Pathogenicity I: Colonisation & Evasion of Host Defence

• What is pathogenicity?

  Ability to cause disease
• What is virulence?

  degree of pathogenicity (ability to cause disease)
• What is virulent bacteria?

  Usually cause disease when they infect
• What is a virulence factor/gene?

  Bacterial/component only involved in pathogenesis
• What's a housekeeping gene?

  Gene involved in all aspects of a bacterium's life, e.g involved in metabolism, protein production, DNA replication
• What is koch's postulates?


  - Pathogen occurs in every case of disease

  
  

  -Pathogen does not occur in healthy subjects

  
  

  -After isolating the pathogen and repeated growth in pure culture, pathogen can induce the disease in an animal
• Is Koch's postulates accurate?

  No, there are many contradictions e.g HIV which cannot be grown in culture and has a poor animal model
• What are molecular Koch's postulates?

  However you still need a good animal model

  
• What are virulence genes often encoded on?

  Mobile genetic elements ( bits of DNA that can be swapped between microbes) e.g. plasmids, transposons, bacteriophages
• Which virulence genes are commonly found on plasmids, bacteriophages and pathogenicity islands?

  Plasmids:

  Adhesin genes, antibiotic resistance genes, toxin genes

  Bacteriophages:

  Toxin genes

  Pathogenicity islands:

  Toxin gene systems
• What factors can define bacterial pathogenicity?

  Transmission (bacteria must be transmitted to cause disease)

  
  

  Adherence (microbe must be able to adhere e.g epithelium or skin)

  
  

  Invasiveness (sometimes into tissues)

  
  

  Ability to cause damage
• How can microbes be transmitted to a host?

  Inhalation

  Ingestion

  Inoculation

  
• How do microbes adhere?

  Flagellae

  Fimbriae (pili)

  Specialised surface proteins:-direct attachment-signalling to eukaryotic cell ( to trigger further adhesion)
• Is adhesion always linked to virulence?

  No

  
  

  -Adhesion may affect virulence and tissue tropism (which specific tissues a microbe will infect/colonise)
• How do bacterium bind to eukaryotic surfaces?

  1. Bacterium binds to eukaryotic surface through pili

  2. This changes gene expression in the bacteria

  3.inducing signalling in bacteria

  4. Production of compounds by cell e.g markers which cause further adhesion

  
• What is colonisation?

  Presence of microbes without an accompanying disease
• What is infection?

  Presence of microbes resulting in disease
• Why do microbes colonise a surface?

  -To gain a source of nutrients

  -To get a more protective environment
• What might a microbe have to do to survive in the host?

  Immune evasion- antigenic shift (bacterial pathogens use to avoid or inactivate host defenses and ensure their own survival within a host)

  Oppose immune function e.g. superoxide dismutase, inactive immune cellsSurvival depends on the host function
• How does a microbe invade the host?

  Penetrates mucosal layer & establishes at systemic sites, usually at places well supplied by blood e.g:

  
  

  spleen, liver, bone, heart, kidney

  
• What will aid a microbe's ability to invade?

  Secrete bacterial enzymes (collagenase, coagulase) which helps destroy tissue/protein structure - easier penetration

  
  

  Have antiphagocytic factors - protects them being phagocytosed

  
  

  Having toxins that control hosts uptake mechanisms
• What are facultative intracellular bacteria?

  Able to survive phagocytosis, grow and reproduce within the immune cells, shielded and can pass through the cells (transcytosis)
• What are obligate intracellular bacteria?

  Cannot produce outside of their host cell and live in there
• How do microbes actually gain entry to their host?

  1. Through phagocytosis

  
  

  2. Induce a target cell to take them up

  
• How do bacteria survive the inhospitable conditions of host cells?

  Modify the phagosomal compartment

  Escape the phagosome into the cytosol

  Nullify host response
• Are viruses obligate?

  Yes, they are genuine obligate intracellular pathogens
• Describe Rickettsiae.

  - obligate intracellular bacteria

  - replicate in cytosol of host endothelial cells

  
• What are the defining features of obligate intracellular bacteria?

  Long generation time

  
  

  Small size with small genome

  
  

  Require exogenous energy supply (e.g use host to generate ATP)

  
  

  May infect non-phagocytic cells

  
  

  Protected from lysosomal degradation

  
  

  Use own expression & replication mechanisms

  
  

  No environmental reservoir

  -acquired from other hosts

  
  

  Cannot be grown by standard bacterial culture techniques

  
  

  Difficult to study
• What are the advantages of intracellular infection?

  Immune evasion ( hiding from immune system so it can't recognise it)

  
  

  Carried around the body easily

  
  

  Obtain nutrients from host

  
  

  Smaller genome size (obligate)

  
• What is the role of immune system in causing disease?

  Pyogenic inflammation (fever, acute)

  Granulomatous inflammation (chronic)

  
• What is a cytokine storm?

  Over-activation of healthy immune system, leading to massive production of cytokines, in particular pro- and anti-inflammatory cytokines
• What are the main effects of a cytokine storm?

  Tissue damage, multiple organ failure, septic shock, death

  
• What are the main cytokine participants in a cytokine storm?

  TNF-alpha & IL-6
• What other specific damages can be caused by the immune system (not just cytokine storms)?

  Mimicry

  -group A beta-haemolytic streptococci (anti-heart) induce harmful antibody response

  Cytokine induction

  -superantigens inappropriately inactivate immune response leading to shock

  -LPS activates immune cells, inducing 'cytokine storm'

  Toxins that inhibit immune function