PLoS ONE (Jan 2016)

Inhibition of Cholera Toxin and Other AB Toxins by Polyphenolic Compounds.

  • Patrick Cherubin,
  • Maria Camila Garcia,
  • David Curtis,
  • Christopher B T Britt,
  • John W Craft,
  • Helen Burress,
  • Chris Berndt,
  • Srikar Reddy,
  • Jessica Guyette,
  • Tianyu Zheng,
  • Qun Huo,
  • Beatriz Quiñones,
  • James M Briggs,
  • Ken Teter

DOI
https://doi.org/10.1371/journal.pone.0166477
Journal volume & issue
Vol. 11, no. 11
p. e0166477

Abstract

Read online

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.