Exam 2 - (1) Clostridia Flashcards
What type of bacteria are Clostridium in relation to oxygen? What is their shape and membrane (gram) classificaiton?
- Strictly anaerobic
- Gram + rods
Clostridium can produce endo____, making it mostly unique among bacteria.
spores
About how many Clostridium(C) species are responsible for human infection?
30
How many C. species are found in the environment (water, soil, animal wastes?)
> 50
C. can produce _______ toxins that are responsible for disease ______.
- proteinaceous (protein)
- symptoms
What C. species causes pseudomembraneous colitis (PMC)?
C. difficile
What C. species is known to cause cellulitis, gas gangrene, and food poisoning?
C. perfringens
What C. species causes botulism?
C. botulinum
What C. species causes tetanus?
C. tetani
Toxin production is linked to all C. diseases save for:
Suppurative wounds and abscesses
Most C. diseases are tissue invasive. T or F?
True
exception: boutulinum food poisoning, infant botulism
possible exceptions: wound botulism, tetanus, PMC
Describe bacteria in it’s endospore form:
metabolically inactive, resistant state in which it can remain for 100s of years.
What conditions are endospores resistant to?
extreme heat, drying, radiation, most chemical disinfectins
What causes endospore induction?
unfavorable environmental conditions (i.e. nutrient depletion)
When will endospores germinate?
when conditions become favorable for vegetative growth
Are C. difficile easy to culture?
NO
Describe PMC
Yellow plaques containing fibrin and cellular debris in ulcers of colonic mucosa
C. difficile is currently the leading cause of _____ diarrhea.
nosocomial (aquired while under medical care/at the hospital)
C. difficile is harbored how?
in a dormant state (small amount) within the bowels of a small number of healthy individuals
What is C. difficile’s mode of transportation?
endospores! (ex: hands of health care professional)
The disease state caused by C. difficile is usually associated with:
antimicrobial drugs (esp. cephalosporins, ampicillin, and clindamycin)
When the normal colonic flora are killed by antibiotics, C. difficile spores can ________ and begin production of _____ resulting in _______. There is no _____ of the bowel wall, however.
- vegetate
- toxin
- diarrhea
- invasion
What are two toxins produced by C. difficile?
- Toxin A
- Toxin B
Describe Toxin A:
it is an enterotoxin that causes fluid production and damages mucosa
Describe Toxin B:
it is a cytotoxin that causes tissue culture cells to round
What is the mechanism of action for both C. difficile’s toxins?
they act in the cytoplasm of the host cell to glycosylate GTP binding proteins (Rho, Rac). As a result, the cells lose their cytoskeletal structure and die.
Name one way to diagnose C. difficile:
an ELISA detection of Toxin A
Where can C. perfringens be found?
Every soil except sahara desert sand and the intestinal tracts of animals.
C. perfringens is a major pathogen in:
wound infections (war wounds 20 - 30%)
C. perfringens has _______ properties which cause ______ damage and ______ effects. This is due to the variety of _______ produced.
- invasive
- local
- systemic
- toxins
Damaged tissue has what conditions which cause spores to germinate?
- anaerobic environment
- compromised blood supply
- calcium ions
- availability of peptides and amino acids
Toxins produced by C. perfringens typically cause ______ that can lead to _____ _______ which is a necrotizing, gas forming process of muscle, associated with systemic signs of shock/
- cellulitis
- gas gangrene
How many toxins can C. perfringens produce?
12
What is C. perfringen’s main toxin which damages cell membranes and causes gas gangrene?
Alpha-toxin (lecithinase)
Describe Alpha-toxin’s mode of action:
it is a phospholipase type C that hydrolyzes phosphatidylcholine and sphingomyelin that leads to cell death
What are the results of Alpha-toxin’s action:
Muscle tissue is destroyed (myonecrosis) and becomes reddish blue to black in color with gas bubbles present. Shock and renal failure usually result, and if untreated, has a 100% fatality rate.
What are some treatment/prevention strategies for a C. perfringens infection?
- surgical removal of the infected muscle
- antibiotics to control the infection (amputation still necessary)
- Antitoxin from horses doesn’t do much
- exposure to high oxygen concentrations (only a subset of cases responded to)
- prompt care is IMPERITIVE to restore arterial blood supply
What cause the third most common type of food poisoning in the US?
C. perfringens
Unrealated to gas gangrene, C. perfringens food poisoning is caused by ______ C. perfringens that produce ________ in the intestines of people who have consumed ______ _______ usually ______.
- sporulating
- enterotoxin
- contaminated food
- meat
C. perfringens food poisoning causes _______ for ___-___ hours, but is ______ _______ and disappears in ___-___ days.
- diarrhea
- 12-24
- self limiting
- 1-3
Where is C. botulinum found?
soils and marine sediments
C. botulinum’s heat resistant spores often survive _____ _____ and will germinate and grow under _______ conditions (canned foods).
- food processing
- anaerobic
What causes botulism?
Intoxication from the ingestion of pre-formed C. botulinum toxin (the organism doesn’t need to be present).
C. botulinum is considered a _______ and can be used by terrorists i.e. enemies of America.
bioweapon
How many neurotoxin types does C. botulinum produce?
8 serotypes (BoNT) A-G
Which serotypes of BoNT are most common in humans?
A, B, and E
BoNT is one of the most poisonous substances known, what is the lethal dose for humans?
> 1 ug (microgram)
Purified BoNT is produced as a stable ____ kDa protein complex containing a _____ kDa toxic compontent and a _____ kDa non-toxic component.
- 900
- 150
- 750
What is BoNT’s mechanism of action?
it prevents the release of acetylcholine neurotransmitter by interfering with neurotransmission at peripheral cholinergic synapses.
What enzyme is key to BoNT’s action and what does it do?
Zinc metalloprotease which cleaves proteins involved with docking at neurotransmitters.
Describe the symptoms/effects of BoNT on the body:
-Flaccid paralysis within 12-36 hrs:
Cranial nerves first (double vision difficulty swallowing)
then descends to lungs causing respiratory failure
What are the 3 types of botulism?
1- food borne botulism
2- wound botulism (rare)
3- Infant botulism
Briefly describe food borne botulism
Ingestion of pre-formed toxin in foods that have not been canned or preserved properly
Briefly describe wound botulism:
a RARE condition in which C. botulinum inhabits wounds and systematically spreads. This can result from trauma, surgery, heroin injections, nasal cocaine abuse (sinusitis)
Briefly describe Infant botulism:
Intestinal colonization of organisms in infants younger than 1 yr with a slow onset that results in a hypotonic (floppy) state. There is a favorable outcome
What is the mortality rate of botulism with good supportive care?
25%
How is botulism treated?
with a trivalent antitoxin isolated from horses (JRH NBR only) that is administered immediately
Even after botulism is treated it may cause some muscles to be permanently damaged. No antibiotics are necessary when treating botulism because:
it is caused by a toxin not an infection
Clostridium tetani is found:
- GI tract of humans and animals
- soil samples
C. tetani spores are resistant to the environment and an infection by it is usually associated with:
traumatic wounds
Germination of C. tetani’s spores goes hand in hand with:
toxin production
One common route of C. tetani infection is:
neonatal contamination of the umbilical cord at delivery
What is C. tetani’s major toxin?
tetanospasmin
tetanospasmin is responsible for all symptoms of Tetanus, T or F?
True
tetanospasmin is a ____ kDa Protein with _____ chain and a _____ chain connected by a ______ bridge (like BoNT). Individual chains are _______
- 150
- heavy
- light
- disulfide
- non-toxic
Describe tetnospasmins mechanism of action:
it rides peripheral nerves (near a wound site) to the CNS and the cranial nerve nuclei. There it inhibits neurotransmitter release (GABA, an inhibitor). This results in reflex spasms and spastic paralysis.
_______ or “lockjaw” is present in ___% of tetanus cases
- Trismus
- 80
Trismus is caused by:
spastic paralysis of the masseter muscles
Once tentanus descends it affects:
- neck and back muscles (opisthontos - bending backwards, spastic paralysis of back extensors)
- abdomen (rigidity)
- extremities (stiffness)
What are the ultimate effects of advanced tetanus?
Tonic seizures and respiratory failure from paralysis of chest muscles
how is tetanus pre-emptively treated?
-DPT vaccine (formalin-inactivated toxid that retains antigenicity)
how is tentanus treated after possible/definite exposure?
- tetanus prone wounds treated with human globulin (passive immunization)
- antitoxin with penicillin G to prevent further paralysis
- surgical debridement of the wound to prevent region of bacterial growth
What is the mortality rate associated with tetanus?
11% usually due to respiratory failure
Why aren’t antibodies produced when tetanus is in effect?
low amount of toxin present.
