# VIRULENCE FACTORS IN THE PATHOGENESIS OF SALMONELLOSIS

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 1987 · $102,404

## Abstract

The pathogenesis of salmonellosis involves intestinal colonization,
epithelial cell invasion, and toxin production.  The precise role of the
Salmonella enterotoxin and cytotoxin in contributing to fluid secretion and
tissue damage is not clear.  The overall objective of the proposed research
is to explain more fully the pathogenesis of salmonellosis, particularly
the involvement of these protein toxins.  Research during the initial
period of support demonstrated that crude, cell-free lysates of Salmonella,
exhibiting these toxic activities, caused tissue damage when instilled into
the lumen of rabbit small intestinal loops.  Furthermore, this intestinal
damage was accompanied by increased mucosal levels of cyclic AMP and
diminished capacity to incorporate H3-leucine into protein.  A major
breakthrough has occurred in our efforts to purify the cytotoxin
responsible for inhibiting H3-leucine incorporation (cytotoxic activity).
We have purified to homogeneity a low molecular weight peptide (3400) that
is cytotoxic in vitro (cell rounding and detachment) for Chinese hamster
ovary cells (greater than 10 mug/ml).  While H3-leucine incorporation in
these cells is inhibited by microgram doses of the purified cytotoxin,
nanogram concentrations stimulate H3-leucine incorporation and elevate
cyclic AMP levels.  The cytotoxin eluded purification earlier because at
neutral pH, it binds firmly to several large protein molecules while
retaining toxicity.  We will continue to refine purification methods to
provide sufficient quantities of purified Salmonella cytotoxin for use in
the proposed studies.  The chemical, biological, and antigenic
characteristics of purified Salmonella cytotoxin will be determined.  The
molecular mechanism of action of Salmonella cytotoxin on eukaryotic cells
will be studied using cellular and in vitro protein synthesis systems.
Using polyclonal antiserum to purified Salmonella cytotoxin, an ELISA and a
colony blot assay will be developed to facilitate quantitation of the
toxin.  Rabbits immunized with the purified Salmonella cytotoxin will be
challenged with Salmonella to assess the extent of protection conferred
against fluid exsorption, epithelial cell invasion, and tissue damage.  We
will continue efforts to purify the Salmonella enterotoxin using
specifically purified cholera antitoxin, immunoaffinity chromatography.
Genetic approaches to the study of the Salmonella enterotoxin will be
continued with the aid of the cholera toxin gene probe.

## Key facts

- **NIH application ID:** 3127911
- **Project number:** 5R01AI018401-06
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **SAM.gov UEI:** MSPWVMXXMN76
- **Principal Investigator:** JOHNNY Wayne PETERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $102,404
- **Award type:** 5
- **Project period:** 1982-09-01 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127911

## Citation

> US National Institutes of Health, RePORTER application 3127911, VIRULENCE FACTORS IN THE PATHOGENESIS OF SALMONELLOSIS (5R01AI018401-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127911. Licensed CC0.

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