Campylobacter colonization and virulence determinants

Summary

Principal Investigator: Alain Stintzi
Abstract: Campylobacter spp, generally food-borne, are the leading cause of gastroenteritis worldwide, surpassing the number of cases of Salmonella and Shigella combined. Campylobacter spp. are also associated with the development of Guillain-Barre syndrome, which is the most common cause of acute neuromuscular paralysis. In addition, since Campylobacter could be easily acquired and spread through our food supply, it constitutes a potential bioterrorism threat. Currently, no vaccine is available against Campylobacter infection, and despite an intensive research effort to understand Campylobacter pathophysiology, conclusions on the exact mechanism of infection are extremely difficult to draw. C. jejuni is adapted to survive both in the environment (mainly water and milk) and in its host organisms (mammals and birds). Upon entrance into the human host, Campylobacter must survive in the intestinal tract, either as a free bacterium in the mucus layer or intracellularly in gut epithelial ceils. To colonize the intestinal tract, C. jejuni must successfully transit through the gastric acid barrier of the stomach to the more alkaline environment of the intestine. While up to 500 commensal species as well as other food-borne pathogens must similarly surmount these host barriers and adapt to the gut environment, very little is known about this process. This proposal focuses on the characterization of Campylobacter jejuni colonization and virulence factors. This proposal is based on the following hypothesis: there are numerous genes expressed in rivo that are influenced by environmental factors, and several of these genes are required for gut colonization and ultimately disease development. C. jejuni colonization and virulence determinants will be identified by in vitro and in vivo survival analysis of insertional mutants using DNA microarray. First, a functional genomic tool will be developed to identify conditionally essential genes in C. jejuni, and validated to examine the mechanism of C. jejuni survival to acid stress. Second, this functional genomic tool will be used to characterize the interactions of C. jejuni with the host gastrointestinal tract using the newborn piglet as an animal model of human infection. Finally, the role of the colonization and virulence determinants in disease and Campylobacter physiology will be assessed using a battery of in vitro biological assays. The identification of these Campylobacter determinants could significantly contribute to the development of more effective methods to diagnose, manage and ultimately prevent Campylobacter infections.
Funding Period: 2003-09-30 - 2009-01-31
more information: NIH RePORT

Top Publications

  1. pmc Campylobacter jejuni ferric-enterobactin receptor CfrA is TonB3 dependent and mediates iron acquisition from structurally different catechol siderophores
    Hemant Naikare
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma 74078, USA
    Metallomics 5:988-96. 2013
  2. pmc Use of genome-wide expression profiling and mutagenesis to study the intestinal lifestyle of Campylobacter jejuni
    Alain Stintzi
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
    Infect Immun 73:1797-810. 2005
  3. pmc Genomic diversity in Campylobacter jejuni: identification of C. jejuni 81-176-specific genes
    Frederic Poly
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
    J Clin Microbiol 43:2330-8. 2005
  4. pmc Major role for FeoB in Campylobacter jejuni ferrous iron acquisition, gut colonization, and intracellular survival
    Hemant Naikare
    Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
    Infect Immun 74:5433-44. 2006
  5. ncbi Proteomic analyses of a robust versus a poor chicken gastrointestinal colonizing isolate of Campylobacter jejuni
    Bruce S Seal
    Poultry Microbiological Safety Research Unit, Russell Research Center, ARS, USDA, 950 College Station Road, Athens, Georgia 30605, USA
    J Proteome Res 6:4582-91. 2007
  6. pmc Identification of Campylobacter jejuni genes contributing to acid adaptation by transcriptional profiling and genome-wide mutagenesis
    Anne N Reid
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
    Appl Environ Microbiol 74:1598-612. 2008
  7. pmc Identification of Campylobacter jejuni genes involved in the response to acidic pH and stomach transit
    Anne N Reid
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
    Appl Environ Microbiol 74:1583-97. 2008
  8. ncbi Genomic differences between Campylobacter jejuni isolates identify surface membrane and flagellar function gene products potentially important for colonizing the chicken intestine
    Kelli L Hiett
    Agricultural Research Service, Poultry Microbiological Safety Research Unit, Russell Research Center, United States Department of Agriculture, P O Box 5677, Athens, GA, 30604 5677, USA
    Funct Integr Genomics 8:407-20. 2008

Scientific Experts

  • Alain Stintzi
  • Kelli L Hiett
  • Bruce S Seal
  • Hemant Naikare
  • Anne N Reid
  • Kiran Palyada
  • Reenu Pandey
  • Frederic Poly
  • Annika Flint
  • Jide Xu
  • James Butcher
  • Kenneth N Raymond
  • Evgueni Doukhanine
  • Lisa Whitworth
  • Roger Panciera
  • Denver Marlow
  • Deborah Threadgill

Detail Information

Publications8

  1. pmc Campylobacter jejuni ferric-enterobactin receptor CfrA is TonB3 dependent and mediates iron acquisition from structurally different catechol siderophores
    Hemant Naikare
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma 74078, USA
    Metallomics 5:988-96. 2013
    ..These results further highlight the importance of iron transport for efficient C. jejuni colonization. ..
  2. pmc Use of genome-wide expression profiling and mutagenesis to study the intestinal lifestyle of Campylobacter jejuni
    Alain Stintzi
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
    Infect Immun 73:1797-810. 2005
    ..Overall, this study provides new insights on the mechanisms of gut colonization, as well as possible strategies employed by Campylobacter to resist or evade the host immune responses...
  3. pmc Genomic diversity in Campylobacter jejuni: identification of C. jejuni 81-176-specific genes
    Frederic Poly
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
    J Clin Microbiol 43:2330-8. 2005
    ..jejuni invasion into epithelial cells. In conclusion, this study extends the repertoire of C. jejuni genes and thus will permit the construction of a composite and more comprehensive microarray of C. jejuni...
  4. pmc Major role for FeoB in Campylobacter jejuni ferrous iron acquisition, gut colonization, and intracellular survival
    Hemant Naikare
    Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
    Infect Immun 74:5433-44. 2006
    ....
  5. ncbi Proteomic analyses of a robust versus a poor chicken gastrointestinal colonizing isolate of Campylobacter jejuni
    Bruce S Seal
    Poultry Microbiological Safety Research Unit, Russell Research Center, ARS, USDA, 950 College Station Road, Athens, Georgia 30605, USA
    J Proteome Res 6:4582-91. 2007
    ..isolates. Interestingly, different gene products potentially involved in robust colonization of chickens by Campylobacter spp. appear to conform to recently identified expression patterns in Biofilm or agar-adapted isolates...
  6. pmc Identification of Campylobacter jejuni genes contributing to acid adaptation by transcriptional profiling and genome-wide mutagenesis
    Anne N Reid
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
    Appl Environ Microbiol 74:1598-612. 2008
    ..As a Cj0415 mutant was acid sensitive, it is likely that these genes are crucial to the acid stress response of C. jejuni and consequently are important for host colonization...
  7. pmc Identification of Campylobacter jejuni genes involved in the response to acidic pH and stomach transit
    Anne N Reid
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
    Appl Environ Microbiol 74:1583-97. 2008
    ..In conclusion, this study has enabled us to understand how C. jejuni modulates gene expression in response to acid shock in vitro and to correlate this with gene expression profiles of C. jejuni as it transits through the host stomach...
  8. ncbi Genomic differences between Campylobacter jejuni isolates identify surface membrane and flagellar function gene products potentially important for colonizing the chicken intestine
    Kelli L Hiett
    Agricultural Research Service, Poultry Microbiological Safety Research Unit, Russell Research Center, United States Department of Agriculture, P O Box 5677, Athens, GA, 30604 5677, USA
    Funct Integr Genomics 8:407-20. 2008
    ..Finally, DNA hybridization analyses of 19 C. jejuni isolates recovered from chickens and humans worldwide over the past 20 years were performed to determine the distribution of a subset of differentially identified gene sequences...