Exotoxins and Endotoxins Flashcards

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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
Q

Shigella spp.–mechanism

A
  • inactive 60S ribosome by removing adenosine from rRNA
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26
Q

Shigella spp.–mechanism

A
  • GI mucosal damage –> dysentery
  • ST also enhances cytokine release causing hemolytic uremic syndrome (HUS)
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27
Q

Enterohemorrhagic E. coli (EHEC)–toxin

A

Shiga like toxin (SLT)

28
Q

Enterohemorrhagic E. coli ​(EHEC)mechanism

A
  • inactivate 60S ribosome by removing adenine from rRNA
29
Q

Enterohemorrhagic E. coli ​(EHEC)–manifestation

A
  • SLT enhances cytokine release causing HUS (prototypically in EHEC serotype O157:H7)
  • unlike Shigella, EHEC does not invade host cells
30
Q

exterotoxigenic E.coli (ETEC)–toxins

A
  • heat labile toxin (LT)
  • heat stable toxin (ST)
31
Q

exterotoxigenic E.coli​ (ETEC) heat labile toxin–mechanism

A
  • overactivates adenylate cyclase (inc cAMP) –> inc Cl- secretion in gut and H2O efflux
32
Q

exterotoxigenic E.coli​ (ETEC) heat stable toxin–mechanism

A
  • overactivates guanylate cyclase (inc cGMP) –> dec resorption of NaCl and H2O in gut
33
Q

exterotoxigenic E.coli​ (ETEC)–manifestation

A
  • watery diarrhea
    • labile in the Air (Adenylate cyclase), stable on the Ground (Guanylate cyclase)
34
Q

Bacillus anthracis–toxin

A
  • edema toxin
    • an AB toxin
35
Q

​Bacillus anthracis–mechanism

A
  • mimics the adenylate cyclase enzyme–inc cAMP
36
Q

​Bacillus anthracis–manifestation

A
  • likely responsible for chracteristic edematous borders of black eschar in cutaneous anthrax
37
Q

Vibrio cholerae–toxin

A

cholera toxin

38
Q

Vibrio cholerae–mechanism

A
  • overactivates adenylate cyclase (inc cAMP) by permanently activating GS –> inc Cl- secretion in gut and H2O efflux
39
Q

Vibrio cholerae–manifestation

A
  • voluminous “rice water” diarrhea
40
Q

Bordetella pertussis–toxin

A

pertussis toxin

41
Q

Bordetella pertussis–mechanism

A
  • overactivates adenylate cyclase (inc cAMP) by disabling Gi –> impairs phagocytosis to permit survival of microbe
42
Q

Bordetella pertussis–manifestation

A
  • 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
Q

Clostridium tetani–toxin

A

tetanospasmin

44
Q

Clostridium tetani–mechanism

A
  • both are proteases that cleave SNARE (soluble NSF attachment protein receptor)–a set of protein required for neurotransmitter release via vesicular fusion
45
Q

Clostridium tetani–manifestation

A
  • spastic paralysis
  • risus sardonicus
  • “lockjaw”
  • toxin prevents release of inhibitory (GABA and glycine) neurotransmitters from Renshaw cells in spinal cord
46
Q

Clostridium botulinum–toxin

A

botulinum toxin

47
Q

Clostridium botulinum–mechanism

A
  • both are proteases that cleave SNARE (soluble NSF attachment protein receptor)–a set of protein required for neurotransmitter release via vesicular fusion
48
Q

Clostridium botulinum–manifestation

A
  • flaccid paralysis
  • floppy baby
  • toxin prevents release of stimulatory (ACh) signals at neuromuscular junctions –> flaccid paralysis
49
Q

Clostridium perfringens–toxin

A

alpha toxin

50
Q

Clostridium perfringens–mechanism

A
  • phospholipase (lecithinase) that degrades tissue and cell membranes
51
Q

Clostridium perfringens–manifestation

A
  • degradation of phospholipids –> myonecrosis (“gas gangrene”) and hemolysis (“double zone”) of hemolysis on blood agar
52
Q

Streptococcus pyogenes–toxin

A

Streptolysin O

53
Q

Streptococcus pyogenes–mechanism

A
  • protein that degrades cell membrane
54
Q

Streptococcus pyogenes––manifestation

A
  • 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
Q

staphylococcus aureus–toxin

A

toxic shock syndrome toxin (TSST-I)

56
Q

staphylococcus aureus–mechanism

A
  • 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
Q

staphylococcus aureus–manifestation

A
  • toxic shock syndrome
    • fever
    • rash
    • shock
  • other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (enterotoxin)
58
Q

Staphylococcus pyogenes–toxin

A

exotoxin A

59
Q

Staphylococcus pyogenes–mechanism

A
  • 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
Q

Staphylococcus pyogenes–manifestation

A
  • toxic shock syndrome
    • fever
    • rash
    • shock
61
Q

endotoxin–effects

A
  • macrophage activation (TLR4)
  • complement activation
  • tissue factor activation
62
Q

which endotoxins cause macrophage activation and what are their effects?

A
  • IL-1, IL-6
    • fever
  • TNF alpha
    • fever and hypotension
  • nitric oxide
    • hypotension
63
Q

which endotoxins cause complement activation and what are their effects?

A
  • C3a
    • histamine release –> hypotension and edema
  • C5a
    • neutrophil chemotaxis
    • histamine release –> hypotension and edema
64
Q

which endotoxins cause tissue factor activation and what are their effects?

A
  • coagulation cascade
    • DIC
65
Q

how do endotoxins work?

A
  • 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
Q

how to remember endotoxins:

A
  • ENDOTOXINS
    • Edema
    • Nitric Oxide
    • DIC/Death
    • Outer membrane
    • TNF-alpha
    • O-antigen + core polysaccharide + lipid A
    • eXtremely heat stable
    • IL-1 and IL-6
    • Neutrophil chemotaxis
    • Shock