1st Edition

Unifying Microbial Mechanisms Shared Strategies of Pathogenesis

By Michael F. Cole Copyright 2019
    364 Pages 151 Color & 17 B/W Illustrations
    by Garland Science

    364 Pages 151 Color & 17 B/W Illustrations
    by Garland Science

    364 Pages 151 Color & 17 B/W Illustrations
    by Garland Science

    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.


    Preface xv

    Acknowledgement xvii

    Chapter 1: Introduction to Pathogenesis 1


    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


    Chapter 2: Normal Microbiotas of the Human Body 17


    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


    Chapter 3: Biofilms 59


    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


    Chapter 4: Adhesion to Host Surfaces 87


    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


    Chapter 5: Facilitated Cell Entry 129


    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


    Key concepts


    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


    Key concepts


    Chapter 7: Extracellular Degradative Enzymes 187



    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


    Chapter 8: Evasion of the Human Innate Immune System 201


    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


    Chapter 9: Evasion of the Human Adaptive Immune System 263


    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


    Chapter 10: Persistent and Latent Infections 295


    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


    Index 337


    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.