Bacteria and disease

• what diseases does S. aureus cause

  • skin diseases
  • respiratory,
  • food poisoning,
  • autoimmune,
  • osteomyelitis,
  • DFI
  • formation of MRSA
• when did bacteria first appear

  3.8 billion years ago
• what is a microbiome

  the collective genomes that can be found within a single microbial ecosystem 
• what is a microbiota

  the community of microorganisms that exist within a single ecosystems
• what is a commensal

  type of microbes that reside on either surface of the body at mucose without harming human health 
• how many microbes are in the human microbiome

  10^13
• what is dysbiosis

  • disruption to normal microbiota and linked to many disease conditions
  • e.g. gut-brain axis, obesity, some cancers
• what is a pathogen

  microorganism that can cause disease 
• what is pathogenesis

  the biochemical mechanisms whereby microorganisms cause disease
• what is an opportunistic pathogen

  • harmless bacteria which become pathogenic due to changes in the host
  • Pseudomonas aeruginosa
• what is a faculative pathogen

  can survive outside of the host as well as infect the host

  • Salmonella enterica
  • Typhimurium serovar - requires intestinal inflammation to sustain replication
• what is an obligate pathogen

  can only survive within the host e.g. chlamydia
• what is virulence

  pathogenic potential of a microorganism compared to another 
• what diseases have low virulence

  • common cold
  • salmonella food poisoning
  • candidiasis
  • athletes foot
• what diseases have high virulence

  • malaria
  • anthrax
  • plague
• what is a virulence factor

  factor produced a microorganism that enables it to infect the host and cause disease 
• definition of infection

  a successful persistence or multiplication of a pathogen on or within the host 
• definition of disease

  an interaction which causes significant overt damage to the host 
• Listeria monocytogenes 

  • gram positive bacterial pathogen
  • facultative intracellular microorganism
  • healthy individuals - gastroenteritis within 24h
  • immunocompromised individuals - septicemia, meningitis, abortion often takes over 30 days
  • mortality rate - 30%
• exposure of L. monocytogenes

  • unpasteurised dairy products particularly soft cheeses
  • deli counter meats and coleslaw
  • bacteria able to survive and grow at low temps (4C), high salt and low pH, similar to Salmonella N.B.
  • Salmonella elongation and cell numbers in low temp storage
  • microbial load - 10^5 - 10^9 per g of food
• adherence of L. monocytogenes

  • bacterial pathogens express a range of different adhesins
  • also important for biofilm formation
  • in L. monocytogenes
  • InlA - binds to human E-cadherin found on intestine and placenta/brain barrier
  • InlB - binds to c-MET allowing colonisation of the liver and spleen
• invasion of L. monocytogenes

  • adhesin InlA and InlB induce host cell actin rearrangement and internalisation
  • each protein alone sufficient enough to induce internalisation
• invasion of E. coli

  induces a pedestal on the surface of intestinal epithelial cells
• multiplication of listeria

  • internalisation leads to vacuole formation
  • secretion of Listeria Lysin O allows escape into cytoplasm
  • bacterium able to access nutrients in cytoplasm for replication
• examples of tissue destroying toxins

  • coagulases
  • proteases
  • hyaluronidases
• examples of cytolytic exotoxins

  • alpha toxin
  • streptolysin O
  • cytotoxin
  • listeria lysin O
• examples of AB-type toxins

  • diphtheria toxin
  • anthrax toxin
  • cholera toxin
• toxicity in listeria

  • release of toxins which lyse open host cell (hemolysins)
  • escape into blood stream - spread to other organs inducing septicemia, meningitis and abortion
• what is ID50

  dose which effects 50% of individuals
• what is immunity

  the ability of an organism to resist infection 
• innate immunity

  • non-specific
  • immediate response
  • no immunological memory
• adaptive immunity

  • specific to antigen
  • lag time from exposure to response
  • immunological memory after exposure
• what are phagocytes

  • cells which engulf foreign particles and can ingest, kill and digest most pathogens
• how many phagocytes are in human blood

  7.0 x 10^6 cells per ml 
• how do phagocytes recognise pathogens

  • pathogen-associated molecular patterns (PAMPs)
  • macromolecules inside and on the surface of pathogens
  • polysaccharides, proteins, nucleic acids and lipids
  • recognised by pattern recognition receptors including toll like receptors
• toll-like receptor 2

  recognises peptidoglycan from gram +ve pathogens
• toll-like receptor 4

  recognises lipopolysaccharides from gram -ve pathogens
• killing of pathogens by phagocytes

  • phagosome containing pathogen fuses with a lysosome to form a phagolysosome
  • activated phagocytes produce chemokines recruiting other immune cells to the site of infection
• pathogen avoidance of phagocytes

  • bacterial capsule preventing pattern recognition - Streptococcus pneumoniae
  • inhibit phagosome and lysosome fusion - Salmonella spp.
  • production of compounds to neutralise phagolysosome - mycobacterium spp.
  • production of toxins to kill phagocytes after phagocytosis - Streptococcus pyogenes and Staphylococcus aureus
• what pathogens are destroyed by natural killer cells

  intracellular pathogens