Bacterial Pathogenesis

The cause and effect relationship between bacteria and infection is summarised by Koch's postulates:

• First postulate: Bacteria must be associated with the lesion
  • However some bacteria are known to colonise without causing symptoms
• Second postulate: Bacteria must be isolated in pure culture
  • However some bacteria cannot be cultured
• Third postulate: Isolated bacteria must produce disease when innoculated into human or animal
• Fourth postulate: Bacteria must be reisolated from intentionally infected animal/human

Bacteria invasion can be either:

• Localised- e.g. an abscess
• Systemic-e.g. septicemia

The toxins produced by some bacteria can be classed as:

• Endotoxins- bacterial cell degradation products, e.g. LPS
• Exotoxins- toxic bacterial proteins, found in both Gram-negative and Gram-positive

Endotoxin pathology

• The endotoxin being referred to is LPS, found on Gram-negative bacteria
• Similar toxins found on Gram-positive bacteria include TSST-1, found on S. aureus
• Effects of LPS are mainly due to excessive cytokine secretion- TNF-alpha, IL-1 and IL-2
• Primarily affects vascular system- sudden drop in blood pressure known as 'endotoxin shock', also 'septic' shock
• Also targets complement system- massive activation by the alternative pathway leads to inflammation and damage to small blood vessels
  • Leakage of fluid into the alveoli leads to a condition known as adult respiratory distress syndrome (ARDS)
• The neurotoxicity attributed to the whooping-cough vaccine is thought to be due to an endotoxin on the B. pertussis bacterium

Types of exotoxin:

• Type 1- bind to target cell surface, excretion mediated by specialised pore-spanning proteins, e.g. superantigens
• Type 2- destroy integrity of membrane of eukaryotic cells, secretion mediated by Sec-dependent apparatus, e.g. phospholipases
• Type 3- one portion binds to host cell surface receptor, other acts on cell target, e.g. botulinum toxin

Toxins in disease:

• Diphtheria toxin- type 3 toxin, produced by C. diphtheriae, causes damage to major organs
• Botulinum toxin- type 3 toxin, produced by C. botulinum, affects control of nerve transmission
• Tetanus toxin- - type 3 toxin, produced by C. tetani, affects nerve transmission
• Alpha toxin- type 2 toxin, produced by C. perfringens, contributes to gangrene
• PMT- produced by P. multocida, causes bone and weight loss
• Ciliary toxin- produced by B. pertussis, inhibits cilia in bronchi

Although the reason why bacteria secrete such toxic compounds is unclear, many are of potential benefit to the microbe:

• Hyaluronidase: produced by Streptococcus, this enzyme allows passage through the tissues
• Enterotoxins: such as those produced by Staphylococcus and Cholera, these cause diarrhoea and subsequent spread
• E. histolytica toxin allows it to penetrate the gut wall

Bacterial Pathogenesis Learning Resources
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