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93 Cards in this Set
- Front
- Back
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What are the 4 properties of a successful pathogen?
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1. Gains access via corret POE
2. Colonizes host tissue 3. Evades host immune defenses 4. Causes damage |
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What are the 2 pathogenic mechanisms of causing damage?
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-Invasiveness
-Toxins |
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What is invasiveness?
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Growing
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What anaerobic pathogen causes damage by invading the host? How?
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Bacteroides - with its capsule
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What anaerobic pathogen causes damage by producing toxins?
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Clostridia
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What are the typical features often seen in anaerobic infections?
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-Mixed with anaerobes+aerobes
-Opportunistic |
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Why are anaerobes often mixed with aerobes?
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Aerobes metabolize O2 and make the environment favorable for anaerobes
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Why can't anaerobes survive in O2?
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They have little superoxide dismutase and catalase so they're sensitive to O2 intermediates
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What type of metabolism do anaerobes do?
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Fermentation
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What are the 4 clinically significant gram negative rods that are anaerobes?
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-Bacteroides fragilis and thetaiotamicron
-Bacteroides non-frag group -Bacteroides bivius -Fusobacterium |
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What type of infection does B. frag cause?
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Intra-abdominal
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What are the anaerobic gram pos rods? (2)
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-Actinomyces israeli
-Propionibacterium acnes |
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What does actinomyces israeli cause?
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Lumpy jaw
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What does propionibacterium acnes cause?
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Infections of prosthetic devices
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What is the gram pos coccus that is anaerobic?
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Peptostreptococcus
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So the 2 sites of infections caused by gram negative anaerobes are:
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-Colon (intrabdominal abscesses)
-Mouth -Skin |
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What is the tip off that an infection is anaerobic?
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Foul smell
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Why do anaerobes cause a foul smell?
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Because of short chain fatty acids produced during fermentations
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What type of environment has to be cultured in order to isolate anaerobic pathogens from the often mixed infections?
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Anoxic - it must be void of aerobic bacteria.
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What is the most common inhabitant of the bowel?
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B frag
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What makes B frag different from all other gram negs?
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Its LPS is modified and does not stimulate TLR/inflammation
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What is the virulence factor used by B. frag?
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Polysaccharide capsule
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How does the capsule allow B. frag to cause infection?
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-Mediates adherence to host cells
-Antiphagocytic |
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In what type of infection and with what other bacterium is B. frag often isolated?
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-Intra abdominal abscess
-With Peptostreptococcus |
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What type of agar is used to isolate B frag?
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BBE - bacteroides bile esculin
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How is B. frag differentiated from e. coli?
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-It hydrolyzes BE (turns black)
-Resists gentamicin |
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What is the gram stain morphology of B. frag?
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Gram neg bacilli
-pleiomorphic -faintly staining |
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What are the 4 main categories of virulence factors in anaerobic gram neg bacilli?
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-Adhesins (capsule/fimbriae)
-Resist oxygen toxicity via SOD and catalase -Antiphagocytic (capsule) -Tissue destruction via enzymes |
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So how is B. frag pathogenic?
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By the production of enzymes that cause tissue destruction and allow INVASION
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How are Clostridium tetani and botulinum pathogenic?
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By the production of neurotoxins which cause paralysis
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What type of paralysis is caused by Clostridium
-tetani -botulinum |
Tetani = spastic
Botulinum = flaccid |
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What is the gram stain morphology of the Clostridia?
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Anaerobic gram pos spore formers
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What type of anaerobe are the clostridia?
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Either OBLIGATE or AEROTOLERANT
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Which of the clostridia is aerotolerant?
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C botulinum
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What is the pathogenicity of Clostridia due to usually?
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Exotoxin
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What do Clostridia grow in?
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Sugars (saccharolytic)
or Amino acids (proteolytic) |
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Where are Clostridia normally found?
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In soil or the intestinal tract
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Which Clostridium species is normal flora in the gut in low amounts?
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C. difficile
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Which is the histotoxic clostridium? What is its mode of pathogenesis?
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C. perfringens - INVASIVE
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Which are the neurotoxic clostridia? What is their mode of pathogenesis?
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C. tetani and C. bot - TOXIGENIC
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What causes antibiotic associated enterocolitis?
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Ampicillin reduction of normal flora in the gut, which allows C. diff to proliferate and cause pseudomembranous colitis.
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What are the 3 species responsible for Histotoxic clostridia infections?
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-C. perfringens
-C. novyi -C. septicum |
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What is C. perfringens the major cause of?
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Clostridial-mediated myonecrosis
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What type of anaerobe is C. perfringens?
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Aerotolerant
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What starts of clostridial myonecrosis?
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A deep wound to tissue/muscle
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What are the steps in pathology of clostridial myonecrosis?
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1. C. perf converts pyruvate to lactate, acid kills host cells
2. C. perf releases endog proteases which allows growth |
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What is the result of killing host cells and C. perfringens GROWING (invading) tissue?
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Gangrenous necrosis and gas production - gas gangrene.
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In addition to causing gas gangrene what can C. perfringens cause?
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Enterocolitis
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What is the structure of the clostridial neurotoxins like?
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A:B toxin - just like the diphtheria toxin!
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How many different serotypes of Botulinum neurotoxin are there?
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7; A-G
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Which of the neurotoxins can humans be vaccinated against?
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Both tetani and botulinum
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What are the clostridium neurotoxins functionally?
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Proteases
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How do the clostridium neurotoxins work?
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By clipping synaptobrevin from neurotransmitter vesicles at neuro synapses, inhibiting the release of NT.
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Why does C. botulinum cause flaccid paralysis?
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Because it inhibits ACh release
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Why does C. tetani cause spastic paralysis?
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Because it inhibits GABA/Glycine release (inhibitors)
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Are C. tetani and botulinum invasive?
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NO
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Where is C. tetani found?
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In dirt
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What type of infection must C. tetani be found in? Why?
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A mixed infection
-So that other bacteria can reduce the redox potential enough to allow enough growth of C. tetani to produce its toxin |
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What has to happen in order for tetanus toxin to be active? Where and by wha?
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Proteolysis and DISULFIDE BOND REDUCTION - in the NT vesicle by Zinc Protease
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What is the result of proteolysis? Where does it occur?
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-In NT vesicles
-Frees the A enzyme from the B subunit to allow it to clip snares from the vesicle membrane |
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What is the only effective way to control tetanus?
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Prevention by imunization
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How is the tetanus vaccine made?
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By formalin inactivation of the tetanus toxin to generate a toxoid
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How are suspected cases of tetanus treated?
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By administering anti-toxin immunoglobulins QUICKLY
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Why does Anti-TT Ig have to be given so quickly after infection?
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Because anti-TT is no use after the toxin is in the cells
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What is the botulinum toxin like structurally?
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Identical to the tetanus toxin
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How many serotypes of bot tox?
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7
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What are the most common bot tox serotypes?
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ABE
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Against which serotype is resistance developing and why?
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Botox, serotype A - because it is used for clinical therapeutic uses so often
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What dose of bot tox is lethal?
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1 ug
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What are the 3 natural infections associated with botulinum toxin?
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1. Food-born botulism
2. Infant botulism 3. Wound botulism |
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What is the main difference in food-born C. perfringens and food-born C. botulinum?
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C perf results in enterocolitis
C bot results in FLACCID PARALYSIS |
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How is C. bot able to survive in poorly cooked food, infants, and wounds?
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By its spores
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Is bot tox heat labile?
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yes
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What are 2 potential modes of transmission of botulism for bioterrorism?
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-Inhalation
-Food contamination |
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At what synaptic junction does TETANUS toxin act, and how does it get there?
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-Interneuronal synapse
-Via RETROAXONAL transport |
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Where does bot tox inhibit NT release?
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At the presynaptic membrane of PERIPHERAL neurons
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Why is botulinum toxin implicated as a potential biological warfare agent?
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Because it is the most potent protein that is toxic to humans
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What is lethality caused by bot tox primarily due to?
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Food borne botulism
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What is the treatment for botulism?
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Supportive/respirative
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How is the vaccine against bot tox made?
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-Generate bot tox against all 7 serotypes in horse serum
-Inactivate with formalin -Watch for hypersensitivity |
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What antisera does the CDC have?
What antisera does the army have? |
CDC: ABE
Army: A-G (all 7) |
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Is botulism contagious?
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No
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What are the 2 ways to prepare for biological warfare using botulinum toxin?
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-Generate vaccines
-Generate passive antibody |
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Which preparatory protocol is better for protecting large populations?
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Vaccines
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Why might there be low public acceptance to a botox vaccine?
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Because it would prevent clinical therapeutic use of the toxoid.
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What is wrong with making toxoid vaccines against C. bot?
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It is a difficult process
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What are 2 new strategies for developing C. bot vaccines?
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Recombination mechanisms
-Nontoxic holotoxin vaccines -Heavy chain vaccines |
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How is a patient treated if they DO contract botulism?
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Antitoxin from the CDC
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When do most patients recover from botulism?
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Weeks-months after a long period of supportive care.
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How would you investigate a deliberate release of botulinum toxin?
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Epidemiological analysis
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What is a clinical use of Bot tox in eye clinics?
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Treating blepharospasms
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What type of spores are seen in
-Bacillus species -Clostridia species |
Bacillus = subterminal
Clostridia = terminal |
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What causes spores to germinate?
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Water and metabolites
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