bacterial toxins Flashcards

(81 cards)

1
Q

bacterial toxins are divided to

A
  1. exotoxin

2. endotoxin

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2
Q

bacterial toxins - source

A

exotoxin –> certain species of gram (+) and gram (-)

endotoxin –> outer cel membrane of most gram (-)

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3
Q

bacterial toxins - secreted from cells ?

A

exotoxin –> YES

endotoxin –> NO (release when lysed or by living cells by blebs detaching from outer surface membrane)

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4
Q

bacterial toxins - chemistry

A

exotoxin –> polypeptide
endotoxin –> Lipopolysaccharide (structural part of bacteria, release when lysed or by living cells by blebs detaching from outer surface membrane)

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5
Q

bacterial toxin - location of genes

A

exotoxin –> plasmids or bacteriophages

endotoxin –> bacterial chromosome

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6
Q

bacterial toxins - toxicity

A

exotoxin –> high (fatal dose on the order of 1 μg)

endotoxin –> low (fatal dose on the order of hundreds of micrograms)

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7
Q

exotoxin vs endotoxin according to fatal dose

A

exotoxin –> 1 μg

endotoxin –> Order of hundreds of micrograms

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8
Q

bacterial toxins - clinical effects

A

exotoxin –> various effects

endotoxin –> fever, shock (hypotension), DIC

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9
Q

bacterial toxins - mode of action

A

exotoxin –> various modes

endotoxin –> induce TNF, IL-1, IL-6

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10
Q

bacterial toxins - antigenicity

A

exotoxin –> induces high-titer antibodies called antitoxins
endotoxin –> poorly antigenic

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11
Q

bacterial toxins - vaccines

A

exotoxin –> toxoids used as vaccines

endotoxin –> no toxoids formed and no vaccine available

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12
Q

bacterial toxins - head stability

A

exotoxin –> destroyed rapidly at 60 c (except staphylococcal)
endotoxin –> stable at 100 c for 1 hr

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13
Q

bacterial toxins - head stability

A

exotoxin –> destroyed rapidly at 60 c (except staphylococcal)
endotoxin –> stable at 100 c for 1 hr

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14
Q

bacterial toxins - typical diseases

A

exotoxin –> tetanus, botulism, diphtheria

endotoxin –> Meningococcemia, sepsis by gram (-) robs

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15
Q

A toxoid is an

A

inactivated or attenuated toxin

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16
Q

exotoxins are divided to .. (according their action)

A
  1. inhibit protein synthesis
  2. Increase fluid secretion
  3. Inhibit phagocytic ability
  4. Inhibit release of neurotransmitter
  5. Lyse cell membranes
  6. Superantigens causing shock
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17
Q

inhibit protein synthesis - exotoxins and bugs?

A

1, Corynebacterium diphteria - Diptheria toxin

  1. Pseudomonas aeruginosa - Exotoxin A
  2. Shigella - Shiga toxin
  3. Enterohemorrhagic E coli (EHEC) - Shiga like toxin
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18
Q

Diptheria toxin - mechanism of action

A

ADP-ribosilation of E2F –> INACTIVATION OF E2F ELONGATION –> inhibition of tRNA translocation –> inhibition of protein synthesis

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19
Q

Diptheria toxin - manifestations

A
  1. pseudomembranous pharyngitis
  2. Lymphadenopathy (bull neck)
  3. myocaridits
  4. arrhythmia
  5. demyelination/paralysis of peripheral nerves
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20
Q

exotoxin A is produced by

A
  1. Pseudomonas aeruginosa
  2. Streptpcoccus pyogenes
    (different toxins)
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21
Q

exotoxin A (P aeruginosa) - mechanism of action

A

ADP-ribosilation of E2F –> INACTIVATION OF E2F ELONGATION –> inhibition of tRNA translocation –> inhibition of protein synthesis

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22
Q

exotoxin A (P aeruginosa) causes (microscopically)

A

Host cell death

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23
Q

shiga toxin is produced by

A

Shigella

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24
Q

shigella toxin - mechanism of action

A

inactivates 60S ribosome by removing adenine from rRNA

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25
shiga toxin - manifestation
1. GI mucosal damage --> dysentery | 2. enchance cytokine release --> hemolytic uremic syndrome
26
Shiga like toxin is produced by
Enterohemorrhagic E coli (EHEC), prototypically EHEC serotype O157:H7
27
Shiga like toxin - mechanism of action
inactivates 60S ribosome by removing adenine from rRNA
28
shiga like toxin inactivates 60S ribosome by
removing adenine from rRNA
29
shiga like toxin - manifestation
enchance cytokine release --> hemolytic uremic syndrome
30
Unlike shigella, EHEC ....
does not invade host cells
31
Increase fluid secretion - exotoxins and bugs?
1. enterotoxigenic E coli (ETEC) --> Head-labile toxin (LT), Heat-stable toxin (ST) 2. Bacillus antrhacis - edema toxin 3. Vibrio cholera - cholera toxin
32
Head-labile toxin (LT) is produced by
enterotoxigenic E coli (ETEC)
33
Head-labile toxin (LT) - mechanism of action
Overactivates adenylate cyclase (increases cAMP) --> increases CL- secretion in gut and H20 efflux
34
Head-labile toxin (LT) - manifestations
watery diarrhea
35
Head-stable toxin (ST) - mechanism of action
overactivates guanylate cyclase (increases cGMP) --> decreases resorption of NaCL and H20 in gut
36
Head-stable toxin (ST) - manifestations
watery diarrhea
37
edema toxin is produced by
Bacillus anthracis
38
edema toxin - mechanism of action
mimics the adenylate cyclase enzyme --> increases cAMP
39
edema toxin - manifestations
likely responsible for characteristic edematous borders of black eschar in cutaneous antrhax
40
cholera toxin - mechanism of action
overactivates adenylate cyclase (increases cAMP) by permanently activateing Gs --> increases CL- secretion in gut and H20 efflux
41
cholera toxin - manifestation
voluminous "rice water" diarrhea
42
inhibit phagocytic ability - exotoxins and bugs?
Bordetella pertusis --> Pertussis toxin
43
Pertussis toxin - mechanism of action
Overactivates adenylate cyclase (increases cAMP) by disabling Gi, imparing phagocytosis to permit survival of microbe
44
Pertussis toxin - manifestation
whooping cough: child cough on expiration and whoops on inspiration --> toxin may not actually be a cause of cough, can cause 100 day cough in adults
45
Inhibit release of neurotransmitter - exotoxins and bugs?
Clostiridium tetani --> Tetanospamin | Clostiridium botulinum --> Botulinum toxin
46
tetanospasin is produced by
Clostiridium tetani
47
tetanospasmin - mechanism of action
protease that cleave SNARE (soluble NSF attachment protein receptor), a set of proteins required for neurotransmitter release via vesicular formation --> prevent release of inhibitory (GABA and glycine) from Renshaw cells in spinal cord
48
tetanospasmin prevents the release of
inhibitory (GABA and glycine) from Renshaw cells in spinal cord
49
tetanospasmin - manifestations
1. spasticity 2. risus sardonicus (raised eyebrows and open grin) 3. Lockjaw (trismus)
50
Botulinum toxin - mechanism of action
protease that cleave SNARE (soluble NSF attachment protein receptor), a set of proteins required for neurotransmitter release via vesicular formation --> prevent release of stimulatory (ACH) signals at neuromuscular junctions
51
Botulinum toxin - prevents the release of
stimulatory (ACH) signals at neuromuscular junctions
52
Botulinum toxin - manifestations
1. flaccid paralysis | 2. floppy babe
53
Lyse cell membranes - exotoxins and bugs?
1. Clostiridium perfingens --> Alpha toxin | 2. Streptococcus pyogenes --> streptolysin 0
54
Alpha toxin is produced by ... / mechanism of action
Clostiridium perfingens: Phospholipase (lecithinase) that degrades tissue and cell membranes
55
Alpha toxin - manifestations
1. myonecrosis (gas gangrene) | 2. hemolysis (double zone of hemolyisis on blood agar)
56
streptolysin 0 is produced by
Streptococcus pyogenes: protein that degrade cell membrane
57
streptolysin 0 - manifestation
Lyses RBCs | contributes to β-hemolysis
58
host antibodies against streptolysin 0 - clinical relevance
used to diagnose rheumatic fever
59
Superantigens causing shock - exotoxins and bugs?
1. Staphylococcus aureus --> Toxic shock syndrome toxin (TSST-1) 2. Streptococcus pyogenes --> Exotoxin A
60
Toxic shock syndrome toxin (TSST-1) - mechanism of action
Binds to MCH II and TCR outside of antigen binding site (polyclonal T-cel activation)to cause overwhelming release of IL-1, IL-2, INF-γ, TNF-α --> shock
61
Toxic shock syndrome toxin (TSST-1) - manifestation
Toxic shock syndrome: fever, rash, shock, vomiting, desquamation, end-organ failure
62
other toxins of Staphylococcus aureus (except TSST-1) (and manifestation)
1. Exfoliative --> scalded skin syndrome | 2. enterotoxin --> rapid food poisoning
63
Exotoxin A is produced by
1. Streptococcus pyogenes 2. Pseudomonas aeruginosa (different toxins)
64
Exotoxin A (S. pyogenes) - mechanism of action
Binds to MCH II and TCR outside of antigen binding site to cause (polyclonal T-cel activation) overwhelming release of IL-1, IL-2, INF-γ, TNF-α --> shock
65
Exotoxin A (S. pyogenes) - manifestation
Toxic shock syndrome: fever, rash, shock
66
Staphylococcal aureus toxins and manifestations
1. Toxic shock syndrome toxin (TSST-1) --> Toxic shock syndrome: fever, rash, shock, vomiting, desquamation, end-organ failure 2. Exfoliative --> scalded skin syndrome 3. enterotoxin --> rapid onset food poisoning
67
endotoxin - structure and location
LPS found in outer membrane of gram (-) bacteria (both cocci and robs
68
gram + with endotoxin/LPS
Listeria monocytogenes
69
LPS - is composed by
``` Lippid A (inner) O polysaccharide (outer) ```
70
LPS function (especially lipid A)
1. activates macrophages (TLR4) --> IL-1 (fever), TNF-α (fever and hypotension), NO (hypotension) 2. activates complement --> C3a (hypotension, edema), C5a (neutrophils hemotaxis) 3. activates tissue factor --> coagulation cascade (DIC)
71
endotoxin - mnemonic
``` ENDOTOXIN EDEMA NO DIC/DEATH OUTER MEMBRANE TNF-α O-antigen Extremely heat stable IL-1 Neutrophil chemotaxis ```
72
all toxins (and the bacteria)
1. Corynobacterium diptheriae --> diphteria toxin 2. Pseudomonas aeruginosa --> Exotoxin A 3. shigella --> shigella toxin 4. Enterohemorrhagic E coli --> Shiga like toxin 5. Enterotoxigenic E coli --> Heat-labile toxin, Heat-stable toxin 6. Bacillus anthracis --> edema toxin 7. Vibrio cholerae --> cholera toxin 8. Bordetella pertussis --> Pertusis toxin 9. Clostiridium tetani --> Tetanospasmin 10. Clostiridium botilinum --> Botulinum toxin 11. Clostiridium perfinges --> Alpha toxin 12. streptococcus pyogenes --> streptolysin 0, Exotoxin A 13. Staphylococcus aureus --> Toxic shock syndrome toxin, exofliative toxin, enterotoxin
73
ADP ribosylating A-B toxin - toxins?
1. diphteria 2. exotoxin A (P. aeroginosa) 3. Shiga toxin 4. shiga like toxin 5. heat labile toxin 6. edema toxin 7. Cholera toxin 8. Pertusis toxin 9. Tetanospamin 10. Botilium ALL EXOTOXINS EXCEPT HEAT STABLE, LYSE MEMBRANE TOXINS, SUPERANTIGENS TOXINS AND STAPH TOXINS
74
all exotoxins are ADP ribosylating A-B toxin except
1. HEAT STABLE 2. LYSE MEMBRANE TOXINS 3. SUPERANTIGENS TOXINS 4. STAPH TOXINS
75
inactivates 60S ribosome by removing adenine from rRNA - toxin?
shiga and shiga like
76
O157:H7 - toxin?
shiga like
77
whooping cough - toxin and bug
pertussis toxin - Bordetella pertussis
78
Hemolytic-uremic syndrome - toxin?
1. shiga toxin | 2. shiga like toxin
79
Toxic shock syndrome - is associated with
1. S. aureus --> vaginal tampons, nasal packing | 2. S. pyogenes --> painful skin infection
80
Clostiridia - toxins
1. Clostiridium tetani --> tetanospasmin 2. Clostiridium botulinum --> Botulinum toxin 3. Clostiridium perfringens --> Alpha toxin 4. Clostiridium difficile --> Toxin A (eneterotoxin), Toxin B (cytotoxin)
81
endotoxins activate macrophage through
TLR4