Unifying Microbial Mechanisms: Shared Strategies of Pathogenesis

Microbial pathogenesis is the study of the mechanisms by which microbes (bacteria, viruses, protozoa, and multicellular parasites) cause infectious disease and make their hosts (humans) ill. Bacterial infections we thought were easily treatable are again a huge cause for concern with the well-publicized rise of antibiotic resistance. There are very few effective antiviral drugs and we live with the threat of epidemics such as bird flu and the outbreaks of viruses such the recent (and ongoing) Ebola crisis. Parasitic diseases such as malaria continue to pose a heavy burden in the developing world and with climate change could spread into the developed world. There is therefore an urgent need to understand microbial mechanisms, with research programmes and university courses dedicated to the subject.

Table of Contents:
Contents Preface xv Acknowledgement xvii Chapter 1: Introduction to Pathogenesis 1 Introduction Henle-Koch postulates and evolving views of infectious disease causation Experimental models of pathogenicity The ethics of using humans, animals and cell lines in pathogenics research 6 Advantages and disadvantages of human experimentation in the study of the pathogenesis of infectious diseases 8 Animal models in the study of the pathogenesis of infectious diseases 8 Other considerations in experimental models of the pathogenesis of infectious diseases 10 Human cell lines as a surrogate for microbe–host interactions 12 Bibliography Chapter 2: Normal Microbiotas of the Human Body 17 Introduction Microbiota of the skin 20 Microbiota of the vagina 22 Microbiota of the urinary tract 25 Microbiota of the conjunctiva 31 Respiratory tract microbiota 31 Microbiota of the alimentary canal Mouth 34 Oesophagus 40 Stomach 40 Small intestine 40 Large intestine 44 Key concepts Bibliography Chapter 3: Biofilms 59 Introduction Biofilms structure and properties Mucosae versus skin 60 Initial steps in biofilm formation 61 Biofilm development and the climax community 63 Quorum sensing in biofilms 65 Biofilm dispersal 67 Biofilms in human infections Peripheral and central i.v. catheters 67 Urinary catheters 68 Bladder biofilms 69 Endotracheal tubes 69 Peritoneal cavity dialysis catheters 70 Prosthetic joints 71 Heart valves 71 Chronic wounds 71 Otitis media 73 Cystic fibrosis 74 Biofilm formation by filamentous fungi Biofilm formation by viruses How biofilms are studied Key concepts Bibliography Chapter 4: Adhesion to Host Surfaces 87 Introduction Barrier epithelia Skin 88 Mucous membranes (mucosae) 89 Blood and lymphatic vessels 91 Blood-brain barrier 92 Foeto-placental interface 93 The extracellular matrix and intercellular adhesion molecules Abiotic surfaces 94 Initial adhesion events 95 Adhesin–receptor interactions Protein–carbohydrate (lectin) interactions 97 Bacteria 98 Fungi 102 Viruses 103 Parasites 106 Protein–protein interactions Microbial surface components recognising adhesive matrix molecules 107 Fibrinogen-binding MSCRAMMs 115 Vitronectin-binding MSCRAMMs 116 Proteoglycan-binding adhesives 117 Bacteria 117 Viruses 117 Parasites 118 Anchorless adhesins (Moonlighting proteins) 119 Bacteria 119 Fungi 120 Protozoa and multicellular parasites 120 Cell wall glycopolymers 121 Capsules 121 Galectins as bridging molecules in microbial adhesions Adhesion to other barriers Endothelium of blood vessels and lymphatics 124 Key concepts References Chapter 5: Facilitated Cell Entry 129 Introduction Crossing intact skin Enzymatic degradation 131 Crossing intact mucosal epithelium Entry via microfold (M) cells 132 Enzymatic degradation 133 Polar tube formation 134 Moving junction 134 Paracytosis 135 Endocytosis 138 Reorganisation of the actin cytoskeleton and endosomal trafficking 141 Exploitation of endocytosis pathways by pathogens Bacteria 145 Zipper mechanism Trigger mechanism 148 Viruses 156 Fungi 156 Microtubule reorganisation Transcytosis Key concepts Bibliography Chapter 6: Exotoxins and Endotoxins 167 Bacterial exotoxins Introduction 167 Membrane-acting toxins 168 Superantigens (SAs) 168 Heat-stable exotoxins (STs) 170 Membrane-damaging exotoxins α-helical pore-forming exotoxins 172 β-barrel pore-forming exotoxins 173 RTX exotoxins 175 MARTX exotoxins 176 Intracellular exotoxins AB exotoxins 177 AB5 exotoxins 179 AB exotoxins 182 Fungal toxins Parasite exotoxins Endotoxins Key concepts Bibliography Chapter 7: Extracellular Degradative Enzymes 187 Introduction Proteases Potential roles of microbial proteases in pathogenesis Tissue destruction and cell internalisation 188 Inactivation of plasma protease inhibitors 189 Activation of bradykinin-generating and blood-clotting cascades 190 Protease-activated receptor 190 Chemoattractant molecules 191 Immunoglobulins 191 Microbe and parasite glycosidases Deglycosylation of immunoglobulins 194 Adhesion 194 Microbe and parasite phospholipases Bacterial phospholipases 196 Fungal phospholipases 198 Parasite phospholipases 198 Key concepts Bibliography Chapter 8: Evasion of the Human Innate Immune System 201 Introduction Antimicrobial peptides Overview 201 Bacterial evasion of AMPSs 204 Fungal evasion of AMPs 205 Virus evasion of AMPs 205 Parasite evasion of AMPs 205 The complement system Recruiting and mimicking RCAs 210 Destroying complement components 213 Microbial envelope/wall components that inhibit complement 214 Evasion resulting from cell wall structure 214 Consuming complement in the fluid phase 214 Circumvention of phagocytosis Chemoattraction 216 Regulation of chemokines 218 Circumventing pattern recognition receptors Subversion of PRR crosstalk 223 Targeting cytosolic PRRs, IPS-1, RIG-I and MDA5 224 Masking microbe-associated molecular patterns 225 Manipulating host inhibitory signaling Pathogen survival inside host cells Bacteria 228 Arresting the phagosome/endosome 229 Diverting the endosomal/phagosomal pathways 232 Survival in the endolysosome/phagolysosome 233 Fungi 235 Parasites 237 Escape to the cytosol Virus interactions with intracellular vacuoles Cytosolic motility of intracellular pathogens Escape of intracellular pathogens from host cells Cytolysis 245 Actin-mediated cell-to-cell spread 245 Protrusion into the extracellular environment (extrusion) 247 Induction of programmed cell death 247 Preventing programmed cell death 248 Interference with the host cell cycle 248 Reprogramming the host cell 249 Evading autophagy Preventing the induction of autophagy 250 Preventing the maturation of the autophagosome into an autolysosome 251 Avoiding pathogen capture by the autophagosome 251 Utilising the autophagosome as a habitat for survival, replication, or escape from the host cell 253 The role of autophagy in eukaryotic pathogens 253 Evading natural killer cells Evasion of the natural killer group 2D receptor 257 Evasion of natural cytotoxicity receptors 258 Key concepts Bibliography Chapter 9: Evasion of the Human Adaptive Immune System 263 Introduction Antigen presentation Linking sensing of MAMPs by pattern-recognition receptors with antigen processing 264 Activating naïve T cells by licenced dendritic cells 265 Follicular helper CD4+ T cells help B cells make high-affinity, class-switched antibodies 267 Inhibition of antigen presentation by MHC class I and class II pathways Viral subversion of the MHC class I antigen-processing pathway 270 Bacterial subversion of the MHC class I antigen-processing pathway 270 Viral subversion of the MHC class II pathway antigen-presenting pathway 271 Bacterial subversion of the MHC class II antigen-processing pathway 273 Parasite evasion of the MHC class II antigen-processing pathway 273 Manipulation of co-stimulatory molecules 275 Manipulation of regulatory receptors and ligands 276 Up-regulation of IL-10 276 Evasion of antibody Antigen modulation Antigenic and phase variation Subverting B lymphocytes (B Cells) Subverting T lymphocytes (T Cells) Key concepts Bibliography Chapter 10: Persistent and Latent Infections 295 Introduction Persistent bacterial infections Introduction 296 Helicobacter pylori 296 Treponema pallidum subspecies pallidum 301 Mycobacterium tuberculosis 302 Salmonella typhi serovar Typhi 307 Persistent virus infections Introduction 308 Herpesviruses 309 Hepatitis B, C and D viruses 313 Measles virus 316 Adenoviruses 317 Human papilloma viruses 317 Human polyomaviruses 319 Human immunodeficiency virus 320 Human T-cell lymphotropic virus type 1 321 Persistent parasite infections Introduction 322 Helminths 322 Plasmodium 323 Leishmania 325 Trypanosoma cruzi 327 Toxoplasma gondii 329 Myeloid-derived suppressor cells in chronic infections 330 Key concepts Bibliography Index 337

About the Author :
Mike Cole is an experienced instructor at Georgetown University where he is professor of microbiology and immunology and teaches microbial pathogenesis, immunology, and bacteriology. His research interests are into the regulation of commensal and pathogenic bacteria at the mucosal surface by the secretory immune response and the ontogeny of the secretory immune system. He regularly attends the ASM education conference and is the author of half the bacterial cases in Case Studies in Infectious Disease.