# ISOLATION OF TOXINS FROM C. DIFFICILE & C. SORDELLII

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 1992 · $258,669

## Abstract

Clostridium difficile is a relatively "new" pathogen that causes
colitis in some patients receiving antibiotic therapy.  The
organism and its toxins occur in about 15% of patients with
diarrhea in hospitals and that is a lot of patients.  If untreated
some of these patients would progress to Pseudomembranous Colitis,
which has a high mortality rate.  The disease is commonly acquired
in hospitals because the organism can only grow in the colon when
the normal flora has been essentially eliminated by large doses of
antibiotics.  Hospitals provide an ideal environment for the spread
of a spore-forming organism that causes diarrhea.  The organism
produces two potent toxins.  Toxin A is an enterotoxin that may be
responsible for the major symptoms of the disease.  Toxin B is a
very potent cytotoxin.  We have shown that toxin A binds to a
Galalpha1-3Galbeta1-4G1cNAc trisaccharide via multiple binding
sites that occur on this huge toxin.  The repeated binding
structures will be analyzed in detail by the construction of
synthetic peptides and by cloning the repeats into both E. coli and
C. perfringens.  We will determine whether this trisaccharide is
the receptor that allows toxin A to initiate the enterotoxicity and
whether this is the receptor to which the toxin binds in adult
human colonic tissue.  Adults may vary in the occurrence of this
trisaccharide in their colons and this could account for
differences in susceptibility to the toxins.  We also will
determine whether babies have this receptor; about half of the
babies born in hospitals get colonized with this organism as
"normal flora" without apparent ill effects and we want to know why
the toxins do not kill them.  The trisaccharide is not degraded by
human intestinal enzymes so we may be able to treat the disease by
giving large amounts of the receptor attached to latex beads.  We
have found that a lectin that binds to this trisaccharide prevents
the action of toxin A so this may be useful in therapy.  A
monoclonal antibody specific for this carbohydrate receptor also
is available and will be tested.  As the active site of the toxin
is sequenced we will attempt to determine the mechanism of action
by comparison to sequences of other toxins and enzymes.  Such hints
as to the mechanisms will be confirmed by collaborations with
research groups working in the respective areas.  As the sequence
of toxin B becomes available we will analyze it in the same manner.
We will continue our collaborative efforts on the mechanism of
action of the toxins and continue to be a source of pure toxins and
specific antibodies.

## Key facts

- **NIH application ID:** 3126417
- **Project number:** 5R01AI015749-14
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **SAM.gov UEI:** QDE5UHE5XD16
- **Principal Investigator:** Tracy D. Wilkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $258,669
- **Award type:** 5
- **Project period:** 1979-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126417

## Citation

> US National Institutes of Health, RePORTER application 3126417, ISOLATION OF TOXINS FROM C. DIFFICILE & C. SORDELLII (5R01AI015749-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126417. Licensed CC0.

---

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