Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans

Stephanie Peters; Ben Pascoe; Zuowei Wu; Sion C. Bayliss; Ximin Zeng; Adam Edwinson; Sakteesh Veerabadhran-Gurunathan; Selina Jawahir; Jessica K. Calland; Evangelos Mourkas; Robin Patel; Terra Wiens; Marijke Decuir; David Boxrud; Kirk Smith; Craig T. Parker; Gianrico Farrugia; Qijing Zhang; Samuel K. Sheppard; Madhusudan Grover

doi:10.1038/s42003-021-02554-8

Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans

Stephanie Peters, Ben Pascoe, Zuowei Wu, Sion C. Bayliss, Ximin Zeng, Adam Edwinson, Sakteesh Veerabadhran-Gurunathan, Selina Jawahir, Jessica K. Calland, Evangelos Mourkas, Robin Patel, Terra Wiens, Marijke Decuir, David Boxrud, Kirk Smith, Craig T. Parker, Gianrico Farrugia, Qijing Zhang, Samuel K. Sheppard, Madhusudan Grover^*

^*Corresponding author for this work

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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.

Original language	English
Article number	1015
Journal	Communications Biology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s42003-021-02554-8
Publication status	Published - 30 Aug 2021

Bibliographical note

Funding Information:
The study was funded by NIDDK K23 DK103911, R03 120745, and Department of Medicine K2R Program Award to M.G. Authors B.P., S.C.B. and S.K.S. are supported by the Medical Research Council (MRC) grant MR/L015080/1. C.T.P is supported by USDA CRIS Project 2030-42000-055-00D. Authors acknowledge Ms. Lori Anderson for administrative support.

Publisher Copyright:
© 2021, The Author(s).

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Peters, S., Pascoe, B., Wu, Z., Bayliss, S. C., Zeng, X., Edwinson, A., Veerabadhran-Gurunathan, S., Jawahir, S., Calland, J. K., Mourkas, E., Patel, R., Wiens, T., Decuir, M., Boxrud, D., Smith, K., Parker, C. T., Farrugia, G., Zhang, Q., Sheppard, S. K., & Grover, M. (2021). Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans. Communications Biology, 4(1), Article 1015. https://doi.org/10.1038/s42003-021-02554-8

@article{585ab4ba1f4f425b8eee67547bd4f564,

title = "Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans",

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.",

author = "Stephanie Peters and Ben Pascoe and Zuowei Wu and Bayliss, {Sion C.} and Ximin Zeng and Adam Edwinson and Sakteesh Veerabadhran-Gurunathan and Selina Jawahir and Calland, {Jessica K.} and Evangelos Mourkas and Robin Patel and Terra Wiens and Marijke Decuir and David Boxrud and Kirk Smith and Parker, {Craig T.} and Gianrico Farrugia and Qijing Zhang and Sheppard, {Samuel K.} and Madhusudan Grover",

note = "Funding Information: The study was funded by NIDDK K23 DK103911, R03 120745, and Department of Medicine K2R Program Award to M.G. Authors B.P., S.C.B. and S.K.S. are supported by the Medical Research Council (MRC) grant MR/L015080/1. C.T.P is supported by USDA CRIS Project 2030-42000-055-00D. Authors acknowledge Ms. Lori Anderson for administrative support. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

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doi = "10.1038/s42003-021-02554-8",

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Peters, S, Pascoe, B, Wu, Z, Bayliss, SC, Zeng, X, Edwinson, A, Veerabadhran-Gurunathan, S, Jawahir, S, Calland, JK, Mourkas, E, Patel, R, Wiens, T, Decuir, M, Boxrud, D, Smith, K, Parker, CT, Farrugia, G, Zhang, Q, Sheppard, SK & Grover, M 2021, 'Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans', Communications Biology, vol. 4, no. 1, 1015. https://doi.org/10.1038/s42003-021-02554-8

TY - JOUR

T1 - Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans

AU - Peters, Stephanie

AU - Pascoe, Ben

AU - Wu, Zuowei

AU - Bayliss, Sion C.

AU - Zeng, Ximin

AU - Edwinson, Adam

AU - Veerabadhran-Gurunathan, Sakteesh

AU - Jawahir, Selina

AU - Calland, Jessica K.

AU - Mourkas, Evangelos

AU - Patel, Robin

AU - Wiens, Terra

AU - Decuir, Marijke

AU - Boxrud, David

AU - Smith, Kirk

AU - Parker, Craig T.

AU - Farrugia, Gianrico

AU - Zhang, Qijing

AU - Sheppard, Samuel K.

AU - Grover, Madhusudan

N1 - Funding Information: The study was funded by NIDDK K23 DK103911, R03 120745, and Department of Medicine K2R Program Award to M.G. Authors B.P., S.C.B. and S.K.S. are supported by the Medical Research Council (MRC) grant MR/L015080/1. C.T.P is supported by USDA CRIS Project 2030-42000-055-00D. Authors acknowledge Ms. Lori Anderson for administrative support. Publisher Copyright: © 2021, The Author(s).

PY - 2021/8/30

Y1 - 2021/8/30

N2 - 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.

AB - 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.

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U2 - 10.1038/s42003-021-02554-8

DO - 10.1038/s42003-021-02554-8

M3 - Article (Academic Journal)

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AN - SCOPUS:85113861352

SN - 2399-3642

VL - 4

JO - Communications Biology

JF - Communications Biology

IS - 1

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ER -

Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans

Abstract

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