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. pmc Structural Characterization of the Extracellular Polysaccharide from Vibrio cholerae O1 El-Tor
    Fitnat Yildiz
    Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America
    PLoS ONE 9:e86751. 2014
  3. pmc Structural basis for biofilm formation via the Vibrio cholerae matrix protein RbmA
    Krista M Giglio
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
    J Bacteriol 195:3277-86. 2013
  4. pmc Molecular architecture and assembly principles of Vibrio cholerae biofilms
    Veysel Berk
    Department of Physics, University of California, Berkeley, CA 94720, USA
    Science 337:236-9. 2012
  5. pmc The transcriptional regulator, CosR, controls compatible solute biosynthesis and transport, motility and biofilm formation in Vibrio cholerae
    Nicholas J Shikuma
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Environ Microbiol 15:1387-99. 2013
  6. pmc You've come a long way: c-di-GMP signaling
    Holger Sondermann
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
    Curr Opin Microbiol 15:140-6. 2012
  7. pmc Role of Vibrio polysaccharide (vps) genes in VPS production, biofilm formation and Vibrio cholerae pathogenesis
    Jiunn C N Fong
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Microbiology 156:2757-69. 2010
  8. pmc 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
  9. pmc 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
  10. pmc 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

Scientific Experts

  • Fitnat H Yildiz
  • Sinem Beyhan
  • Jiunn C N Fong
  • Nicholas J Shikuma
  • Holger Sondermann
  • Bentley Lim
  • Kivanc Bilecen
  • Krista M Giglio
  • Veysel Berk
  • Petya V Krasteva
  • Anna D Tischler
  • Andrew Camilli
  • Jiunn C Fong
  • Kimberly R Davis
  • Jiunn N C Fong
  • Jan Liphardt
  • Graham T Dempsey
  • Xiaowei Zhuang
  • Steven Chu
  • Omer N Develioglu
  • Khalid A Syed
  • Karl E Klose
  • Marcos V A S Navarro
  • Michael T Laub
  • Barrett S Perchuk
  • Lindsay S Odell
  • Sofie R Salama
  • Catharina Casper-Lindley
  • James Meir
  • Gary K Schoolnik
  • Kevin Karplus

Detail Information

Publications19

  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. pmc Structural Characterization of the Extracellular Polysaccharide from Vibrio cholerae O1 El-Tor
    Fitnat Yildiz
    Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America
    PLoS ONE 9:e86751. 2014
    ..The only reliable method to remove this component at present is a treatment of the whole glycoconjugate with concentrated hydrochloric acid. ..
  3. pmc Structural basis for biofilm formation via the Vibrio cholerae matrix protein RbmA
    Krista M Giglio
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
    J Bacteriol 195:3277-86. 2013
    ..On the basis of the structure, we hypothesize that RbmA serves as a tether by maintaining flexible linkages between cells and the extracellular matrix. ..
  4. pmc Molecular architecture and assembly principles of Vibrio cholerae biofilms
    Veysel Berk
    Department of Physics, University of California, Berkeley, CA 94720, USA
    Science 337:236-9. 2012
    ....
  5. pmc The transcriptional regulator, CosR, controls compatible solute biosynthesis and transport, motility and biofilm formation in Vibrio cholerae
    Nicholas J Shikuma
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Environ Microbiol 15:1387-99. 2013
    ..This is the first study to characterize a compatible solute regulator in V. cholerae and couples the regulation of osmotic tolerance with biofilm formation and motility...
  6. pmc You've come a long way: c-di-GMP signaling
    Holger Sondermann
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
    Curr Opin Microbiol 15:140-6. 2012
    ..Recent studies revealing the molecular basis of c-di-GMP signaling mechanisms enhanced our understanding of how this molecule controls downstream biological processes and how c-di-GMP signaling specificity is achieved...
  7. pmc Role of Vibrio polysaccharide (vps) genes in VPS production, biofilm formation and Vibrio cholerae pathogenesis
    Jiunn C N Fong
    Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Microbiology 156:2757-69. 2010
    ..cholerae...
  8. pmc 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...
  9. pmc 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...
  10. pmc 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...
  11. pmc 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...
  12. 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...
  13. pmc 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...
  14. pmc 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...
  15. pmc 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...
  16. pmc 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...
  17. pmc 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...
  18. 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...
  19. pmc 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...