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Author: Amelia Virostko

1. Overview of Mechanisms of Damage

  1. Toxins
  2. Lytic enzymes: degrade proteins and extracellular matrix to facilitate dissemination
  3. Intracellular growth: protects bacteria from host immune response
  4. Growth outside the normal site of colonization
  5. Overgrowth of bacteria in normal niches: often after antibiotic therapy
  6. Host immune response

2. Toxins - Significance and Mechanisms

  1. Disrupt cell function or kill host cell
  2. Provide access to nutrients sequestered in host cells
  3. Break down epithelial barrier to enable bacterial spread
  4. Act on cell surface or in cytosol
    1. Cell surface: form pores in cell membrane, cleave surface proteins, or cross-link TCR and MHC to activate T cells without specificity
  5. A-B toxins: receptor-mediated endocytosis leads to A domain entry into cytosol
  6. Type III effectors: bacteria bind to host cell and inject toxin (syringe complex)

3. Cholera

  1. A-B toxin that works through ADP-ribosylation of proteins
  2. B domain binds crypt and villus cells in small intestine
  3. ADP-ribosylates Gs* inhibiting its GTPase activity causing continuous adenylate cyclase activity and increased cAMP levels
    1. Decreased Na absorption, increased Cl secretion, and decreased water uptake secondary to osmotic forces
    2. Disease is self-limiting and treat with oral rehydration therapy

4. Anthrax

  1. Forms spores enabling storage for long periods of time and easy aerosolization
  2. Symptoms resemble viral illness
  3. High fatality rate, even with use of antibiotics such as Cipro
  4. Edema toxin (ET) and lethal toxin (LT) share B subunit
    1. ET: A subunit increases cAMP leading to cutaneous edema
    2. LT: A domain is a metalloproteinase with particular affinity for macrophages that produces systemic shock and death

5. Botulism

  1. Flaccid paralysis
  2. B subunit targets peripheral nerves blocking the release of excitatory neurotransmitters

6. Tetanus

  1. Spastic paralysis
  2. Binds peripheral nerves at neuromuscular junction and prevents the release of
    1. Inhibitory neurotransmitters