chain
of 35,000 Mr. CPE has been shown to produce all symptoms associated with
C. perfringens food poisoning and recent studies strongly suggest that
CPE may also be involved in other forms of serious gastrointestinal
disease. CPE has a unique action distinguishable from all other
enterotoxins. CPE produces changes in membrane permeability which lead to
secondary effects, such as inhibition of macromolecular synthesis.

The principal goal of the proposed research is to extend understanding of
the action of CPE to the biochemical/molecular level. To accomplish this
goal the following research is proposed; 1) Identification and
purification of the CPE receptor by use of receptor purification,
antibody reactivity studies and CPE: CPE receptor crosslinking. 2)
Insertion of CPE into intestinal brush border membranes (PFMs) will be
further investigated using photoreactive membrane probes and protease-
release studies. The importance of insertion in CPE action will be
determined. 3) The action of CPE will be investigated to determine if CPE
has any action beyond insertion. This will be determined by low-
temperature studies, proteoliposome experiments and experiments with
colonic cells (these cells bind but do not respond to CPE). 4) The intact
CPE gene will be cloned and DNA sequenced. The cloned gene and gene
fragments will be used as a probe in Southern or Northern blotting
experiments to study CPE synthesis and regulation. 5) Defined mutations
will be engineered into the CPE gene or gene fragments and, after
expression, the effects of these mutations on CPE activities,
particularly on binding, will be determined to help dissect steps in CPE
action.

These studies should significantly increase our understanding of how CPE
acts at the molecular level. Increased knowledge of CPE action should
allow valuable comparisons of CPE action with pathways used by other
agents producing intestinal disease. As the membrane action of CPE is
clarified, CPE should also become a useful probe to examine
structure/function relationships in intestinal BBMs. These findings would
have long-term significance to numerous medical disciplines seeking to
understand intestinal physiology under normal and disease conditions.
Additionally, these studies may contribute to improved diagnostic assays
for CPE and possibly lead to development of a CPE vaccine.

## Key facts

- **NIH application ID:** 3129285
- **Project number:** 5R01AI019844-09
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** Bruce A Mc Clane
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $148,267
- **Award type:** 5
- **Project period:** 1982-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129285

## Citation

> US National Institutes of Health, RePORTER application 3129285, MECHANISM OF ACTION OF C PERFRINGENS ENTEROTOXIN (5R01AI019844-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129285. Licensed CC0.

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