Keywords

Diphtheria toxin (dt), p. aeruginosa exotoxin a (eta), ricin, shiga toxin, cholera toxin (ct), grape seed extract, phenolic compounds, polyphenolic compounds, corynebacterium diphtheriae, pseudomonas aeruginosa, ricinus communis, shigella dysentariae, vibrio cholerae

Abstract

Corynebacterium diphtheriae, Pseudomonas aeruginosa, Ricinus communis, Shigella dysentariae, and Vibrio cholerae produce AB toxins which share the same basic structural characteristics: a catalytic A subunit attached to a cell-binding B subunit. All AB toxins have cytosolic targets despite an initial extracellular location. AB toxins use different methods to reach the cytosol and have different effects on the target cell. Broad-spectrum inhibitors against these toxins are therefore hard to develop because they use different surface receptors, entry mechanisms, enzyme activities, and cytosolic targets. We have found that grape seed extract provides resistance to five different AB toxins: diphtheria toxin (DT), P. aeruginosa exotoxin A (ETA), ricin, Shiga toxin, and cholera toxin (CT). To identify individual compounds in grape seed extract that are capable of inhibiting the activities of these AB toxins, we screened twenty common phenolic compounds of grape seed extract for anti-toxin properties. Three compounds inhibited DT, four inhibited ETA, one inhibited ricin, and twelve inhibited CT. Additional studies were performed to determine the mechanism of inhibition against CT. Two compounds inhibited CT binding to the cell surface and even stripped bound CT off the plasma membrane of a target cell. Two other compounds inhibited the enzymatic activity of CT. We have thus identified individual toxin inhibitors from grape seed extract and some of their mechanisms of inhibition against CT. This work will help to formulate a defined mixture of phenolic compounds that could potentially be used as a therapeutic against a broad range of AB toxins.

Notes

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Graduation Date

2014

Semester

Summer

Advisor

Teter, Kenneth

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Molecular Biology and Microbiology

Degree Program

Biotechnology

Format

application/pdf

Identifier

CFE0005315

URL

http://purl.fcla.edu/fcla/etd/CFE0005315

Language

English

Release Date

August 2017

Length of Campus-only Access

3 years

Access Status

Masters Thesis (Open Access)

Subjects

Dissertations, Academic -- Medicine; Medicine -- Dissertations, Academic

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