Note: Intro -- Preface -- Contents -- Abbreviations -- The Story of Helicobacter pylori: Depicting Human Migrations from the Phylogeography -- 1 Introduction -- 2 Characterization the Population Genetics of H. pylori -- 3 The Phylogeographic of H. pylori from Out of Africa to the Pacific -- 3.1 Observation of Asia2 and EastAsian Split from CagA Perspective -- 3.2 Peopling of Australians and New Guineans: hpSahul -- 4 The Migration Inside Africa and the Intimation with the Host -- 4.1 The Origin of H. pylori and Split of hpAfrica2 -- 4.2 The hpNEAfrica and the Acquisition of cagPAI -- 4.3 The hpAfrica1: The Marker of Bantu Speakers -- 5 The Recombination During Post Colonial Expansion -- 6 Conclusions -- References -- Epidemiology, Diagnosis and Risk Factors of Helicobacter pylori Infection -- 1 Introduction -- 2 Epidemiology of H. pylori Infection -- 3 Diagnosis of H. pylori Infection -- 3.1 Histology -- 3.2 Rapid Urease Test -- 3.3 Culture -- 3.4 Polymerase Chain Reaction (PCR) -- 3.5 Serology -- 3.6 Urea Breath Test -- 3.7 Stool Antigen Test -- 4 Risk Factors of H. pylori Infection -- 4.1 Socioeconomic Status and Environmental Conditions -- 4.1.1 Familial Context and Source of Transmission -- Breast-Feeding -- Microbiota -- 4.1.2 Environmental Context -- Rural vs. Urban Living Conditions -- Water and Access to Sanitary and Hygiene -- 4.2 Lifestyle Habits -- 4.2.1 Food -- 4.2.2 Alcohol Drinking and Smoking Habits -- 4.3 Occupational Hazards -- 5 Conclusions -- References -- Activity and Functional Importance of Helicobacter pylori Virulence Factors -- 1 Introduction -- 2 Assembly and Function of the cag PAI-Encoded T4SS -- 3 CagA, a Multifunctional Master Key -- 4 H. pylori Secretes the Serine Protease HtrA to Shape the Epithelial Barrier -- 5 H. pylori VacA, GGT and CGT Are Involved in Immune Suppression and Evasion. , 6 Vacuolating Cytotoxin A (VacA) -- 7 Gamma-Glutamyl Transpeptidase (GGT) -- 8 Cholesterol-α-Glucosyltransferase (CGT) -- 9 Concluding Remarks -- References -- Roles of Adhesion to Epithelial Cells in Gastric Colonization by Helicobacter pylori -- 1 Introduction -- 2 OMP Domain Organization -- 3 Adhesins -- 3.1 Adhesins with Known Small Ligands -- 3.1.1 BabA/BabB/BabC -- 3.1.2 SabA/SabB -- 3.1.3 HopD -- 3.2 Adhesins with Known Proteins -- 3.2.1 HopQ -- 3.2.2 AlpA/AlpB -- 3.2.3 CagL -- 3.3 Adhesins with Unknown Ligands or Proteins -- 3.3.1 HorB -- 3.3.2 HomA/HomB/HomC/HomD -- 3.3.3 OipA -- 3.3.4 HopZ -- 4 Conclusions -- References -- Immune Cell Signaling by Helicobacter pylori: Impact on Gastric Pathology -- 1 Introduction -- 2 The Role of H. pylori GGT on Immune Tolerance -- 3 Interference of VacA with T-Cell Receptor/IL-2 and Nuclear Factor of Activated T-Cells (NFAT) Signaling -- 4 Activities of VacA on Dendritic Cells and Macrophages -- 5 GGT Manipulates T Cell Proliferation and Cell Cycle Progression -- 6 Function of the Neutrophil Activating Protein NapA -- 7 Role of Cholesterol in H. pylori Interactions with Immune Cells -- 8 H. pylori Manipulates Antigen Presentation and Bacterial Recognition -- 9 TLR Signaling in Immune Cells Induced by H. pylori -- 10 Pro- and Anti-inflammatory Signaling by H. pylori -- 11 Inflammasome Activation Through TLR2 and NOD2 Signal Transduction -- 12 Resolution of Inflammation by H. pylori -- 13 Conclusions -- References -- Helicobacter pylori Infection in Children and Adolescents -- 1 Introduction -- 2 Epidemiology and Transmission in Children and Adolescents -- 2.1 Prevalence of H. pylori Infection in Children and Adolescents -- 2.2 Acquisition and Transmission -- 3 Clinical Manifestations -- 3.1 Gastrointestinal Manifestations -- 3.1.1 Gastritis and Peptic Ulcer -- 3.1.2 Atrophic Gastritis. , 3.1.3 Dyspepsia and Other Abdominal Complaints -- 3.1.4 Gastric Cancer -- 3.2 Extra-Gastrointestinal Manifestations -- 3.2.1 Iron Deficiency Anemia (IDA) -- 3.2.2 Chronic Immune Thrombocytopenic Purpura (cITP) -- 3.2.3 Allergic Disorders -- 4 Diagnosis -- 5 Treatment -- 5.1 Treatment Regimes -- 5.2 Drug Resistance -- 5.3 Reinfection After Successful Eradication -- 6 Screen-and-Treat for Preventing Future Gastric Cancer -- 7 Conclusions -- References -- Non-malignant Helicobacter pylori-Associated Diseases -- 1 Helicobacter pylori Gastritis -- 1.1 The Sydney Classification System -- 1.2 Intestinal Metaplasia and Atrophy -- 1.3 The Individuality of H. pylori Gastritis -- 1.4 H. pylori vs. Other Helicobacter Species -- 1.5 Special Forms of Gastritis -- 1.5.1 Atrophic Gastritis -- 1.5.2 Autoimmune Gastritis -- 1.5.3 Ex-Helicobacter-Gastritis -- 1.5.4 Lymphocytic Gastritis -- 2 H. pylori-Induced Diseases Other Than Gastritis -- 2.1 Gastro-Esophageal Reflux Disease -- 2.2 Gastric and Duodenal Ulcer -- 2.3 Extra-Gastric Helicobacter Infections -- 3 Concluding Remarks -- References -- Malignant Helicobacter pylori-Associated Diseases: Gastric Cancer and MALT Lymphoma -- 1 Introduction -- 2 H. pylori Infection and Gastric Cancer -- 3 H. pylori Infection and MALT Lymphoma -- 4 Involvement of H. pylori cagA-Positive Strains in Human Malignancies -- 5 Molecular Structure of the H. pylori CagA Protein -- 6 Pathobiological Actions of CagA Delivered into Host Cells -- 7 Oncogenic Role of H. pylori CagA In Vivo -- 8 Geographic Polymorphisms of H. pylori CagA -- 9 Conclusions -- References -- The Role of Host Genetic Polymorphisms in Helicobacter pylori Mediated Disease Outcome -- 1 Introduction -- 2 Host Genetic Polymorphisms -- 2.1 Interleukin-1 Beta (IL-1β) -- 2.2 Tumour Necrosis Factor Alpha (TNF-α) -- 2.3 Other Cytokines -- 2.4 Toll-Like Receptors (TLRs). , 2.5 TLR Signalling Pathway -- 2.6 Nucleotide-Binding Oligomerisation Domain (NOD) Like Receptors (NLRs) -- 2.7 Autophagy -- 2.8 Prostate Stem Cell Antigen (PSCA) -- 2.9 DNA Repair -- 2.10 DNA Methylation -- 3 Gene Amplification and Gene Deletions -- 4 Conclusions -- References -- Helicobacter pylori Genetic Polymorphisms in Gastric Disease Development -- 1 Introduction -- 2 Virulence Factors -- 2.1 Adhesins and OMPs -- 2.1.1 Bab Proteins -- 2.1.2 Hom Proteins -- 2.1.3 HopQ -- 2.1.4 Additional OMPs -- 2.2 iceA -- 2.3 Secreted and Injected Proteins -- 2.3.1 vacA -- 2.3.2 cagA -- 3 Combinations of Genotypes -- 4 Conclusions -- References -- Helicobacter pylori Infection, the Gastric Microbiome and Gastric Cancer -- 1 Introduction -- 2 Gastric Cancer -- 3 H. pylori Infection and Gastric Cancer -- 4 The Gastric Microbiota, Is There More Than H. pylori? -- 5 The Gastric Microbiota in Gastric Carcinogenesis -- 6 Revisiting Correa´s Hypothesis of Gastric Carcinogenesis -- 7 Conclusions -- References -- Current and Future Treatment of Helicobacter pylori Infections -- 1 Introduction -- 1.1 H. pylori as a Bacterial Infection -- 2 History of H. pylori Therapies -- 2.1 Antibiotic Resistance -- 2.1.1 Other Triple Therapies -- 2.1.2 Sequential-Concomitant, Hybrid Therapies -- 2.1.3 Bismuth Therapies -- 2.2 Alternate Bismuth Quadruple Therapies -- 2.3 Dual Therapy -- 2.3.1 Vonoprazan -- 2.3.2 Probiotics -- 3 Recent Guidelines and Consensus Reports -- 4 Modern Approach to Therapy -- 5 Recommended Therapies -- 5.1 Approach after Treatment Failure -- 5.1.1 Vaccination -- 6 Conclusions -- References -- Structural Aspects of Helicobacter pylori Antibiotic Resistance -- 1 Introduction -- 2 Inhibitors of the Protein Synthesis Through Interaction with the Ribosome Machinery -- 2.1 Resistance to Macrolide Clarithromycin (CLR) -- 2.2 Resistance to Tetracyclines. , 2.3 Resistance to Aminoglycoside -- 3 Inhibitors that Interfere with DNA or RNA Machinery -- 3.1 Resistance to Fluoroquinolones -- 3.2 Resistance to Rifamycinoid Antibiotics -- 4 Mixed Resistances -- 4.1 Resistance to β-Lactams -- 5 Resistance Due to Indirect Effects -- 5.1 Resistance to Nitroimidazoles -- 6 Resistance Due to Efflux Pumps -- 6.1 Outer Membrane Proteins and Efflux Pumps -- 6.2 RND Efflux Systems -- 6.3 Tetracycline Efflux Protein -- 7 Conclusions -- References -- Role of Probiotics in Eradication Therapy for Helicobacter pylori Infection -- 1 Definition, Classification and Properties of Probiotics -- 2 In Vitro Effect of Probiotics on Helicobacter pylori -- 3 In Vivo Effect of Probiotics on H. pylori -- 4 Effect of Probiotics in Eradication Therapy for H. pylori Infection -- 4.1 The Effect of Single Treatment with Probiotics on H. pylori infection -- 4.2 Combination Effect of Probiotics with Other Drugs -- 4.3 Combined Effect of Probiotics with Eradication Therapy -- 5 Conclusions -- References -- Immunity and Vaccine Development Against Helicobacter pylori -- 1 Introduction -- 2 The Natural Immune Response to H. pylori - A Tight Balance of Chronic Inflammation and Suppression That Ultimately Fails to ... -- 2.1 First Contact- the Intensity of the Initial Inflammatory Response Is Limited by Host Factors -- 2.2 H. pylori Drives Dendritic Cells (DC) to a Tolerogenic Phenotype -- 2.3 Reduced Inflammatory Responses in H. pylori Positive Children -- 2.4 Chronic- Active Gastritis Is Driven by the Actions of TH1/17 and Treg -- 2.5 Treg Sub-populations and the Control of Gastritis -- 2.6 Unconventional Lymphocytes in H. pylori Infections -- 2.7 Acute Infection, Spontaneous Clearance and Re-Infection in Adults -- 3 Progress Towards a Vaccine Against H. pylori -- 3.1 The Need for a Vaccine and Its Potential. , 3.2 Current Status of Clinical Trials of Candidate H. pylori Vaccines.

Note: Intro -- Foreword: New Directions for Investigating Detrimental and Enabling Interactions Between Helicobacter pylori and Its Host -- Contents -- Abbreviations -- Inflammation, Immunity, and Vaccine Development for the Gastric Pathogen Helicobacter pylori -- 1 Introduction -- 2 Host Immune Response to H. pylori Infection -- 3 Obstacles in Developing H. pylori Vaccine -- 4 Establishing the Principles for H. pylori Vaccination -- 5 Varied Vaccination Strategies Employed in Clinical Trials -- 6 Unique Aspects of a Successful Clinical Trial -- 7 Concluding Remarks -- References -- Impact of Helicobacter pylori Virulence Factors on the Host Immune Response and Gastric Pathology -- 1 Introduction -- 2 Vacuolating Cytotoxin -- 2.1 Heterogeneity and the Epidemiology of Gastric Disease -- 2.2 Animal Models and Cell Biology -- 3 Cag Pathogenicity Island -- 3.1 Epidemiology -- 3.2 Genetic Organization -- 3.3 T4SS -- 3.4 T4SS Effectors -- 3.5 Hijacking Host Signaling -- 4 Outer Membrane Proteins (OMPs) -- 4.1 Paralogous OMP Gene Families -- 4.2 H. pylori OMPs and Clinical Disease -- 4.3 OMPs and Pathogenesis -- 5 Modulation of the Host Response: Bacterial Virulence from the Bacterial Perspective -- 6 Concluding Remarks -- References -- Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences -- 1 Introduction -- 2 Gastric Cancer Development is Related to H. pylori Infection -- 3 H. pylori Virulence Factors and Gastric Cancer Risk -- 4 Host Genetic Susceptibility to Gastric Cancer -- 4.1 Immuno-Regulatory Cytokines -- 4.2 Pattern Recognition Receptors (PRRs) -- 4.3 DNA Repair Enzymes -- 4.4 Genetic Polymorphisms in Other Factors -- 5 Concluding Remarks -- References -- MALT Lymphoma as a Model of Chronic Inflammation-Induced Gastric Tumor Development -- 1 Introduction -- 2 Clinical and Pathological Features. , 3 Pathogenesis -- 3.1 First Step: Gastric Acquisition of MALT -- 3.2 Second Step: Acquisition of Genetic Abnormalities -- 3.3 Third Step: Dysregulation of NF-κB Signaling -- 4 Treatment and Follow-up -- 5 Concluding Remarks -- References -- Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis -- 1 Introduction -- 2 H. pylori and Inflammation -- 3 Mechanisms of DNA Damage -- 3.1 Oxidative Stress -- 3.2 DNA-Modifying Enzymes -- 3.3 DNA Repair System -- 4 Genetic Alterations During Gastric Carcinogenesis -- 4.1 Mutational Landscape of Gastric Cancer -- 4.2 Stem Cells -- 5 Concluding Remarks -- References -- Importance of Toll-like Receptors in Pro-inflammatory and Anti-inflammatory Responses by Helicobacter pylori Infection -- 1 Introduction -- 2 Overview of TLRs -- 3 Lipopolysaccharide and TLR Interaction -- 4 TLRs and H. pylori Research -- 5 Microbes Drive TLR Evolution -- 6 TLR2/TLR10 and H. pylori LPS -- 7 TLR10 and Anti-inflammatory Responses -- 8 Concluding Remarks -- References -- Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection -- 1 Introduction -- 2 H. pylori Induction of NF-κB Signalling in Human Epithelial Cells -- 2.1 The H. pylori cagPAI Is Required for Induction of NF-κB Activation in Epithelial Cells -- 2.2 cagPAI-Encoded Proteins Associated with NF-κB Activation -- 2.3 H. pylori Activates the NF-κB Pathway in Epithelial Cells via NOD1 -- 3 Role of NOD1 in Host Immune Responses to H. pylori In Vivo -- 4 TIFA, A New Host Factor Mediating NF-κB-Dependent Responses to H. pylori Infection -- 5 Concluding Remarks -- References -- Carbohydrate-Dependent and Antimicrobial Peptide Defence Mechanisms Against Helicobacter pylori Infections -- 1 Introduction -- 2 Mucus, Mucins and Glycolipids -- 3 Helicobacter pylori Components Involved in Adhesion. , 3.1 The Blood Group-Binding Adhesin BabA -- 3.2 The Sialic Acid-Binding Adhesin SabA -- 3.3 Other H. pylori Molecules Involved in Adhesion to Host Structures -- 3.4 Lipopolysaccharide (LPS) -- 3.5 Secreted H. pylori Proteins that Bind to Glycans -- 4 Regulation and Consequences of H. pylori Binding to Mucins -- 4.1 Infection Induced Changes in Mucin Production, Localization and Glycosylation -- 4.2 Competition Between Binding to Mucins and Glycolipids -- 4.3 Regulation of H. pylori Adhesin Expression -- 4.4 Effects of Glycans on H. pylori Growth -- 5 Antimicrobial Peptides in the Gastric Mucosa -- 6 Bactericidal Activity of AMPs Against H. pylori -- 7 H. pylori-Mediated Regulation of Defensin Expression -- 8 AMP Regulation of Immune Cell Functions -- 9 AMPs and Glycans as Therapeutics for Eradication of H. pylori -- 10 Concluding Remarks -- References -- The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections -- 1 Introduction -- 2 Inflammation Induced by H. pylori -- 3 Epithelial Defense Molecules: Antimicrobial Potential Against H. pylori -- 4 Cholesterol Glucosides in H. pylori: Implications for Virulence -- 5 H. pylori Targets Host Cholesterol to Block the Epithelial Response to IFN-γ and Related Cytokines -- 6 Concluding Remarks -- References -- Helicobacter pylori Deregulates T and B Cell Signaling to Trigger Immune Evasion -- 1 Introduction -- 2 B and T Lymphocyte Development -- 2.1 B Lymphocyte -- 2.2 T Lymphocyte -- 3 B and T Lymphocyte Activation -- 3.1 B Lymphocyte -- 3.2 T Lymphocyte -- 4 T Cell Subsets and Reprogramming -- 4.1 T Cell Subsets -- 5 Reprogramming and Plasticity -- 6 H. pylori Induction and Evasion of the Host Immune Response -- 7 Concluding Remarks -- References -- Mechanisms of Inflammasome Signaling, microRNA Induction and Resolution of Inflammation by Helicobacter pylori. , 1 Introduction -- 2 Inflammasome Activation Through NOD2 and TLR2 Signal Transduction -- 3 Role of microRNAs in H. pylori Interaction with Host Cells -- 4 H. pylori Manipulates TLR Signaling and Bacterial Recognition -- 5 Pro- and Anti-inflammatory Cytokine Signaling by H. pylori -- 6 Resolution of Inflammation by H. pylori -- 7 Concluding Remarks -- References -- Impact of the Gastrointestinal Microbiome in Health and Disease: Co-evolution with the Host Immune System -- 1 Introduction -- 2 Early Life Colonization and H. pylori Infection in Childhood -- 3 H. pylori and Immunoregulation -- 4 Helicobacter pylori and the Oesophageal Microbiome -- 5 Helicobacter pylori and the Gastric Microbiome -- 5.1 The Gastric Cancer Microbiome -- 6 Helicobacter pylori and the Colonic Microbiome -- 7 Concluding Remarks -- References -- Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy -- 1 Introduction -- 2 Inflammatory Mediators of Gastritis and the Tumor Microenvironment (TME) -- 2.1 Chronic Inflammation in H. pylori -- 2.2 The TME in Gastric Cancer -- 3 Anti-cancer Strategies Targeting the Pro-inflammatory Mediators in the TME -- 3.1 Cell Signaling Inhibitors -- 3.2 Cytokine Antagonists (IL-1, IL-6, IL-18, TNF) -- 3.3 Non-steroidal Anti-inflammatory Drugs -- 4 Strategies Targeting Growth Factors Involved in Angiogenesis -- 4.1 Growth Factors as Target (VEGF/VEGFR2, CSF1/CSF1R, EGF/EGFR) -- 4.2 Strategies Inhibiting M1 to M2 Transitions and Promoting M1 Phenotype -- 4.3 Inhibition of Myeloid-derived Suppressor Cells (MDSCs) -- 4.4 Targeting Chemokines and Their Receptors -- 5 Enhancing Anti-tumor Immunity (Therapy-Induced Inflammation) -- 5.1 Checkpoint Inhibitors (Anti-PD-1/L1, Anti-CTLA4) -- 5.2 Other Immunotherapies-Immunoconjugates -- 6 Concluding Remarks -- References.

Note: Intro -- Foreword -- Contents -- Abbreviations -- Human Campylobacteriosis-A Serious Infectious Threat in a One Health Perspective -- 1 Introduction -- 2 The One Health Concept: General Theory and Practical Approaches -- 3 Human Campylobacteriosis-From Clinical Investigations to Novel Treatment Options Using Innovative Murine Models of Infection -- 3.1 Human Campylobacteriosis-Basic Characteristics -- 3.2 Burden of Disease -- 3.3 Molecular Concepts of C. jejuni-Induced Intestinal Pathogenesis -- 3.4 Novel Murine Models of C. jejuni Infection Offering Detailed Investigations and Treatment Strategies for Campylobacteriosis and Associated Long-Term Sequelae -- 4 Concluding Remarks -- References -- The Data Behind Risk Analysis of Campylobacter Jejuni and Campylobacter Coli Infections -- 1 Introduction -- 2 Risk Assessment of Human Campylobacteriosis -- 2.1 Hazard Identification -- 2.2 Hazard Characterization -- 2.3 Exposure Assessment -- 2.4 Risk Characterization -- 3 Current Surveillance Strategies of Campylobacter -- 4 Risk Management -- 4.1 Control in Poultry Meat -- 4.2 Control of Campylobacter Sources Other Than Poultry Meat -- 5 Risk Communication -- 6 Concluding Remarks -- References -- Population Biology and Comparative Genomics of Campylobacter Species -- 1 Introduction -- 2 Evolution Theory and Concepts for the Genus Campylobacter -- 3 Population Structure -- 3.1 Diversity and Population Structure of C. Jejuni and C. Coli -- 3.2 Inter Species Recombination and Hybrid Species -- 3.3 Additional Species -- 4 Host Association of Campylobacter -- 4.1 Impact of Genomic High-Throughput Methods -- 4.2 Source Attribution in Clinical and Agricultural Setting -- 4.3 Relevance for Public Health (Applications) -- 5 Concluding Remarks -- References. , Management Strategies for Prevention of Campylobacter Infections Through the Poultry Food Chain: A European Perspective -- 1 Introduction -- 2 Management Practices and Control Options -- 2.1 Farm Level -- 2.2 Abattoir Level -- 2.3 Post-harvest Level -- 2.4 Retail and Consumer Phase -- 2.5 Management and Responsibilities -- 3 Concluding Remarks -- References -- Emission Sources of Campylobacter from Agricultural Farms, Impact on Environmental Contamination and Intervention Strategies -- 1 Introduction -- 2 Colonization of Campylobacter in Livestock -- 3 Emission Sources -- 3.1 Manure -- 3.2 Air -- 3.3 Insects and Rodents -- 3.4 Personnel, Equipment, Vehicles -- 3.5 Waterborne Emission -- 4 Tenacity of Campylobacter in the Environment -- 5 Viable but Non-culturable Form of Campylobacter in the Environment -- 6 Intervention Against Emission -- 7 Concluding Remarks -- References -- Phage Biocontrol of Campylobacter: A One Health Approach -- 1 Introduction -- 2 Campylobacter Bacteriophages in a One Health Approach -- 3 Interactions of Bacteria with Their Bacteriophages and the Development of Resistance -- 4 Phage Treatment of Campylobacter in the Literature -- 4.1 Experimental Phage Treatment of Contaminated Meat -- 4.2 Experimental Phage Treatment of Colonized Chickens -- 5 Practical Hurdles and Open Questions that Need to Be Addressed -- 6 Resistance of Campylobacter Phages -- 7 Regulatory Aspects and Safety of Campylobacter Bacteriophages -- 8 Concluding Remarks -- References -- Campylobacter Virulence Factors and Molecular Host-Pathogen Interactions -- 1 Introduction -- 2 Bacterial Virulence Factors and Epithelial Cell Responses -- 2.1 Specialized Metabolism and Enteric Life Style -- 2.2 Campylobacter Motility and Chemotaxis -- 2.3 CDT Toxin Production -- 2.4 Serine Protease HtrA and Epithelial Barrier Disruption. , 2.5 Outer Membrane Adhesins and Host Cell Binding -- 2.6 The Flagellum as a Specialized Type III Secretion System -- 2.7 Bacterial Factors and Signaling Involved in Host Cell Invasion -- 2.8 Intracellular Survival and Trafficking of Campylobacter -- 3 Bacterial Virulence Factors and Immune Cell Responses -- 3.1 Interaction with Toll-Like Receptors -- 3.2 Role of Siglec Receptors -- 3.3 Activation of the NLRP3 Inflammasome -- 4 Concluding Remarks -- References -- Diarrheal Mechanisms and the Role of Intestinal Barrier Dysfunction in Campylobacter Infections -- 1 Introduction -- 2 Pathogenetic Principles and Diarrheal Mechanisms in campylobacteriosis -- 2.1 Barrier Dysfunction, Leak Flux and Leaky Gut -- 2.2 Immune Cell Response and Barrier Function -- 3 Barrier Dysfunction in Campylobacter Infection -- 3.1 Barrier Defects by C. jejuni, C. coli, C. fetus, C. concisus and Related Bacteria -- 3.2 Protective Approaches -- 4 Concluding Remarks -- References -- Murine Models for the Investigation of Colonization Resistance and Innate Immune Responses in Campylobacter Jejuni Infections -- 1 Introduction -- 2 Factors Affecting Campylobacter Colonization and Infection -- 3 Susceptibility to Lipooligosaccharide Determines Host Specificity of Campylobacter Colonization Versus Infection -- 3.1 Chickens -- 3.2 Mice -- 3.3 Humans -- 4 Murine Infection Models in Campylobacteriosis Research -- 4.1 Germfree and Secondary Abiotic Mice -- 4.2 Human Microbiota-Associated Mice -- 4.3 Infant Mice -- 4.4 Zinc-Deficient Mice -- 4.5 SIGIRR-Deficient Mice -- 4.6 IL-10 Deficient Mice -- 5 Concluding Remarks -- References -- Natural Competence and Horizontal Gene Transfer in Campylobacter -- 1 Introduction -- 2 Mechanisms of Horizontal Gene Transfer -- 2.1 Natural Transformation and Uptake of Free DNA -- 2.2 Conjugative Gene Transfer. , 2.3 Phage Transduction and Genomic Rearrangements -- 3 Barriers to Horizontal Gene Transfer -- 3.1 CRISPR-Cas and Nucleases -- 3.2 Methylation-Dependent DNA Recognition -- 4 Impact of Gene Transfer on Campylobacter Fitness -- 4.1 Spread of Resistomes and Persistence Factors -- 4.2 Interspecies Gene Transfer -- 5 Concluding Remarks -- References -- Molecular Mechanisms of Campylobacter Biofilm Formation and Quorum Sensing -- 1 Introduction -- 2 Microbial Biofilm Formation -- 2.1 Building and Dispersion of Microbial Biofilms -- 2.2 Methods to Analyse Biofilms -- 2.3 Environmental Conditions Influencing Campylobacter jejuni Biofilm Formation -- 2.4 Genetic Background and Genes Impacting Biofilm Formation of C. jejuni -- 2.5 Control Strategies Targeting C. jejuni Biofilms -- 3 Quorum Sensing -- 3.1 Quorum Sensing Signalling Mechanisms -- 3.2 Phenotypes of C. jejuni luxS Mutants -- 3.3 Quorum Quenching -- 4 Concluding Remarks -- References -- Correction to: Fighting Campylobacter Infections -- Correction to: S. Backert (ed.), Fighting Campylobacter Infections, Current Topics in Microbiology and Immunology 431, https://doi.org/10.1007/978-3-030-65481-8.

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.

Note: Intro -- Foreword -- Helicobacter pylori, the Gastric Bacterium Which Still Infects Half the World´s Population, Is an Important Part of Gastroente... -- Contents -- Part I: Bacteriology and Molecular Biology -- Chapter 1: Helicobacter pylori: Genetics, Recombination, Population Structure, and Human Migrations -- 1.1 Introduction -- 1.2 The Coevolution of Helicobacter pylori and Humans -- 1.2.1 H. pylori´s Housekeeping Genes -- 1.2.2 Geographic Clustering of Housekeeping Gene Sequences -- 1.2.2.1 Recent Human Population Movements -- 1.2.2.2 Prehistoric Human Migrations -- Bantu speakers: hpAfrica1 -- Nilo-Saharan speakers: hpNEAfrica -- Australians and New Guineans: hpSahul -- Central and Southeast Asians: hpAsia2 -- Native Americans, Han Chinese, and the Austronesians: hpEastAsia -- 1.2.3 Formal Comparisons with Human DNA Data -- 1.2.4 Recombination and Its Effect on Evolutionary Inference -- 1.2.4.1 Population Trees -- 1.2.4.2 The Linkage Model: The Concept of Ancestral Populations -- 1.2.5 Enter Coalescence -- 1.2.5.1 The Global H. pylori Phylogeny -- 1.2.5.2 Age of the H. pylori Human Association -- 1.2.5.3 Sahul Was Colonized Only Once -- 1.2.5.4 The Austronesian Expansion -- 1.2.5.5 San Hunter-Gatherers Are the Original Hosts of hpAfrica2 -- 1.2.5.6 A Second More Recent Out-of-Africa Migration -- 1.2.5.7 Pygmy Hunter-Gatherers Contracted H. pylori Recently from Neolithic Bantus -- 1.2.6 Outlook: Genomics, Aboriginal Populations, and Ancient DNA -- References -- Chapter 2: Adaptation of Helicobacter pylori Metabolism to Persistent Gastric Colonization -- 2.1 Introduction -- 2.2 H. pylori Facing Acidity -- 2.2.1 The Dangers of Low pH -- 2.2.2 Acid Adaptation and Acclimation of H. pylori to the Gastric Niche -- 2.2.3 Establishing the Response to Acidity -- 2.3 Urease, the Major Player in H. pylori Resistance to Acidity. , 2.3.1 Urease Enzymatic Activity -- 2.3.2 Acid-Gated Transport of Urea by the UreI Channel -- 2.3.3 Regulation of the Expression of the Urease Genes -- 2.3.4 Role of the Carbonic Anhydrases in H. pylori -- 2.4 Ammonia Metabolism in H. pylori -- 2.4.1 Minimalist Pathways for Nitrogen Assimilation -- 2.4.2 Central Role of Glutamine Synthetase in Ammonia Metabolism and Possible Coupling with Urease -- 2.4.3 Transport and Metabolism of Amidated Amino Acids -- 2.4.3.1 Asp/Asn and Glu/Gln Uptake in H. pylori -- 2.4.3.2 Asparagine and Glutamine in Translation -- 2.4.3.3 How Are Asn-tRNA and Gln-tRNA Generated in H. pylori? -- 2.4.3.4 The AmiE and AmiF Aliphatic Amidases -- 2.5 Metabolic Enzymes Involved in Virulence -- 2.5.1 Asparaginase -- 2.5.2 Arginase -- 2.6 Metabolism of Nickel, an Essential Metal for the Virulence of Helicobacter pylori -- 2.6.1 Nickel Is a Virulence Determinant for H. pylori -- 2.6.2 Nickel Transport and Efflux -- 2.6.3 Nickel Chaperones and Storage Proteins -- 2.6.3.1 Role of HspA, the Helicobacter-Specific GroES Homolog -- 2.6.3.2 Hpn and Hpn-2: Two Remarkable Histidine-Rich Proteins -- 2.6.4 Urease and Hydrogenase Maturation -- 2.6.4.1 Urease Maturation -- 2.6.4.2 Hydrogenase Maturation -- 2.6.4.3 A Molecular Cross Talk Between Urease and Hydrogenase Maturation Machineries -- 2.7 Conclusions and Outlook -- References -- Chapter 3: Virulence Mechanisms of Helicobacter pylori: An Overview -- 3.1 Introduction -- 3.2 H. pylori Colonisation and Adherence -- 3.2.1 Escape from the Stomach Lumen -- 3.2.2 Adhesion of H. pylori to Gastric Epithelial Cells -- 3.3 Major H. pylori Virulence Factors Involved in Pathogenesis -- 3.3.1 cag Pathogenicity Island (cagPAI) -- 3.3.2 Vacuolating Cytotoxin VacA -- 3.3.3 Other Putative Autotransporter Proteins of H. pylori -- 3.3.4 gamma-Glutamyl Transpeptidase. , 3.3.5 High Temperature Requirement A (HtrA) Serine Protease -- 3.3.6 Other Pro-inflammatory Virulence Factors of H. pylori -- 3.4 Avoidance and Modulation of the Host Immune Response -- 3.4.1 Evasion of Detection by the Innate Immune System -- 3.4.2 Modulation of Phagocytosis and Neutrophil Function -- 3.4.3 Inhibition of Lymphocyte Proliferation -- 3.4.4 Skewing of Adaptive Immune Responses Toward Tolerogenicity -- 3.5 Mitigation of Inflammatory Responses -- 3.6 Modulation of Apoptosis and Autophagy by H. pylori -- 3.6.1 Apoptosis -- 3.6.2 Autophagy -- 3.7 Conclusions and Outlook -- References -- Chapter 4: Roles of the cagPAI and CagA on Gastroduodenal Diseases -- 4.1 Introduction -- 4.2 The cagPAI Encodes a Type IV Secretion System -- 4.3 Crystal Structures of cagPAI Proteins -- 4.4 Pathological Function of the cagPAI Type IV Secretion System -- 4.5 Phosphorylation-Dependent Host Cell Signaling of Translocated CagA -- 4.6 Phosphorylation-Independent Signaling of CagA -- 4.7 T4SS-Dependent but CagA-Independent Cellular Signaling Induced by H. pylori -- 4.8 Conclusions -- References -- Chapter 5: Helicobacter pylori Vacuolating Toxin -- 5.1 Introduction -- 5.2 The vacA Gene vacA Transcription -- 5.3 Secretion and Proteolytic Processing of VacA -- 5.4 Properties of the 88kDa Secreted VacA Protein -- 5.5 VacA Allelic Diversity and Association of vacA Genotypes with Disease -- 5.6 Membrane Channel Formation by VacA -- 5.7 VacA Interactions with Host Cells: Binding, Uptake, and Trafficking -- 5.7.1 Intracellular Actions of VacA -- 5.7.2 Interactions of VacA with the Epithelial Cell Surface -- 5.7.3 Uptake of VacA into an Intracellular Compartment -- 5.7.4 VacA Trafficking to Mitochondria -- 5.7.5 VacA Uptake and Trafficking in Immune Cells -- 5.8 Effects of VacA on Host Cells In Vitro -- 5.8.1 VacA as a Modulator of Epithelial Cell Function. , 5.8.1.1 Alterations in Endosomal Compartments -- 5.8.1.2 Autophagy -- 5.8.1.3 Cell Death -- 5.8.1.4 Alterations in Mitochondria -- 5.8.1.5 Effects of VacA on Cellular Signal Transduction Pathways -- 5.8.1.6 Effects of VacA on Epithelial Cell Permeability and the Cytoskeleton -- 5.8.2 VacA as a Modulator of Immune Cell Function -- 5.8.2.1 Effects of VacA on T and B Lymphocytes -- 5.8.2.2 Effects of VacA on Other Types of Immune Cells -- 5.8.3 Effects of VacA on Parietal Cells and Acid/Base Balance -- 5.9 Synergistic and Antagonistic Associations Between VacA and CagA -- 5.10 Role of VacA In Vivo -- 5.10.1 Role of VacA in H. pylori Colonization of the Stomach -- 5.10.2 Role of VacA in Gastroduodenal Disease -- 5.11 Conclusions and Outlook -- References -- Chapter 6: Roles of the BabA and the SabA Adhesins in Gastroduodenal Diseases -- 6.1 Introduction -- 6.2 The Blood Group Antigen-Binding Adhesin BabA -- 6.2.1 Identification of the Blood Group Antigen-Binding Adhesin BabA -- 6.2.2 Location of the babA Gene -- 6.2.3 Mechanisms That Switches BabA Expression On and Off -- 6.2.4 Regulation of BabA Expression Levels -- 6.2.5 BabA Expression and Gastric Disease -- 6.3 The Sialic Acid-Binding Adhesin SabA -- 6.3.1 H. pylori Binding to the Inflammation-Associated Sialyl-Lewis x/a Antigen Receptor -- 6.3.2 Identification of the Sialic Acid-Binding Adhesin SabA -- 6.3.3 The SabA Adhesin Is the H. pylori Hemagglutinin -- 6.3.4 Mechanisms for Regulation of SabA Expression -- 6.3.5 SabA Expression and Regulation by Acidic Conditions -- 6.3.6 SabA and Gastroduodenal Diseases -- 6.4 BabA- and SabA-Mediated Binding to Mucins -- 6.5 BabA- and SabA-Mediated Adhesion of H. pylori Outer Membrane Vesicles to the Gastric Mucosa -- 6.6 Conclusion and Outlook -- References -- Chapter 7: Emerging Novel Virulence Factors of Helicobacter pylori -- 7.1 Introduction. , 7.2 The Effects of GGT on Epithelial Cells and Immune Cells -- 7.3 NapA Affects the Host Immune System -- 7.4 Tipα: A Multifunctional Factor? -- 7.5 JHP0940 Encodes the Bacterial Kinase CtkA -- 7.6 Helicobacter pylori Secretes Proteases That Target Host Cell Proteins with Important Functions in Pathogenesis -- 7.7 HtrA Can Affect H. pylori Pathogenesis via Direct Cleavage of E-Cadherin and Fibronectin -- 7.8 The Helicobacter Outer Membrane Proteins HopQ and HopZ Contribute to Bacterial Adherence -- 7.9 DupA as a Marker for H. pylori-Associated Disorders -- 7.10 Conclusions and Outlook -- References -- Chapter 8: The Primary Transcriptome and Noncoding RNA Repertoire of Helicobacter pylori -- 8.1 Introduction -- 8.2 Primary Transcriptome Analysis of Helicobacter pylori -- 8.2.1 Bacterial Transcriptome Analysis Using RNA-Seq -- 8.2.2 Differential RNA-Seq for Primary Transcriptome Analysis -- 8.3 Helicobacter Transcriptome Features Identified by dRNA-Seq -- 8.3.1 Global Transcriptional Start Site Maps -- 8.3.2 5 UTR Lengths -- 8.3.3 Operon and Suboperon Structure -- 8.3.4 Noncoding RNAs -- 8.3.4.1 Housekeeping RNAs -- 8.3.4.2 Mechanisms and Functions of Antisense/Base-Pairing RNAs in H. pylori -- Trans-Encoded Antisense RNAs -- Cis-Encoded Antisense RNAs -- 8.3.5 Class I Toxin-Antitoxin Loci -- 8.4 Protein Factors Involved in Posttranscriptional Regulation -- 8.4.1 RNA-Binding Proteins -- 8.4.2 Ribonucleases -- 8.5 Conclusions and Outlook -- References -- Chapter 9: Genome Evolution: Helicobacter pylori as an Extreme Model -- 9.1 Prologue -- 9.2 Phylogeny and Population Structure -- 9.2.1 Genome Trees vs. Gene Trees -- 9.2.2 Inference of Population Structure from Mutual Homologous Recombination -- 9.3 Evolution of Individual Genes -- 9.3.1 The cagA Oncogene -- 9.3.2 Decay of Molybdenum-Related Genes -- 9.3.3 Outer Membrane Proteins. , 9.4 Evolution of Chromosome Synteny.

Note: Intro -- Preface -- Contents -- Abbreviations -- 1 General Strategies in Inflammasome Biology -- Abstract -- 1 Introduction: PRRs, PAMPs, and DAMPs -- 2 PRRs as Inflammasome Scaffolds -- 3 Inflammasome Activation Mechanisms -- 3.1 The NLRP3 Inflammasome -- 3.2 The NLRP1 Inflammasome -- 3.3 The NLRC4 Inflammasome -- 3.4 The AIM2 Inflammasome -- 3.5 The Pyrin Inflammasome -- 4 Concluding Remarks -- Acknowledgments -- References -- 2 Structural Mechanisms in NLR Inflammasome Assembly and Signaling -- Abstract -- 1 Introduction -- 2 Overviews of NOD-Like Receptors -- 3 Auto-Inhibition Mechanism of NLRC4 -- 4 Mechanism of NAIP-NLRC4 Inflammasome Activation and Assembly -- 5 A Positive Role of the C-Terminal LRR Domain in the Activation of NAIP-NLRC4 Inflammasomes? -- 6 Activation of Other NLR Inflammasomes -- 7 Insights into the Assembly of ASC-Dependent Inflammasomes -- 8 Concluding Remarks -- References -- 3 Salmonella and the Inflammasome: Battle for Intracellular Dominance -- Abstract -- 1 Introduction -- 1.1 Salmonella -- 1.2 Inflammasomes -- 2 Salmonella and the Immune Cell Inflammasome -- 2.1 Macrophages -- 2.1.1 Naip1-6, hNAIP, and Nlrc4 -- 2.1.2 Nlrp3 and Asc -- 2.1.3 Caspase-11 -- 2.1.4 Other Inflammasomes Involved in Salmonella Detection -- 2.2 Dendritic Cells (DCs) -- 2.3 Neutrophils -- 3 Salmonella and the Intestinal Epithelial Inflammasome -- 4 Inflammasome Evasion by Salmonella -- 5 Concluding Remarks -- References -- 4 Activation and Evasion of Inflammasomes by Yersinia -- Abstract -- 1 Introduction -- 1.1 Evolutionary Relationships Among the Pathogenic Yersinia -- 1.2 Features of Yersinia-Induced Cell Death -- 2 Mechanisms of Yersinia-Induced Cell Death -- 2.1 YopJ-Induced Death via the Extrinsic Apoptosis Pathway -- 2.2 Inflammasome Sensing of Yersinia Infection and Its Evasion by YopK -- 2.3 Evasion of Inflammasome by YopM. , 3 Interactions Between Yersinia and Cell Death Pathways In Vivo -- 3.1 Impact of Yersinia-Induced Cell Death on Pathogenesis and Host Defense -- 3.2 Activation of Cell Death by Yersinia Virulence Factors In Vivo -- 3.3 In Vivo Interactions Between Yersinia and Inflammasome Responses -- 4 Concluding Remarks -- Acknowledgments -- References -- 5 The Orchestra and Its Maestro: Shigella's Fine-Tuning of the Inflammasome Platforms -- Abstract -- 1 Introduction -- 2 Epithelial Cells -- 3 Macrophages -- 4 Neutrophils -- 5 Dendritic Cells -- 6 Lymphocytes -- 7 Shigella and the Inflammasome-Who's Holding the Conducting Baton? -- References -- 6 Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity -- Abstract -- 1 Introduction -- 1.1 H. pylori Is a Prime Example of Chronic Infections and Gastric Disease Development -- 1.2 Host Genetic Polymorphisms Are Crucial for& -- !blank -- Gastric Pathology -- 2 Importance of IL-1β in Gastric Cancer Development -- 3 Inflammasome Responses During H. pylori Infection -- 3.1 Inflammasome Activation by H. pylori -- 3.2 Regulation of Inflammasome Activation upon H. pylori Infection -- 3.3 Inflammasome Activation-Mediated Host-Specific Immunity in H. pylori Infection -- 3.4 Inflammasome-Mediated IL-1β Secretion in Cultured Human and Mouse Cells -- 4 Concluding Remarks -- Acknowledgments -- References -- 7 Listeria monocytogenes and the Inflammasome: From Cytosolic Bacteriolysis to Tumor Immunotherapy -- Abstract -- 1 Introduction -- 1.1 Overview -- 1.2 Life Cycle -- 1.3 Innate Immune Response -- 2 Activation of Different Inflammasomes -- 2.1 NLRP3 Activation -- 2.2 NLRC4 Activation -- 2.3 AIM2 Activation -- 2.4 Other NLR Engagement -- 3 Avoidance of Inflammasome Activation -- 3.1 Avoidance of NLRP3 -- 3.2 Avoidance of NLRC4 -- 3.3 Avoidance of AIM2. , 3.4 Active Inhibition of the Inflammasome -- 4 Role in Pathogenesis -- 4.1 Role of Caspase-1/11 -- 4.2 Role of ASC -- 4.3 Role of IL-1β and IL-18 -- 4.4 Innate Immune Cell Infiltrate -- 5 Adaptive Immune Response to L. monocytogenes -- 5.1 Protective Immunity -- 5.2 Influence of Cytokines -- 6 Concluding Remarks -- Acknowledgments -- References -- 8 Inflammasome Recognition and Regulation of the Legionella Flagellum -- Abstract -- 1 Introduction: The Facultative Intracellular Pathogen Legionella pneumophila -- 1.1 Environmental Niches, Human Infection and Mouse Models -- 1.2 Intracellular Replication Within the Legionella-Containing Vacuole -- 1.3 The Biphasic Life Cycle of L. pneumophila -- 2 Modulation of Inflammasome Activity by L. pneumophila -- 2.1 Pattern Recognition Receptors Implicated in L. pneumophila Infection -- 2.2 Inflammasome Activation by L. pneumophila Flagellin -- 2.3 Regulation of Cell Death by Icm/Dot- Translocated Effectors -- 3 Regulation of Legionella Flagellin and Motility -- 3.1 Legionella Flagellin as a Transmissive and Virulence Factor -- 3.2 Regulation of Legionella Motility by the Signaling Molecule LAI-1 -- 3.3 The Flagellar Regulon of Legionella -- 4 Concluding Remarks -- Acknowledgments -- References -- 9 Inflammasome Activation and Function During Infection with Mycobacterium tuberculosis -- Abstract -- 1 Introduction -- 2 Early Events in M. tuberculosis-Infected Phagocytes -- 3 Regulation of Inflammasome Activation via the Mycobacterial Type VII Secretion System (T7SS) -- 4 M. tuberculosis Activates the Inflammasome in Macrophages -- 5 M. tuberculosis Triggers Inflammasome-Dependent and Inflammasome-Independent IL-1β Production in Various Myeloid Cells -- 6 Activation of Cytosolic "Non-Inflammasome" Sensors -- 7 Regulation of Inflammasome Activity During M. tuberculosis Infection. , 8 In Vivo Regulation of IL-1β and the Inflammasome in Host Protection -- 9 Concluding Remarks -- References -- 10 Role of Canonical and Non-canonical Inflammasomes During Burkholderia Infection -- Abstract -- 1 Introduction -- 2 Innate Immune Response to Burkholderia Infection -- 3 Role of Caspase-1 -- 4 Role of NLRC4 Inflammasome -- 5 Role of NLRP3 Inflammasome -- 6 Opposing Function of IL-1β and IL-18 -- 7 Role of the Caspase-11 Non-canonical Inflammasome -- 8 Different Contribution of the Canonical and Non-canonical Inflammasomes -- 9 Role of the Human Non-canonical Inflammasome -- 10 Concluding Remarks -- References -- 11 Inflammasomes in Pneumococcal Infection: Innate Immune Sensing and Bacterial Evasion Strategies -- Abstract -- 1 Introduction -- 2 Brief Overview of the Innate Immune Response to S. Pneumoniae Infection -- 3 Sensing of S. Pneumoniae by Inflammasomes -- 4 Role of Inflammasomes in Pneumococcal Infections -- 5 Evasion of Inflammasome-Dependent Sensing by Emerging Strains -- 6 Concluding Remarks -- Acknowledgments -- References -- 12 Francisella Inflammasomes: Integrated Responses to a Cytosolic Stealth Bacterium -- Abstract -- 1 Introduction -- 1.1 The Francisella Genus -- 1.2 Francisella tularensis, the Agent of Tularemia -- 1.3 Intracellular Life Cycle -- 2 Overview of the Innate Immune Responses to Francisella Infection -- 2.1 TLRs and NF-κB Activation -- 2.2 Signaling Pathways Leading to Type I IFN Production -- 3 Francisella Activates the Aim2 Inflammasome in Murine Phagocytes -- 3.1 Aim2 Inflammasome and the IFN Requirement -- 3.1.1 In Vitro and In Vivo Role of the Inflammasome -- 3.1.2 Type I IFN Signaling Is Required for Francisella-mediated Inflammasome Activation -- 3.1.3 Aim2 Is the Inflammasome Receptor Detecting Francisella in the Host Cytosol. , 3.2 Gbp-mediated Bacteriolysis Is Required to Trigger Aim2 Inflammasome Activation -- 3.3 TLR2 Controls pro-IL-1β Level and the Kinetics of AIM2 Inflammasome Activation -- 4 Francisella and the Non-canonical Inflammasomes -- 4.1 Francisella LPS Escapes Caspase-11 Recognition -- 4.2 ASC-dependent Caspase-1-independent Pathways -- 5 Inflammasome Activation in Human Cells -- 6 Lessons from the Bacterial Side: Study of Hypercytotoxic Mutants -- 7 Hypervirulent Strains Escape Inflammasome Detection -- 8 Concluding Remarks -- References -- 13 Inflammasome Activation Can Mediate Tissue-Specific Pathogenesis or Protection in Staphylococcus aureus Infection -- Abstract -- 1 Introduction -- 2 Inflammasomes that are Activated by S. aureus -- 3 Role of Inflammasome Activation in Infection Models -- 3.1 The NLRP3 Inflammasome Responds to Hemolysins to Control S. aureus Dermal Infections -- 3.2 IL-1β Signaling Is Critical for Combating Soft Tissue Infections -- 3.3 S. aureus Hijacks the NLRP3 Inflammasome to Exacerbate Lung Infection Pathology -- 3.4 Microglia Activate NLRP3 In Vitro but Depend on AIM2 to Clear S. aureus Central Nervous System Infections -- 4 How the Host Inflammasome Can Affect Other Inflammatory Processes -- 5 Integrating Inflammasome Studies to Improve Patient Care -- 6 Concluding Remarks -- Acknowledgments -- References.

Note: Intro -- Foreword -- Preface -- Contents -- Abbreviations -- 1 The Human Stomach in Health and Disease: Infection Strategies by Helicobacter pylori -- Abstract -- 1 Introduction -- 2 H. pylori Infection and Strategies of Persistence -- 3 H. pylori Infection in Health and Disease -- 3.1 Gastritis -- 3.2 Peptic Ulcer Disease -- 3.3 Gastric Adenocarcinoma -- 3.4 MALT Lymphoma -- 4 H. pylori Virulence Factors and their Association with Disease -- 4.1 The cag Pathogenicity Island -- 4.2 Vacuolating Cytotoxin (VacA) -- 4.3 DupA and tfs4 -- 4.4 NapA -- 4.5 Adhesins -- 5 Environmental Factors and their Association with Disease -- 6 Treatment of H. pylori and Prospects for a Vaccine -- 7 Concluding Remarks -- Acknowledgements -- References -- 2 Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases -- Abstract -- 1 Helicobacter pylori: From Infection to Diseases -- 2 The Chemokine CXCL8 -- 2.1 Induction of CXCL8 by H. pylori -- 2.2 CXCL8 Gene Polymorphisms -- 3 Induction and Role of ROS -- 3.1 ROS During H. pylori Infection -- 3.2 Expression and Role of NOX1 -- 3.3 Expression and Role of NOX2 -- 3.4 Expression and Role of SMOX -- 3.5 Epigenetic Regulation of SMOX -- 4 Nitrosative Stress -- 4.1 H. pylori Infection and NOS2 -- 4.2 NO-Mediated H. pylori Carcinogenesis -- 4.3 NOS2 Polymorphisms -- 5 The Host and Bacteria Coevolution: The Crystal Ball of H. pylori Pathogenesis? -- 6 Concluding Remarks -- References -- 3 Immune Evasion Strategies and Persistence of Helicobacter pylori -- Abstract -- 1 Introduction -- 2 Innate Immune Evasion Strategies of H. pylori -- 2.1 Evasion and Manipulation of Pattern Recognition Receptors -- 2.1.1 Evasion of TLR Recognition and Manipulation of TLR-Mediated Signaling -- 2.1.2 Inhibition of CLR-Mediated Signaling. , 2.2 Inhibition of Phagocytosis and Killing by Reactive Oxygen Species and Nitric Oxide -- 2.3 Inhibition of Antimicrobial Peptides -- 3 Immune Tolerance Driven by H. pylori Interaction with Dendritic Cells -- 4 Manipulation and Inhibition of Effector T Cell Responses -- 5 Bacterial Plasticity and Immune Evasion -- 6 Concluding Remarks -- References -- 4 Recent Advances in Helicobacter pylori Replication: Possible Implications in Adaptation to a Pathogenic Lifestyle and Perspectives for Drug Design -- Abstract -- 1 Introduction -- 2 Chromosome Replication in Bacteria -- 3 Chromosome Replication in Helicobacter pylori -- 3.1 Initiation -- 3.2 Elongation -- 3.3 Termination -- 3.4 Segregation -- 4 Regulation of H. pylori Chromosome Replication -- 5 Plasmid Replication in Bacteria -- 6 Plasmid Replication in Helicobacter pylori -- 7 Beyond the Replication Flowchart -- 8 Concluding Remarks -- Acknowledgements -- References -- 5 The Helicobacter pylori Methylome: Roles in Gene Regulation and Virulence -- Abstract -- 1 Introduction -- 2 The Restriction-Modification (R-M) Systems and Their Diversity in H. pylori -- 3 The H. pylori Methylomes -- 4 Roles of H. pylori Methyltransferases (Mtases) in Gene Regulation -- 4.1 Gene Regulation by E. coli Deoxyadenosine Methyltransferase (Dam) and Its Homologues -- 4.2 Regulation of Gene Expression by H. pylori Type I and Type II Mtases -- 4.3 The H. pylori Mtase-Based Phasevarion, ModH, Plays Key Roles in the Regulation of Virulence Genes -- 5 Concluding Remarks -- Acknowledgements -- References -- 6 Structural Insights into Helicobacter pylori Cag Protein Interactions with Host Cell Factors -- Abstract -- 1 The Helicobacter pylori Cytotoxin-Associated Gene Pathogenicity Island (CagPAI) -- 2 Integrins as Receptors of the CagT4SS -- 3 CagL, a CagT4SS-Associated Pilus Adhesin. , 4 Structures and Interaction Motifs of CagL -- 5 CagA Interaction with Host Cell Components -- 5.1 Structural Properties of CagA -- 5.2 CagA Interaction with Membrane Components -- 5.3 CagA Interactions with Oncosuppressors RUNX3 and ASPP2 -- 5.4 CagA Interaction with Host Cell Signalling Proteins -- 6 Concluding Remarks -- Acknowledgements -- References -- 7 Gastric Organoids: An Emerging Model System to Study Helicobacter pylori Pathogenesis -- Abstract -- 1 Introduction -- 1.1 Current Models for H. pylori Research -- 2 Understanding of Adult Stem Cells and Their Niche Led to the Development of Organoid Culture -- 2.1 The Gastric Epithelium -- 2.2 Gastric Stem Cells -- 2.3 Organoids: Self-organizing Three-Dimensional Systems of Stem Cells and Differentiated Cells -- 3 Gastric Organoids -- 3.1 Organoids Grown from Adult or Pluripotent Stem Cells -- 3.2 Long-Term Self-renewing Purely Epithelial Organoids -- 3.3 Epithelial/Mesenchymal Organoids Derived from Adult Stem Cells -- 3.4 Epithelial/Mesenchymal Organoids Derived from PSC -- 3.5 2D Monolayers Derived from Epithelial Organoids -- 4 The Use of Stem Cell-Derived Organoids for H. pylori Research -- 5 Concluding Remarks -- Acknowledgements -- References -- 8 DNA Transfer and Toll-like Receptor Modulation by Helicobacter pylori -- Abstract -- 1 Introduction -- 2 Toll-like Receptor Modulation by H. pylori -- 2.1 Toll-like Receptors -- 2.2 TLR4/H. pylori Lipopolysaccharide Interactions -- 2.3 TLR5/H. pylori Flagellin Interactions -- 3 TLR9 Functions in the Innate Immune Response -- 3.1 TLR9 Regulation and Signaling -- 3.2 Duality of TLR9-Mediated Responses -- 4 DNA Translocation Strategies -- 4.1 DNA Translocation Through the T4SS -- 4.2 The H. pylori cag Pathogenicity Island (PAI) -- 4.3 Structure of the H. pylori Cag T4SS -- 4.4 H. pylori T4SS ComB -- 4.5 tfs3 and tfs4 Secretion Systems. , 5 H. pylori/TLR9 Interactions -- 5.1 TLR9-Mediated Responses to H. pylori -- 5.2 H. pylori Activates TLR9 via the T4SS -- 6 Conclusions and Outlook -- Acknowledgements -- References -- 9 Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions -- Abstract -- 1 Introduction -- 1.1 The Polarized Epithelium as the First Barrier for H. pylori Colonization -- 1.2 Mechanisms of H. pylori-Triggered Reprogramming of Epithelial Cell Differentiation -- 2 Structure and Composition of Polarized Cell Monolayers in the Healthy Epithelium -- 3 Depolarization of Epithelial Cells by H. pylori Involves Alterations in Tight and Adherens Junctions -- 3.1 Direct Targeting of Tight Junction Factors by H. pylori Effector Proteins -- 3.1.1 Selective Opening of Tight Junctions by H. pylori VacA -- 3.1.2 Disruption of Tight Junctions by Ectopic CagA -- 3.1.3 Urease-Dependent Targeting of Tight Junctions via MLCK and MLC -- 3.2 H. pylori Actively Disrupts Adherens Junctions to Induce an EMT-like Phenotype -- 3.2.1 Interference of H. pylori CagA with the Integrity of Adherens Junctions -- 3.2.2 Disruption of E-Cadherin-Mediated Adherens Junctions by Secreted HtrA -- 3.3 Direct Targeting of Tight and Adherens Junction Proteins by Changing Nuclear Responses -- 4 Multistep Model for H. pylori-Induced Epithelial Barrier Disruption -- 5 Concluding Remarks -- Acknowledgements -- References -- 10 Helicobacter pylori-Induced Changes in Gastric Acid Secretion and Upper Gastrointestinal Disease -- Abstract -- 1 Gastric Acid Secretion -- 1.1 Introduction -- 1.2 Physiology of Gastric Acid Secretion -- 1.2.1 Neural, Hormonal, and Paracrine Regulation -- 1.2.2 H,K-ATPase: The Parietal Cell Proton Pump -- 2 H. pylori Infection of the Stomach -- 2.1 Colonization of Favored Gastric Niches -- 2.2 Immune Response. , 3 H. pylori-Induced Changes in Gastric Acid Secretion -- 3.1 Acute Hypochlorhydria -- 3.2 Chronic Hypochlorhydria -- 3.3 Hyperchlorhydria -- 4 H. pylori in Gastric and Esophageal Diseases -- 4.1 Gastric Atrophy, Intestinal Metaplasia, and Adenocarcinoma -- 4.2 Esophageal Gastroesophageal Reflux Disease, Barrett's Esophagus and Adenocarcinoma -- 5 Concluding Remarks -- References -- 11 Impact of the Microbiota and Gastric Disease Development by Helicobacter pylori -- Abstract -- 1 Introduction -- 2 The Stomach -- 3 How We Can Assess the Composition of Microbiota -- 3.1 Culture -- 3.2 Molecular Methods -- 3.3 Methods of Analysis -- 4 Microbiota Composition of the Stomach -- 4.1 Differences in Antrum and Corpus -- 4.2 Modification of Gastric Microbiome -- 5 Differences in Gastric Microbiota in H. pylori-Positive and H. pylori-Negative Subjects -- 6 Effect of the Histopathological Changes in the Gastric Mucosa Associated with H. pylori Over the Microbiota -- 6.1 Gastritis -- 6.2 Peptic Ulcer -- 6.3 Gastric Cancer -- 6.4 Mechanisms of Carcinogenesis -- 7 Effect of H. pylori Infection in the Intestinal Microbiome -- 8 Effect of Probiotics -- 9 Concluding Remarks -- References -- 12 Pathogenesis of Gastric Cancer: Genetics and Molecular Classification -- Abstract -- 1 Gastric Cancer Epidemiology -- 2 Histological Phenotypes of Gastric Cancer -- 3 Helicobacter pylori Infection and Gastric Cancer -- 4 Epstein-Barr Virus Infection and Gastric Cancer -- 5 Molecular Phenotypes of Sporadic Gastric Cancer -- 5.1 Tumors with Chromosomal Instability -- 5.2 Tumors with Microsatellite Instability -- 5.3 Genomically Stable Tumors -- 5.4 EBV-Positive Tumors -- 6 Hereditary Gastric Cancer -- 7 Concluding Remarks -- References -- 13 Helicobacter pylori-Mediated Genetic Instability and Gastric Carcinogenesis -- Abstract. , 1 Genetic Abnormalities in Gastric Cancer Tissues Related to H. pylori Infection.

Note: Förderkennzeichen BMBF 01KI1725E , Verbundnummer 01180521 , Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden , Sprache der Zusammenfassungen: Deutsch, Englisch