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Flashcards in bacterial toxins Deck (81):
1

bacterial toxins are divided to

1. exotoxin
2. endotoxin

2

bacterial toxins - source

exotoxin --> certain species of gram (+) and gram (-)
endotoxin --> outer cel membrane of most gram (-)

3

bacterial toxins - secreted from cells ?

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

4

bacterial toxins - chemistry

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

5

bacterial toxin - location of genes

exotoxin --> plasmids or bacteriophages
endotoxin --> bacterial chromosome

6

bacterial toxins - toxicity

exotoxin --> high (fatal dose on the order of 1 μg)
endotoxin --> low (fatal dose on the order of hundreds of micrograms)

7

exotoxin vs endotoxin according to fatal dose

exotoxin --> 1 μg
endotoxin --> Order of hundreds of micrograms

8

bacterial toxins - clinical effects

exotoxin --> various effects
endotoxin --> fever, shock (hypotension), DIC

9

bacterial toxins - mode of action

exotoxin --> various modes
endotoxin --> induce TNF, IL-1, IL-6

10

bacterial toxins - antigenicity

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

11

bacterial toxins - vaccines

exotoxin --> toxoids used as vaccines
endotoxin --> no toxoids formed and no vaccine available

12

bacterial toxins - head stability

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

13

bacterial toxins - head stability

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

14

bacterial toxins - typical diseases

exotoxin --> tetanus, botulism, diphtheria
endotoxin --> Meningococcemia, sepsis by gram (-) robs

15

A toxoid is an

inactivated or attenuated toxin

16

exotoxins are divided to .. (according their action)

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

17

inhibit protein synthesis - exotoxins and bugs?

1, Corynebacterium diphteria - Diptheria toxin
2. Pseudomonas aeruginosa - Exotoxin A
3. Shigella - Shiga toxin
4. Enterohemorrhagic E coli (EHEC) - Shiga like toxin

18

Diptheria toxin - mechanism of action

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

19

Diptheria toxin - manifestations

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

20

exotoxin A is produced by

1. Pseudomonas aeruginosa
2. Streptpcoccus pyogenes
(different toxins)

21

exotoxin A (P aeruginosa) - mechanism of action

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

22

exotoxin A (P aeruginosa) causes (microscopically)

Host cell death

23

shiga toxin is produced by

Shigella

24

shigella toxin - mechanism of action

inactivates 60S ribosome by removing adenine from rRNA

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