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bacterial toxins Flashcards

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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
Q

shiga toxin - manifestation

A
  1. GI mucosal damage –> dysentery

2. enchance cytokine release –> hemolytic uremic syndrome

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26
Q

Shiga like toxin is produced by

A

Enterohemorrhagic E coli (EHEC), prototypically EHEC serotype O157:H7

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27
Q

Shiga like toxin - mechanism of action

A

inactivates 60S ribosome by removing adenine from rRNA

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28
Q

shiga like toxin inactivates 60S ribosome by

A

removing adenine from rRNA

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29
Q

shiga like toxin - manifestation

A

enchance cytokine release –> hemolytic uremic syndrome

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30
Q

Unlike shigella, EHEC ….

A

does not invade host cells

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31
Q

Increase fluid secretion - exotoxins and bugs?

A
  1. enterotoxigenic E coli (ETEC) –> Head-labile toxin (LT), Heat-stable toxin (ST)
  2. Bacillus antrhacis - edema toxin
  3. Vibrio cholera - cholera toxin
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32
Q

Head-labile toxin (LT) is produced by

A

enterotoxigenic E coli (ETEC)

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33
Q

Head-labile toxin (LT) - mechanism of action

A

Overactivates adenylate cyclase (increases cAMP) –> increases CL- secretion in gut and H20 efflux

34
Q

Head-labile toxin (LT) - manifestations

A

watery diarrhea

35
Q

Head-stable toxin (ST) - mechanism of action

A

overactivates guanylate cyclase (increases cGMP) –> decreases resorption of NaCL and H20 in gut

36
Q

Head-stable toxin (ST) - manifestations

A

watery diarrhea

37
Q

edema toxin is produced by

A

Bacillus anthracis

38
Q

edema toxin - mechanism of action

A

mimics the adenylate cyclase enzyme –> increases cAMP

39
Q

edema toxin - manifestations

A

likely responsible for characteristic edematous borders of black eschar in cutaneous antrhax

40
Q

cholera toxin - mechanism of action

A

overactivates adenylate cyclase (increases cAMP) by permanently activateing Gs –> increases CL- secretion in gut and H20 efflux

41
Q

cholera toxin - manifestation

A

voluminous “rice water” diarrhea

42
Q

inhibit phagocytic ability - exotoxins and bugs?

A

Bordetella pertusis –> Pertussis toxin

43
Q

Pertussis toxin - mechanism of action

A

Overactivates adenylate cyclase (increases cAMP) by disabling Gi, imparing phagocytosis to permit survival of microbe

44
Q

Pertussis toxin - manifestation

A

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
Q

Inhibit release of neurotransmitter - exotoxins and bugs?

A

Clostiridium tetani –> Tetanospamin

Clostiridium botulinum –> Botulinum toxin

46
Q

tetanospasin is produced by

A

Clostiridium tetani

47
Q

tetanospasmin - mechanism of action

A

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
Q

tetanospasmin prevents the release of

A

inhibitory (GABA and glycine) from Renshaw cells in spinal cord

49
Q

tetanospasmin - manifestations

A
  1. spasticity
  2. risus sardonicus (raised eyebrows and open grin)
  3. Lockjaw (trismus)
50
Q

Botulinum toxin - mechanism of action

A

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
Q

Botulinum toxin - prevents the release of

A

stimulatory (ACH) signals at neuromuscular junctions

52
Q

Botulinum toxin - manifestations

A
  1. flaccid paralysis

2. floppy babe

53
Q

Lyse cell membranes - exotoxins and bugs?

A
  1. Clostiridium perfingens –> Alpha toxin

2. Streptococcus pyogenes –> streptolysin 0

54
Q

Alpha toxin is produced by … / mechanism of action

A

Clostiridium perfingens: Phospholipase (lecithinase) that degrades tissue and cell membranes

55
Q

Alpha toxin - manifestations

A
  1. myonecrosis (gas gangrene)

2. hemolysis (double zone of hemolyisis on blood agar)

56
Q

streptolysin 0 is produced by

A

Streptococcus pyogenes: protein that degrade cell membrane

57
Q

streptolysin 0 - manifestation

A

Lyses RBCs

contributes to β-hemolysis

58
Q

host antibodies against streptolysin 0 - clinical relevance

A

used to diagnose rheumatic fever

59
Q

Superantigens causing shock - exotoxins and bugs?

A
  1. Staphylococcus aureus –> Toxic shock syndrome toxin (TSST-1)
  2. Streptococcus pyogenes –> Exotoxin A
60
Q

Toxic shock syndrome toxin (TSST-1) - mechanism of action

A

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
Q

Toxic shock syndrome toxin (TSST-1) - manifestation

A

Toxic shock syndrome: fever, rash, shock, vomiting, desquamation, end-organ failure

62
Q

other toxins of Staphylococcus aureus (except TSST-1) (and manifestation)

A
  1. Exfoliative –> scalded skin syndrome

2. enterotoxin –> rapid food poisoning

63
Q

Exotoxin A is produced by

A
  1. Streptococcus pyogenes
  2. Pseudomonas aeruginosa
    (different toxins)
64
Q

Exotoxin A (S. pyogenes) - mechanism of action

A

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
Q

Exotoxin A (S. pyogenes) - manifestation

A

Toxic shock syndrome: fever, rash, shock

66
Q

Staphylococcal aureus toxins and manifestations

A
  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
Q

endotoxin - structure and location

A

LPS found in outer membrane of gram (-) bacteria (both cocci and robs

68
Q

gram + with endotoxin/LPS

A

Listeria monocytogenes

69
Q

LPS - is composed by

A 
Lippid A (inner)
O polysaccharide (outer)
70
Q

LPS function (especially lipid A)

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
Q

endotoxin - mnemonic

A 
ENDOTOXIN 
EDEMA
NO
DIC/DEATH
OUTER MEMBRANE
TNF-α
O-antigen
Extremely heat stable
IL-1
Neutrophil chemotaxis
72
Q

all toxins (and the bacteria)

A
  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
Q

ADP ribosylating A-B toxin - toxins?

A
  1. diphteria 2. exotoxin A (P. aeroginosa)
  2. Shiga toxin 4. shiga like toxin
  3. heat labile toxin 6. edema toxin 7. Cholera toxin
  4. Pertusis toxin 9. Tetanospamin 10. Botilium
    ALL EXOTOXINS EXCEPT HEAT STABLE, LYSE MEMBRANE TOXINS, SUPERANTIGENS TOXINS AND STAPH TOXINS
74
Q

all exotoxins are ADP ribosylating A-B toxin except

A
  1. HEAT STABLE
  2. LYSE MEMBRANE TOXINS
  3. SUPERANTIGENS TOXINS
  4. STAPH TOXINS
75
Q

inactivates 60S ribosome by removing adenine from rRNA - toxin?

A

shiga and shiga like

76
Q

O157:H7 - toxin?

A

shiga like

77
Q

whooping cough - toxin and bug

A

pertussis toxin - Bordetella pertussis

78
Q

Hemolytic-uremic syndrome - toxin?

A
  1. shiga toxin

2. shiga like toxin

79
Q

Toxic shock syndrome - is associated with

A
  1. S. aureus –> vaginal tampons, nasal packing

2. S. pyogenes –> painful skin infection

80
Q

Clostiridia - toxins

A
  1. Clostiridium tetani –> tetanospasmin
  2. Clostiridium botulinum –> Botulinum toxin
  3. Clostiridium perfringens –> Alpha toxin
  4. Clostiridium difficile –> Toxin A (eneterotoxin), Toxin B (cytotoxin)
81
Q

endotoxins activate macrophage through

A

TLR4

Microbiology (25 decks)

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