Campylobacter jejuni flagellar regulation and synthesis

Summary

Principal Investigator: DAVID HENDRIXSON
Affiliation: University of Texas Southwestern Medical Center
Country: USA
Abstract: Campylobacter jejuni is a commensal bacterium of the gastrointestinal tracts of many animals, specifically birds. However, when C. jejuni infects the gastrointestinal tracts of humans, the bacterium often causes a mild to severe, bloody diarrheal syndrome. C. jejuni is currently recognized as a leading cause of food-borne bacterial gastroenteritis in humans world wide. The flagellum of C. jejuni has been identified as a virulence and colonization factor involved in promoting both pathogenesis and commensalism. However, knowledge regarding flagellar gene regulation and biosynthesis in C. jejuni is limited compared to other bacteria. We have found that C. jejuni tightly controls transcription of sigma 54-dependent flagellar genes encoding essential components of the flagellum. The overall objective of this proposal is to determine how the functions of key flagellar and regulatory proteins converge to control sigma 54-dependent transcription of flagellar genes. The central hypothesis of the proposed research is that C. jejuni coordinately requires FlhF, the flagellar export apparatus proteins, and the FlgS/FlgR two-component regulatory system for transcription of sigma 54-dependent genes essential for flagellar motility. The specific aims of this project are: 1) to assess the role of FlhF in flagellar gene regulation and biosynthesis; 2) to determine how flagellar assembly influences activation of transcription of sigma 54-dependent flagellar genes; and 3) to investigate possible additional layers of regulating flagellar gene transcription and biosynthesis and determine how these flagellar regulatory mechanisms may influence commensalism in birds. Accomplishment of these aims will aid in: 1) understanding connections between key flagellar proteins and how they influence genetic mechanisms to control flagellar gene regulation and biosynthesis; and 2) increase our understanding of genetic regulatory pathways used by C. jejuni for controlling expression of virulence and colonization factors. The bacterium Campylobacterjejuni produces a structure on its surface called a flagellum that is required for motility, promotion of diarrheal disease in humans, and colonization of animals. The proposed research activities will determine how certain proteins of C.jejunifunction together to control production of flagellar proteins that make up the flagellar structure.
Funding Period: 2006-02-15 - 2011-01-31
more information: NIH RePORT

Top Publications

  1. ncbi A phase-variable mechanism controlling the Campylobacter jejuni FlgR response regulator influences commensalism
    David R Hendrixson
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Microbiol 61:1646-59. 2006
  2. ncbi Characterization of two putative cytochrome c peroxidases of Campylobacter jejuni involved in promoting commensal colonization of poultry
    Lacey K Bingham-Ramos
    University of Texas Southwestern Medical Center, Department of Microbiology, 5323 Harry Hines Boulevard, Dallas, TX 75390 9048, USA
    Infect Immun 76:1105-14. 2008
  3. ncbi Analysis of the Campylobacter jejuni FlgR response regulator suggests integration of diverse mechanisms to activate an NtrC-like protein
    Stephanie N Joslin
    University of Texas Southwestern Medical School, Department of Microbiology, Dallas, TX 75390, USA
    J Bacteriol 190:2422-33. 2008
  4. ncbi Restoration of flagellar biosynthesis by varied mutational events in Campylobacter jejuni
    David R Hendrixson
    Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
    Mol Microbiol 70:519-36. 2008
  5. ncbi Activation of the Campylobacter jejuni FlgSR two-component system is linked to the flagellar export apparatus
    Stephanie N Joslin
    University of Texas Southwestern Medical School, Department of Microbiology, 5323 Harry Hines Boulevard, Dallas, TX 75390 9048, USA
    J Bacteriol 191:2656-67. 2009
  6. ncbi FlhF and its GTPase activity are required for distinct processes in flagellar gene regulation and biosynthesis in Campylobacter jejuni
    Murat Balaban
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9048, USA
    J Bacteriol 191:6602-11. 2009

Scientific Experts

Detail Information

Publications6

  1. ncbi A phase-variable mechanism controlling the Campylobacter jejuni FlgR response regulator influences commensalism
    David R Hendrixson
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Microbiol 61:1646-59. 2006
    ..jejuni that is absent in other Campylobacter species and contribute to reasons why C. jejuni is more frequently found as a commensal organism in poultry and as the cause of disease in humans...
  2. ncbi Characterization of two putative cytochrome c peroxidases of Campylobacter jejuni involved in promoting commensal colonization of poultry
    Lacey K Bingham-Ramos
    University of Texas Southwestern Medical Center, Department of Microbiology, 5323 Harry Hines Boulevard, Dallas, TX 75390 9048, USA
    Infect Immun 76:1105-14. 2008
    ..Our data suggest that DocA and Cjj0382 have characteristics of CCPs but likely perform different physiological functions for the bacterium in colonization that are not related to resisting oxidative stress...
  3. ncbi Analysis of the Campylobacter jejuni FlgR response regulator suggests integration of diverse mechanisms to activate an NtrC-like protein
    Stephanie N Joslin
    University of Texas Southwestern Medical School, Department of Microbiology, Dallas, TX 75390, USA
    J Bacteriol 190:2422-33. 2008
    ..Our results demonstrate that FlgR activation mechanisms are unusual among characterized NtrC-like proteins and emphasize that various means are utilized by the NtrC family of proteins to control the transcription of target genes...
  4. ncbi Restoration of flagellar biosynthesis by varied mutational events in Campylobacter jejuni
    David R Hendrixson
    Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
    Mol Microbiol 70:519-36. 2008
    ..jejuni and suggests that the bacterium may possess a repertoire of mutational mechanisms to overcome genetic lesions that impair production of virulence and colonization determinants while lacking a normal mismatch repair system...
  5. ncbi Activation of the Campylobacter jejuni FlgSR two-component system is linked to the flagellar export apparatus
    Stephanie N Joslin
    University of Texas Southwestern Medical School, Department of Microbiology, 5323 Harry Hines Boulevard, Dallas, TX 75390 9048, USA
    J Bacteriol 191:2656-67. 2009
    ..This study indicates that these apparatuses have broader functions beyond flagellar protein secretion, including activation of essential two-component regulatory systems required for expression of sigma(54)-dependent flagellar genes...
  6. ncbi FlhF and its GTPase activity are required for distinct processes in flagellar gene regulation and biosynthesis in Campylobacter jejuni
    Murat Balaban
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9048, USA
    J Bacteriol 191:6602-11. 2009
    ..jejuni FlhF GTPase are required for distinct steps in flagellar gene expression and biosynthesis. Our findings are likely applicable to many polarly flagellated bacteria that utilize FlhF in flagellar biosynthesis processes...