Exotoxin producing clostridia Flashcards
what are the two major mechanisms with which bacteria cause disease? Examples.
1) toxin-mediated - no organisms required for infection, botulism toxin or staph aureus enterotoxin are examples
2) invasion and inflammation - direct tissue invasion and over-reactive immune response, clostridium perfringens is an example
two pathogenic possibilities for ingesting toxin
1) toxin already in food
2) ingestion of microorganisms, colonization, toxin formed in gut
what is the metabolic nature of clostridium?
obligate anaerobe
clostridium gram + or -?
+
shape of clostridium?
rod/bacilli
does clostridium form spores?
yes
what type of clostridium is indicated by terminal spores?
clostridium tetani
clostridium catalase + or -?
-
clostridium oxidase + or -?
-
which clostridium species causes botulism?
C. botulinum
which clostridium species causes tetanus?
C. tetani
which clostridium species causes pseudomembranous enterocolitis?
C. difficile
which clostridium species causes gas gangrene?
C. perfringens
which clostridium species is invasive in malignancy?
C. septicum
major symptom of botulism toxin:
flaccid paralysis
major symptom of tetanus toxin:
tetanus - spastic paralysis (locked jaw)
major symptoms of exotoxins A and B:
cause diarrhea in pseudomembranous enterocolitis due to C. difficile
major symptoms of alpha toxin:
gas gangrene - in combination with other degradative enzymes
what does a tennis racket shape indicate?
terminal spore - must be C. tetani which causes tetanus
symptom of tetanus in developing countries:
infected umbilical stump
is C. tetani invasive or toxin mediated?
toxin mediated
how many serological types of C. tetani are there?
only one
what type of toxin is tetanus toxin?
- it’s a neurotoxin - goes from site of infection to peripheral and CNS nerves
- two subunits A and B
what does tetanus toxin do exactly?
binds to neuronal gangliosides and prevents release of GABA and glycine resulting in convulsive contractions (locked jaw)
C. tetani incubation period?
4 days to weeks
in C. tetani spasms, which muscles are predominant?
flexors
will those with C. tetani have a fever?
no
will those with C. tetani have sensory deficit?
no
what is often the cause of death in tetanus?
- involvement of respiratory muscles leads to respiratory failure, aspiration, dysphagia, with oral pharyngeal involvement
- potential for pulmonary infections and respiratory problems
diagnosis of tetanus:
- mostly clinical
- not likely to find organism in wound
- culture positive in 39%
how is tetanus generally treated?
- human tetanus immunoglobulin
- penicillin (or metronidazole if allergic) plus wound debridement
- respiratory support
- immunization with tetanus toxin
what is the fatality rate with tetanus?
60%
describe the tetanus immunization
- three doses in first six months of life (toxin inactivated by formaldehyde)
- given as part of DPT
- booster at one year, before school entry, and every ten years after
tetanus prophylaxis
1) immunized - just clean the wound and keep getting booster every 10 years
2) dirty wound in uncertain immunization - anti-tetanus immunglobulin and complete immunization
3) unimmunized - complete immunization
describe the spores of C. botulinum:
- subterminal oval
- non-diagnostic
shape of C. botulinum
rod/bacilli
C. botulinum gram + or -?
+
C. botulinum spores heat labile?
no
botulism toxin heat labile?
yes
what happens to C. botulinum spores in canned foods?
They grow in anaerobic conditions and produce botulism toxin within 2-3 days.
what does wound associated botulism require?
requires spore germination in the wound
what does infant botulism require?
- ingestion of spore by infant (in honey)
- germination and intestinal colonization
how potent is botulism toxin?
very. 1mg killed 200,000 mice.
is botulism toxin destroyed by stomach?
no
how many types of botulism toxin are there and which three are most common?
A to G, but A, B, and E are most common.
what are the subunits of the botulism toxin?
A and B
is C. botulinum invasive or toxin mediated?
toxin mediated
what type of toxin is botulism toxin?
- neurotoxin - absorbed by intestine and carried by blood to peripheral nerve synapses
- protease - interferes with proteolytic processing
the release of which NT is inhibited by botulism toxin?
acetylcholine
what is the mental status of someone with botulism?
normal
is there a fever with botulism?
no
incubation period for botulism toxin?
18-36 hours
which nerves does botulism affect?
peripheral nerves
symptoms of botulism
- flaccid paralysis
- dysphagia (trouble swallowing)
- diplopia (double vision)
- dry throat
- dilated pupils
is there is a sensory deficit with botulism?
no
botulism diagnosis:
- usually clinical
- detect toxin in serum, vomit, feces
- detect toxin in food
- EMG (electromyography) - diminished action potential of the peripheral nerves
why aren’t cultures useful for botulism?
toxin matters much more than organism
diseases on differential diagnosis with botulism:
- myasthenia gravis
- Guillain-Barre syndrome
botulism fatality rate
12%
botulism therapy
- removal of toxin from stomach (lavage)
- antitoxin, horse serum, A, B, E
- respiratory support
what ages usually get infant botulism?
1-8 months
why is infant botulism different?
- immature immune system allows colonization in gut.
symptoms of infant botulism:
- more subtle than adult botulism
- constipation
- weak head control
- cranial nerve deficit common
diagnosis of infant botulism
toxin or organism in stool
C. difficile gram + or -?
+
C. difficile invasive or toxin mediated?
toxin mediated
what percent of the population has C difficile in GI tract?
3%
what percent of hospital acquired C. difficile likely comes from hospital personnel?
30%
pathogenesis of C. difficile
- proliferates under antibiotic induced suppression of normal flora
- exotoxins bind and damage colonic mucosa (bloody diarrhea)
- damage to colon by exotoxin B leads to pseudomembrane formation
what are the two C. difficile exotoxins?
A and B
what does C. difficile exotoxin A do?
binds to gut receptor
what does C. difficult exotoxin B do? chemical mechanism?
- cytotoxin - damages colonic mucosa
- ADP-ribosylating Rho (GTP-binding protein)
what is the appearance of the C. difficile pseudomembrane?
- yellow-white plaque on colonoscopy/sigmoidoscopy
- usually not bloody but can be
diagnosis of C. difficile
- history of antibiotic use
- exotoxin B in stool
- ELISA for toxins
- stool culture for C. difficile (not useful alone)
- sigmoidoscopy for pseudomembranes
C. difficile treatment
- stop offending antibiotics
- treat with metronidazole, vancomycin, or fidazomicin
is C. perfringens invasive or toxin mediated?
invasive and highly progressive
Clostridium species other than perfringens that can cause gas gangrene?
septicum, bifermentans, ramosum (hallmark is tissue necrosis)
what is lecithinase?
alpha toxin - from C. perfringens - damages host cell membrane including capillary and host erythrocytes
what is collagenase?
- from C. perfringens - breaks down collagen supporting tissue underlying host cells
what is hyaluronidase?
- from C. perfringens - breaks down hyaluronic acid in the host matrix
what gases are referred to in “gas gangrene”
H2 and CO2 - byproducts of anaerobic growth in wound or dead tissue
clinical syndromes with gas gangrene:
1) cellulitis (superficial)
2) necrotizing cellulitis (dermis and underlying capillaries)
3) necrotizing faciitis (fascia around muscle)
4) myositis or myonecrosis (into muscle)
diagnostic tools for gas gangrene:
- crepitus upon pressing skin
- discoloration and edema of skin
- serous dark exudates (maybe)
- gram stain of fluid
- culture of wound (anaerobic media)
- x-ray
diagnosis of C. perfringens food poisoning
ELISA for enterotoxin in feces or implicated food
treatment for gas gangrene
- surgical wound debridement
- penicillin
- hyperbaric oxygen
