The Actin Cytoskeleton and Bacterial Infection (Current Topics in Microbiology and Immunology Book 399)

This volume describes the mechanisms which bacteria have created to secure their survival, proliferation and dissemination by subverting the actin cytoskeleton of host cells. Bacteria have developed a veritable arsenal of toxins, effector proteins and virulence factors that allow them to modify the properties of the intracellular actin cytoskeleton for their own purposes. Bacterial factors either modify actin directly as the main component of this part of the cytoskeleton or functionally subvert regulatory or signalling proteins terminating at the actin cytoskeleton. In short, this volume provides an overview of the various tricks bacteria have evolved to ℓ́ℓact on actinℓ́ℓ in order to hijack this essential host cell component for their own needs. As such, it will be of interest to scientists from many fields, as well as clinicians whose work involves infectious diseases Preface 6 Contents 9 45 Actin: Structure, Function, Dynamics, and Interactions with Bacterial Toxins 11 Abstract 11 1 Introduction 12 2 Actin 13 2.1 Actin Structure 14 2.2 Binding Sites on Actin for Actin-Binding Proteins 16 2.3 Filamentous (F-) Actin 16 2.4 Actin Dynamics: Polymerization Behaviour 18 3 Interactions with Actin-Binding Proteins (ABPs) 19 3.1 G-actin-Sequestering Proteins 21 3.2 F-actin-Nucleating Proteins and Their Nucleation-Promoting Factors (NPFs) 21 3.3 F-actin-Elongating Proteins 22 3.4 F-actin-Capping Proteins 22 3.5 F-actin-Bundling and Cross-linking Proteins 23 3.6 F-actin-Stabilizing Proteins 23 3.7 F-actin-Severing Proteins 23 3.8 Regulation of the Activity and Localization of ABPs 24 4 Examples of Bacterial Proteins that Subvert the Host Actin Cytoskeleton 24 4.1 Direct Interactions of Bacterial Effectors with Actin 30 4.1.1 Direct Modifications of G-actin 30 4.1.2 F-actin Dynamics Modifying Bacterial Proteins 32 4.2 Manipulation of Actin-Binding Proteins by Bacterial Effectors 33 4.2.1 Recruitment and Regulation of the Host F-actin Nucleation Machinery 33 4.2.2 Interactions of Bacterial Effectors with Actin-Binding Proteins (ABPs) 34 4.2.3 Manipulation of Host ABP Regulation: Rho GTPases, Kinases, and Phospholipids as Bacterial Targets 34 5 Conclusions 35 References 36 25 Formation of Nanotube-Like Protrusions, Regulation of Septin Organization and Re-guidance of Vesicle Traffic by Depolymerization of the Actin Cytoskeleton Induced by Binary Bacterial Protein Toxins 45 Abstract 45 1 Introduction 46 2 Actin-Depolymerizing Toxins 46 2.1 Structure of Binary Toxins 47 2.2 Receptors and Uptake 48 3 Modification of Actin by ADP-Ribosylating Toxins 48 4 Cellular Consequences of the ADP-Ribosylation of Actin in Arginine-177 50 4.1 Effects of Actin-Depolymerizing Toxins on Microtubules 50 4.2 Mechanisms Involved in Protrusion Formation: A Role for Septins 52 4.3 Role and Functions of Toxin-Induced Cell Protrusions 54 4.3.1 Re-guidance of Vesicle Traffic 55 5 Conclusions 55 References 56 43 Photorhabdus luminescens Toxins TccC3 and TccC5 Affect the Interaction of Actin with Actin-Binding Proteins Essential for Treadmilling 62 Abstract 62 1 Introduction 63 2 Life Cycle and Tc Toxins of Photorhabdus luminescens 64 3 ADP-Ribosylation of Actin by P. luminescens TccC3 65 3.1 Thr148-ADP-Ribosylation Promotes Actin Polymerization 65 3.2 Impaired Interactions of Thr148-ADP-Ribosylated Actin with a Number of Actin-Binding Proteins 69 4 ADP-Ribosylation of Rho GTPases by Photorhabdus luminescens TccC5 71 5 Conclusions 73 References 73 23 Comparative Studies of Actin- and Rho-Specific ADP-Ribosylating Toxins: Insight from Structural Biology 77 Abstract 77 1 Introduction 78 2 Functional and Structural Studies of Actin- and Rho-Specific ADP-Ribosylating Toxins 79 3 Comparative Studies of Substrate Recognition by Actin- and Rho-Specific ARTs 82 4 Cell Entry Mechanism Between Actin- and Rho-Specific ARTs 86 5 Conclusion 89 Acknowledgements 90 References 90 22 Pathogenic Mechanisms of Actin Cross-Linking Toxins: Peeling Away the Layers 95 Abstract 95 1 Introduction 96 2 Discovery of ACD 97 3 ACD-Containing Toxins and ACD-Producing Organisms 98 3.1 ACD Protein Family 98 3.1.1 Originally Identified ACD Toxins 98 3.1.2 Extended List of ACD Toxins 99 3.2 ACD-Producing Organisms 101 3.3 ACD Pathogenesis 102 3.3.1 Pathological Role of ACD-Containing Toxins in Animal Models 102 3.3.2 Cellular Toxicity of ACD 103 4 Mechanism of the Cross-Linking Reaction 104 4.1 Substrate and Cofactors of ACD 104 4.2 Nature of the Cross-Link 105 4.3 Structure of ACD and Its Homology to Glutamine Synthetases 106 4.3.1 ACD Homology to Glutamine Synthetases 106 4.3.2 Crystal Structure of ACD 107 4.3.3 Metal Cofactors 109 5 Layers of the ACD Pathogenesis: Toxicity Amplification by Actin-Binding Proteins 110 5.1 Role of G-Actin-Sequestering Proteins in the ACD Pathogenesis 110 5.2 Role of Actin Assembly Factors in the Mechanisms of ACD Toxicity 112 6 Conclusions and Future Perspectives 114 Acknowledgements 115 References 115 30 ActA of Listeria monocytogenes and Its Manifold Activities as an Important Listerial Virulence Factor 121 Abstract 121 1 Introduction 122 2 ActA as a Virulence Factor of L. monocytogenes 123 3 actA Expression and Its Localization 125 3.1 Regulation of actA Expression 125 3.2 Modification of ActA 126 3.3 Localisation of ActA 127 4 ActA Interaction with Actin 127 4.1 ActA-Mediated Intracellular Movement 127 4.2 ActA-Triggered Spread to Neighboring Cells 129 5 Interaction of L. monocytogenes with Stathmin via ActA 130 6 ActA and Autophagy 131 6.1 The Autophagic Machinery 131 6.2 ActA-Mediated Avoidance of Autophagy by L. monocytogenes 132 6.3 Strain-Specific Evasion of Autophagy by L. monocytogenes 132 7 ActA-Triggered Activation of NF-κB 133 8 Involvement of ActA in Aggregation and Biofilm Formation 133 9 Invasion and Phagosomal Disruption 134 10 Conclusions 134 Acknowledgements 135 References 135 26 Actin-Dependent Regulation of Borrelia burgdorferi Phagocytosis by Macrophages 141 Abstract 141 1 Introduction 142 2 Borrelia and the Stages of Lyme Disease 144 3 Phagocytic Uptake of Borrelia by Macrophages 145 4 Actin-Rich Uptake Structures: Filopodia and Coiling Pseudopods 147 5 Actin Dynamics During Borrelia Phagocytosis: The Roles of Formins and Arp2/3 Complex 151 6 Intracellular Processing of Borrelia—A Central Role for RabGTPases 154 7 Conclusions 157 Acknowledgements 158 References 158 27 New Aspects on Bacterial Effectors Targeting Rho GTPases 163 Abstract 163 1 Introduction 164 2 Switching On and Off the Rho GTPases with Virulence Factors 165 2.1 General Aspects of Rho GTPases 165 2.2 Bacterial Factors Targeting Rho GTPases 167 2.3 Targeting Rho GTPases in Infection 169 3 Ubiquitin and Proteasomal System Control of Rho GTPases 169 3.1 Ubiquitin and Proteasomal Machineries 169 3.2 Control of Rho GTPases by Ubiquitin and Proteasomal Machineries 170 4 Corruption of the Endothelial Barrier 172 4.1 Induction of Cellular Dewetting by Toxins 172 4.2 Invasive Properties of Virulence Factors Targeting RhoA 174 5 Corruption of Innate Immunity 174 5.1 Virulence Factors Activating Rho GTPases and the Inflammasome 174 5.2 RhoA-Inactivating Toxins and the Inflammasome 176 6 Conclusions 177 Acknowledgements 177 References 177 35 Type III Secreted Virulence Factors Manipulating Signaling to Actin Dynamics 183 Abstract 183 1 Introduction 184 2 WxxxE Effectors 185 3 Salmonella 186 4 Shigella 187 5 A/E Lesion Pathogens 188 5.1 Pedestal Formation 190 5.2 Phosphorylation of Tir 190 5.3 Recruiting the Actin Machinery 191 5.4 Deciphering the Different Pathways Leading to Pedestal Formation 192 5.4.1 The Tyrosine—474 Pathway in EPEC 192 5.4.2 The Tyrosine—454 Pathway in EPEC 192 5.4.3 The tyrosine—458 pathway in EHEC 194 5.5 Other Factors Influencing Actin Pedestals 196 6 Concluding Remarks 198 References 199 33 Acting on Actin: Rac and Rho Played by Yersinia 208 Abstract 208 1 Introduction 209 2 Invasion of Cells by Enteropathogenic Yersinia Spp 210 3 Yersinia Effector Proteins and an Exotoxin Manipulating Rho Proteins and the Actin Cytoskeleton 213 3.1 YopE 213 3.2 YopT 214 3.3 YopO/YpkA 215 3.4 Other Yops Affecting the Cytoskeleton 217 3.5 Cytotoxic Necrotizing Factor-Y 218 4 Regulation of T3SS-Mediated Effector Delivery by Manipulation of Rho GTP-Binding Protein Activity and the Actin Cytoskeleton 218 5 Synopsis 221 References 221 31 Bacterial Actins and Their Interactors 228 Abstract 228 1 Family of Bacterial Actins 229 1.1 Structure of Bacterial Actins 229 1.1.1 Monomer 230 1.1.2 Protofilament 230 1.1.3 Filament Architecture 232 1.2 Dynamics of Filament Assembly 235 1.2.1 MreB 235 1.2.2 Bacterial Actins in Plasmid Segregation 236 1.2.3 MamK 236 1.2.4 FtsA 237 2 Interactors of Bacterial Actins 237 2.1 Interactors of MreB 238 2.1.1 RodZ 238 2.1.2 MbiA 239 2.1.3 YeeU and YeeV 239 2.1.4 Interaction Partners in Myxococcus xanthus Motility 240 2.1.5 Filament Interactors of MreB 241 2.2 Filament Stabilizers and Nucleators of Bacterial Actins in Plasmid Segregation 241 2.3 Interactors of MamK 243 2.4 Interactors of FtsA 244 3 Comparison Between Interacting Proteins of Eukaryotic and Bacterial Actins 245 Acknowledgements 246 References 246 Front Matter....Pages i-x Actin: Structure, Function, Dynamics, and Interactions with Bacterial Toxins....Pages 1-34 Formation of Nanotube-Like Protrusions, Regulation of Septin Organization and Re-guidance of Vesicle Traffic by Depolymerization of the Actin Cytoskeleton Induced by Binary Bacterial Protein Toxins....Pages 35-51 Photorhabdus luminescens Toxins TccC3 and TccC5 Affect the Interaction of Actin with Actin-Binding Proteins Essential for Treadmilling....Pages 53-67 Comparative Studies of Actin- and Rho-Specific ADP-Ribosylating Toxins: Insight from Structural Biology....Pages 69-86 Pathogenic Mechanisms of Actin Cross-Linking Toxins: Peeling Away the Layers....Pages 87-112 ActA of Listeria monocytogenes and Its Manifold Activities as an Important Listerial Virulence Factor....Pages 113-132 Actin-Dependent Regulation of Borrelia burgdorferi Phagocytosis by Macrophages....Pages 133-154 New Aspects on Bacterial Effectors Targeting Rho GTPases....Pages 155-174 Type III Secreted Virulence Factors Manipulating Signaling to Actin Dynamics....Pages 175-199 Acting on Actin: Rac and Rho Played by Yersinia ....Pages 201-220 Bacterial Actins and Their Interactors....Pages 221-242 This volume describes the mechanisms which bacteria have created to secure their survival, proliferation and dissemination by subverting the actin cytoskeleton of host cells. Bacteria have developed a veritable arsenal of toxins, effector proteins and virulence factors that allow them to modify the properties of the intracellular actin cytoskeleton for their own purposes. Bacterial factors either modify actin directly as the main component of this part of the cytoskeleton or functionally subvert regulatory or signalling proteins terminating at the actin cytoskeleton. In short, this volume provides an overview of the various tricks bacteria have evolved to ĺlact on actinĺl in order to hijack this essential host cell component for their own needs. As such, it will be of interest to scientists from many fields, as well as clinicians whose work involves infectious diseases