10 Flashcards
Clostridium
Strictly anaerobic
Gram positive rods
Produce endospores
~30 species that are responsible for human infections
>50 more species found in environment (soil, water, animal wastes)
Produce proteinaceous toxins that are responsible for disease symptoms
Clostridium species
C. difficile – pseudomembranous colitis (PMC) – case study example
C. perfringens – cellulitis, gas gangrene, food poisoning
C. botulinum - botulism
C. tetani - tetanus
Spore vs. Vegetative Cells - bacterial endospore
Bacterial endospores
Few bacteria have the ability to form endospores (i.e. Bacillus, Clostridium)
Metabolically inactive state in which organisms can remain viable for hundreds of years
Resistant to adverse conditions
Extreme heat, drying, radiation, most chemical disinfections
Spore induction caused by unfavorable environmental conditions (i.e., nutrient depletion)
Spores will readily germinate when conditions become favorable for vegetative growth
C. difficile
Not easy to culture (“difficult clostridium”)
Pseudomembranous colitis (PMC)
Yellow plaques containing fibrin and cellular debris in ulcers of colonic mucosa
Currently the leading cause of nosocomial diarrhea
Harbored in a dormant state in the large intestine of small percentage of healthy humans in low numbers
Mode of transmission is the endospore
Hands of health care personnel
Disease state usually associated with antimicrobial drugs, especially cephalosporins, ampicillin, and clindamycin
C. difficile spores are resistant to antibiotics
Normal flora killed
Spores vegetate, toxin production begins resulting in diarrhea
Invasion of the bowel wall does not occur
Similar to E. coli and V. cholerae
C. difficile toxin a
Enterotoxin - fluid production and damage to the mucosa
Both toxins act in cytoplasm of host cell to glycosylate GTP-binding proteins (e.g., Rho, Rac)
Cells loses cytoskeletal structure and die
ELISA detection of Toxin A is diagnostic
C. difficile toxinb
Cytotoxin – rounding of tissue-culture cells
C. perfringens
Soil and intestinal tract of animals
Environmental pathogen found in every soil except Sahara desert sand
Major pathogen of wound infections
Especially prevalent in war wounds (20-30%)
Local damage and systemic effects
Invasive properties
Due to variety of toxins produced
C. perfringens Tissue Infections
Severe trauma introduces spores from the environment that germinate under these conditions:
Anaerobic
Compromised blood supply
Calcium ions
Availability of peptides and amino acids
Toxins produced typically cause cellulitis that can lead to gas gangrene, a necrotizing, gas-forming process of muscle associated with systemic signs of shock
C. perfringens Toxins
Produces 12 toxins Alpha-toxin (lecithinase) - damages cell membranes, and causes gas gangrene Phospholipase Type C Hydrolyzes phosphatidylcholine and sphingomyelin that leads to cell death Muscle tissue is destroyed (myonecrosis) Reddish blue to black in color Gas bubbles present Shock and renal failure usually result Untreated = 100% fatality rate
C. perfringens Treatment and Prevention
Surgical removal of the infected muscle
Antibiotics to control the infection, but surgery (amputation) still necessary
Antitoxin from horses, relatively little effect
High oxygen concentrations
Only subset of cases respond to
Prompt care is imperative
Restore arterial blood supply
C. perfringens Food Poisoning
Third most common type of food poisoning in United States
Unrelated to gas gangrene
Sporulating C. perfringens that produce enterotoxin in intestines of people who have consumed contaminated food (usually meat)
Diarrhea in 12-24 hours
Self-limiting; disappears in 1-3 days
Clostridium botulinum
Soils and marine sediments
Heat-resistant spores (not toxins) often survive food processing
Germinate and grow under anaerobic conditions (such as in canned foods)
Causative agent of botulism
Intoxication of ingestion of pre-formed toxin (don’t need the organism to be present)
Bioweapon and bioterrorism threat
C. botulinum Toxins
Produces eight neurotoxin (BoNT) serotypes A-G
A, B, E are most common in humans
Among the most poisonous substances known
Lethal dose to humans <1 mg
Purified BoNT is produced as a stable 900 kDa protein complex containing:
A 150 kDa toxic component
A 750 kDa non-toxic component
C. botulinum Toxin Mechanism of Action
Prevents release of acetylcholine neurotransmitter
Interferes with neurotransmission at peripheral cholinergic synapses
Zinc metalloprotease
Cleaves proteins involved in docking of neurotransmitter vesicles
Flaccid paralysis within 12 to 36 hours
Cranial nerves affected first
Double vision, difficulty swallowing
Paralysis descends
Respiratory failure
Three Types of Botulism
food borne, wound botulism (rare), infant
Food-borne botulism
Ingestion of preformed toxin in foods that have not been canned or preserved properly
Wound botulism (rare)
Systemic spread of toxin produced by organisms inhabiting wounds
Trauma, surgery, subcutaneous heroin injection, and sinusitis from intranasal cocaine abuse
Infant botulism
Intestinal colonization of organisms in infants younger than 1 year
Slow onset
Favorable outcome
Hypotonic (“floppy”) state
C. botulinum Treatment
Current mortality rate, with good supportive care, is 25%
A trivalent antitoxin, isolated from horses, should be administered ASAP
Hypersensitivity
Some muscles may be permanently damaged, and never recover
No antibiotics necessary…Why?
C. tetani
Ubiquitous in the GI tract of humans and animals
Also in soil samples
Spores resistant to environment
Infection usually associated with traumatic wounds
C. tetani Tetanus
Germination of spores and production of toxin
Neonatal contamination of umbilical cord at delivery
Major toxin: tetanospasmin
Responsible for all symptoms
150 kDa Protein
Heavy chain and light chain (A-B) connected by disulfide bridge (just like BoNT)
Individual chains are non-toxic
C. tetani Tetanospasmin Me chanism of Action
Attaches to peripheral nerves near wound and is transmitted to cranial nerve nuclei
Inhibits neurotransmitter release (g-aminobutyric acid (GABA)) and normal inhibitory input
Result - Reflex spasms, spastic paralysis
C. tetani Generalized Tetanus
Trismus – “lockjaw” (80% of cases)
Tetanic spasm of masseter muscles that prevents opening of mouth
Descends to neck and back muscles and produces rigidity of abdomen and stiffness of extremities
Tonic seizures
Respiratory failure from paralysis of chest muscles
C. tetani Treatment and Prevention
Completely preventable with DPT vaccine
The “T” of the DPT vaccine (what is “P”?)
Tetanus toxoid (formalin-inactivated toxin that retains antigenicity)
Human globulin sometimes given as passive immunization in “tetanus-prone wounds”
11% mortality, usually due to respiratory failure
Antitoxin should be administered immediately, along with penicillin G to prevent further paralysis
Antibodies not produced due to low amounts of toxin present
Surgical debridement of the wound to prevent region of bacterial growth
