1. 病原生物学教研室 Department of pathogenic Biology of Gannan Medical University 医学微生物学 Medical Microbiology 张文平

2. Anaerobic bacteria

3. Clostridium Tetani

4. Structure  anaerobic gram-positive rod that forms terminal spores  motile with peritrichous flagella  colonies often swarm on agar plates  does not produce acid from glucose  contains a plasmid that produces a toxin called tetanospasmin

5. Pathogenesis Tetanospasmin is responsible for the infamous toxemia called tetanus.

6. two toxins  tetanolysin, a hemolysin that is inactivated by cholesterol and has no role in pathogenesis.  tetanospasmin, a spasmogenic toxin responsible for the classical symptoms of the disease.

7. Tetanus Toxin (tetanospasmin) (LONG) single polypeptide chain (called the progenitor toxin) cleaved into a heavy chain (fragment B) and light chain (fragment A) Fragment B binds to the receptor of nerve (ganglioside) The A fragment has toxic (enzymatic) activity. It is transported within the axon and across synaptic junctions until it reaches the central nervous system. There it becomes rapidly fixed to gangliosides at the presynaptic inhibitory motor nerve endings, and is taken up into the axon by endocytosis. The effect of the toxin is to block the release of inhibitory neurotransmitters (glycine and gamma-amino butyric acid) across the synaptic cleft, which is required to check the nervous impulse.

8. sardonic smile (risus sardonicus) lockjaw Rigid paralysis

9. Diagnosis  Diagnosis of tetanus is obvious in advanced cases.  The patient should be treated on a clinical basis without waiting for laboratory data.

10. Treatment and Control Human tetanus immunoglobulin (HTIG  Treatment depends on early diagnosis and the use of Human tetanus immunoglobulin (HTIG) before a lethal amount of toxin becomes fixed to neural tissue..  Control: Injections of tetanus toxoid are prophylactic

11. Clostridium perfringens

12. Pathogenesis degrading enzymes  Produces several tissue degrading enzymes (including lecithinase [ α － toxin], proteolytic and saccharolytic enzymes).  Necrosis and destruction of blood vessels and the surrounding tissue result.  This creates an anaerobic environment in adjacent tissue and the organism spreads systemically.

13. Diseases  Gas gangrene, once initiated, may spread and cause death within hours.

14. Diseases  A significant cause of food poisoning by enterotoxin producing strains.

15. Diagnosis  Nagler reaction: exploits the action of its lecithinase.  On the egg yolk medium, colonies are surrounded by zones of turbidity, and the effect is specifically inhibited if C. perfringens antiserum containing α antitoxin is present on the medium.

16. Nagler reaction stormy fermentation

17. Clostridium Botulinum

18. Morphology  a large anaerobic bacillus that forms subterminal endospores

19. Botulinum Toxin (neurotoxin)  heat-labile(boiling)  the most potent toxin  The botulinum toxin is specific for peripheral nerve endings.  The toxin binds to the motor neuron and prevents the release of acetylcholine which is required for a nerve to simulate the muscle.  flaccid paralysis Pathogenesis

20. Diagnosis  Food-borne Botulism : blurred vision, inability to swallow, difficulty in speech, descending weakness of skeletal muscles and respiratory paralysis  Infant Botulism : constipation and weak sucking ability and generalized weakness

21. Control and Treatment  A multivalent toxoid evokes good protective antibiody response.  Treat: intravenous injection of antitoxin  Once the botulinum toxin has bound to nerve endings, its activity is unaffected by antitoxin.

22. endogenous versus exogenous infection  Most anaerobes in the normal flora are non-spore formers and anaerobic infections often occur from this source.  Non-spore-formers rarely produce exotoxins in contrast to spore-formers.  Contamination of wounds can also occur with anaerobic spore-formers (e.g. clostridia) which are common in the environment (e.g. soil).