Mechanisms of cyclic-di-GMP signaling in bacteria.

Cyclic-di-GMP is a ubiquitous second messenger in bacteria. The recent discovery that c-di-GMP antagonistically controls motility and virulence of single, planktonic cells on one hand and cell adhesion and persistence of multicellular communities on the other has spurred interest in this regulatory compound. Cellular levels of c-di-GMP are controlled through the opposing activities of diguanylate cyclases and phosphodiesterases, which represent two large families of output domains found in bacterial one- and two-component systems. This review concentrates on structural and functional aspects of diguanylate cyclases and phosphodiesterases, and on their role in transmitting environmental stimuli into a range of different cellular functions. In addition, we examine several well-established model systems for c-di-GMP signaling, including Pseudomonas, Vibrio, Caulobacter, and Salmonella.

[1]  A. Dricot,et al.  Attenuated Signature-Tagged Mutagenesis Mutants ofBrucella melitensis Identified during the Acute Phase ofInfection inMice , 2003, Infection and Immunity.

[2]  L. McCarter,et al.  Genetic determinants of biofilm development of opaque and translucent Vibrio parahaemolyticus , 2004, Molecular microbiology.

[3]  Michael J. MacCoss,et al.  Aminoglycoside antibiotics induce bacterial biofilm formation , 2005, Nature.

[4]  A. Camilli,et al.  Cyclic Diguanylate Regulates Vibrio cholerae Virulence Gene Expression , 2005, Infection and Immunity.

[5]  A. Newton,et al.  Identification of a novel response regulator required for the swarmer-to-stalked-cell transition in Caulobacter crescentus , 1995, Journal of bacteriology.

[6]  J. Hupp,et al.  Mucin–Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance , 2006, Molecular microbiology.

[7]  Matthew R. Johnson,et al.  Population density‐dependent regulation of exopolysaccharide formation in the hyperthermophilic bacterium Thermotoga maritima , 2004, Molecular microbiology.

[8]  J. Ghigo,et al.  A CsgD-Independent Pathway for Cellulose Production and Biofilm Formation in Escherichia coli , 2006, Journal of bacteriology.

[9]  Roger A. Jones,et al.  A glutamate‐alanine‐leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP , 2005, Molecular microbiology.

[10]  Lucy Shapiro,et al.  A Bacterial Cell-Cycle Regulatory Network Operating in Time and Space , 2003, Science.

[11]  R Mayer,et al.  Cellulose biosynthesis and function in bacteria. , 1991, Microbiological reviews.

[12]  P. Watnick,et al.  Identification and Characterization of a Vibrio cholerae Gene, mbaA , Involved in Maintenance of Biofilm Architecture , 2022 .

[13]  A. Wilde,et al.  The cyanobacterial phytochrome Cph2 inhibits phototaxis towards blue light , 2002, Molecular microbiology.

[14]  D. Michaeli,et al.  An unusual guanyl oligonucleotide regulates cellulose synthesis in Acetobacter xylinum , 1985, FEBS letters.

[15]  D. Tifrea,et al.  A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Kazmierczak,et al.  Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa , 2006, Molecular microbiology.

[17]  E V Koonin,et al.  The HD domain defines a new superfamily of metal-dependent phosphohydrolases. , 1998, Trends in biochemical sciences.

[18]  Y Comeau,et al.  Initiation of Biofilm Formation byPseudomonas aeruginosa 57RP Correlates with Emergence of Hyperpiliated and Highly Adherent Phenotypic Variants Deficient in Swimming, Swarming, and Twitching Motilities , 2001, Journal of bacteriology.

[19]  Matthew R. Parsek,et al.  Characterization of Colony Morphology Variants Isolated from Pseudomonas aeruginosa Biofilms , 2005, Applied and Environmental Microbiology.

[20]  V. Bindokas,et al.  Visualizing calcium signaling in cells by digitized wide-field and confocal fluorescent microscopy. , 2006, Methods in molecular biology.

[21]  C. Solano,et al.  Role of the GGDEF protein family in Salmonella cellulose biosynthesis and biofilm formation , 2004, Molecular microbiology.

[22]  A. Spormann,et al.  Control of Formation and Cellular Detachment from Shewanella oneidensis MR-1 Biofilms by Cyclic di-GMP , 2006, Journal of bacteriology.

[23]  Mark Gomelsky,et al.  Cyclic Diguanylate Is a Ubiquitous Signaling Molecule in Bacteria: Insights into Biochemistry of the GGDEF Protein Domain , 2005, Journal of bacteriology.

[24]  A. Camilli,et al.  Cyclic diguanylate (c‐di‐GMP) regulates Vibrio cholerae biofilm formation , 2004, Molecular microbiology.

[25]  A. Camilli,et al.  The EAL Domain Protein VieA Is a Cyclic Diguanylate Phosphodiesterase* , 2005, Journal of Biological Chemistry.

[26]  M. Parsek,et al.  Identification of psl, a Locus Encoding a Potential Exopolysaccharide That Is Essential for Pseudomonas aeruginosa PAO1 Biofilm Formation , 2004, Journal of bacteriology.

[27]  G. O’Toole,et al.  Keeping Their Options Open: Acute versus Persistent Infections , 2006, Journal of bacteriology.

[28]  U. Römling,et al.  Production of Cellulose and Curli Fimbriae by Members of the Family Enterobacteriaceae Isolated from the Human Gastrointestinal Tract , 2003, Infection and Immunity.

[29]  B. Tümmler,et al.  Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. , 2003, Journal of medical microbiology.

[30]  D. Amikam,et al.  The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phosphothioate derivatives. , 1990, The Journal of biological chemistry.

[31]  R. Kaushal,et al.  Formation of cellulose by certain species of Acetobacter. , 1951, The Biochemical journal.

[32]  L. Glaser The synthesis of cellulose in cell-free extracts of Acetobacter xylinum. , 1958, The Journal of biological chemistry.

[33]  S. Häussler Biofilm formation by the small colony variant phenotype of Pseudomonas aeruginosa. , 2004, Environmental microbiology.

[34]  J. M. Dow,et al.  Biofilm dispersal in Xanthomonas campestris is controlled by cell–cell signaling and is required for full virulence to plants , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Kohout,et al.  Targeting of Cyclic AMP Degradation to β2-Adrenergic Receptors by β-Arrestins , 2002, Science.

[36]  N. Grishin,et al.  GGDEF domain is homologous to adenylyl cyclase , 2001, Proteins.

[37]  D. Delmer,et al.  Solubilization of the UDP-glucose:1,4-beta-D-glucan 4-beta-D-glucosyltransferase (cellulose synthase) from Acetobacter xylinum. A comparison of regulatory properties with those of the membrane-bound form of the enzyme. , 1983, The Journal of biological chemistry.

[38]  R. Kolter,et al.  Two Genetic Loci Produce Distinct Carbohydrate-Rich Structural Components of the Pseudomonas aeruginosa Biofilm Matrix , 2004, Journal of bacteriology.

[39]  Carole A. Parent,et al.  Adenylyl Cyclase Localization Regulates Streaming during Chemotaxis , 2003, Cell.

[40]  Daniel G. Lee,et al.  Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3'-5')-cyclic-GMP in virulence. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[41]  L. McCarter,et al.  Vibrio parahaemolyticus scrABC, a Novel Operon Affecting Swarming and Capsular Polysaccharide Regulation , 2002, Journal of bacteriology.

[42]  R. Proctor,et al.  Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections , 2006, Nature Reviews Microbiology.

[43]  Frederick M. Ausubel,et al.  Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation , 2002, Nature.

[44]  S. Lory,et al.  The chaperone/usher pathways of Pseudomonas aeruginosa: Identification of fimbrial gene clusters (cup) and their involvement in biofilm formation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  B. Tümmler,et al.  Small-colony variants of Pseudomonas aeruginosa in cystic fibrosis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[46]  Young Ran Kim,et al.  Characterization and Pathogenic Significance of Vibrio vulnificus Antigens Preferentially Expressed in Septicemic Patients , 2003, Infection and Immunity.

[47]  C. Knight,et al.  Adaptive Divergence in Experimental Populations of Pseudomonas fluorescens. III. Mutational Origins of Wrinkly Spreader Diversity , 2007, Genetics.

[48]  S. Lory,et al.  A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. , 2004, Developmental cell.

[49]  A. G. Bobrov,et al.  Temperature Regulation of the Hemin Storage (Hms+) Phenotype of Yersinia pestis Is Posttranscriptional , 2004, Journal of bacteriology.

[50]  L. McCarter,et al.  Multiple Regulators Control Capsular Polysaccharide Production in Vibrio parahaemolyticus , 2003, Journal of bacteriology.

[51]  H. Lam,et al.  A Landmark Protein Essential for Establishing and Perpetuating the Polarity of a Bacterial Cell , 2006, Cell.

[52]  D. Amikam,et al.  c‐di‐GMP‐binding protein, a new factor regulating cellulose synthesis in Acetobacter xylinum , 1997, FEBS letters.

[53]  D. Delmer Biosynthesis of cellulose. , 1983, Advances in carbohydrate chemistry and biochemistry.

[54]  Hua Jin,et al.  Subtype-specific roles of cAMP phosphodiesterases in regulation of atrial natriuretic peptide release. , 2002, European journal of pharmacology.

[55]  A. G. Bobrov,et al.  HmsP, a putative phosphodiesterase, and HmsT, a putative diguanylate cyclase, control Hms‐dependent biofilm formation in Yersinia pestis , 2004, Molecular microbiology.

[56]  David A. D'Argenio,et al.  Autolysis and Autoaggregation in Pseudomonas aeruginosa Colony Morphology Mutants , 2002, Journal of bacteriology.

[57]  M. Gilles-Gonzalez,et al.  Phosphodiesterase A1, a regulator of cellulose synthesis in Acetobacter xylinum, is a heme-based sensor. , 2001, Biochemistry.

[58]  D. Cooper Compartmentalization of adenylate cyclase and cAMP signalling. , 2005, Biochemical Society transactions.

[59]  U. Römling,et al.  GGDEF and EAL domains inversely regulate cyclic di‐GMP levels and transition from sessility to motility , 2004, Molecular microbiology.

[60]  Brian H. Raphael,et al.  The Campylobacter jejuni Response Regulator, CbrR, Modulates Sodium Deoxycholate Resistance and Chicken Colonization , 2005, Journal of bacteriology.

[61]  D. Baker,et al.  Structure, function and evolution of microbial adenylyl and guanylyl cyclases , 2004, Molecular microbiology.

[62]  Stephan Frings,et al.  Regulation of cyclic nucleotide-gated channels , 2005, Current Opinion in Neurobiology.

[63]  Luke E. Ulrich,et al.  One-component systems dominate signal transduction in prokaryotes. , 2005, Trends in microbiology.

[64]  D. Delmer,et al.  Unique regulatory properties of the UDP-glucose:. beta. -1,4-glucan synthetase of Acetobacter xylinum. [Acetobacter xylinum] , 1983 .

[65]  A. G. Bobrov,et al.  The phosphodiesterase activity of the HmsP EAL domain is required for negative regulation of biofilm formation in Yersinia pestis. , 2005, FEMS microbiology letters.

[66]  R. Rappuoli,et al.  Sequences required for expression of Bordetella pertussis virulence factors share homology with prokaryotic signal transduction proteins. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[67]  U. Römling,et al.  Hierarchical involvement of various GGDEF domain proteins in rdar morphotype development of Salmonella enterica serovar Typhimurium , 2006, Molecular microbiology.

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

[69]  Peter Ross,et al.  Three cdg Operons Control Cellular Turnover of Cyclic Di-GMP in Acetobacter xylinum: Genetic Organization and Occurrence of Conserved Domains in Isoenzymes , 1998, Journal of bacteriology.

[70]  Jeffrey Green,et al.  Functional versatility in the CRP-FNR superfamily of transcription factors: FNR and FLP. , 2001, Advances in microbial physiology.

[71]  J. Connolly,et al.  A Three-Component Regulatory System Regulates Biofilm Maturation and Type III Secretion in Pseudomonas aeruginosa , 2005, Journal of bacteriology.

[72]  S. Lory,et al.  A novel two‐component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes , 2004, Molecular microbiology.

[73]  A. Camilli,et al.  Transcriptome and Phenotypic Responses of Vibrio cholerae to Increased Cyclic di-GMP Level , 2006, Journal of bacteriology.

[74]  A. Camilli,et al.  The Vibrio cholerae vieSAB Locus Encodes a Pathway Contributing to Cholera Toxin Production , 2002, Journal of bacteriology.

[75]  J. H. Boom,et al.  Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid , 1987, Nature.

[76]  Chankyu Park,et al.  Two novel flagellar components and H-NS are involved in the motor function of Escherichia coli. , 2000, Journal of molecular biology.

[77]  Michael Travisano,et al.  Adaptive radiation in a heterogeneous environment , 1998, Nature.

[78]  David A. D'Argenio,et al.  Cyclic di-GMP as a bacterial second messenger. , 2004, Microbiology.

[79]  D. Amikam,et al.  Polypeptide composition of bacterial cyclic diguanylic acid-dependent cellulose synthase and the occurrence of immunologically crossreacting proteins in higher plants. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[80]  D. Delmer,et al.  Achievement of high rates of in vitro synthesis of 1,4-beta-D-glucan: activation by cooperative interaction of the Acetobacter xylinum enzyme system with GTP, polyethylene glycol, and a protein factor. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[81]  E. Huitema,et al.  Bacterial Birth Scar Proteins Mark Future Flagellum Assembly Site , 2006, Cell.

[82]  Michael Y. Galperin,et al.  Novel domains of the prokaryotic two-component signal transduction systems. , 2001, FEMS microbiology letters.

[83]  S. Molin,et al.  Characterization of starvation-induced dispersion in Pseudomonas putida biofilms. , 2005, Environmental microbiology.

[84]  U. Jenal,et al.  Cell cycle‐dependent degradation of a flagellar motor component requires a novel‐type response regulator , 1999, Molecular microbiology.

[85]  Bonnie L. Bassler,et al.  Bacterial Small-Molecule Signaling Pathways , 2006, Science.

[86]  Matthias Christen,et al.  Identification and Characterization of a Cyclic di-GMP-specific Phosphodiesterase and Its Allosteric Control by GTP* , 2005, Journal of Biological Chemistry.

[87]  P. Watnick,et al.  NspS, a Predicted Polyamine Sensor, Mediates Activation of Vibrio cholerae Biofilm Formation by Norspermidine , 2005, Journal of bacteriology.

[88]  Michael Y. Galperin,et al.  C‐di‐GMP: the dawning of a novel bacterial signalling system , 2005, Molecular microbiology.

[89]  Michael Y. Galperin,et al.  PilZ domain is part of the bacterial c-di-GMP binding protein , 2006, Bioinform..

[90]  Patrick Goymer,et al.  Role of the GGDEF regulator PleD in polar development of Caulobacter crescentus , 2003, Molecular microbiology.

[91]  M. Rohde,et al.  The multicellular morphotypes of Salmonella typhimurium and Escherichia coli produce cellulose as the second component of the extracellular matrix , 2001, Molecular microbiology.

[92]  Y. Hayakawa,et al.  Genome-wide Transcriptional Profile of Escherichia coli in Response to High Levels of the Second Messenger 3′,5′-Cyclic Diguanylic Acid* , 2006, Journal of Biological Chemistry.

[93]  B. Giese,et al.  Structural basis of activity and allosteric control of diguanylate cyclase. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[94]  A. Spiers,et al.  Biofilm formation at the air–liquid interface by the Pseudomonas fluorescens SBW25 wrinkly spreader requires an acetylated form of cellulose , 2003, Molecular microbiology.

[95]  M. Travisano,et al.  Adaptive divergence in experimental populations of Pseudomonas fluorescens. I. Genetic and phenotypic bases of wrinkly spreader fitness. , 2002, Genetics.

[96]  K. Moffat,et al.  Purification and Initial Characterization of a Putative Blue Light–regulated Phosphodiesterase from Escherichia coli¶ , 2004, Photochemistry and photobiology.

[97]  J. Shabb Physiological substrates of cAMP-dependent protein kinase. , 2001, Chemical reviews.

[98]  U. Jenal Cyclic di-guanosine-monophosphate comes of age: a novel secondary messenger involved in modulating cell surface structures in bacteria? , 2004, Current opinion in microbiology.

[99]  Y. Brun,et al.  Development of Surface Adhesion in Caulobacter crescentus , 2004, Journal of bacteriology.

[100]  U. Jenal,et al.  Holdfast Formation in Motile Swarmer Cells Optimizes Surface Attachment during Caulobacter crescentus Development , 2006, Journal of bacteriology.

[101]  Lian-Hui Zhang,et al.  MorA Defines a New Class of Regulators Affecting Flagellar Development and Biofilm Formation in Diverse Pseudomonas Species , 2004, Journal of bacteriology.

[102]  D. Michaeli,et al.  Control of cellulose synthesis Acetobacter xylinum. A unique guanyl oligonucleotide is the immediate activator of the cellulose synthase , 1986 .

[103]  B. Giese,et al.  Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. , 2004, Genes & development.

[104]  A. Spiers,et al.  Adaptive Divergence in Experimental Populations of Pseudomonas fluorescens. II. Role of the GGDEF Regulator WspR in Evolution and Development of the Wrinkly Spreader Phenotype , 2006, Genetics.

[105]  Michael Y. Galperin,et al.  A census of membrane-bound and intracellular signal transduction proteins in bacteria: Bacterial IQ, extroverts and introverts , 2005, BMC Microbiology.

[106]  M. Parsek,et al.  Bacterial biofilms: an emerging link to disease pathogenesis. , 2003, Annual review of microbiology.

[107]  Markus Meuwly,et al.  Allosteric Control of Cyclic di-GMP Signaling* , 2006, Journal of Biological Chemistry.

[108]  G. Kovacikova,et al.  Dual regulation of genes involved in acetoin biosynthesis and motility/biofilm formation by the virulence activator AphA and the acetate‐responsive LysR‐type regulator AlsR in Vibrio cholerae , 2005, Molecular microbiology.

[109]  L. Gallagher,et al.  Pseudomonas aeruginosa PAO1 KillsCaenorhabditis elegans by Cyanide Poisoning , 2001, Journal of bacteriology.

[110]  J. M. Dow,et al.  Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[111]  Dorit Amikam,et al.  Cyclic di-GMP as a second messenger. , 2006, Current opinion in microbiology.

[112]  J. Mattick,et al.  FimX, a Multidomain Protein Connecting EnvironmentalSignals to Twitching Motility in Pseudomonasaeruginosa , 2003, Journal of bacteriology.

[113]  Afsar Ali,et al.  Identification of genes involved in the switch between the smooth and rugose phenotypes of Vibrio cholerae. , 2003, FEMS microbiology letters.

[114]  Andrew J. Schmidt,et al.  The Ubiquitous Protein Domain EAL Is a Cyclic Diguanylate-Specific Phosphodiesterase: Enzymatically Active and Inactive EAL Domains , 2005, Journal of bacteriology.

[115]  Bentley Lim,et al.  Cyclic‐diGMP signal transduction systems in Vibrio cholerae: modulation of rugosity and biofilm formation , 2006, Molecular microbiology.

[116]  Paul Stoodley,et al.  Bacterial biofilms: from the Natural environment to infectious diseases , 2004, Nature Reviews Microbiology.