# BASIS FOR CELLULAR SUSCEPTIBILITY TO BACTERIAL TOXINS

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 1987 · $138,468

## Abstract

Pseudomonas and diphtheria toxins (PE and DT) are virulence factors
produced by Pseudomonas aeruginosa and Corynebacterium diphtheriae
respectively.  These distinct protein toxins both inhibit mammalian cell
protein synthesis by inactivating cytoplasmic elongation factor 2.
Evidence from our laboratory shows that PE and DT enter sensitive cells by
receptor mediated endocytosis, following clustering over specialized
clathri-coated areas on the cell surface, move in membrane bound vesicles
to the Golgi region and then to the lysosomes.  This pathway is essential
for expression of toxicity.

The specific aims of the research are:

l. To definitively characterize organelles involved in intracellular
processing of DT and PE.

2. To determine the site of conversion from proenzyme to enzyme active form.

3. To initiate purification and characterization of DT and PE binding
proteins.

4. To visualize toxin-receptor uncoupling, and entry of toxin into
cytoplasm.

Biochemical and electron microscopic studies will be carried out in
parallel to compare the movement of PE and DT in both sensitive and
resistant cells.  Subcellular fractionation studies also will be used to
localize iodinated toxins in cells.  Agents which stop the intoxication
process at different steps will be used to determine where the toxins are
activated and where they, or an enzyme active fragment, enter the cell
cytoplasm.  Immunocytochemistry will be used to determine where toxin and
ligand dissociate, and toxin enters the cytoplasm.

## Key facts

- **NIH application ID:** 3127264
- **Project number:** 5R01AI017529-07
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **SAM.gov UEI:** DZ4YCZ3QSPR5
- **Principal Investigator:** CATHARINE B SAELINGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $138,468
- **Award type:** 5
- **Project period:** 1980-12-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127264

## Citation

> US National Institutes of Health, RePORTER application 3127264, BASIS FOR CELLULAR SUSCEPTIBILITY TO BACTERIAL TOXINS (5R01AI017529-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127264. Licensed CC0.

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