Novel GM1 ganglioside-like peptide mimics prevent the association of cholera toxin to human intestinal epithelial cells in vitro

Robert K Yu, Seigo Usuki, Yutaka Itokazu, Han Chung Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cholera is an acute diarrheal disease caused by infection in the gastrointestinal tract by the gram-negative bacterium, Vibrio cholerae, and is a serious public health threat worldwide. There has not been any effective treatment for this infectious disease. Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells. The present study was undertaken to generate peptides that are conformationally similar to the carbohydrate epitope of GM1 for use in the treatment of cholera and related bacterial infection. For this purpose, we used cholera toxin B (CTB) subunit to select CTB-binding peptides that structurally mimic GM1 from a dodecamer phage-display library. Six GM1-replica peptides were selected by biopanning based on CTB recognition. Five of the six peptides showed inhibitory activity for GM1 binding to CTB. To test the potential of employing the peptide mimics for intervening with the bacterial infection, those peptides were examined for their binding capacity, functional inhibitory activity and in vitro effects using a human intestinal epithelial cell line, Caco-2 cells. One of the peptides, P3 (IPQVWRDWFKLP), was most effective in inhibiting cellular uptake of CTB and suppressing CT-stimulated cyclic adenosine monophosphate production in the cells. Our results thus provide convincing evidence that GM1-replica peptides could serve as novel agents to block CTB binding on epithelial cells and prevent the ensuing physiological effects of CT.

Original languageEnglish (US)
Pages (from-to)63-73
Number of pages11
JournalGlycobiology
Volume26
Issue number1
DOIs
StatePublished - Jun 11 2015

Fingerprint

G(M1) Ganglioside
Cholera Toxin
Epithelial Cells
Peptides
Vibrio cholerae
Cholera
Bacterial Infections
In Vitro Techniques
Bacteriophages
Caco-2 Cells
Acute Disease
Public health
Cell membranes
Gram-Negative Bacteria
Cyclic AMP
Libraries
Communicable Diseases
Gastrointestinal Tract
Epitopes
Bacteria

Keywords

  • GM1 ganglioside
  • bacterial infection
  • cAMP
  • cholera toxin
  • epithelial cell

ASJC Scopus subject areas

  • Biochemistry

Cite this

Novel GM1 ganglioside-like peptide mimics prevent the association of cholera toxin to human intestinal epithelial cells in vitro. / Yu, Robert K; Usuki, Seigo; Itokazu, Yutaka; Wu, Han Chung.

In: Glycobiology, Vol. 26, No. 1, 11.06.2015, p. 63-73.

Research output: Contribution to journalArticle

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