Bistability in bacteria

Gene expression in bacteria is traditionally studied from the average behaviour of cells in a population, which has led to the assumption that under a particular set of conditions all cells express genes in an approximately uniform manner. The advent of methods for visualizing gene expression in individual cells reveals, however, that populations of genetically identical bacteria are sometimes heterogeneous, with certain genes being expressed in a non‐uniform manner across the population. In some cases, heterogeneity is manifested by the bifurcation into distinct subpopulations, and we adopt the common usage, referring to this phenomenon as bistability. Here we consider four cases of bistability, three from Bacillus subtilis and one from Escherichia coli, with an emphasis on random switching mechanisms that generate alternative cell states and the biological significance of phenotypic heterogeneity. A review describing additional examples of bistability in bacteria has been published recently.

[1]  D. Dubnau,et al.  Bistability in the Bacillus subtilis K‐state (competence) system requires a positive feedback loop , 2005, Molecular microbiology.

[2]  D. Dubnau,et al.  The competence transcription factor of Bacillus subtilis recognizes short A/T-rich sequences arranged in a unique, flexible pattern along the DNA helix. , 1998, Genes & development.

[3]  J. Ferrell.  Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. , 2002, Current opinion in cell biology.

[4]  B. Séraphin,et al.  Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion , 2001, The EMBO journal.

[5]  N. Pride,et al.  Treatment of Staphylococcal Infections with Methicillin , 1962, British medical journal.

[6]  J. Hoch,et al.  Initiation of sporulation in B. subtilis is controlled by a multicomponent phosphorelay , 1991, Cell.

[7]  A. Grossman,et al.  Gene expression in single cells of Bacillus subtilis: evidence that a threshold mechanism controls the initiation of sporulation , 1994, Journal of bacteriology.

[8]  A. Grossman,et al.  Biochemical and genetic characterization of a competence pheromone from B. subtilis , 1994, Cell.

[9]  M. Ptashne.  A Genetic Switch , 1986 .

[10]  R. Losick,et al.  Genes governing swarming in Bacillus subtilis and evidence for a phase variation mechanism controlling surface motility , 2004, Molecular microbiology.

[11]  D. Dubnau,et al.  The regulation of competence transcription factor synthesis constitutes a critical control point in the regulation of competence in Bacillus subtilis , 1994, Journal of bacteriology.

[12]  M. Nowak,et al.  Adaptive evolution of highly mutable loci in pathogenic bacteria , 1994, Current Biology.

[13]  Oscar P. Kuipers,et al.  Phenotypic variation in bacteria: the role of feedback regulation , 2006, Nature Reviews Microbiology.

[14]  Masaya Fujita,et al.  Evidence that entry into sporulation in Bacillus subtilis is governed by a gradual increase in the level and activity of the master regulator Spo0A. , 2005, Genes & development.

[15]  P. Serror,et al.  CodY is required for nutritional repression of Bacillus subtilis genetic competence , 1996, Journal of bacteriology.

[16]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[17]  J. Bigger.  TREATMENT OF STAPHYLOCOCCAL INFECTIONS WITH PENICILLIN BY INTERMITTENT STERILISATION , 1944 .

[18]  Oscar P Kuipers,et al.  Phosphatases modulate the bistable sporulation gene expression pattern in Bacillus subtilis , 2005, Molecular microbiology.

[19]  D. Sinderen,et al.  comK acts as an autoregulatory control switch in the signal transduction route to competence in Bacillus subtilis , 1994, Journal of bacteriology.

[20]  S. Leibler,et al.  Phenotypic Diversity, Population Growth, and Information in Fluctuating Environments , 2005, Science.

[21]  R. Losick,et al.  Cell population heterogeneity during growth of Bacillus subtilis. , 2005, Genes & development.

[22]  M. Pagni,et al.  Bacillus subtilis 168 gene lytF encodes a gamma-D-glutamate-meso-diaminopimelate muropeptidase expressed by the alternative vegetative sigma factor, sigmaD. , 1999, Microbiology.

[23]  D. Dubnau,et al.  Competence in Bacillus subtilis is controlled by regulated proteolysis of a transcription factor , 1998, The EMBO journal.

[24]  H. Moyed,et al.  hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis , 1983, Journal of bacteriology.

[25]  P. Swain,et al.  Intrinsic and extrinsic contributions to stochasticity in gene expression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Sierd Bron,et al.  Stripping Bacillus: ComK auto‐stimulation is responsible for the bistable response in competence development , 2005, Molecular microbiology.

[27]  M. Simon,et al.  Recombinational switch for gene expression. , 1977, Science.

[28]  M. Chamberlin,et al.  The Bacillus subtilis flagellin gene (hag) is transcribed by the sigma 28 form of RNA polymerase , 1989, Journal of bacteriology.

[29]  D. Dubnau,et al.  The pleiotropic response regulator DegU functions as a priming protein in competence development in Bacillus subtilis. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Gürol M. Süel,et al.  An excitable gene regulatory circuit induces transient cellular differentiation , 2006, Nature.

[31]  Oliver Hobert,et al.  MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Leibler,et al.  Bacterial Persistence as a Phenotypic Switch , 2004, Science.

[33]  Michael T. Laub,et al.  Cell-cycle progression and the generation of asymmetry in Caulobacter crescentus , 2004, Nature Reviews Microbiology.

[34]  D. Dubnau,et al.  The Ins and Outs of DNA Transfer in Bacteria , 2005, Science.

[35]  K. Lewis,et al.  Specialized Persister Cells and the Mechanism of Multidrug Tolerance in Escherichia coli , 2004, Journal of bacteriology.

[36]  R. Losick,et al.  Cannibalism by Sporulating Bacteria , 2003, Science.

[37]  Mark Albano,et al.  Rok (YkuW) regulates genetic competence in Bacillus subtilis by directly repressing comK , 2002, Molecular microbiology.

[38]  D. Dubnau,et al.  comK encodes the competence transcription factor, the key regulatory protein for competence development in Bacillus subtilis , 1995, Molecular microbiology.

[39]  M. Pagni,et al.  Bacillus subtilis 168 gene lytF encodes a γ-D-glutamate-meso-diaminopimelate muropeptidase expressed by the alternative vegetative sigma factor, σD , 1999 .

[40]  R. Losick,et al.  The master regulator for entry into sporulation in Bacillus subtilis becomes a cell-specific transcription factor after asymmetric division. , 2003, Genes & development.

[41]  The Bacillus subtilis transition state regulator AbrB binds to the -35 promoter region of comK. , 2003, FEMS microbiology letters.