Note: Intro -- Foreword -- T4SS-Then and Now -- Contents -- Abbreviations -- 1 Biological Diversity and Evolution of Type IV Secretion Systems -- Abstract -- 1 Introduction: The ABC's of T4SS Classification -- 2 Function, Structure, and Diversification of T4ASS and T4BSSs -- 2.1 The VirD4 Receptor and Its Role in Substrate Selection -- 2.2 The Role of Accessory Factors in Substrate Recruitment -- 2.3 The Inner Membrane Complex (IMC) -- 2.4 Evolutionary Adaptations of IMC Subunits -- 2.5 The Outer Membrane Core Complex (OMCC) -- 2.6 Evolutionary Adaptations of OMCC Subunits -- 3 T4SS-Mediated Modulation of Target Cell Attachment -- 3.1 T4ASS P- and F-pili -- 3.2 Evolutionary Adaptations of T4ASS-Associated Surface Structures -- 3.3 T4BSS DNA Transfer and Dot/Icm Systems -- 4 Evolution of Dot/Icm Secretion System -- 5 Comparisons of Effectors Secreted Through Different Dot/Icm Secretion Systems -- 6 Concluding Remarks -- Acknowledgements -- References -- 2 Structural and Molecular Biology of Type IV Secretion Systems -- Abstract -- 1 Architectures and Functions of Type IV Secretion Systems -- 1.1 Classification and Overview -- 1.2 Composition of T4SSs -- 2 Structures of Individual Components -- 2.1 ATPases -- 2.1.1 VirB11 -- 2.1.2 VirD4 -- 2.1.3 VirB4 -- 2.2 Inner Membrane -- 2.2.1 VirB3 -- 2.2.2 VirB6 -- 2.2.3 VirB8 -- 2.3 Outer Membrane and Periplasm -- 2.3.1 VirB1 -- 2.3.2 VirB7 and VirB9 -- 2.3.3 VirB10 -- 2.4 Pilus Protein(s) -- 2.4.1 VirB2 -- 2.4.2 VirB5 -- 3 Structures of T4SS Molecular Assemblies -- 3.1 The Core (or Outer Membrane) Complex -- 3.2 The T4SS3-10 Complex -- 3.3 Structure of the Pilus -- 4 Mechanism of Substrate Transport -- 5 Concluding Remarks -- Acknowledgements -- References -- 3 Prokaryotic Information Games: How and When to Take up and Secrete DNA -- Abstract -- 1 DNA Secretion by Bacterial Conjugation. , 1.1 Transfer Competence Development and Heterogeneity of Isogenic Populations -- 1.2 Bistability and Excitability in Genetic Networks -- 1.3 Non-stochastic Switching to Transfer Competence -- 1.3.1 Cell-to-Cell Signaling and Quorum Sensing -- 1.3.2 Environmental Signals -- 1.4 Stochastic Switching: No Signals and Rules, just Random Amplification of Noise? -- 1.4.1 Bet Hedging in Bacterial Conjugation -- 2 Bacterial DNA Uptake Competence and Transport Mechanisms -- 2.1 Principles of DNA Uptake -- 2.1.1 DNA Uptake via a T4SS-How to Take up DNA? -- 2.1.2 Components of the ComB T4SS of Helicobacter pylori -- 2.1.3 Visualization of DNA Uptake in Single Cells of Helicobacter pylori -- 2.2 Competence Development-When to Take up DNA? -- 2.2.1 Decision Making for Competence Development Is Species-Specific -- 2.2.2 How Is Competence Limited in a T4SS-Mediated DNA Uptake System? -- 3 Concluding Remarks -- References -- 4 Relaxases and Plasmid Transfer in Gram-Negative Bacteria -- Abstract -- 1 Biochemistry of Relaxases -- 2 Relaxase-DNA Binding -- 3 Relaxosome -- 4 Intracellular Trafficking and Relaxase Recruitment to the Conjugative Pore -- 5 Bifunctional Relaxase-DNA Helicase Enzymes -- 6 Domain-Specific DNA Interactions -- 7 Cryo-EM Structure of TraI Relaxase -- 8 Model of Relaxosome Function -- 9 Concluding Remarks -- Acknowledgements -- References -- 5 Mechanisms of Conjugative Transfer and Type IV Secretion-Mediated Effector Transport in Gram-Positive Bacteria -- Abstract -- 1 Introduction -- 2 Conjugative Plasmids and ICEs in Gram+ Bacteria -- 2.1 Conjugative Plasmids in Enterococci, Streptococci, and Staphylococci -- 2.2 Conjugative Plasmids in Clostridia -- 2.3 Conjugative Plasmids and ICEs in Bacillus -- 2.4 Conjugative Plasmids in Actinomycetes -- 2.4.1 Relaxase Encoding Plasmids -- 2.4.2 TraB Encoding Streptomyces Plasmids. , 3 Pathogenicity/Genomic Islands in Firmicutes -- 4 Key Factors of Gram+ Conjugation Systems -- 4.1 Key Factors of Gram+ Bacterial T4SSs -- 4.2 The Streptomyces Translocase TraB -- 5 Structure-Function Relationships of Gram+ T4SSs -- 6 Regulation of T4SS-Dependent Conjugative Transfer in Gram+ Bacteria -- 7 T4SS-Independent Transfer Systems in Gram+ Bacteria -- 8 Concluding Remarks -- Acknowledgements -- References -- 6 Coupling Proteins in Type IV Secretion -- Abstract -- 1 Coupling Proteins in Type IV Secretion -- 2 The Cytoplasmic Soluble Domain -- 3 The Transmembrane Domain -- 4 Molecular Interactions -- 5 Proposed Roles -- 5.1 Substrate Recruitment -- 5.2 Energization of Substrate Translocation -- 5.3 DNA Transport -- 5.4 Signal Transmission -- 6 T4CP Origin and Evolution -- 7 Biotechnological Applications -- 8 Concluding Remarks -- Acknowledgements -- References -- 7 Type IV Secretion in Agrobacterium tumefaciens and Development of Specific Inhibitors -- Abstract -- 1 Overview of the Biology of Type IV Secretion Systems -- 2 Components of the Agrobacterium tumefaciens T4SS -- 2.1 VirB1-Like Proteins -- 2.2 T-Pilus Components VirB2 and VirB5 -- 2.3 VirB3 -- 2.4 VirB4 Cytoplasmic ATPase -- 2.5 Polytopic Inner Membrane Protein VirB6 -- 2.6 Lipoprotein VirB7 -- 2.7 Assembly Factor VirB8 -- 2.8 VirB9 -- 2.9 VirB10 Envelope-Spanning Protein -- 2.10 VirB11 ATPase and Inhibitor Target -- 2.11 Coupling Protein VirD4 -- 3 Structural Insights into the Agrobacterium T4SS and Plant Cell Contact -- 4 Structures of VirB8-like Proteins -- 5 Inhibition of VirB8-like Proteins by Small Molecules -- 6 Concluding Remarks -- Acknowledgements -- References -- 8 The Helicobacter pylori Type IV Secretion System Encoded by the cag Pathogenicity Island: Architecture, Function, and Signaling -- Abstract -- 1 Introduction. , 2 Features, Components, and Assembly of the cagT4SS -- 3 T4SS Structure and Pilus Formation -- 4 T4SS-Dependent Signal Transduction in Epithelial Cells -- 4.1 Translocation of CagA into Epithelial Cells -- 4.1.1 Role of Structural Cag Proteins and Integrins in Type IV Secretion of CagA -- 4.1.2 Delivery of CagA into Host Cells Using Integrin β1 Receptor -- 4.2 T4SS Crosstalk of H. pylori with Other Host Cell Receptors -- 4.2.1 Interaction of HopQ with CEACAMs -- 4.2.2 Role of gp130 Engagement -- 4.2.3 Activation of EGFR and Her2/Neu Receptors -- 4.2.4 E-cadherin and c-Met Signaling -- 4.3 CagA-Dependent Signal Transduction in Epithelial Cells -- 4.3.1 Activation and Deactivation of CagA -- 4.3.2 Phospho-Dependent CagA Signaling -- 4.3.3 Phospho-Independent CagA Signaling -- 4.4 CagA-Independent T4SS Signal Transduction in Epithelial Host Cells -- 4.4.1 H. pylori Directs Activation and Termination of the Immediate Early Response Factor NF-κB -- 4.4.2 H. pylori-Induced JNK Phosphorylation Regulates AP-1 Activity -- 4.4.3 p38 Signaling in H. pylori Infection -- 5 Concluding Remarks -- Acknowledgements -- References -- 9 Subversion of Host Membrane Dynamics by the Legionella Dot/Icm Type IV Secretion System -- Abstract -- 1 Introduction -- 2 Formation of the Legionella-Containing Vacuole -- 3 The L. pneumophila T4SS, Effectors, and Metaeffectors -- 3.1 Dot/Icm-Translocated Effectors -- 3.2 Metaeffectors and the Effector Interactome -- 4 Manipulation of the Endocytic Pathway by L. pneumophila -- 5 Inhibition of the Retrograde Pathway by L. pneumophila -- 6 Subversion of Autophagy by L. pneumophila -- 7 Concluding Remarks -- Acknowledgements -- References -- 10 Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis -- Abstract -- 1 Introduction -- 2 Toward System Biology of Coxiella Infections. , 3 Getting Comfortable Behind Enemy Lines, Biogenesis of the Coxiella-Containing Vacuole -- 3.1 Autophagy and the CCV -- 3.2 Clathrin-Mediated Traffic -- 3.3 Lipids and CCVs -- 4 Control of Host Defensive Measures, Coxiella-Mediated Inhibition of Host Cell Death -- 4.1 Apoptosis -- 4.2 Pyroptosis -- 5 From Coverslips to Animals: Development of In Vivo Models -- 6 Concluding Remarks -- References -- 11 Type IV Effector Secretion and Subversion of Host Functions by Bartonella and Brucella Species -- Abstract -- 1 Introduction -- 2 T4SS in Bartonella -- 2.1 Recurrent Acquisitions of T4SS Loci by the Bartonella Lineage -- 2.2 Parallel Evolution of Bartonella Effector Protein (Bep) Repertories -- 2.3 Genomic Organization and Regulation of the virB/virD4/bep loci -- 2.4 Multi-domain Architectures of the Beps -- 2.4.1 The BID Domain Mediates T4SS-Dependent Secretion and May Additionally Adapt Effector Functions Within Host Cells -- 2.4.2 The Enzymatic FIC Domain Mediates Post-translation Modification of Target Proteins -- 2.4.3 Tandem-Repeated Tyrosine Phosphorylation Motifs Assemble Signaling Complexes in Host Cells -- 2.5 Role of VirB/VirD4 T4SS and Bep Effectors in Animal Infection Models -- 2.6 Role of VirB/VirD4 T4SS and Bep Effectors in Cellular Infection Models -- 3 T4SS in Brucella -- 3.1 Canonical and Non-canonical Features of the Brucella VirB T4SS -- 3.2 Effector Repertoires in Sequenced Brucella Species -- 3.3 Known Cellular Functions of T4SS and Effectors -- 3.3.1 Interactions with Infected Host Cells -- 3.3.2 Modulation of Innate Immunity -- 3.4 Mechanism of Substrate Translocation via the T4SS -- 3.5 Role of the T4SS and Effectors in Transmission of Brucella spp. -- 4 Concluding Remarks -- References -- 12 Role and Function of the Type IV Secretion System in Anaplasma and Ehrlichia Species -- Abstract -- 1 Introduction. , 2 Subversion and Manipulation of Host Cells.