Inhibition of Cholera Toxin and Other AB Toxins by Polyphenolic Compounds.
Cholera toxin (CT) is an AB-type protein toxin that contains a catalytic A1 subunit, an A2 linker, and a cell-binding B homopentamer. The CT holotoxin is released into the extracellular environment, but CTA1 attacks a target within the cytosol of a host cell. We recently reported that grape extract confers substantial resistance to CT. Here, we used a cell culture system to identify twelve individual phenolic compounds from grape extract that inhibit CT. Additional studies determined the mechanism of inhibition for a subset of the compounds: two inhibited CT binding to the cell surface and even stripped CT from the plasma membrane of a target cell; two inhibited the enzymatic activity of CTA1; and four blocked cytosolic toxin activity without directly affecting the enzymatic function of CTA1. Individual polyphenolic compounds from grape extract could also generate cellular resistance to diphtheria toxin, exotoxin A, and ricin. We have thus identified individual toxin inhibitors from grape extract and some of their mechanisms of inhibition against CT.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Patrick
P
Cherubin
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Maria Camila
MC
Garcia
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
David
D
Curtis
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Christopher B T
CB
Britt
Department of Biology & Biochemistry, University of Houston, Houston, Texas, United States of America.
John W
JW
Craft
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Helen
H
Burress
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Chris
C
Berndt
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Srikar
S
Reddy
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Jessica
J
Guyette
NanoScience Technology Center and Department of Chemistry, University of Central Florida, Orlando, Florida, United States of America.
Tianyu
T
Zheng
NanoScience Technology Center and Department of Chemistry, University of Central Florida, Orlando, Florida, United States of America.
Qun
Q
Huo
Produce Safety and Microbiology Research Unit, Western Regional Research Center, United States Department of Agriculture - Agricultural Research Service, Albany, California, United States of America.
Beatriz
B
Quiñones
Department of Biology & Biochemistry, University of Houston, Houston, Texas, United States of America.
James M
JM
Briggs
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
Ken
http://orcid.org/0000-0003-4176-9361
K
Teter
D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors; D044946:Biflavonoids / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D016466:CHO Cells; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002772:Cholera Toxin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003412:Cricetulus; D004167:Diphtheria Toxin / Q000037:antagonists & inhibitors; D005098:Exotoxins / Q000037:antagonists & inhibitors; D005638:Fruit / Q000737:chemistry; D056604:Grape Seed Extract / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D012276:Ricin / Q000037:antagonists & inhibitors; D014709:Vero Cells; D037521:Virulence Factors / Q000037:antagonists & inhibitors; D027843:Vitis / Q000737:chemistry; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D044946:Biflavonoids; D002392:Catechin; D002772:Cholera Toxin; D004167:Diphtheria Toxin; D005098:Exotoxins; D056604:Grape Seed Extract; D010636:Phenols; D010936:Plant Extracts; D044945:Proanthocyanidins; D012276:Ricin; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C479580:procyanidin B2; C045651:epigallocatechin gallate