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93 Cards in this Set

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  • Back
What are the 4 properties of a successful pathogen?
1. Gains access via corret POE
2. Colonizes host tissue
3. Evades host immune defenses
4. Causes damage
What are the 2 pathogenic mechanisms of causing damage?
What is invasiveness?
What anaerobic pathogen causes damage by invading the host? How?
Bacteroides - with its capsule
What anaerobic pathogen causes damage by producing toxins?
What are the typical features often seen in anaerobic infections?
-Mixed with anaerobes+aerobes
Why are anaerobes often mixed with aerobes?
Aerobes metabolize O2 and make the environment favorable for anaerobes
Why can't anaerobes survive in O2?
They have little superoxide dismutase and catalase so they're sensitive to O2 intermediates
What type of metabolism do anaerobes do?
What are the 4 clinically significant gram negative rods that are anaerobes?
-Bacteroides fragilis and thetaiotamicron
-Bacteroides non-frag group
-Bacteroides bivius
What type of infection does B. frag cause?
What are the anaerobic gram pos rods? (2)
-Actinomyces israeli
-Propionibacterium acnes
What does actinomyces israeli cause?
Lumpy jaw
What does propionibacterium acnes cause?
Infections of prosthetic devices
What is the gram pos coccus that is anaerobic?
So the 2 sites of infections caused by gram negative anaerobes are:
-Colon (intrabdominal abscesses)
What is the tip off that an infection is anaerobic?
Foul smell
Why do anaerobes cause a foul smell?
Because of short chain fatty acids produced during fermentations
What type of environment has to be cultured in order to isolate anaerobic pathogens from the often mixed infections?
Anoxic - it must be void of aerobic bacteria.
What is the most common inhabitant of the bowel?
B frag
What makes B frag different from all other gram negs?
Its LPS is modified and does not stimulate TLR/inflammation
What is the virulence factor used by B. frag?
Polysaccharide capsule
How does the capsule allow B. frag to cause infection?
-Mediates adherence to host cells
In what type of infection and with what other bacterium is B. frag often isolated?
-Intra abdominal abscess
-With Peptostreptococcus
What type of agar is used to isolate B frag?
BBE - bacteroides bile esculin
How is B. frag differentiated from e. coli?
-It hydrolyzes BE (turns black)
-Resists gentamicin
What is the gram stain morphology of B. frag?
Gram neg bacilli
-faintly staining
What are the 4 main categories of virulence factors in anaerobic gram neg bacilli?
-Adhesins (capsule/fimbriae)
-Resist oxygen toxicity via SOD and catalase
-Antiphagocytic (capsule)
-Tissue destruction via enzymes
So how is B. frag pathogenic?
By the production of enzymes that cause tissue destruction and allow INVASION
How are Clostridium tetani and botulinum pathogenic?
By the production of neurotoxins which cause paralysis
What type of paralysis is caused by Clostridium
Tetani = spastic

Botulinum = flaccid
What is the gram stain morphology of the Clostridia?
Anaerobic gram pos spore formers
What type of anaerobe are the clostridia?
Which of the clostridia is aerotolerant?
C botulinum
What is the pathogenicity of Clostridia due to usually?
What do Clostridia grow in?
Sugars (saccharolytic)
Amino acids (proteolytic)
Where are Clostridia normally found?
In soil or the intestinal tract
Which Clostridium species is normal flora in the gut in low amounts?
C. difficile
Which is the histotoxic clostridium? What is its mode of pathogenesis?
C. perfringens - INVASIVE
Which are the neurotoxic clostridia? What is their mode of pathogenesis?
C. tetani and C. bot - TOXIGENIC
What causes antibiotic associated enterocolitis?
Ampicillin reduction of normal flora in the gut, which allows C. diff to proliferate and cause pseudomembranous colitis.
What are the 3 species responsible for Histotoxic clostridia infections?
-C. perfringens
-C. novyi
-C. septicum
What is C. perfringens the major cause of?
Clostridial-mediated myonecrosis
What type of anaerobe is C. perfringens?
What starts of clostridial myonecrosis?
A deep wound to tissue/muscle
What are the steps in pathology of clostridial myonecrosis?
1. C. perf converts pyruvate to lactate, acid kills host cells
2. C. perf releases endog proteases which allows growth
What is the result of killing host cells and C. perfringens GROWING (invading) tissue?
Gangrenous necrosis and gas production - gas gangrene.
In addition to causing gas gangrene what can C. perfringens cause?
What is the structure of the clostridial neurotoxins like?
A:B toxin - just like the diphtheria toxin!
How many different serotypes of Botulinum neurotoxin are there?
7; A-G
Which of the neurotoxins can humans be vaccinated against?
Both tetani and botulinum
What are the clostridium neurotoxins functionally?
How do the clostridium neurotoxins work?
By clipping synaptobrevin from neurotransmitter vesicles at neuro synapses, inhibiting the release of NT.
Why does C. botulinum cause flaccid paralysis?
Because it inhibits ACh release
Why does C. tetani cause spastic paralysis?
Because it inhibits GABA/Glycine release (inhibitors)
Are C. tetani and botulinum invasive?
Where is C. tetani found?
In dirt
What type of infection must C. tetani be found in? Why?
A mixed infection
-So that other bacteria can reduce the redox potential enough to allow enough growth of C. tetani to produce its toxin
What has to happen in order for tetanus toxin to be active? Where and by wha?
Proteolysis and DISULFIDE BOND REDUCTION - in the NT vesicle by Zinc Protease
What is the result of proteolysis? Where does it occur?
-In NT vesicles
-Frees the A enzyme from the B subunit to allow it to clip snares from the vesicle membrane
What is the only effective way to control tetanus?
Prevention by imunization
How is the tetanus vaccine made?
By formalin inactivation of the tetanus toxin to generate a toxoid
How are suspected cases of tetanus treated?
By administering anti-toxin immunoglobulins QUICKLY
Why does Anti-TT Ig have to be given so quickly after infection?
Because anti-TT is no use after the toxin is in the cells
What is the botulinum toxin like structurally?
Identical to the tetanus toxin
How many serotypes of bot tox?
What are the most common bot tox serotypes?
Against which serotype is resistance developing and why?
Botox, serotype A - because it is used for clinical therapeutic uses so often
What dose of bot tox is lethal?
1 ug
What are the 3 natural infections associated with botulinum toxin?
1. Food-born botulism
2. Infant botulism
3. Wound botulism
What is the main difference in food-born C. perfringens and food-born C. botulinum?
C perf results in enterocolitis
C bot results in FLACCID PARALYSIS
How is C. bot able to survive in poorly cooked food, infants, and wounds?
By its spores
Is bot tox heat labile?
What are 2 potential modes of transmission of botulism for bioterrorism?
-Food contamination
At what synaptic junction does TETANUS toxin act, and how does it get there?
-Interneuronal synapse
-Via RETROAXONAL transport
Where does bot tox inhibit NT release?
At the presynaptic membrane of PERIPHERAL neurons
Why is botulinum toxin implicated as a potential biological warfare agent?
Because it is the most potent protein that is toxic to humans
What is lethality caused by bot tox primarily due to?
Food borne botulism
What is the treatment for botulism?
How is the vaccine against bot tox made?
-Generate bot tox against all 7 serotypes in horse serum
-Inactivate with formalin
-Watch for hypersensitivity
What antisera does the CDC have?
What antisera does the army have?
Army: A-G (all 7)
Is botulism contagious?
What are the 2 ways to prepare for biological warfare using botulinum toxin?
-Generate vaccines
-Generate passive antibody
Which preparatory protocol is better for protecting large populations?
Why might there be low public acceptance to a botox vaccine?
Because it would prevent clinical therapeutic use of the toxoid.
What is wrong with making toxoid vaccines against C. bot?
It is a difficult process
What are 2 new strategies for developing C. bot vaccines?
Recombination mechanisms
-Nontoxic holotoxin vaccines
-Heavy chain vaccines
How is a patient treated if they DO contract botulism?
Antitoxin from the CDC
When do most patients recover from botulism?
Weeks-months after a long period of supportive care.
How would you investigate a deliberate release of botulinum toxin?
Epidemiological analysis
What is a clinical use of Bot tox in eye clinics?
Treating blepharospasms
What type of spores are seen in
-Bacillus species
-Clostridia species
Bacillus = subterminal
Clostridia = terminal
What causes spores to germinate?
Water and metabolites