Read the summary and the most important questions on Advanced Medical Microbiology - Bacteriology

• 1 Deeltoets 3

• 1.1 Gene regulation

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• Slipped strand misparing

  Slipped strand misparing happens when DNA polymerase makes mistakes when it encounter regions of repetitive DNA
  

  • leads to deletions or insertions, which affects transcription and translation

  
  
  

  1. Pili have diversity because of different sequence through slipping.
     
  2. PorA: slippin gin spacer, affects expression of porA gene

• Iron limitation in vivo

  Iron limitation in vivo leads to expression of proteins to uptake iron --> virulence factors
  
  Growth conditions encountered in vivo trigger the expression of genes involved in survival of bacteria in the host cells, virulence factors
  

  • proteins can be identify through genomic or transcriptome
  1. make cDNA en sequence the fragments
  2. map reads and count

• RNA thermometer (RNATs)

  RNA thermometer operate by changing the structure in response to temperature fluctuation by a zipper like mechanism.
  

  • regulates expression of virulence genes
  • when temp is high, ribosome can bind due to open structure
  • when temp is low, bacteria does not need virulence factors to survive

• 1.2 Cellular heterogeneity

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• Bistable induction in vitro

  Prerequisites:
  1) Auto-stimulatory loop
  2) Treshold level for activation
  
  3) Stochastic fluctuation

• 1.4 Genome plasticity

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• Mechanism of HGT in bacteria

  1. Bacterial transformation
     
  • taken up and intregrate DNA
  2. transduction
  • through phage
  3. conjugation
  • to donate a plasmid containing genes that encode proteins responsible for resistance to an antibiotic
    

• 1.6 Tuberculosis

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• Proteins secretion in mycobacterium

  They use type VII secretion system. It mediate transport of proteins across this cell envelope
  

  • mycobacterium block fusion with lysosome as they enter the cytosol, where they can replicate
  • ESX-1 is crucial for this escape and intracellulair survival

  
  
  ESX-5 is essential for growth
  

  • mediates the insertion of nutrients transporters in the OM

• 1.8 Staphylococcus aureus

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• Hurdles: immune evasion

  1. Evasion of bacterial opsonization
     
  • proteins that interfere with antibody binding to bacterial surface or inhibit complement system
  2. evasion of pahocytosis and killing
     
  • CHIPS: blocks C5a receptor for neutrophil recruitment
  • FLIPr: blocks Fc receptor for antibody-mediated pahogyctosis
  • Nuclease degrades NETs
  3. targeting immune cells
  • pore-forming toxins
  • superantigens: T cell over-activation

• Hurdles: translation and strain variation

  Translation: Mice is not natural host, trials with mice model are difficult to translate to human
  
  Strain variation: antigenic/phase variation

• 2 Deeltoets 4

• 2.3 Antibiotics and resistance

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• Resistance: target site change

  Normal, antibiotic bind to target protein. However, mutation in target protein can lead to no binding of antibiotic. Or other proteins binds to target protein, which prevent binding to antibiotic (protection)
  

  • MRSA express PBP2a, which causes penicillins not to bind to and so peptidoglycan synthesis is not affected
  • TetM protect ribosome from tetracycline binding

• Resistance: direct interactions with antibiotics

  Inactivation of antibiotic by hydrolysis (degradation) or steric hindrance cause resistance.
  

  • inactivation by hydrolysis: b-lactamases. Resistance target b-lactamases in antibiotics
  • by counteracting b-lactamases can prevent resistance and antibiotic containing b-lactamases will work again