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 Hemerythrins in the microaerophilic bacterium Campylobacter jejuni help protect key iron-sulphur cluster enzymes from oxidative damage
    John J Kendall
    Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, UK
    Environ Microbiol 16:1105-21. 2014
  2. pmc A regulatory checkpoint during flagellar biogenesis in Campylobacter jejuni initiates signal transduction to activate transcription of flagellar genes
    Joseph M Boll
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    MBio 4:e00432-13. 2013
  3. pmc Spatial and numerical regulation of flagellar biosynthesis in polarly flagellated bacteria
    Barbara I Kazmierczak
    Departments of Medicine and Microbial Pathogenesis, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520 8022, USA
    Mol Microbiol 88:655-63. 2013
  4. pmc Architecture of the major component of the type III secretion system export apparatus
    Patrizia Abrusci
    Sir William Dunn School of Pathology, Oxford University, Oxford, UK
    Nat Struct Mol Biol 20:99-104. 2013
  5. pmc EptC of Campylobacter jejuni mediates phenotypes involved in host interactions and virulence
    Thomas W Cullen
    Section of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA
    Infect Immun 81:430-40. 2013
  6. pmc Structural diversity of bacterial flagellar motors
    Songye Chen
    Division of Biology, California Institute of Technology, Pasadena, CA, USA
    EMBO J 30:2972-81. 2011
  7. pmc A specificity determinant for phosphorylation in a response regulator prevents in vivo cross-talk and modification by acetyl phosphate
    Joseph M Boll
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9048, USA
    Proc Natl Acad Sci U S A 108:20160-5. 2011
  8. pmc Polar flagellar biosynthesis and a regulator of flagellar number influence spatial parameters of cell division in Campylobacter jejuni
    Murat Balaban
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS Pathog 7:e1002420. 2011
  9. pmc Identification and analysis of flagellar coexpressed determinants (Feds) of Campylobacter jejuni involved in colonization
    Angelica M Barrero-Tobon
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9048, USA
    Mol Microbiol 84:352-69. 2012
  10. pmc Analysis of the LIV system of Campylobacter jejuni reveals alternative roles for LivJ and LivK in commensalism beyond branched-chain amino acid transport
    Deborah A Ribardo
    Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Room NL 4 138A, Dallas, TX 75390 9048, USA
    J Bacteriol 193:6233-43. 2011

Scientific Experts

  • DAVID HENDRIXSON
  • Stephanie N Joslin
  • Joseph M Boll
  • Deborah A Ribardo
  • Murat Balaban
  • Angelica M Barrero-Tobon
  • Lacey K Bingham-Ramos
  • John J Kendall
  • Patrizia Abrusci
  • Barbara I Kazmierczak
  • Thomas W Cullen
  • Grant J Jensen
  • Songye Chen
  • Paphavee Lertsethtakarn
  • Jeremy J Gilbreath
  • David J Kelly
  • Steven Johnson
  • Rhonda I Hobb
  • Marta Vergara-Irigaray
  • Miriam E Friede
  • David K Giles
  • M Stephen Trent
  • Janet E Deane
  • Pietro Roversi
  • Susan M Lea
  • Christoph M Tang
  • John P O'Brien
  • Morgan D Beeby
  • Stuart A Thompson
  • Jennifer S Brodbelt
  • Axel Muller
  • William L Cody
  • Gavin E Murphy
  • Elitza I Tocheva
  • Jian Shi
  • D Scott Merrell
  • Karen M Ottemann
  • Zhuo Li
  • Morgan Beeby
  • Jared R Leadbetter
  • Megan J Dobro
  • Ariane Briegel

Detail Information

Publications19

  1. ncbi Hemerythrins in the microaerophilic bacterium Campylobacter jejuni help protect key iron-sulphur cluster enzymes from oxidative damage
    John J Kendall
    Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, UK
    Environ Microbiol 16:1105-21. 2014
    ..We conclude that oxygen lability and poor repair of Por and Oor are major contributors to microaerophily in C. jejuni; hemerythrins help prevent enzyme damage microaerobically or during oxygen transients. ..
  2. pmc A regulatory checkpoint during flagellar biogenesis in Campylobacter jejuni initiates signal transduction to activate transcription of flagellar genes
    Joseph M Boll
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    MBio 4:e00432-13. 2013
    ..jejuni, this regulatory checkpoint may exist in a broad range of bacteria to influence similar TCSs and flagellar gene transcription...
  3. pmc Spatial and numerical regulation of flagellar biosynthesis in polarly flagellated bacteria
    Barbara I Kazmierczak
    Departments of Medicine and Microbial Pathogenesis, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520 8022, USA
    Mol Microbiol 88:655-63. 2013
    ..Continued examination of these proteins in polar flagellates is expected to reveal how different bacteria have adapted FlhF or FlhG with specific activities to tailor flagellar biosynthesis and motility to fit the needs of each species...
  4. pmc Architecture of the major component of the type III secretion system export apparatus
    Patrizia Abrusci
    Sir William Dunn School of Pathology, Oxford University, Oxford, UK
    Nat Struct Mol Biol 20:99-104. 2013
    ..This defines the molecular architecture of the dominant component of the export apparatus and allows us to propose a model for the molecular mechanisms controlling secretion...
  5. pmc EptC of Campylobacter jejuni mediates phenotypes involved in host interactions and virulence
    Thomas W Cullen
    Section of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA
    Infect Immun 81:430-40. 2013
    ..Our results indicate that modification of surface structures with pEtN by EptC is key to its ability to promote commensalism in an avian host and to survive in the mammalian gastrointestinal environment...
  6. pmc Structural diversity of bacterial flagellar motors
    Songye Chen
    Division of Biology, California Institute of Technology, Pasadena, CA, USA
    EMBO J 30:2972-81. 2011
    ..The combination of conserved and specially-adapted structures seen here sheds light on how this complex protein nanomachine has evolved to meet the needs of different species...
  7. pmc A specificity determinant for phosphorylation in a response regulator prevents in vivo cross-talk and modification by acetyl phosphate
    Joseph M Boll
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9048, USA
    Proc Natl Acad Sci U S A 108:20160-5. 2011
    ..In addition to mechanisms limiting cross-talk between noncognate HKs and RRs, our work suggests that RRs can possess domains that prevent in vivo cross-talk between RRs and the endogenous metabolite AcP to ensure signaling specificity...
  8. pmc Polar flagellar biosynthesis and a regulator of flagellar number influence spatial parameters of cell division in Campylobacter jejuni
    Murat Balaban
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS Pathog 7:e1002420. 2011
    ..Furthermore, we found that other polarly-flagellated bacteria produce FlhG proteins that influence cell division, suggesting that FlhG and polar flagella may function together in a broad range of bacteria to spatially regulate division...
  9. pmc Identification and analysis of flagellar coexpressed determinants (Feds) of Campylobacter jejuni involved in colonization
    Angelica M Barrero-Tobon
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9048, USA
    Mol Microbiol 84:352-69. 2012
    ....
  10. pmc Analysis of the LIV system of Campylobacter jejuni reveals alternative roles for LivJ and LivK in commensalism beyond branched-chain amino acid transport
    Deborah A Ribardo
    Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Room NL 4 138A, Dallas, TX 75390 9048, USA
    J Bacteriol 193:6233-43. 2011
    ..In contrast to other studies indicating a requirement and utilization of other specific amino acids for colonization, acquisition of branched-chain amino acids does not appear to be a determinant for C. jejuni during commensalism...
  11. doi Motility and chemotaxis in Campylobacter and Helicobacter
    Paphavee Lertsethtakarn
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California 95064, USA
    Annu Rev Microbiol 65:389-410. 2011
    ..Chemoreceptors in these bacteria contain nonconserved ligand binding domains, with several chemoreceptors matched to environmental signals. Together, these mechanisms allow for swimming motility that is essential for colonization...
  12. pmc Change is good: variations in common biological mechanisms in the epsilonproteobacterial genera Campylobacter and Helicobacter
    Jeremy J Gilbreath
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    Microbiol Mol Biol Rev 75:84-132. 2011
    ....
  13. pmc Functional analysis of the RdxA and RdxB nitroreductases of Campylobacter jejuni reveals that mutations in rdxA confer metronidazole resistance
    Deborah A Ribardo
    University of Texas Southwestern Medical School, Department of Microbiology, Dallas, TX 75390 9048, USA
    J Bacteriol 192:1890-901. 2010
    ....
  14. pmc 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...
  15. pmc 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...
  16. pmc 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...
  17. pmc 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...
  18. pmc 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...
  19. 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...