Exotoxins and Endotoxins Flashcards

1
Q

exotoxin vs. endotoxin: source

A
  • exotoxin:
    • certain species of gram + and gram - bacteria
  • endotoxin:
    • outer cell membrane of most gram - bacteria
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2
Q

exotoxin vs. endotoxin: secreted from cell

A
  • exotoxin:
    • yes
  • endotoxin:
    • no
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3
Q

exotoxin vs. endotoxin: chemistry

A
  • exotoxin:
    • polypeptide
  • endotoxin:
    • lipid A component of LPS (structural part of bacteria–released when cell is lysed)
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4
Q

exotoxin vs. endotoxin: location of genes

A
  • exotoxin:
    • plasmid or bacteriophage
  • endotoxin:
    • bacterial chromosome
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5
Q

exotoxin vs. endotoxin: adverse effects

A
  • exotoxin:
    • high
      • fatal dose on order of 1 microgram
  • endotoxin:
    • low
      • fatal dose on order of hundreds of micrograms
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6
Q

exotoxin vs. endotoxin: clinical effects

A
  • exotoxin:
    • various
  • endotoxin:
    • fever
    • shock (hypotension)
    • DIC
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7
Q

exotoxin vs. endotoxin: mode of action

A
  • exotoxin:
    • inhibit protein synthesis
    • increase fluid secretion
    • inhibit phagocytic ability
    • inhibit release of neurotransmitter
    • lyse cell membranes
    • superantigens causing shock
  • endotoxin:
    • induces TNK, IL-1, and IL-6
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8
Q

exotoxin vs. endotoxin: antigenicity

A
  • exotoxin:
    • induces high titer antibiotics called antitoxins
  • endotoxin:
    • poorly antigenic
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9
Q

exotoxin vs. endotoxin: vaccines

A
  • exotoxin:
    • toxoids used as vaccines
  • endotoxin:
    • no toxoids formed
    • no vaccines available
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10
Q

exotoxin vs. endotoxin: heat stability

A
  • exotoxin:
    • destroyed rapidly at 60 deg C
      • except staphylococcal enterotoxin
  • endotoxin:
    • stable at 100 deg C for 1 hour
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11
Q

exotoxin vs. endotoxin: typical diseases

A
  • exotoxin:
    • tetanus
    • botulism
    • diphtheria
  • endotoxin:
    • meningococcemia
    • sepsis by gram - rods
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12
Q

which bugs with exotoxins act by inhibiting protein synthesis?

A
  • Corynebacterium diphtheriae
  • Pseudomonas aeruginosa
  • Shigella spp.
  • Enterohemorrhagic E.coli (EHEC)
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13
Q

which bugs with exotoxins act by increasing fluid secretion?

A
  • Enterotoxigenic E. coli (ETEC)
  • Bacillus anthracis
  • Vibrio cholerae
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14
Q

which bugs with exotoxins act by inhibiting phagocytic ability?

A
  • Bordetella pertussis
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15
Q

which bugs with exotoxins inhibit release of neurotransmitters?

A
  • Clostridium tetani
  • Clostridium botulinum
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16
Q

which bugs with exotoxins lyse cell membranes?

A
  • Clostridium perfringens
  • Streptococcus pyogenes
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17
Q

which bugs with exotoxins have superantigens that cause shock?

A
  • Staphylococcus aureus
  • Streptoccus pyogenes
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18
Q

Corynebacterium diphtheriae–toxin

A

Diphtheria toxin

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19
Q

Corynebacterium diphtheriae–mechanism

A
  • inactivates elongation factor (EF-2)
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20
Q

Corynebacterium diphtheriae–manifestation

A
  • pharyngitis with pseudomembranes in throat
  • severe lymphadenopathy
    • bull neck
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21
Q

Pseudomonas aeruginosa–toxin

A

exotoxin A

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22
Q

Pseudomonas aeruginosa–mechanism

A

inactivation elongation factor (EF-2)

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23
Q

Pseudomonas aeruginosa–manifestation

A

host cell death

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24
Q

Shigella spp.–toxin

A
  • Shiga toxin (ST)
    • an AB toxin with B enabling binding and triggering uptake (endocytosis) of active A component
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25
*Shigella spp.*--mechanism
* inactive 60S ribosome by removing adenosine from rRNA
26
*Shigella spp.*--mechanism
* GI mucosal damage --\> dysentery * ST also enhances cytokine release causing hemolytic uremic syndrome (HUS)
27
Enterohemorrhagic *E. coli* (EHEC)--toxin
Shiga like toxin (SLT)
28
Enterohemorrhagic *E. coli ​*(EHEC)*--*mechanism
* inactivate 60S ribosome by removing adenine from rRNA
29
Enterohemorrhagic *E. coli ​*(EHEC)--manifestation
* SLT enhances cytokine release causing HUS (prototypically in EHEC serotype O157:H7) * unlike *Shigella*, EHEC does not invade host cells
30
exterotoxigenic *E.coli* (ETEC)--toxins
* heat labile toxin (LT) * heat stable toxin (ST)
31
exterotoxigenic *E.coli​* (ETEC) heat labile toxin--mechanism
* overactivates adenylate cyclase (inc c**A**MP) --\> inc Cl- secretion in gut and H2O efflux
32
exterotoxigenic E.coli​ (ETEC) heat stable toxin--mechanism
* overactivates guanylate cyclase (inc c**G**MP) --\> dec resorption of NaCl and H2O in gut
33
exterotoxigenic *E.coli​* (ETEC)--manifestation
* watery diarrhea * "**labile** in the **A**ir (**A**denylate cyclase), **stable** on the **G**round (**G**uanylate cyclase)
34
*Bacillus anthracis*--toxin
* edema toxin * an AB toxin
35
*​Bacillus anthracis*--mechanism
* mimics the adenylate cyclase enzyme--inc cAMP
36
*​Bacillus anthracis*--manifestation
* likely responsible for chracteristic edematous borders of black eschar in cutaneous anthrax
37
*Vibrio cholerae*--toxin
cholera toxin
38
*Vibrio cholerae*--mechanism
* overactivates adenylate cyclase (inc cAMP) by permanently activating GS --\> inc Cl- secretion in gut and H2O efflux
39
*Vibrio cholerae*--manifestation
* voluminous "rice water" diarrhea
40
*Bordetella pertussis*--toxin
pertussis toxin
41
*Bordetella pertussis--*mechanism
* overactivates adenylate cyclase (inc cAMP) by disabling Gi --\> impairs phagocytosis to permit survival of microbe
42
*Bordetella pertussis--*manifestation
* whooping cough * child coughs on expiration and "whoops" on inspiration * toxin may not actually be a cause of cough * can cause 100 day cough in adults
43
*Clostridium tetani*--toxin
tetanospasmin
44
*Clostridium tetani*--mechanism
* both are proteases that cleave SNARE (soluble NSF attachment protein receptor)--a set of protein required for neurotransmitter release via vesicular fusion
45
*Clostridium tetani*--manifestation
* spastic paralysis * risus sardonicus * "lockjaw" * toxin prevents release of _inhibitory_ (GABA and glycine) neurotransmitters from Renshaw cells in spinal cord
46
*Clostridium botulinum*--toxin
botulinum toxin
47
*Clostridium botulinum*--mechanism
* both are proteases that cleave SNARE (soluble NSF attachment protein receptor)--a set of protein required for neurotransmitter release via vesicular fusion
48
*Clostridium botulinum*--manifestation
* flaccid paralysis * floppy baby * toxin prevents release of _stimulatory_ (ACh) signals at neuromuscular junctions --\> flaccid paralysis
49
*Clostridium perfringens*--toxin
alpha toxin
50
*Clostridium perfringens--*mechanism
* phospholipase (lecithinase) that degrades tissue and cell membranes
51
*Clostridium perfringens--*manifestation
* degradation of phospholipids --\> myonecrosis ("gas gangrene") and hemolysis ("double zone") of hemolysis on blood agar
52
*Streptococcus pyogenes*--toxin
Streptolysin O
53
*Streptococcus pyogenes--*mechanism
* protein that degrades cell membrane
54
*Streptococcus pyogenes--*--manifestation
* lyses RBCs * contributes to beta hemolysis * host antibodies against toxin (ASO) used to diagnose rheumatic fever * do not confuse with immune complexes of poststreptococcal glomerulonephritis
55
*staphylococcus aureus*--toxin
toxic shock syndrome toxin (TSST-I)
56
*staphylococcus aureus--*mechanism
* binds to MHC II and TCR outside of antigen binding site to cause overwhelming release if IL-1, IL-2, IFN gamma, and TNF alpha --\> shock
57
*staphylococcus aureus*--manifestation
* toxic shock syndrome * fever * rash * shock * other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (enterotoxin)
58
*Staphylococcus pyogenes*--toxin
exotoxin A
59
*Staphylococcus pyogenes*--mechanism
* binds to MHC II and TCR outside of antigen binding site to cause overwhelming release if IL-1, IL-2, IFN gamma, and TNF alpha --\> shock
60
*Staphylococcus pyogenes*--manifestation
* toxic shock syndrome * fever * rash * shock
61
endotoxin--effects
* macrophage activation (TLR4) * complement activation * tissue factor activation
62
which endotoxins cause macrophage activation and what are their effects?
* IL-1, IL-6 * fever * TNF alpha * fever and hypotension * nitric oxide * hypotension
63
which endotoxins cause complement activation and what are their effects?
* C3a * histamine release --\> hypotension and edema * C5a * neutrophil chemotaxis * histamine release --\> hypotension and edema
64
which endotoxins cause tissue factor activation and what are their effects?
* coagulation cascade * DIC
65
how do endotoxins work?
* LPS found in outer membrane of gram - bacteria (both cocci and rods) * composed of O antigen + core polysaccharide + lipid A (the toxic component) * released upon cell lysis or by living cells by blebs detaching from outer surface membrane (vs. exotoxin, which is actively sereted)
66
how to remember endotoxins:
* **ENDOTOXINS** * **E**dema * **N**itric Oxide * **D**IC/**D**eath * **O**uter membrane * **T**NF-alpha * **O**-antigen + core polysaccharide + lipid A * e**X**tremely heat stable * **I**L-1 and **I**L-6 * **N**eutrophil chemotaxis * **S**hock