Smooth to Rugose phase variation in Vibrio cholerae

Summary

Principal Investigator: Fitnat H Yildiz
Affiliation: University of California
Country: USA
Abstract: Cholera is a global disease; endemic to Bangladesh, regions of South America, Africa and Australia, and also the Gulf Coast of the United States with the potential for epidemic in all aquatic environments. It is estimated that 120,000 people worldwide die from cholera annually. V. cholerae causes periodic, seasonal outbreaks in regions where it is an established member of the indigenous aquatic flora and this capacity is linked to its survival under diverse environmental conditions. V. cholerae switches its colonial morphology from smooth and translucent type to wrinkled and opaque type termed rugose variant when exposed to environmental stresses. We hypothesize that the phase variation mediated changes in population composition of V. cholerae can increase aquatic survival chances of the organism. The tong term goal of this project is to understand how V. cholerae survives between epidemics by focusing on the molecular mechanism of smooth to rugose phase variation, its physiological consequences and its effect on the aquatic survival of the organism. Towards this goal, we will focus on the following specific aims: 1) determine and characterize the molecular basis of the smooth to rugose phase variation, 2) characterize the transcriptional network governing rugose specific gene expression and characterize the physiological and behavioral changes in the organism resulting from phase variation 3) elucidate the effects of diverse environmental parameters on the aquatic survival properties of the smooth and rugose variants and on the frequency of phase variation. Understanding how the smooth to rugose phase variation is contributing to persistence and survival of V. choterae O1 El Tor in environmental aquatic habitats, and elucidation of the genes and processes regulating the phase variation will further our understanding of aquatic life cycle of an important human pathogen. Results obtained from this study should lead to the development of molecular tools that can be used to identify transcripts or proteins that are predicted to provide better environmental fitness to the organism in natural aquatic habitats. This information will prove useful in the prediction and/or control of cholera epidemics. Smooth to rugose phase variation presents another challenge in public heath since this process renders the organism resistant to oxidative stress and chlorine-mediated killing. Chlorination is used as a first line of defense against V. cholerae and many other waterborne pathogens. Understanding the mechanism and regulation of phase variation may aid in designing methods/inhibitors for modulating the frequency of phase variation and thus biocide resistance in V. cholerae and other aquatic pathogens.
Funding Period: 2003-09-30 - 2008-09-15
more information: NIH RePORT

Top Publications

  1. ncbi Smooth to rugose phase variation in Vibrio cholerae can be mediated by a single nucleotide change that targets c-di-GMP signalling pathway
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Mol Microbiol 63:995-1007. 2007
  2. ncbi Identification and characterization of RbmA, a novel protein required for the development of rugose colony morphology and biofilm structure in Vibrio cholerae
    Jiunn C N Fong
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 188:1049-59. 2006
  3. ncbi Overexpression of VpsS, a hybrid sensor kinase, enhances biofilm formation in Vibrio cholerae
    Nicholas J Shikuma
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 191:5147-58. 2009
  4. ncbi Identification of a calcium-controlled negative regulatory system affecting Vibrio cholerae biofilm formation
    Kivanc Bilecen
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA
    Environ Microbiol 11:2015-29. 2009
  5. ncbi Vibrio biofilms: so much the same yet so different
    Fitnat H Yildiz
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Trends Microbiol 17:109-18. 2009
  6. ncbi Processes controlling the transmission of bacterial pathogens in the environment
    Fitnat H Yildiz
    Department of Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    Res Microbiol 158:195-202. 2007
  7. ncbi The rbmBCDEF gene cluster modulates development of rugose colony morphology and biofilm formation in Vibrio cholerae
    Jiunn C N Fong
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 189:2319-30. 2007
  8. ncbi Regulation of Vibrio polysaccharide synthesis and virulence factor production by CdgC, a GGDEF-EAL domain protein, in Vibrio cholerae
    Bentley Lim
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 189:717-29. 2007
  9. ncbi Regulation of rugosity and biofilm formation in Vibrio cholerae: comparison of VpsT and VpsR regulons and epistasis analysis of vpsT, vpsR, and hapR
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA
    J Bacteriol 189:388-402. 2007
  10. ncbi Differences in gene expression between the classical and El Tor biotypes of Vibrio cholerae O1
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Infect Immun 74:3633-42. 2006

Scientific Experts

  • Fitnat H Yildiz
  • Sinem Beyhan
  • Jiunn C N Fong
  • Bentley Lim
  • Nicholas J Shikuma
  • Kivanc Bilecen
  • Petya V Krasteva
  • Andrew Camilli
  • Anna D Tischler
  • Marcos V A S Navarro
  • Holger Sondermann
  • Barrett S Perchuk
  • Michael T Laub
  • Lindsay S Odell
  • Catharina Casper Lindley
  • Sofie R Salama
  • Catharina Casper-Lindley
  • Gary K Schoolnik
  • James Meir
  • Kevin Karplus

Detail Information

Publications13

  1. ncbi Smooth to rugose phase variation in Vibrio cholerae can be mediated by a single nucleotide change that targets c-di-GMP signalling pathway
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Mol Microbiol 63:995-1007. 2007
    ..As phage infection is known to control populations of V. cholerae and thus outbreaks of cholera, phase variation may increase the evolutionary success of the pathogen...
  2. ncbi Identification and characterization of RbmA, a novel protein required for the development of rugose colony morphology and biofilm structure in Vibrio cholerae
    Jiunn C N Fong
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 188:1049-59. 2006
    ..cholerae. Transcription of rbmA is positively regulated by the response regulator VpsR but not VpsT...
  3. ncbi Overexpression of VpsS, a hybrid sensor kinase, enhances biofilm formation in Vibrio cholerae
    Nicholas J Shikuma
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 191:5147-58. 2009
    ..The induction of vps expression via VpsS was also shown to occur independent of HapR. Thus, VpsS utilizes components of the quorum-sensing pathway to modulate biofilm formation in V. cholerae...
  4. ncbi Identification of a calcium-controlled negative regulatory system affecting Vibrio cholerae biofilm formation
    Kivanc Bilecen
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA
    Environ Microbiol 11:2015-29. 2009
    ..Through epistasis analysis we determined that CarR acts in parallel with HapR, the negative regulator of vps gene expression...
  5. ncbi Vibrio biofilms: so much the same yet so different
    Fitnat H Yildiz
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Trends Microbiol 17:109-18. 2009
    ..Although many aspects are the same, others differ dramatically. Crucial questions that remain to be answered regarding the molecular underpinnings of Vibrio biofilm formation are also discussed...
  6. ncbi Processes controlling the transmission of bacterial pathogens in the environment
    Fitnat H Yildiz
    Department of Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    Res Microbiol 158:195-202. 2007
    ..A better understanding of these mechanisms is thus necessary for predicting and preventing future outbreaks...
  7. ncbi The rbmBCDEF gene cluster modulates development of rugose colony morphology and biofilm formation in Vibrio cholerae
    Jiunn C N Fong
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 189:2319-30. 2007
    ..Taken together, these results indicate that vps intergenic region genes encode proteins that are involved in biofilm matrix production and maintenance of biofilm structure and stability...
  8. ncbi Regulation of Vibrio polysaccharide synthesis and virulence factor production by CdgC, a GGDEF-EAL domain protein, in Vibrio cholerae
    Bentley Lim
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Bacteriol 189:717-29. 2007
    ..cholerae...
  9. ncbi Regulation of rugosity and biofilm formation in Vibrio cholerae: comparison of VpsT and VpsR regulons and epistasis analysis of vpsT, vpsR, and hapR
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA
    J Bacteriol 189:388-402. 2007
    ..These results show that a complex regulatory interplay among VpsT, VpsR, HapR, and GGDEF/EAL family proteins controls transcription of the genes required for Vibrio polysaccharide and virulence factor production in V. cholerae...
  10. ncbi Differences in gene expression between the classical and El Tor biotypes of Vibrio cholerae O1
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Infect Immun 74:3633-42. 2006
    ..Thus, VieA is a major regulator of genes in the classical biotype under virulence gene-inducing conditions...
  11. ncbi Transcriptome and phenotypic responses of Vibrio cholerae to increased cyclic di-GMP level
    Sinem Beyhan
    Department of Environmental Toxicology, University of California, Santa Cruz, 95064, USA
    J Bacteriol 188:3600-13. 2006
    ..The functions of other c-di-GMP-regulated genes in V. cholerae are yet to be identified...
  12. ncbi Cyclic-diGMP signal transduction systems in Vibrio cholerae: modulation of rugosity and biofilm formation
    Bentley Lim
    Department of Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    Mol Microbiol 60:331-48. 2006
    ..Furthermore, epistasis analysis suggested that cdgC, rocS and mbaA act in convergent pathways to regulate the phenotypic properties of the rugose and smooth variants, and are part of the VpsR, VpsT and HapR signal transduction pathway...
  13. ncbi Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP
    Petya V Krasteva
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
    Science 327:866-8. 2010
    ..Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerization on c-di-GMP binding...