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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Produce Safety and Microbiology Research » Research » Publications at this Location » Publication #386479

Research Project: Elucidating the Factors that Determine the Ecology of Human Pathogens in Foods

Location: Produce Safety and Microbiology Research

Title: Campylobacter jejuni genotypes associated with post-infection irritable bowel syndrome.

Author
item PETERS, STEPHANIE - Mayo Clinic
item PASCOE, BEN - University Of Bath
item WU, ZUOWEI - Iowa State University
item BAYLISS, SION - University Of Bath
item ZENG, XIMIN - Mayo Clinic
item EDWINSON, ADAM - Mayo Clinic
item VEERABADHAM, SAKTEESH - Mayo Clinic
item JAWAHIR, SELINA - Minnesota Department Of Health
item CALLAND, JESSICA - University Of Bath
item MOURKAS, EVANGELOS - University Of Bath
item PATEL, ROBIN - Mayo Clinic
item WIENS, TERRA - Minnesota Department Of Health
item DECUIR, MARIJKE - Minnesota Department Of Health
item BOXRUD, DAVID - Minnesota Department Of Health
item SMITH, KIRK - Minnesota Department Of Health
item Parker, Craig
item FARRUGIA, GIANRICO - Mayo Clinic
item ZHANG, QIJING - Iowa State University
item SHEPPARD, SAMUEL - University Of Bath
item GROVER, MADHUSUDAN - Mayo Clinic

Submitted to: Communications Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/13/2021
Publication Date: 8/30/2021
Citation: Peters, S., Pascoe, B., Wu, Z., Bayliss, S.C., Zeng, X., Edwinson, A., Veerabadham, S., Jawahir, S., Calland, J.K., Mourkas, E., Patel, R., Wiens, T., Decuir, M., Boxrud, D., Smith, K., Parker, C., Farrugia, G., Zhang, Q., Sheppard, S.K., Grover, M. 2021. Campylobacter jejuni genotypes associated with post-infection irritable bowel syndrome.. Communications Biology. 4:1015. https://doi.org/10.1038/s42003-021-02554-8.
DOI: https://doi.org/10.1038/s42003-021-02554-8

Interpretive 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. 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. 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 TNFa 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.

Technical Abstract: Irritable bowel syndrome (IBS) is a chronic, disabling gastrointestinal disorder that affects up to 15% of people worldwide. Patients suffer from chronic symptoms of abdominal pain and alteration in frequency and/or form of the stool. Acute infectious gastroenteritis is a major risk factor for development of this condition with the onset of chronic symptoms often emerging post infection (PI-IBS). Campylobacter enterocolitis may lead to 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. This study provides the first systematic evaluation of bacterial genomics and in vitro virulence using isolates acquired from a prospectively identified cohort of patients developing Campylobacter PI-IBS. 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 TNFa 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.