Abstract
Campylobacter enterocolitis may lead to post-infection irritable bowel syndrome (PI-IBS) and while some C. jejuni strains are more likely than others to cause human disease, genomic and virulence characteristics promoting PI-IBS development remain uncharacterized. We combined pangenome-wide association studies and phenotypic assays to compare C. jejuni isolates from patients who developed PI-IBS with those who did not. We show that variation in bacterial stress response (Cj0145_phoX), adhesion protein (Cj0628_CapA), and core biosynthetic pathway genes (biotin: Cj0308_bioD; purine: Cj0514_purQ; isoprenoid: Cj0894c_ispH) were associated with PI-IBS development. In vitro assays demonstrated greater adhesion, invasion, IL-8 and TNFα secretion on colonocytes with PI-IBS compared to PI-no-IBS strains. A risk-score for PI-IBS development was generated using 22 genomic markers, four of which were from Cj1631c, a putative heme oxidase gene linked to virulence. Our finding that specific Campylobacter genotypes confer greater in vitro virulence and increased risk of PI-IBS has potential to improve understanding of the complex host-pathogen interactions underlying this condition.
Highlights
Campylobacter enterocolitis may lead to post-infection irritable bowel syndrome (PI-Irritable bowel syndrome (IBS)) and while some C. jejuni strains are more likely than others to cause human disease, genomic and virulence characteristics promoting PI-IBS development remain uncharacterized
Applying a genome-wide association study (GWAS) approach linked to clinically relevant phenotypes tested in vitro, we identify genes and genetic elements associated with pathogenicity and prediction of PI-IBS development
The epidemiology of PI-IBS is well established but understanding the pathophysiology remains an obstacle to effective interventions[6]
Summary
Campylobacter enterocolitis may lead to post-infection irritable bowel syndrome (PI-IBS) and while some C. jejuni strains are more likely than others to cause human disease, genomic and virulence characteristics promoting PI-IBS development remain uncharacterized. Applying a genome-wide association study (GWAS) approach linked to clinically relevant phenotypes tested in vitro, we identify genes and genetic elements associated with pathogenicity and prediction of PI-IBS development. This approach has the potential to improve understanding of the genetic determinants of virulence and allows the calculation of a risk score for individual genotypes that, with further validation, could be a basis for medical interventions aimed at preventing PI-IBS following Campylobacter infection
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