Bacterial Pathogenesis
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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
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