Bacteria Pathogenesis

Bacteria Pathogenesis思维导图：包含Normal Microbiota，Difference between Pathogens &Normal microbiota，Enter the body，Colonisation of the Host，Invasion of the host cell等等

Bacteria Pathogenesis

• Normal Microbiota
  • Restricted to our body surfaces (skin, gut)
    • Abundant to our external-facing surfaces and membrane
    • Contributes to development of immune system, GI tract, mucosal physiology
    • Provide us with nutrients and help keep us healthy
  • Protective against infection from other microorganisms by compeptition
    • Has complex and interconnected microbial community
      • Estimated the humans body has 10x more microbial than human cells
      • Inhabitants make it difficult, or inhospitable, for others to colonise
  • Acquired at brith
    • Further develops over the lifespan of the individuals
  • In healthy humans:
    • Internal tissues are normally devoid of microorganisms — normally sterile places
      • Blood
      • Lymph
      • CSF
      • Muscles
  • In diseased or infected states:
    • Microorganisms are found in these deeper tissue — they are not meant to be there
      • Often result in stimulation of an immune response
• Difference between Pathogens & Normal microbiota
  • Normal Microbiota
    • Possible causes of infections if certain body sites are injured
      • Normal microbiota are potential pathogen if provided an opportunity to colonise / cause disease
    • Causes and consequences of colonisation / growth of non-normal (or dysregulated) microbiota at certain body sites
      • Possible contributions to various human disease conditions
    • The role of normal microbiota regulating the host immune response
  • Pathogens
    • Pathogens express virulence factors
      • Which are not expressed by normal microbiota
      • Can mediate
        • Adhesin - ligand of host cells
        • Anti-phagocytic - capsule
        • Damage - toxin
      • Know an organisms is a pathogen through Koch’s Postulates
• Enter the body
  • Physical Barriers:
    • High salt, fatty acids, dry, (wounds) — skin
    • Acid - stomach
    • Mucous and cilia - LRT lower respiratory tract
    • Peristalsis - GI tract
    • Soluble membrane - lysozyme in salvia and tears
  • Innate Immune Response:
    • Complement
    • Phagocytosis by professional phagocytes
      • Neutrophil / macrophage
    • Inflammation
      • Toll-like receptors signalling, cytokine, via recognition of bacterial products
  • Adaptive Immune Response:
    • Antibodies
    • Cytotoxic T cells
• Colonisation of the Host
  • Must overcome physical barrier and innate immune response
  • Must out compete the Norma microbiota
  • Requires adherence of the bacteria to a mucosal surface
    • Bacterial cell surface structures mediate adherence
    • Adherence is normally both host-specific and tissue-specific
      • Loss attachment of the bacteria to the mucosal surface
      • Close adhesion of bacteria to epithelial cells
      • Invasion of epithelial cells
  • Adherence to Host cells
    • Adhesin
      • An external structure on the surface of bacteria (mediate adherence)
      • Include:
        • Pili (fimbriae)
          • Establish ‘loose’ or non-intimate adhesion
            • Facilitate adherence to the host cell
              • Complex strucutre
              • Rod shaped, hollow cylinder
              • Ordered helical array of protein subunits of pilin
            • Tips of pilus mediates adhesion
              • May be pilin, or other protein
              • Confers host cell / tissue specificity
            • May be all over cell (peritrichous) or polar
        • Afimbrial adhesins
          • Establish ‘ close’ or intimate adhesion
            • Establish close to intimate association with the host cell
              • Usually membrane-embedded proteins
                • Typically cell envelop components GP or outer membrane proteins GN
              • Can bind to proteins or carbohydrate receptors on the host cell
            • Pathogens my posses > 1 afimbrial adhesin
      • One type of pathogen may produce multiple adhesins
    • Capsules
      • Extracellular material
        • Made of polysaccharide
        • Well organised, difficult to wash off the cell
        • Occur in GN ad GP bacteria
      • Can help prevent
        • Desiccation
        • Immune evasion (avoid phagocytosis)
      • Sticky
        • Aid adherence to surface, tissues, and to other bacteria
    • Dental Plaque
      • Biofilm that develops on the surface of teeth
        • Plaque formation initiated by attachment of salivary protein
          • Followed by attachment of bacteria
        • Provides an anaerobic environment that allows some bacteria to flourish
• Invasion of the host cell
  • Mediated by Invasins
    • Single proteins, or complexes of proteins
    • Binding of the invasin to the host cell receptor causes internalisation of the bacteria
      • Requires alternation of the host cell cytoskeleton - facilitate invasion
    • Can be a passive or active uptake processes by host cells
    • Is usually mediated by the host cell in response to a bacterial trigger or signal
  • Zipper mechanism
    • Listeria monocytogenes
      • Intestinal epithelial cells - invasive
      • Phagocytes - invasive
      • In this pathogen, binding of internalin to host cell receptor - cadherin
      • Host cell receptor (cadherin) clustering and formation of phagocytes cup, followed by closure and retraction
  • Trigger Mechanism
    • Salmonella Typhimurium
      • Intestinal epithelial cells - invasive
      • Intestinal macrophages - invasive
      • In this pathogen, directly inject invasins into the host cell to activated membrane ruffling - Sip
      • Uptakes of bacteria by macropinocytosis and endosomal trafficking