Microbial pathogenesis is the study of the mechanisms by which microbes cause infectious disease and make their hosts ill. With the rise of antibiotic resistance, there is an urgent need to understand microbial mechanisms through research programmes and university courses dedicated to the subject.

ContentsPreface xvAcknowledgement xviiChapter 1: Introduction to Pathogenesis 1IntroductionHenle-Koch postulates and evolvingviews of infectious disease causationExperimental models of pathogenicityThe ethics of using humans, animals and cell lines inpathogenics research 6Advantages and disadvantages of human experimentationin the study of the pathogenesis of infectious diseases 8Animal models in the study of the pathogenesis ofinfectious diseases 8Other considerations in experimental models of thepathogenesis of infectious diseases 10Human cell lines as a surrogate for microbe–host interactions 12BibliographyChapter 2: Normal Microbiotas of the Human Body 17IntroductionMicrobiota of the skin 20Microbiota of the vagina 22Microbiota of the urinary tract 25Microbiota of the conjunctiva 31Respiratory tract microbiota 31Microbiota of the alimentary canalMouth 34Oesophagus 40Stomach 40Small intestine 40Large intestine 44Key conceptsBibliographyChapter 3: Biofilms 59IntroductionBiofilms structure and propertiesMucosae versus skin 60Initial steps in biofilm formation 61Biofilm development and the climax community 63Quorum sensing in biofilms 65Biofilm dispersal 67Biofilms in human infectionsPeripheral and central i.v. catheters 67Urinary catheters 68Bladder biofilms 69Endotracheal tubes 69Peritoneal cavity dialysis catheters 70Prosthetic joints 71Heart valves 71Chronic wounds 71Otitis media 73Cystic fibrosis 74Biofilm formation by filamentous fungiBiofilm formation by virusesHow biofilms are studiedKey conceptsBibliographyChapter 4: Adhesion to Host Surfaces 87IntroductionBarrier epitheliaSkin 88Mucous membranes (mucosae) 89Blood and lymphatic vessels 91Blood-brain barrier 92Foeto-placental interface 93The extracellular matrix and intercellular adhesion moleculesAbiotic surfaces 94Initial adhesion events 95Adhesin–receptor interactionsProtein–carbohydrate (lectin) interactions 97Bacteria 98Fungi 102Viruses 103Parasites 106Protein–protein interactionsMicrobial surface components recognising adhesive matrixmolecules 107Fibrinogen-binding MSCRAMMs 115Vitronectin-binding MSCRAMMs 116Proteoglycan-binding adhesives 117Bacteria 117Viruses 117Parasites 118Anchorless adhesins (Moonlighting proteins) 119Bacteria 119Fungi 120Protozoa and multicellular parasites 120Cell wall glycopolymers 121Capsules 121Galectins as bridging molecules in microbial adhesionsAdhesion to other barriersEndothelium of blood vessels and lymphatics 124Key conceptsReferencesChapter 5: Facilitated Cell Entry 129IntroductionCrossing intact skinEnzymatic degradation 131Crossing intact mucosal epitheliumEntry via microfold (M) cells 132Enzymatic degradation 133Polar tube formation 134Moving junction 134Paracytosis 135Endocytosis 138Reorganisation of the actin cytoskeleton and endosomaltrafficking 141Exploitation of endocytosis pathways by pathogensBacteria 145Zipper mechanismTrigger mechanism 148Viruses 156Fungi 156Microtubule reorganisationTranscytosisKey conceptsBibliographyChapter 6: Exotoxins and Endotoxins 167Bacterial exotoxinsIntroduction 167Membrane-acting toxins 168Superantigens (SAs) 168Heat-stable exotoxins (STs) 170Membrane-damaging exotoxinsα-helical pore-forming exotoxins 172β-barrel pore-forming exotoxins 173RTX exotoxins 175MARTX exotoxins 176Intracellular exotoxinsAB exotoxins 177AB5 exotoxins 179AB exotoxins 182Fungal toxinsParasite exotoxinsEndotoxinsKey conceptsBibliographyChapter 7: Extracellular Degradative Enzymes 187IntroductionProteasesPotential roles of microbial proteases in pathogenesisTissue destruction and cell internalisation 188Inactivation of plasma protease inhibitors 189Activation of bradykinin-generating and blood-clottingcascades 190Protease-activated receptor 190Chemoattractant molecules 191Immunoglobulins 191Microbe and parasite glycosidasesDeglycosylation of immunoglobulins 194Adhesion 194Microbe and parasite phospholipasesBacterial phospholipases 196Fungal phospholipases 198Parasite phospholipases 198Key conceptsBibliographyChapter 8: Evasion of the Human Innate Immune System 201IntroductionAntimicrobial peptidesOverview 201Bacterial evasion of AMPSs 204Fungal evasion of AMPs 205Virus evasion of AMPs 205Parasite evasion of AMPs 205The complement systemRecruiting and mimicking RCAs 210Destroying complement components 213Microbial envelope/wall components that inhibitcomplement 214Evasion resulting from cell wall structure 214Consuming complement in the fluid phase 214Circumvention of phagocytosisChemoattraction 216Regulation of chemokines 218Circumventing pattern recognition receptorsSubversion of PRR crosstalk 223Targeting cytosolic PRRs, IPS-1, RIG-I and MDA5 224Masking microbe-associated molecular patterns 225Manipulating host inhibitory signalingPathogen survival inside host cellsBacteria 228Arresting the phagosome/endosome 229Diverting the endosomal/phagosomal pathways 232Survival in the endolysosome/phagolysosome 233Fungi 235Parasites 237Escape to the cytosolVirus interactions with intracellular vacuolesCytosolic motility of intracellular pathogensEscape of intracellular pathogens from host cellsCytolysis 245Actin-mediated cell-to-cell spread 245Protrusion into the extracellular environment (extrusion) 247Induction of programmed cell death 247Preventing programmed cell death 248Interference with the host cell cycle 248Reprogramming the host cell 249Evading autophagyPreventing the induction of autophagy 250Preventing the maturation of the autophagosome into anautolysosome 251Avoiding pathogen capture by the autophagosome 251Utilising the autophagosome as a habitat for survival,replication, or escape from the host cell 253The role of autophagy in eukaryotic pathogens 253Evading natural killer cellsEvasion of the natural killer group 2D receptor 257Evasion of natural cytotoxicity receptors 258Key conceptsBibliographyChapter 9: Evasion of the Human Adaptive Immune System 263IntroductionAntigen presentationLinking sensing of MAMPs by pattern-recognitionreceptors with antigen processing 264Activating naïve T cells by licenced dendritic cells 265Follicular helper CD4+ T cells help B cells makehigh-affinity, class-switched antibodies 267Inhibition of antigen presentation byMHC class I and class II pathwaysViral subversion of the MHC class I antigen-processingpathway 270Bacterial subversion of the MHC class I antigen-processingpathway 270Viral subversion of the MHC class II pathwayantigen-presenting pathway 271Bacterial subversion of the MHC class II antigen-processingpathway 273Parasite evasion of the MHC class II antigen-processingpathway 273Manipulation of co-stimulatory molecules 275Manipulation of regulatory receptors and ligands 276Up-regulation of IL-10 276Evasion of antibodyAntigen modulationAntigenic and phase variationSubverting B lymphocytes (B Cells)Subverting T lymphocytes (T Cells)Key conceptsBibliographyChapter 10: Persistent and Latent Infections 295IntroductionPersistent bacterial infectionsIntroduction 296Helicobacter pylori 296Treponema pallidum subspecies pallidum 301Mycobacterium tuberculosis 302Salmonella typhi serovar Typhi 307Persistent virus infectionsIntroduction 308Herpesviruses 309Hepatitis B, C and D viruses 313Measles virus 316Adenoviruses 317Human papilloma viruses 317Human polyomaviruses 319Human immunodeficiency virus 320Human T-cell lymphotropic virus type 1 321Persistent parasite infectionsIntroduction 322Helminths 322Plasmodium 323Leishmania 325Trypanosoma cruzi 327Toxoplasma gondii 329Myeloid-derived suppressor cells in chronic infections 330Key conceptsBibliographyIndex 337