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Western University
Microbiology and Immunology
Microbiology and Immunology 2500A/B

Lecture 7: Clostridia 09/21/2012 Clostridia  Gram-positive, rod shaped, endospore formers  Strict anaerobes, vegetative cells kille2 by O – oxygen is toxic, cannot grow in the presence of oxygen  Endspores – resistant structure, critical for the development of diseases they cause  Generally found in soil and intestinal tracts of animals  Responsible for several unrelated diseases  More than 80 species of Clostridia  Important human pathogens: o Clostridium difficile - pseudomembranous colitis o Clostridium tetani - tetanus o Clostridium botulinum - botulism o Clostridium perfringens – food-borne illness and gas gangrene  Can cause life threatening diseases mediated by exotoxins  Endospore formation: o “endo” means “within” o These structures are formed from within the cell o Endospores are highly resistant to heat, drying, harsh chemical and nutrient depletion o Function as “survival structures” o Also used for dispersal through air, water and intestinal tracts o Clostridia produce terminal endospores o Best studied in Bacillus and Clostridium species – also gram positive rods o Sporulation due to lack of nutrients or stress o A dormant stage in the bacterial life cycle o Endospores can remain dormant for years but can revert back to vegetative cells rapidly (within minutes) o Vegetative cells – do not have endospores o Occurs through a complex series of events o Exosporium and spore coat are composed of protein o Core wall is peptidoglycan o The cortex contains DNA, cytoplasm, ribosomes, etc. o Dipicolinic acid complex with with Ca helps to dehydrate the cortex – consistency of a gel but very resistant to heat, chemicals, etc. o Pasteurization (63-72°C) will not kill endospores o Autoclaving at 121°C will kill endospores The Pathogen: Clostridium difficile (“C. diff”)  Cause of pseudomembranous colitis, also called antibiotic-associated diarrhea  Can exist as: o Asymptomatic carrier state – does not cause any disease o Cause of mild to moderate diarrhea o Cause of life-threatening pseudomembranous colitis  C. difficile can be harbored in the large intestine in low numbers o About 3% of healthy adults are colonized  Often found in nursing homes and hospital environments o A nosocomial pathogen (HA pathogen)  Under harsh conditions – reverts to the highly resistant spore  Spores can be very difficult to eradicate from the environment o Cultured from floor, bed pans, toilets, hands and clothing of medical personnel  Mode of transmission is through the spore: fecal-oral route The Disease: pseudomembranous colitis  Most symptomatic patients have recently received an antimicrobial agent o This is the single most important risk factor  Antibiotics are used to cure infections, but they also kill the normal microbiota  Suppression of normal flora + persistence of C. difficile endospores  In response to the antibiotic, C. difficile enters the endospore state  After the antibiotic is stopped, spores germinate, overgrowth of C. difficile occurs with production of toxins  C. difficile does not invade, but the toxins damage the intestinal lining of the large intestine The Pathogen: Clostridium difficile (“C. diff”)  C. difficile produces A-B toxins called the large clostridial cytotoxins  “A-B” serves to designate two domains: o The A domain denotes the active portion of the toxin that carries the enzymatic activity – responsible for inducing damage o The B domain denotes the portion of the toxin molecule responsible for binding and uptake by the host cell  “A” domain functions to inactivate key regulatory proteins (called G proteins) of host cells  Causes disregulation of multiple cell processes including cytoskeletal rearrangements – causes cell death and inflammation  Most vegetative cells are killed in the stomach  Endospores enter intestinal tract, germinate or remain in the stomach, and then start to colonize The Disease: Pseudomembranous colitis  An inflammatory condition of the large intestine  Offensive smelling diarrhea, abdominal pain, fever, nausea, dehydration  Patients usually have “constitutional” symptoms  Symptoms may occur 1-2 days after antibiotics or several weeks after the antibiotic is discontinued  In serious cases, can lead to low blood pressure, kidney failure, perforated colon, toxic megacolon  Endoscopy can show characteristic yellow lesions  Lesions can enlarge to cover substantial portions of inflamed mucosa and can be stripped off → the pseudomembrane  Diagnosis and treatment: o History (antibiotic use), symptoms and laboratory tests to confirm C. difficile o Endoscopy and toxin detection assays o Discontinue inciting antibiotics if still being used o Fluids are given o Antibiotics more specific for “C. diff” are given – typically Metronidazole o Avoid antidiarrheal agents – you don’t want colonic stasis and decreased toxin clearance Fecal Microbiota Transplantation  Healthy donor’s microbiota is transplanted into patient to restore microbiota  Extremely effective The Pathogen: Clostridium tetani  Causative agent of tetanus, a very severe disease  Also called “lockjaw”  Organisms found in soil and intestinal tracts of various animals  Produces tetanus toxin – an “A:B” neurotoxin – targets nervous system  Symptoms of generalized tetanus include a descending pattern of muscle spasms o Incubation of 3 days to 3 weeks o Lockjaw, stiff n
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