skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species

Abstract

In this study, bile plays an important role in digestion, absorption of fats, and the excretion of waste products, while concurrently providing a critical barrier against colonization by harmful bacteria. Previous studies have demonstrated that gut pathogens react to bile by adapting their protein synthesis. The ability of pathogens to respond to bile is remarkably complex and still incompletely understood. Here we show that Campylobacter jejuni, a leading bacterial cause of human diarrheal illness worldwide, responds to deoxycholate, a component of bile, by altering global gene transcription in a manner consistent with a strategy to mitigate exposure to reactive oxygen stress. More specifically, continuous growth of C. jejuni in deoxycholate was found to: induce the production of reactive oxygen species (ROS); decrease succinate dehydrogenase activity (complex II of the electron transport chain); increase catalase activity that is involved in H2O2 breakdown; and result in DNA strand breaks. Congruently, by adding 4-hydroxy-TEMPO (TEMPOL), a superoxide dismutase mimic, that reacts with superoxide to cultures under deoxycholate-mediated ROS stress, C. jejuni growth in the presence of deoxycholate was rescued. We postulate that continuous exposure of a number of enteric pathogens to deoxycholate stimulates a conserved survival response to this stressor.

Authors:
 [1];  [1];  [2]; ORCiD logo [2];  [1]
  1. Washington State Univ., Pullman, WA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1416687
Report Number(s):
PNNL-SA-122926
Journal ID: ISSN 2045-2322; WN9030198
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Proteomics; RNA-Seq; Transcriptomics

Citation Formats

Negretti, Nicholas M., Gourley, Christopher R., Clair, Geremy, Adkins, Joshua N., and Konkel, Michael E. The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species. United States: N. p., 2017. Web. doi:10.1038/s41598-017-15379-5.
Negretti, Nicholas M., Gourley, Christopher R., Clair, Geremy, Adkins, Joshua N., & Konkel, Michael E. The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species. United States. doi:10.1038/s41598-017-15379-5.
Negretti, Nicholas M., Gourley, Christopher R., Clair, Geremy, Adkins, Joshua N., and Konkel, Michael E. Mon . "The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species". United States. doi:10.1038/s41598-017-15379-5. https://www.osti.gov/servlets/purl/1416687.
@article{osti_1416687,
title = {The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species},
author = {Negretti, Nicholas M. and Gourley, Christopher R. and Clair, Geremy and Adkins, Joshua N. and Konkel, Michael E.},
abstractNote = {In this study, bile plays an important role in digestion, absorption of fats, and the excretion of waste products, while concurrently providing a critical barrier against colonization by harmful bacteria. Previous studies have demonstrated that gut pathogens react to bile by adapting their protein synthesis. The ability of pathogens to respond to bile is remarkably complex and still incompletely understood. Here we show that Campylobacter jejuni, a leading bacterial cause of human diarrheal illness worldwide, responds to deoxycholate, a component of bile, by altering global gene transcription in a manner consistent with a strategy to mitigate exposure to reactive oxygen stress. More specifically, continuous growth of C. jejuni in deoxycholate was found to: induce the production of reactive oxygen species (ROS); decrease succinate dehydrogenase activity (complex II of the electron transport chain); increase catalase activity that is involved in H2O2 breakdown; and result in DNA strand breaks. Congruently, by adding 4-hydroxy-TEMPO (TEMPOL), a superoxide dismutase mimic, that reacts with superoxide to cultures under deoxycholate-mediated ROS stress, C. jejuni growth in the presence of deoxycholate was rescued. We postulate that continuous exposure of a number of enteric pathogens to deoxycholate stimulates a conserved survival response to this stressor.},
doi = {10.1038/s41598-017-15379-5},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

CmeR Functions as a Transcriptional Repressor for the Multidrug Efflux Pump CmeABC in Campylobacter jejuni
journal, February 2005


Reactive oxygen species: the unavoidable environmental insult?
journal, July 1999

  • Gracy, R. W.; Talent, J. M.; Kong, Y.
  • Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 428, Issue 1-2
  • DOI: 10.1016/S1383-5742(99)00027-7

The Iron-Binding Protein Dps Confers Hydrogen Peroxide Stress Resistance to Campylobacter jejuni
journal, February 2003


Human Hepatic Mitochondria Generate Reactive Oxygen Species and Undergo the Permeability Transition in Response to Hydrophobic Bile Acids
journal, January 2005


The Health Burden of Campylobacter Infection and the Impact of Antimicrobial Resistance: Playing Chicken
journal, March 2007

  • Ruiz-Palacios, G. M.
  • Clinical Infectious Diseases, Vol. 44, Issue 5
  • DOI: 10.1086/509936

Secretion of the Virulence‐Associated Campylobacter Invasion Antigens from Campylobacter jejuni Requires a Stimulatory Signal
journal, June 2001

  • Rivera‐Amill, Vanessa; Kim, Bong J.; Seshu, J.
  • The Journal of Infectious Diseases, Vol. 183, Issue 11
  • DOI: 10.1086/320704

8-hydroxy-2′ -deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis
journal, May 2009

  • Valavanidis, Athanasios; Vlachogianni, Thomais; Fiotakis, Constantinos
  • Journal of Environmental Science and Health, Part C, Vol. 27, Issue 2
  • DOI: 10.1080/10590500902885684

2016 update of the PRIDE database and its related tools
journal, November 2015

  • Vizcaíno, Juan Antonio; Csordas, Attila; del-Toro, Noemi
  • Nucleic Acids Research, Vol. 44, Issue D1
  • DOI: 10.1093/nar/gkv1145

Mechanisms of bacterial resistance and response to bile
journal, July 2000


Bile-Induced DNA Damage in Salmonella enterica
journal, December 2004


Oxyradicals and DNA damage
journal, March 2000


A Point-Source Outbreak of Campylobacteriosis Associated with Consumption of Raw Milk
journal, September 1985

  • Korlath, J. A.; Osterholm, M. T.; Judy, L. A.
  • Journal of Infectious Diseases, Vol. 152, Issue 3
  • DOI: 10.1093/infdis/152.3.592

Fast gapped-read alignment with Bowtie 2
journal, March 2012

  • Langmead, Ben; Salzberg, Steven L.
  • Nature Methods, Vol. 9, Issue 4
  • DOI: 10.1038/nmeth.1923

Mauve: Multiple Alignment of Conserved Genomic Sequence With Rearrangements
journal, June 2004


A novel immunoproteomics method for identifying in vivo-induced Campylobacter jejuni antigens using pre-adsorbed sera from infected patients
journal, November 2013

  • Hu, Yuanqing; Shang, Yuwei; Huang, Jinlin
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1830, Issue 11
  • DOI: 10.1016/j.bbagen.2013.06.042

The Campylobacter jejuni Response Regulator, CbrR, Modulates Sodium Deoxycholate Resistance and Chicken Colonization
journal, May 2005


Colonization of chicks by motility mutants of Campylobacter jejuni demonstrates the importance of flagellin A expression
journal, June 1993

  • Wassenaar, T. M.; van der Zeijst, B. A. M.; Ayling, R.
  • Journal of General Microbiology, Vol. 139, Issue 6
  • DOI: 10.1099/00221287-139-6-1171

The Escherichia coli SOS Gene dinF Protects against Oxidative Stress and Bile Salts
journal, April 2012

  • Rodríguez-Beltrán, Jerónimo; Rodríguez-Rojas, Alexandro; Guelfo, Javier R.
  • PLoS ONE, Vol. 7, Issue 4
  • DOI: 10.1371/journal.pone.0034791

Effects of the Campylobacter jejuni CJIE1 prophage homologs on adherence and invasion in culture, patient symptoms, and source of infection
journal, January 2012

  • Clark, Clifford G.; Grant, Christopher CR; Pollari, Frank
  • BMC Microbiology, Vol. 12, Issue 1
  • DOI: 10.1186/1471-2180-12-269

RNAseq Reveals Complex Response of Campylobacter jejuni to Ovine Bile and In vivo Gallbladder Environment
journal, May 2017

  • Kreuder, Amanda J.; Schleining, Jennifer A.; Yaeger, Michael
  • Frontiers in Microbiology, Vol. 8
  • DOI: 10.3389/fmicb.2017.00940

Culture of Campylobacter jejuni with Sodium Deoxycholate Induces Virulence Gene Expression
journal, January 2008

  • Malik-Kale, P.; Parker, C. T.; Konkel, M. E.
  • Journal of Bacteriology, Vol. 190, Issue 7
  • DOI: 10.1128/JB.01736-07

featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
journal, November 2013


Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides
journal, December 2008

  • Wilcox, Christopher S.; Pearlman, Adam
  • Pharmacological Reviews, Vol. 60, Issue 4
  • DOI: 10.1124/pr.108.000240

Proteomic analysis of human bile and potential applications for cancer diagnosis
journal, June 2009

  • Farina, Annarita; Dumonceau, Jean-Marc; Lescuyer, Pierre
  • Expert Review of Proteomics, Vol. 6, Issue 3
  • DOI: 10.1586/epr.09.12

Role of two flagellin genes in Campylobacter motility.
journal, August 1991


The CJIE1 prophage of Campylobacter jejuni affects protein expression in growth media with and without bile salts
journal, January 2014

  • Clark, Clifford G.; Chong, Patrick M.; McCorrister, Stuart J.
  • BMC Microbiology, Vol. 14, Issue 1
  • DOI: 10.1186/1471-2180-14-70

Regulation of oxidative stress resistance in Campylobacter jejuni, a microaerophilic foodborne pathogen
journal, July 2015


Pathways of Oxidative Damage
journal, October 2003


Colorimetric assay of catalase
journal, June 1972


Characterization of the oxidative stress stimulon and PerR regulon of Campylobacter jejuni
journal, January 2009


The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences
journal, February 2000

  • Parkhill, J.; Wren, B. W.; Mungall, K.
  • Nature, Vol. 403, Issue 6770
  • DOI: 10.1038/35001088

Phenotypic Screening of a Targeted Mutant Library Reveals Campylobacter jejuni Defenses against Oxidative Stress
journal, March 2014

  • Flint, A.; Sun, Y. -Q.; Butcher, J.
  • Infection and Immunity, Vol. 82, Issue 6
  • DOI: 10.1128/IAI.01528-13

Identification and molecular cloning of a gene encoding a fibronectin‐binding protein (CadF) from Campylobacter jejuni
journal, June 1997


Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: Relevance to dopamine pathology in schizophrenia
journal, February 2008

  • Brenner-Lavie, Hanit; Klein, Ehud; Zuk, Rosa
  • Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1777, Issue 2
  • DOI: 10.1016/j.bbabio.2007.10.006

Dissecting the in Vivo Metabolic Potential of Two Human Gut Acetogens
journal, May 2010

  • Rey, Federico E.; Faith, Jeremiah J.; Bain, James
  • Journal of Biological Chemistry, Vol. 285, Issue 29
  • DOI: 10.1074/jbc.M110.117713

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
journal, December 2014


Reduction of Clofazimine by Mycobacterial Type 2 NADH:Quinone Oxidoreductase: A PATHWAY FOR THE GENERATION OF BACTERICIDAL LEVELS OF REACTIVE OXYGEN SPECIES
journal, December 2010

  • Yano, Takahiro; Kassovska-Bratinova, Sacha; Teh, J. Shin
  • Journal of Biological Chemistry, Vol. 286, Issue 12
  • DOI: 10.1074/jbc.M110.200501

Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump in Campylobacter jejuni
journal, October 2005


Inactivation of Campylobacter jejuni flagellin genes by homologous recombination demonstrates that flaA but not flaB is required for invasion.
journal, August 1991


    Works referencing / citing this record:

    Microbial metabolite deoxycholic acid shapes microbiota against Campylobacter jejuni chicken colonization
    journal, July 2019


    Microbial metabolite deoxycholic acid shapes microbiota against Campylobacter jejuni chicken colonization
    journal, July 2019


    Campylobacter jejuni Demonstrates Conserved Proteomic and Transcriptomic Responses When Co-cultured With Human INT 407 and Caco-2 Epithelial Cells
    journal, April 2019

    • Negretti, Nicholas M.; Clair, Geremy; Talukdar, Prabhat K.
    • Frontiers in Microbiology, Vol. 10
    • DOI: 10.3389/fmicb.2019.00755