CLOSTRIDIUM THE CLASSIFICATION AND GENERAL CHARACTERISTICS OF ASFGPR · Family = clostridiaceae, genus = clostridium · Gram positive rods 1um x 20um · Motile · Ubiquitous saprophytes (feed from the dead) / mammalian intestine · Low GC content within genome · Produce endospores · Strictly anaerobic metabolism ANAEROBIC RESPIRATION AND FERMENTATION · Anaerobic respiration - electron acceptor exogenous (SO42-), ETC creates PMF (proton motive force) to generate ATP which promotes bacterial growth, no oxygen · Fermentation - electron acceptor endogenous (pyruvate), no ETC, no oxygen, products include butyric acid, lactate, ethanol etc. SPORULATION AND GERMINATION · Endospores = dormant, dehydrated, highly resistant 'survival' structures carrying bacterial DNA - produced in unfavourable conditions · Composed of exosporium, spore coat (protein), cortex (peptidoglycan), core (low water content, small acid soluble spore proteins SASP and DPA-Ca2+ which protects DNA) · Germination: 1. Exposure to specific germinate and activation - irreversible 2. Partial rehydration, DPA-Ca2+ release, loss of some resistance 3. Cortex hydrolysis, full core rehydration and expansion, full loss of resistance and dormancy 4. SASP degradation, metabolism, escape from spore coat and division - outgrowth TETANUS · Characteristics: · Round terminal spores (appear like drumsticks/tennis rackets) · Virulence factors = spore former and produces exotoxins (tetanolysin and tetanospasmin) · Incidence = high in India, China and Africa · Mortality = half a million deaths worldwide (80% of this is Africa and Asia) PATHOGENESIS OF C. TETANI · Adhere to host cells via fibronectin binding proteins, S-layer surface proteins and peritrichous flagella · Produces haemolytic III, tetanolysin, collagenase (breaks peptide bonds in collagen) · Tetanospasmin (TeTx): · Type III (intracellular) · Have A/B subunits (150kDa) · Potent neurotoxin · moA = prevents inhibitory neurotransmitters GABA and glycine from being released - resulting in spastic paralysis · Mode of action: · The light chain cleaves synpatobrevin (V snare), preventing the docking of inhibitory neurotransmitters vesicles to presynaptic membrane · V snare forms snare complex with T snare on presynaptic terminal CLINICAL MANIFESTATIONS AND COMPLICATIONS OF TETANUS · Trimus (lockjaw) - results in Risus sardonicus (sardonic smile) · Opisthotonus - spasm of axial muscles (back) TREATMENT AND PREVENTION OF TETANUS · Treatment: · Limit growth and kill C. tetani - antibiotics · Neutralise toxin - TIG · Supportive measures - wound cleaning, ventilation etc. · Prevention = toxoid vaccination