Microbial Cyclic Di-Nucleotide Signaling

✍ Scribed by Shan-Ho Chou; Nicolas Guiliani; Vincent T. Lee; Ute Römling

• Publisher: Springer Nature
• Year: 2020
• Tongue: English
• Leaves: 640
• Category: Library

✦ Synopsis

This book explores the broad and diverse biological and physiological impacts of established and newly discovered cyclic di-nucleotide second messenger signaling systems, while also providing descriptions of the intriguing biochemical characteristics of multiple turnover enzymes and receptors. The respective chapters discuss the commonalities and diversity of cyclic di-GMP, cyclic di-AMP and recently discovered cyclic GMP-AMP signaling systems in manifold Gram-negative and Gram-positive bacteria. The global human pathogens Mycobacterium tuberculosis, Vibrio cholerae, Salmonella typhimurium, Escherichia coli and Streptococcus pneumoniae, the facultative human pathogen Pseudomonas aeruginosa, global plant pathogens as exemplified by Xanthomonas campestris and Burkholderia spp., and the omnipresent probiotic Lactobacilli, as well as environmentally important photoautotrophic cyanobacteria, the multicellular Myxococcus xanthus, and chemolithotrophic Acidithiobacillus are among the representatives of the microbial kingdom that are described. In turn, the various aspects of bacterial physiology affected by these signaling systems– e.g. biofilm formation and dispersal, the cell cycle, motility, virulence, production of antimicrobials, fundamental metabolism and osmohomeostasis – are discussed in detail in the context of different microorganisms. Dedicated chapters focus on the population diversity of cyclic dinucleotide signaling systems, their tendency to be horizontally transferred, the cyclic di-GMP signaling system in the social amoeba Dictyostelium, honorary cyclic (di)nucleotides, and the development of strategies for interfering with cyclic dinucleotide signaling in order to manipulate microbial behavior. Taken together, the chapters provide an authoritative source of information for a broad readership: beginners and advanced researchers from various disciplines; individuals seeking a broad overview of cyclic di-nucleotide signaling; and those who want to learn more about specific aspects. Also featuring reviews with a forward-looking perspective, the book offers a valuable source of inspiration for future research directions.

✦ Table of Contents

Foreword
Role and Importance of Cyclic Di-Nucleotide Second Messenger Signaling
References
Preface
Acknowledgments
Contents
Part I: Biochemistry/Structural Biology-Enzymes
Chapter 1: Cyclic Dinucleotide Signaling in Mycobacteria
1.1 Introduction
1.2 Synthesis and Hydrolysis of CDNs
1.2.1 Cyclic di-GMP Metabolism
1.2.2 Cyclic di-AMP Metabolism
1.3 CDN Effectors
1.3.1 Cyclic di-GMP Binding Transcription Factor LtmA
1.3.2 Cyclic di-GMP Binding Transcription Factor HpoR
1.3.3 Cyclic di-GMP Binding Transcription Factor EthR
1.3.4 Cyclic di-AMP Binding Transcription Factor DarR
1.3.5 Cyclic di-AMP Binding Protein RecA
1.4 Physiological Roles of the CDNs
1.4.1 Phenotypes Regulated by Cyclic di-GMP
1.4.2 Phenotypes Regulated by Cyclic di-AMP
1.5 CDN Homeostasis
1.5.1 Cyclic di-GMP Homeostasis
1.5.2 Cyclic di-AMP Homeostasis
1.6 Crosstalk Between Different Second Messengers in Bacteria
1.7 Crosstalk Between Second Messengers of Host and Pathogen
1.8 Summary
1.9 Future Perspectives
References
Chapter 2: Structure and Regulation of EAL Domain Proteins
2.1 Introduction
2.2 The Road to the Structure and Catalytic Mechanism of EAL Domain Cyclic di-GMP Phosphodiesterases
2.3 The First Structures of EAL Domain Proteins
2.4 EAL Domain PDE Activity, Regulation and Diversity
2.5 How Many Metals Are Really Required for EAL Domain Activity?
2.6 Outlook
References
Chapter 3: Insights into the Molecular Basis of Biofilm Dispersal from Crystal Structures of Didomain Containing Proteins
3.1 Importance of Cyclic di-GMP and Enzymatic Domains Involved in Its Synthesis and Hydrolysis
3.2 Structural Data on Didomain Containing Proteins
3.2.1 LapD
3.2.2 MorA
3.3 Diffusible Signal Factor (DSF) and the DSF Receptor Regulation of Pathogenicity Factor R (RpfR)
3.3.1 PA0575 Protein from Pseudomonas aeruginosa
References
Chapter 4: Structure and Function of HD-GYP Phosphodiesterases
4.1 Introduction
4.2 Distribution and Domain Organization
4.3 Functions of HD-GYP Proteins
4.4 Catalytic Activity of HD-GYP Proteins
4.5 Structural Features of HD-GYP Proteins
4.6 Concluding Remarks and Future Perspectives
References
Chapter 5: A Unified Catalytic Mechanism for Cyclic di-NMP Hydrolysis by DHH-DHHA1 Phosphodiesterases
5.1 Introduction
5.2 Cyclic di-AMP Conformation
5.3 The DHH-DHHA1 Domain Containing Phosphodiesterases
5.4 Structure of DHH-DHHA1 Domain with a Binuclear Metal Center
5.5 Hydrolysis of the 3′-5′ Phosphodiester Bond by the DHH-DHHA1 Domain
5.6 Detailed Two-Step Hydrolysis of cyclic di-AMP
5.7 G Subsite of the DHH-DHHA1 Domain Determines the Substrate Selectivity for Cyclic Dinucleotides
References
Chapter 6: Enzymatic Degradation of Linear Dinucleotide Intermediates of Cyclic Dinucleotides
6.1 Introduction
6.2 Intracellular Effects of pGpG
6.3 Oligoribonuclease (Orn) Is the Primary Phosphodiesterase That Degrades pGpG to GMP
6.4 Discovery of Orn and Its Functions in RNA Degradation
6.5 NanoRNAses as Linear Dinucleotide Phosphodiesterases
6.6 Other Linear Dinucleotides
6.7 Conclusion and Future Directions
References
Part II: Biochemistry/Structural Biology-Receptors
Chapter 7: Detection of Cyclic Dinucleotide Binding Proteins
7.1 Introduction
7.2 Unbiased Approaches: Identifying Novel Receptors
7.2.1 Bioinformatic Approach
7.2.2 Affinity Pull-down
7.2.3 Differential Radial Capillary Action of Ligand Assay (DRaCALA)-Based ORFeome Screens
7.2.4 Summary
7.3 Assays to Characterize Interactions Between Cyclic Dinucleotides and Candidate Receptor Proteins
7.3.1 Detection Using Radiolabeled Cyclic Dinucleotides
7.3.1.1 Crosslink and Electrophoretic Mobility Shift Assay (EMSA)
7.3.1.2 Pull-Down of Labeled Cyclic Dinucleotide by Affinity-Tagged Proteins
7.3.1.3 Filter Binding
7.3.1.4 Differential Radial Capillary Action of Ligand Assay (DRaCALA)
7.3.2 Detection of Binding Interaction with Unlabeled Cyclic Dinucleotides Using Biophysical Techniques
7.3.3 Detection of Binding Using Covalently Modified Cyclic Dinucleotides
7.3.4 Structural Biological Approaches
7.3.5 Follow-Up Studies
7.4 Conclusion
References
Chapter 8: Noncanonical Cyclic di-GMP Binding Modes
8.1 Cyclic di-GMP Binding in the Active Site of a Diguanylate Cyclase Containing the Canonical GGDEF Motif Without an Inhibito...
8.1.1 XCC4471GGDEF Forms a Dimer with Two Cyclic di-GMP Partially Stacking to Each Other
8.1.2 The Highly Conserved GGDE Motif Is Involved in Interaction with the Cyclic di-GMP Molecule
8.2 A PilZ Domain Structure Interrupted in the Middle by Two Long α-Helices that Self-Assembles into a Tetramer via the Leucin...
8.3 Cyclic di-GMP Adopts a New Bulge Conformation with One Guanine Base Flipping from anti to syn When It Binds to the Degener...
References
Part III: Biochemistry/Structural Biology-Sensing
Chapter 9: Sensory Domains That Control Cyclic di-GMP-Modulating Proteins: A Critical Frontier in Bacterial Signal Transduction
9.1 Introduction
9.2 Examples of PAS-Domain-Containing Proteins with Potential to Modulate Cyclic di-GMP Levels
9.2.1 O2-Sensing Proteins in the Komagataeibacter xylinus and Escherichia coli Cyclic di-GMP-Modulating Networks
9.2.2 The Pseudomonas aeruginosa Phosphodiesterases RmcA and DipA/Pch
9.2.3 Pseudomonas aeruginosa TdcA, a Thermosensory Diguanylate Cyclase
9.2.4 RpfR from Burkholderia cenocepacia and Other Species
9.2.5 Light-Sensing DGCs and PDEs from Thermosynechococcus vulcanus
9.3 Structure-Based Modeling of PAS Domains from E. coli and P. aeruginosa GGDEF/EAL Proteins
9.3.1 PAS-GGDEF/EAL Proteins in E. coli
9.3.2 PAS-GGDEF/EAL Proteins in P. aeruginosa
9.4 Concluding Remarks
References
Part IV: Cyclic di-AMP: Biochemistry and Physiology
Chapter 10: Metabolic Regulation by Cyclic di-AMP Signaling
10.1 Introduction
10.2 Regulation of Pyruvate Carboxylase (PC) by Cyclic di-AMP
10.2.1 Identification of PC as a Direct Target of Cyclic di-AMP
10.2.2 Molecular Mechanism of PC Regulation by Cyclic di-AMP
10.2.3 Biological Impacts of PC Regulation by Cyclic di-AMP
10.3 Regulation of Host Metabolic Enzyme RECON by Cyclic di-AMP
10.3.1 Identification of RECON as a Direct Target for Cyclic di-AMP
10.3.2 Molecular Mechanism of RECON Binding by Cyclic di-AMP
10.3.3 Biological Impacts of RECON Binding by Cyclic di-AMP
10.4 Regulation of the ydaO Riboswitch by Cyclic di-AMP
10.4.1 Identification of the ydaO Riboswitch as a Direct Target for Cyclic di-AMP
10.4.2 Molecular Mechanism of ydaO Regulation by Cyclic di-AMP
10.4.3 Biological Impacts of ydaO Riboswitch Regulation by Cyclic di-AMP
10.5 Conclusions
References
Chapter 11: Osmoregulation via Cyclic di-AMP Signaling
11.1 Introduction
11.2 Altered Osmoresistance Phenotypes Are Observed in Cells with Elevated or Reduced Cyclic di-AMP Levels
11.3 Suppressor Screens Using Low- and High-Cyclic di-AMP Level Mutants Reveal Dysregulation of Osmolyte Transporter Activities
11.4 Cyclic di-AMP Binding Receptors Play Key Roles in Osmoregulation
11.5 Regulation of Cyclic di-AMP Levels by Osmotic Signals
11.6 Conclusions
References
Part V: Population Diversity
Chapter 12: Measuring Individual Cell Cyclic di-GMP: Identifying Population Diversity and Cyclic di-GMP Heterogeneity
12.1 Introduction
12.2 New Technologies to Measure Cyclic di-GMP Concentrations Within Living Bacteria
12.3 Cyclic di-GMP Concentrations Within a Single Population of Bacteria Are Heterogeneous and Diverse
12.3.1 Polar Localization of the DGC PleD in Caulobacter crescentus
12.3.2 Polar Localization of the PDE Pch in Pseudomonas aeruginosa
12.3.3 Alternative Potentially Segregated Organelles as Heterogeneity-Generating Structures
12.3.4 Heterogeneous Expression and Stochastic Segregation of CMEs
12.4 The Consequences of a Heterogeneous Population
References
Part VI: Cyclic di-GMP and Exopolysaccharide Regulation
Chapter 13: Activation of Bacterial Cellulose Biosynthesis by Cyclic di-GMP
13.1 Introduction
13.2 Cyclic di-GMP Activation of Bacterial Cellulose Synthase
13.3 Cyclic di-GMP Allosterically Activates Cellulose Synthase
13.4 Cyclic di-GMP Binding Releases BcsA´s Auto-Inhibition
13.5 A Constitutively Active Cellulose Synthase
13.6 A Putative Two-Tiered Regulatory System in Enterobacteria
13.7 AdrA, a Membrane-Bound Diguanylate Cyclase
13.8 Concluding Remarks
References
Chapter 14: The Regulation of Alginate Biosynthesis via Cyclic di-GMP Signaling
14.1 Alginates, Their General Properties, and Biological Functions
14.2 Biosynthesis of Alginates
14.3 Cyclic di-GMP Turnover Targeting Alginate Polymerization
14.4 Posttranslational Regulation of Alginate Biosynthesis by Cyclic di-GMP Signaling
14.5 Activation of Alginate Polymerization upon Cyclic di-GMP Binding
14.6 Conclusion and Future Trends
References
Part VII: Environmental Bacteria
Chapter 15: Cyclic di-GMP Signaling in Bacillus subtilis
15.1 Bacillus subtilis Lifestyles
15.2 Enzymes that Regulate Cyclic di-GMP Levels in B. subtilis
15.3 Cyclic di-GMP Receptors in B. subtilis
15.4 Cyclic di-GMP Regulation of B. subtilis Motility
15.5 Cyclic di-GMP Regulation of B. subtilis Biofilm Formation
15.6 Concluding Remarks
References
Chapter 16: Cyclic di-GMP Signaling Systems in the Gram-Positive Bacillus cereus Group
16.1 Introduction
16.2 Metabolism of Cyclic di-GMP
16.3 Cyclic di-GMP Receptor
16.3.1 Protein Receptors
16.3.2 RNA-Like Receptors
16.4 Biological Functions of Cyclic di-GMP
16.4.1 Regulation of Bacterial Motility
16.4.2 Regulation of Biofilm Formation
16.4.3 Other Phenotypic Regulation
16.5 Summary and Outlook
References
Chapter 17: Cyclic di-AMP in Bacillus subtilis Biofilm Formation
17.1 Biofilms Thrive in Diverse Environments
17.2 Bacillus subtilis Biofilm Formation
17.2.1 Bacillus subtilis Cell-Type Differentiation in Biofilms
17.2.2 Environmental Interactions That Impact B. subtilis Biofilm Formation
17.3 Cyclic di-AMP in B. subtilis
17.3.1 Cyclic di-AMP Synthesis, Degradation, and Regulation
17.3.2 Cyclic di-AMP Regulation of Biofilm Matrix Gene Expression in B. subtilis
17.3.3 Cyclic di-AMP Receptors, Potassium Ion Transport, and Their Link to B. subtilis Biofilm Formation
17.3.4 Other Molecular Mechanisms of Cyclic di-AMP in B. subtilis Biofilm Formation and Sporulation
17.3.5 Cyclic di-AMP Levels Impact Plant Attachment
17.4 B. subtilis Secretes Cyclic di-AMP
17.4.1 B. subtilis Transporters Are Necessary for Cyclic di-AMP Secretion and Plant Attachment
17.4.2 Implications of Cyclic di-AMP Secretion in Multispecies Biofilm Communities
17.5 Conclusions
References
Chapter 18: Regulation by Cyclic di-GMP in Myxococcus xanthus
18.1 Introduction
18.2 Introduction to Myxococcus xanthus
18.3 Bioinformatics-Based Analysis of Cyclic di-GMP Metabolism in M. xanthus
18.4 Cyclic di-GMP Accumulates in M. xanthus and Is Important for Motility and Development
18.5 GGDEF Domain Proteins Important for T4P-Dependent motility
18.6 GGDEF Domain Proteins Important for Development
18.7 PmxA, an HD-GYP Type PDE Is Important for Development
18.8 Cyclic di-GMP Effectors in M. xanthus
18.9 Conclusions and Outlook
References
Chapter 19: Light-Regulated Nucleotide Second Messenger Signaling in Cyanobacteria
19.1 Cyclic di-GMP Dependent Cell Aggregation in Thermosynechococcus
19.2 Cyclic di-GMP Signaling in Phototactic Motility in Synechocystis
19.3 Cyclic di-GMP Signaling in Other Cyanobacteria
19.4 Other Nucleotide Second Messengers in Cyanobacteria
19.5 Cyanobacterial Photoreceptors as Light-Controlled Tools to Manipulate Second Messenger Signaling
19.6 Concluding Remarks
References
Chapter 20: Cyclic di-GMP-Dependent Regulation of Antibiotic Biosynthesis in Lysobacter
References
Chapter 21: Cyclic di-GMP Signaling in Extreme Acidophilic Bacteria
21.1 Acidophilic Microorganisms
21.2 General Overview of Nucleotide Second Messenger Metabolism in Acidophilic Microorganisms
21.3 Cyclic di-GMP in Acidophilic Bacteria
21.4 Cyclic di-GMP Pathway in Acidithiobacillus
21.5 Concluding Remarks
References
Part VIII: Pathogens
Chapter 22: Signals Modulating Cyclic di-GMP Pathways in Vibrio cholerae
22.1 Introduction
22.2 Cyclic di-GMP Enhances Biofilm Formation
22.3 Cyclic di-GMP Inhibits Motility
22.4 Cyclic di-GMP Inhibits Virulence Factor Production
22.5 Cyclic di-GMP Regulates Other Cellular Processes
22.5.1 Type VI Secretion System
22.5.2 Type II Secretion System
22.5.3 DNA Repair
22.5.4 Acetoin Synthesis
22.6 Signals that Regulate Cyclic di-GMP-Associated Phenotypes
22.6.1 Polyamines
22.6.2 Hemerythrin
22.6.3 Temperature
22.6.4 Bile Acids
22.6.5 Inorganic Phosphate
22.7 Quorum Sensing Regulation of Cyclic di-GMP Levels
22.8 Conclusion and Future Directions
References
Chapter 23: Cyclic di-GMP Regulation of Gene Expression
23.1 Cyclic di-GMP Signaling
23.2 Cyclic di-GMP-Dependent Transcription Factors
23.3 Post-transcription Regulation by Cyclic di-GMP via Riboswitches
23.4 Conclusion
References
Chapter 24: Cyclic di-GMP Signaling in Salmonella enterica serovar Typhimurium
24.1 Introduction
24.2 The Salmonella typhimurium Cyclic di-GMP Signaling System: Cyclic di-GMP Turnover Proteins
24.3 The Salmonella typhimurium Cyclic di-GMP Signaling System: N-terminal Sensory Domains
24.4 The Salmonella typhimurium Cyclic di-GMP Signaling System: Input Signals
24.5 The Salmonella typhimurium Cyclic di-GMP Signaling System: Cyclic di-GMP Receptors
24.6 Physiological Roles of the Cyclic di-GMP Signaling Network in Salmonella typhimurium
24.6.1 Role of the Cyclic di-GMP Signaling Network in Salmonella typhimurium Biofilm Formation
24.6.2 Regulation of Motility by Cyclic di-GMP Signaling
24.6.3 Regulation of Virulence by the Cyclic di-GMP Signaling Network in Salmonella typhimurium
24.6.4 Role of Cyclic di-GMP in Environmental Survival and Transmission
24.7 Comparison of the Cyclic di-GMP Signaling Network Between Salmonella typhimurium ATCC14028 and E. coli K-12
24.8 Phylogeny of Cyclic di-GMP Signaling
24.9 Conclusions
References
Chapter 25: Cyclic di-GMP Signaling in the Phytopathogen Xanthomonas campestris pv. campestris
25.1 Xcc Is Important in Both Agriculture and Molecular Plant Pathology
25.2 Xcc Contains Multiple Genes for Cyclic di-GMP Metabolism
25.3 Cyclic di-GMP Signaling Is Associated with Xcc Adaptation and Virulence
25.3.1 RpfC/RpfG-Dependent Cyclic di-GMP Signaling System Senses Cell Population and Controls Diverse Biological Functions
25.3.2 RavS/RavR/RavA-Dependent Cyclic di-GMP Signaling Is Involved in Hypoxia Sensing
25.3.3 Other Cyclic di-GMP Signaling Systems Involved in Xcc Adaptation and Virulence
25.4 Effectors Mediating Cyclic di-GMP Signaling in Xcc
25.4.1 Clp Is a Crucial Transcriptional Effector of Cyclic di-GMP
25.4.2 YajQ Is a New Class of Cyclic di-GMP Effector that Regulates Xcc Virulence
25.4.3 PilZ Domain-Containing Proteins Affect Xcc Pathogenicity
25.5 Conclusion and Perspective
References
Chapter 26: Cyclic di-AMP in Mycobacterium tuberculosis
26.1 Introduction
26.2 Synthesis of Cyclic di-AMP in Mtb
26.3 Degradation of Cyclic di-AMP in Mtb
26.4 Cyclic di-AMP Functions in Mtb Physiology
26.5 The Role of Cyclic di-AMP in Mtb Pathogenesis
26.6 The Role of Cyclic di-AMP in Mtb-Host Interaction
26.7 Cyclic di-AMP in TB-Complex Mycobacteria and Vaccine Consideration
26.8 Future Perspective
References
Chapter 27: Cyclic di-AMP Signaling in Streptococcus pneumoniae
27.1 Introduction
27.2 Pneumococcal Cyclic di-AMP Homeostasis
27.3 Effects of Cyclic di-AMP on Pneumococcal Virulence
27.4 A Trk-Family Cyclic di-AMP Effector Protein in S. pneumoniae
27.5 Cyclic di-AMP Controls the Pneumococcal Stress Response
27.6 Looking Forward
References
Part IX: Gram-Negative Bacteria
Chapter 28: Regulation of Cyclic di-GMP Signaling in Pseudomonas aeruginosa
28.1 Overview and Relevance of Pseudomonas aeruginosa
28.2 Principals of Cyclic di-GMP Regulation and Signaling Inputs
28.3 P. aeruginosa Cyclic di-GMP Synthesis, Degradation, and Regulation
28.3.1 Cell Motility
28.3.2 Biofilm Matrix Production
28.3.3 Biofilm Dispersal
28.4 Conclusions and Moving Forward
References
Chapter 29: Unconventional Cyclic di-GMP Signaling in Escherichia coli
29.1 Escherichia coli: A Very Versatile Species
29.1.1 Commensal and Pathogenic Escherichia coli
29.1.2 Extraintestinal Pathogenic Escherichia coli
29.2 Prerequisites for Unconventional Cyclic di-GMP Signaling
29.2.1 Conventional Cyclic di-GMP Signaling
29.2.2 Loss of RpoS Activity
29.2.3 Presence of Stand-Alone Cyclic di-GMP Enzymes
29.3 The Role of the Unconventional Cyclic di-GMP Signaling in ExPEC
29.3.1 The Role of Conventional Cyclic di-GMP Signaling in E. coli
29.3.2 Differential Fimbrial Expression
29.3.3 Citrate Utilization
29.3.4 Ferric Citrate Uptake
29.4 Future Perspectives
References
Chapter 30: Cyclic di-GMP in Burkholderia spp.
30.1 The Genus Burkholderia
30.2 Conservation of Genes Encoding Cyclic di-GMP Signaling Components in Burkholderia spp.
30.3 Burkholderia pseudomallei Complex (Bpc)
30.4 B. mallei
30.5 B. cenocepacia Complex (Bcc)
30.6 Additional Burkholderia spp.
30.7 Outstanding Questions in Burkholderia and Cyclic di-GMP Signaling
References
Chapter 31: Cyclic di-GMP and the Regulation of Biofilm Dispersion
31.1 Dispersion as a Flight Response
31.2 Dispersion Induces a Switch in the Mode of Growth
31.3 Translation of Dispersion Cue Perception into the Modulation of the Intracellular Cyclic di-GMP Pool
31.3.1 Fatty Acids as Dispersion Signals
31.3.2 Nutrient-Induced Dispersion
31.3.3 NO-Induced Dispersion
31.4 The Dispersion Phenotype
31.5 Cyclic di-GMP Levels and Downstream Pathways
31.6 Concluding Remarks
References
Part X: Cyclic di-GMP Signaling in Eukaryotes
Chapter 32: Cyclic di-GMP Activates Adenylate Cyclase A and Protein Kinase A to Induce Stalk Formation in Dictyostelium
32.1 Introduction
32.2 Secreted Cyclic di-GMP Triggers Formation of the Fruiting Body Stalk
32.3 Interactions Between Cyclic di-GMP and DIF-1
32.4 Identification of Cyclic di-GMP Target Genes and Elucidation of Its Mode of Action
32.5 Cyclic di-GMP Acting on ACA Links Morphogenetic Movement with Stalk Formation
32.6 Open Questions
32.6.1 Unknown Signal Transduction Components
32.6.2 Cell-Type Specificity
32.6.3 Evolutionary Conservation
References
Part XI: Interference Strategies
Chapter 33: Targeting Cyclic Dinucleotide Signaling with Small Molecules
33.1 Introduction
33.2 Cellular Metabolism of Cyclic di-GMP, Cyclic di-AMP, and Cyclic GAMP
33.3 Modulators of Cyclic Dinucleotide Signaling
33.4 Perspective on Targeting Cyclic Dinucleotide-Related Enzymes
33.5 Conclusions
References
Part XII: Novel Cyclic Di-Nucleotides
Chapter 34: Cyclic di-GMP Signaling Gone Astray: Cyclic GAMP Signaling via Hypr GGDEF and HD-GYP Enzymes
34.1 Introduction
34.2 Hypr GGDEF Enzymes Function as GMP-AMP Cyclases (GACs)
34.2.1 Discovery of Hypr GGDEFs
34.2.2 Structure of Hypr Versus Canonical GGDEFs
34.2.3 Signaling Specificity of Hypr GGDEFs
34.2.4 Mechanism of Hypr GGDEFs
34.3 HD-GYP Enzymes Function as GMP-AMP Phosphodiesterases (GAPs)
34.3.1 Discovery of V-cGAPs
34.3.2 Discovery of Cyclic GAMP-Specific GAPs
34.4 Conclusions
References
Chapter 35: Microbial Cyclic GMP-AMP Signaling Pathways
35.1 Discovery of Bacterial Cyclic GMP-AMP (cGAMP)
35.2 Mechanism of Cyclic GAMP Synthesis and Degradation in V. cholerae
35.3 The Functions of Cyclic GAMP in V. cholerae Biology
35.4 Bacterial Cyclic GAMP Signaling Outside of Vibrio
35.5 Cyclic GAMP Signaling in Metazoans
35.6 Outlook and Future Directions
References
Part XIII: Honorary Cyclic Nucleotides
Chapter 36: 2′,3′-Cyclic Mononucleotide Metabolism and Possible Roles in Bacterial Physiology
36.1 2′,3′-cNMPs in Mammalian Systems
36.2 2′,3′-cNMPs and Plant Stress Responses
36.3 Identification of 2′,3′-cNMPs and Possible Binding Protein in Bacteria
36.4 Synthesis of 2′,3′-cNMPs in E. coli
36.5 Possible Links with Nucleotide Metabolism
36.6 RNase I, 2′,3′-cNMPs, and Biofilm Formation
References
Part XIV: Horizontal Gene Transfer
Chapter 37: Horizontal Transfer of Cyclic di-GMP Associated Genes. Theoretical Underpinnings and Future Perspectives
37.1 Plasmid-Mediated Horizontal Transfer of Cyclic di-GMP Associated Genes
37.1.1 Dodging Cyclic di-GMP Regulation
37.1.2 Cyclic di-GMP Associated Gene Are Common on Natural Plasmids
37.2 Most Types of MGEs Have Been Associated with Cyclic di-GMP Genes
37.2.1 Integrative and Conjugative Elements
37.2.2 Bacteriophages
37.2.3 Transposons
37.2.4 Genomic Islands
37.3 The Cyclic di-GMP Signaling System; An ``Obvious Target´´ for HGT?
37.4 The Dawn of a New Day: Conclusive Remarks and Perspective
References
Part XV: Conclusion
Chapter 38: Conclusions