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.
Highlights
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
A schematic of the LOS outer core structures of each strain used in this study is depicted in Fig. 1, along with GM1 ganglioside for comparison
Since CT is capable of binding to C. jejuni GM1 ganglioside mimics[22], and the toxin genes are encoded by a V. cholerae bacteriophage[36], we thought it was possible for CT to possess an antibacterial function
Summary
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. The A-subunit of CT ADP-ribosylates the Gsα protein of adenylate cyclase, causing it to bind GTP and constitutively stimulate conversion of ATP to cyclic AMP (cAMP)[12] This leads to increased efflux of ions into the intestinal lumen, resulting in the rice-water diarrhea and severe dehydration that are hallmarks of the disease[13]. It was originally believed that CTB bound to GM1 gangliosides on the apical surface of intestinal epithelial cells to achieve entry[16] This hypothesis predominated in part due to CT’s exceptionally high affinity for its receptor, with a reported dissociation constant of 0.73 nM17. CT is capable of binding to fucosylated structures that serve as functional receptors for the toxin[19,20,21]
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