Interactions between Campylobacter jejuni and AB5 toxins in the gut

Campylobacter jejuni is a ubiquitous commensal in chickens, but a major cause of human diarrheal disease worldwide. To avoid immune detection by its host, most C. jejuni isolates express human ganglioside‐mimicking lipooligosaccharide (LOS) structures and it has been shown that host recognition of these antigens as non‐self results in the development of Guillain‐Barré syndrome. In addition to immune evasion, expression of ganglioside mimics in C. jejuni has been associated with improved host cell invasion and resistance to human serum. Although only positive benefits for ganglioside mimic expression have been described for C. jejuni, the organism has the ability to quickly switch off the mimicry through a phase‐variable galactosyltransferase, CgtB, involved in LOS biosynthesis. Vibrio cholerae secretes the bacteriophage‐encoded cholera toxin (CT) which binds to GM1 ganglioside structures on human cells as well as to C. jejuni GM1 ganglioside‐mimics. Enterotoxigenic Escherichia coli secretes heat‐labile enterotoxin I (LT), which also binds to these structures. Since C. jejuni, V. cholerae and E. coli can co‐infect the same niche, we examined the effects of these AB5 toxins on C. jejuni biology in order to determine if this relationship could represent a new mechanism for interpathogen competition in the intestine. We demonstrate that CT and LT specifically bind only to C. jejuni strains expressing GM1 mimics. Interestingly, our experiments show that addition of CT or LT to C. jejuni strains expressing GM1‐mimicking LOS partially clears cell growth on agar. LOS from bacteria remaining inside these zones of clearance was isolated and compared to LOS from untreated bacteria. SDS‐PAGE and silver staining of the LOS showed the loss of a band from the exposed cells compared to untreated cells, and Western blot analysis revealed reduced binding of LOS to CT. Sequencing cgtB in these two groups demonstrated that this enzyme is “on” or “off” in the unexposed group, while cgtB in the CT‐ and LT‐treated cells showed a frameshift mutation, causing premature truncation of the galactosyltransferase. Examination of an engineered E. coli strain expressing GM1 mimics shows that CT is capable of binding to the mimicking cells without inducing growth clearance, pointing toward a Campylobacter‐specific mechanism of action. These results suggest that CT and LT have a negative influence on C. jejuni and could contribute to competition between these pathogens. Further studies describing the interactions between these zoonotic pathogens, the resident gut microbiome and poultry will be described. Support or Funding Information CMS is an Alberta Innovates Technology Futures iCORE Strategic Chair in Bacterial Glycomics.

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