Clostridium Bacteria Types PDF

Clostridiu mgangrene; food poisoning C. perfringens: gas C. tetani: tetanus C. botulinum: botulism C. difficile: pseudomembranous colitis Physiology and Structure Anaerobic. Large gram-positive rods. The spores are usually wider than the rods, and are located term...

Clostridiu mgangrene; food poisoning C. perfringens: gas C. tetani: tetanus C. botulinum: botulism C. difficile: pseudomembranous colitis Physiology and Structure Anaerobic. Large gram-positive rods. The spores are usually wider than the rods, and are located terminally or subterminally. Most clostridia are motile by peritrichous flagella.  C. tetani Physiology and Structure Small, motile; Spore-forming (drumstick appearance); Extremely sensitive to oxygen toxicity. Pathogenesis and Immunity Tetanospasmin is responsible for clinical manifestations of tetanus. An A-B toxin, released when the bacteria lyse. Subunit A is a zinc endopeptidase that acts on CNS: Inhibits release of an inhibitory mediator (e.g., GABA or glycine) which acts on postsynaptic spinal neurons (causing spastic paralysis).  C. Pathogenesis tetani Contamination of devitalized tissue (wound, burn, injury, umbilical stump, surgical suture) with the spores germination of the spores release of tetanospasmin the toxin reaches CNS by retrograde axonal transport or via the bloodstream the toxin is fixed to gangliosides in spinal cord or brainstem and exerts its actions. Germination of the spore and production of toxin are aided by conditions that lead to low oxidation-reduction potential: Necrotic tissue; calcium salts; associated pyogenic infections. Tetanospasmin is encoded on a plasmid which is present in all toxigenic strains.  C. tetani Clinical Diseases Generalized tetanus Incubation period: 4-5 days. Symptoms: convulsive tonic contraction of voluntary muscles. Spasms involve first the area of injury, then the muscles of the jaw (trismus or lockjaw; risus sardonicus). Other voluntary muscles become involved gradually, resulting in generalized tonic spasms (opisthotonos). Death usually results from interference with respiration. The mortality rate of generalized tetanus: ~50%. In more severe cases, the autonomic nervous systems are also involved. Localized tetanus (confined to the musculature of primary site of infection) Cephalic tetanus (site of infection: head) Neonatal tetanus (infection of the umbilical wound): mortality > 90%, and developmental defects are present in survivors.  C. tetani Laboratory Diagnosis Diagnosis depends on the clinical picture and a history of injury. Proof of isolation of C. tetani from contaminated wounds depends on production of toxin and its neutralization by specific antitoxin. Treatment, Prevention, and Control Prevention is much more 2. Proper care of wounds. important than treatment: Surgical débridement to remove 1. Active immunization the necrotic tissue. with toxoid. 3. Prophylactic use of antitoxin. ‘Booster shot’ for 4. Antibiotic treatment. previously immunized Metronidazole individuals. This may be accompanied by antitoxin *Patients with symptoms of tetanus injected into a different should receive muscle relaxants, area of the body. sedation and assisted ventilation.  C. tetani Control Active immunization with tetanus toxoid (toxin detoxified with formalin) Aluminum salt-adsorbed toxoid DPT vaccine C. botulinum  C. botulinum C. botulinum is a large anaerobic bacillus that forms subterminal endospores. It is widely distributed in soil, sediments of lakes and ponds, and decaying vegetation. Hence, the intestinal tracts of birds, mammals and fish may occasionally contain the organism as a transient. 8 toxigenic types of the organism exist, each producing an immunologically distinct form of botulinum toxin. The toxins are designated A, B, C1, D, E, F, G and H). In the U.S. type A is the most significant cause of botulism, involved in 62% of the cases. Not all strains of C. botulinum produce the botulinum toxin. Lysogenic phages encode toxin serotypes C and D, and non lysogenized bacteria (which exist in nature) do not produce the toxin. Type G toxin is thought to be plasmid encoded.  C. botulinum Physiology and Structure A-B toxins. The subunit A is a zinc endopeptidase blocking release of acetylcholine at peripheral cholinergic synapses. Destroyed by heating for 20 min. at 100 oC. Types A, B, E, and F are most commonly associated with human illness. subterminal endospores.  C. botulinum Pathogenicity and Immunity An intoxication. Ingestion of food (spiced, smoked, vacuum-packed, or canned alkaline foods) in which C. botulinum has grown and produced toxin the toxin acts on both the voluntary and autonomic nervous systems at synapses and neuromuscular junctions flaccid paralysis.  C. botulinum A-Food-borne Botulism In food-borne botulism the botulinum toxin is ingested with food in which spores have germinated and the organism has grown. The toxin is absorbed by the upper part of the GI tract in the duodenum and jejunum, and passes into the blood stream by which it reaches the peripheral neuromuscular synapses. The toxin binds to the presynaptic stimulatory terminals and blocks the release of the neurotransmitter acetylcholine which is required for a nerve to simulate the muscle. C. botulinum spores are relatively heat resistant and may survive the sterilizing process of improper canning procedures. The anaerobic environment produced by the canning process may further encourage the outgrowth of spores. The organisms grow best in neutral or "low acid" vegetables (>pH4.5). Clinical symptoms of botulism begin 18-36 hours after toxin ingestion with weakness, dizziness and dryness of the mouth. Nausea and vomiting may occur. Neurologic features soon develop: blurred vision, inability to swallow, difficulty in speech, descending weakness of skeletal muscles and respiratory paralysis.  C. botulinum B-Infant botulism Occurs in the first month of life. Weakness, signs of paralysis, C. botulinum and its toxin are found in feces. May be caused by ingestion of the bacteria or spores which grow in the gut and produce toxin. Feeding of honey has been implicated as a possible cause. Patients recover with supportive therapy alone. The possible role of infant botulism in "sudden infant death syndrome-SIDS" has been suggested and is under investigation. C. botulinum, its toxin, or both have been found in the bowel contents of several infants who have died suddenly and unexpectedly. C-Wound botulism Develops from contaminated wounds. Symptoms similar to those of food borne botulism with longer incubation time. Less GI symptoms.  Toxin Action The botulinum toxin is specific for peripheral nerve endings at the point where a motor neuron stimulates a muscle. The toxin binds to the neuron and prevents the release of acetylcholine across the synaptic cleft. The heavy chain of the toxin mediates binding to presynaptic receptors. The toxin (A fragment) enters the cell by receptor mediated endocytosis. Once inside a neuron, the toxin inhibit acetylcholine release, (i.e., proteolytic cleavage of synaptobrevin II). The affected cells fail to release a neurotransmitter, thus producing paralysis of the motor system. Once damaged, the synapse is rendered permanently useless. The recovery of function requires sprouting of a new presynaptic axon and the subsequent formation of a new synapse. otulism Toxin Mechanism  C. botulinum Laboratory Diagnosis Culture of C. botulinum in patient feces and implicated food. Detection of toxin in feces or serum from the patient and in leftover food: i.p. injection of mice die rapidly. Toxin may also be detected by other serological tests. Typing of toxin is done by neutralization with specific antitoxin in mice. Treatment Stomach lavage and high enemas Trivalent (A, B, E) antitoxin administered intravenously promptly. Adequate ventilation by mechanical respirator. enemas (a procedure in which liquid or gas is injected into the rectum, to expel its contents or to introduce drugs or permit X-ray imaging)  C. botulinum Prevention and Control Spores of C. botulinum are widely distributed in soil and often contaminate vegetables, fruits etc. Strict regulation of commercial canning has largely reduced the danger of widespread outbreaks. The chief danger lies in home-canned foods (vegetables, smoked fish or vacuum-packed fresh fish). The cans with toxic food may swell or may show innocuous appearance. The risk from home-canned food can be reduced by boiling the food for 20 min. Children younger than 1 year should not eat honey. C. difficile  C. difficile C. difficile is responsible for antibiotic-associated gastrointestinal disease ranging from self-limited diarrhea to severe, life threatening psudomembranous colitis. It is a part of normal intestinal flora in a small number of healthy people and hospitalized patients. The spores can contaminate an environment for many months and can be a major source of nosocomial outbreaks. This organism produces two toxins: Toxin A (an enterotoxin) induces release of cytokines, hypersecretion of fluid, and development of hemorrhagic necrosis. Toxin B (a cytotoxin) causes tissue damage.  C. difficile Pseudomembranous colitis Administration of antibiotics results in proliferation of drug-resistant C. difficile. Antibiotics that are most commonly associated with pseudomembranous colitis are, cephalosporins, clindamycin and ampicillin. Disease occurs if the organism proliferates in the colon and produces toxins: watery or bloody diarrhea, abdominal cramps, leukocytosis and fever. Laboratory diagnosis depends on isolation of C. difficile in the feces and detection of toxins with tissue culture cells (cytotoxicity assay). The disease is treated by discontinuing the offending antibiotic, and orally giving either metronidazole or vancomycin in severe cases. Clostridium difficile  General Characteristics Source – feces of nondiarrheic humans: 5 - 10% – hospital environment: up to 25% of patients – soil, marine sediments – dogs and cats: up to 35% – wide variety of other animals Clinical Disease Antibiotics disrupt normal flora Loss of competitive exclusion Uncontrolled proliferation of C. difficile Onset 4 - 10 days after start of antibiotic, up to 2 weeks after termination  Clinical Disease Transmission via spores (vegetative cells oxygen sensitive) – fecal-oral contaminated clothing, surfaces – aerosols Pass through stomach, bile acids – induce germination? Antibiotics - compromised normal flora C. difficile grows rapidly in unoccupied niches Vegetative cells produce toxins  Clinical Disease Damage to colonic mucosa – pseudomembrane – separate lesions coalesce Symptoms – severe abdominal pain – watery diarrhea – high number of neutrophils in stool Lesions of C. difficile  Pathogenesis Large clostridial cytotoxins – AB-like cytotoxins A- enzymatic portion B- functions as a ligand – Endocytosed via coated pits – Endosomal acidification - conformational change Pathogenesis Toxin A – 308 kDa (largest known exotoxin) – Enterotoxic in vivo: cells can no longer control water movement fluid accumulation with tissue damage (blood and mucus) – Causes diarrhea w/ intense inflammation Chemotactic for neutrophils – Must be internalized for toxic effect  Pathogenesis Toxin A – C-terminal 1/3 (B fragment): host cell binding – recognizes a carbohydrate moiety on the apical surface not toxic but required for toxic effect – N-terminal 1/3 (A fragment): toxin-domain – Glycosyltransferase activity in the cytosol glycosylation of rho-subfamily proteins – rho-type proteins are signal transduction molecules » form’n of actin filaments & cell adhesion structures – inactivates these proteins breakdown of actin filament network opening of tight junctions/apoptosis/necrosis Actin is fundamental to maintenance of cell shape, polarity and intracellular adhesions.  Pathogenesis Toxin B – 269 kDa – Has no enterotoxic activity in vivo – Trace amounts of toxin A or mucosal damage necessary for toxic effect in rodent bowel – Cytotoxic in vitro (~ 1000 times more active than toxin A)  Pathogenesis Toxin B – N-terminal domain: highly conserved, same activity as in toxin A – C-terminal domain: quite different, may recognize different receptor – Toxins act synergistically – Toxin A damage to mucosal cells allows toxin B maximal effect  Clinical Disease Diagnosis: – Detection of the organism culture of feces for C. difficile (48-72 h) immunoassay – Detection of toxins tissue culture immunoassay  Outcome and Treatment Treatment – cessation of antibiotic, if possible – treatment with anti-C. difficile-drugs: vancomycin, metronidazole extended course to prevent recurrence – restoration of normal intestinal flora: “fecal enema” from family member Prophylaxis Feeding of Saccharomyces boulardii (yeast) Administration of toxin-neutralizing antibodies Parenteral immunization against toxins