Bacterial AB5 toxins inhibit the growth of gut bacteria by targeting ganglioside-like glycoconjugates

Nat Commun. 2019 Mar 27;10(1):1390. doi: 10.1038/s41467-019-09362-z.

Abstract

The AB5 toxins cholera toxin (CT) from Vibrio cholerae and heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli are notorious for their roles in diarrheal disease, but their effect on other intestinal bacteria remains unexplored. Another foodborne pathogen, Campylobacter jejuni, can mimic the GM1 ganglioside receptor of CT and LT. Here we demonstrate that the toxin B-subunits (CTB and LTB) inhibit C. jejuni growth by binding to GM1-mimicking lipooligosaccharides and increasing permeability of the cell membrane. Furthermore, incubation of CTB or LTB with a C. jejuni isolate capable of altering its lipooligosaccharide structure selects for variants lacking the GM1 mimic. Examining the chicken GI tract with immunofluorescence microscopy demonstrates that GM1 reactive structures are abundant on epithelial cells and commensal bacteria, further emphasizing the relevance of this mimicry. Exposure of chickens to CTB or LTB causes shifts in the gut microbial composition, providing evidence for new toxin functions in bacterial gut competition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Bacterial Toxins / pharmacology*
  • Campylobacter jejuni / drug effects*
  • Campylobacter jejuni / metabolism
  • Cell Membrane Permeability / drug effects*
  • Chickens
  • Cholera Toxin / pharmacology*
  • Enterotoxins / pharmacology*
  • Escherichia coli Proteins / pharmacology*
  • G(M1) Ganglioside / metabolism
  • Gastrointestinal Microbiome / drug effects*
  • Glycoconjugates / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / metabolism*
  • Microscopy, Fluorescence
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / metabolism

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Glycoconjugates
  • Lipopolysaccharides
  • Receptors, Cell Surface
  • ganglioside receptor
  • lipid-linked oligosaccharides
  • G(M1) Ganglioside
  • Cholera Toxin
  • heat-labile enterotoxin, E coli