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Toxins Flashcards

1
Q

What is the definition of a toxin?

A

A bacterial product that either causes direct harm or triggers a destructive process

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2
Q

Compare and contrast endotoxins vs. exotoxins (3 points)

A

Exotoxin

  • Produced by gram neg & pos bacteria
  • Proteins, released by the bacteria
  • Heat labile

Endotoxin

  • Cell wall components of gram neg bacteria
  • LPS of outer membrane
  • Heat stable
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3
Q

Exotoxins can appear in 2 forms, what are they?

A

A-B toxins of cytolytic toxins

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4
Q

what are exotoxins classified by?

A

Their site of action

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5
Q

what are the 4 types of exotoxins?

A
  1. Enterotoxins
  2. Neurotoxins
  3. Cytotoxins
  4. Pyrogenic toxins
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6
Q

For AB toxins, how many types are there? which subunit does what? specific or non-specific binding?

A

B subunit binds, A subunit has the active action

can be AB or AB5

Binding is specific

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7
Q

What are superantigens able to do?

A

able to stimulate non specific T cell proliferation leading to a significant immune response regardless of antigenic specificity

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8
Q

what are two examples of superantigens?

A
  1. Staphylococcus aureus TSST-1

2. Streptococcal pyrogenic exotoxins

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9
Q

What kinds of symptoms does LPS induce at low concentrations? At high concentrations?

A

Low concentration: Fever, Vasodilation, Inflammatory response

High concentration: Fever, vasodilation, DIC, hypotension, shock/death

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10
Q

What kind of bacteria are Clostridium species?

A

gram positive (although can stain gram variable), spore forming, anaerobic rods

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11
Q

What are the 4 Clostridium sp. we discussed and what do each of them cause?

A
  1. C. tetani: tetanus
  2. C. botulinum: botulism (ingestion or wound)
  3. C. perfringens: gangrene, food poisoning
  4. C. difficile: CDAD
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12
Q

Tetanus is most often associated with what kind of wound?

A

A puncture wound

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13
Q

What two toxins are involved in tetanus infections?

A
  1. Tetanolysin

2. Tetanospasmin

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14
Q

What is tetanolysin? what does it do?

A

Oxygen labile hemolysin

- RBC lysis

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15
Q

What is tetanospasmin?

A

Heat labile neurotoxin

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16
Q

What form of toxin is tetanospasmin? what is it encoded on?

A

plasmid encoded AB toxin

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17
Q

Where does tetanospasmin bind? how does it exert its effects?

A
  1. Binds to specific sialic acid receptors/glycoproteins of motor neurons
  2. Internalized in endosome
  3. Travels by retrograde axonal transport to CNS
  4. Blocks inhibitory impulse to motor neurons by blocking neurotransmitter release
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18
Q

How does tetanospasmin block the inhibitory impulse/neurotransmitters?

A

Inactivates proteins that regulate release of inhibitory neurotransmitters glycine & gamma-aminobutryic acid (GABA)

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19
Q

Is binding of the tetanus toxin reversible or irreversible?

A

Irreversible

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20
Q

What kind of paralysis does tetanus cause?

A

Spastic paralysis

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21
Q

Botulism is what kind of disease?

A

Neuroparalytic

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22
Q

What are 3 main types of botulism?

A
  1. Foodborne
  2. Wound botulism
  3. Infant botulism
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23
Q

How do people normally get foodborne botulism ?

A

ingestion of preformed botulinal toxin in contaminated food (classically associated with home canned foods that were not prepared sterilely)

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24
Q

What is occurring at the site of infection when people get wound botulism?

A

elaboration of botulinal toxin in vivo after the growth of C. botulinum in an infected wound

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25
What is happening in the infant with botulism ?
botulinal toxin is elaborated in vivo in the gastrointestinal tract of an infant colonized with C. botulinum…after ingestion of spores from honey, soil…
26
What kind of toxin is botulinum toxin?
AB exotoxin
27
How many different types of botulinum toxins are there? which cause disease in humans?
7 (A-G) only A,B, E and F cause disease in humans
28
Where does the botulinum toxin bind? How is the progression similar or different to tetanus?
1. Also binds specific sialic acid receptors + glycoproteins (different ones from tetanus) 2. Brought in via endosome 3. Remains at neuromuscular junction 4. Toxin prevents release of acetylcholine at the peripheral nerve endings leading to acute flaccid paralysis
29
Clostridium perfringens is the causative agent of which 3 things?
1. gas gangrene 2. food poisoning 3. Enteritis necroticans
30
What is enteritis necroticans?
Ischemic necrosis of the jejunum, associated with pig feasts, Alpha & Beta toxin (mainly)
31
What kinds of toxins does C. perfringens have?
Alpha, Beta, and Theta toxins
32
What kind of injury do you need to be infected with C. perfringens?
Need a fairly significant injury to occur where the open wounds are exposed to dirt contaminated with spores
33
Which two toxins are the causative agents in gas gangrene?
1. Alpha/Lecithinase toxin | 2. Theta/perfringolysin
34
What is the alpha/lecithinase toxin in gas gangrene? how does it work?
has both phospholipase C and sphingomyelinase activities causes intravascular activation of platelets and clot formation blocks of the arterioles/venules/capilaries and leads to an anaerobic environment where the bacteria can flourish
35
How do people normally get food poisoning from C. perfringens?
Contaminated meat not cooked properly - spores survive Spores germinate and the vegetative cells proliferate and are ingested Enterotoxin produced by vegetative cells in the individual
36
What kind of symptoms are caused by C. perfringens food poisoning?
generally mild, self limiting diarrhea
37
What is the most common cause of infectious diarrhea in hospitals?
C. difficile
38
What is the clinical spectrum of CDAD?
colonized to mild disease to severe disease to severe with toxic megacolon
39
What two toxins does C. difficile produce? where do they act on? which one is needed to be pathogenic?
``` Toxin A (TcdA), enterotoxin Toxin B (TcdB), cytotoxin - toxin B is needed to be pathogenic ```
40
How does C. difficile establish an infection?
1. Vegetative cells and spores are ingested 2. Cells die in stomach but spores survive 3. spores germinate in the small bowel when exposed to bile salts 4. Cells release toxins and adhere to the mucosa in the colon and then multiply - will often proliferate following disruption of normal microflora
41
Which bacteria shares a high degree of relation with Shigella but has distinctive pathogenesis?
E. coli
42
What kind of bacteria are E.coli?
Gram negative, facultative, mobile rods
43
Most strains of E.coli cause?
Intestinal/Diarrheal disease; Diarrheagenic E.coli
44
Other strains of E. coli can cause?
Urinary tract infection Neonatal meningitis Septicemia
45
How many types of diarrhea producing E.coli are there? How many are toxigenic?
6, 2 are toxigenic
46
Which of the diarrhea causing strains of E.coli are toxigenic?
ETEC: Enterotoxigenic EHEC: Enterohemorrhagic
47
What does ETEC cause? How is it acquired?
Contaminated food/water - fecal oral Causes traveller's diarrhea and watery diarrhea in children in developing countries
48
How many organisms of ETEC E.coli do you need to cause disease?
10^8-10^10 in a healthy individual
49
What two toxins do ETEC E. coli produce? What other pathogenic mechanism does it use?
LT(heat labile) / ST(heat stabile) also uses fimbriae to attach to the intestine
50
What is the LT toxin? How does it work? what is it similar to?
Heat labile, AB5 toxin Similar to cholera Stimulates adenylate cyclase, increases cAMP, leading to electrolytes & water excretion in intestinal lumen (watery diarrhea)
51
What is the ST toxin? How does it work?
Heat-stabile, STA and STB forms Activates guanylate cyclase,↑cyclic guanosine monophosphate, ↑ fluid & electrolyte excretion (watery diarrhea)
52
What is another name for EHEC ?
Also called Shiga toxin producing E.coli or Verotoxogenic E.coli
53
What does EHEC cause?
hemorrhagic colitis (bloody diarrhea) & may lead to hemolytic urea syndrome
54
How do people become infected with EHEC?
contaminated food: undercooked ground beef, raw milk, unpasteurized apple juice, vegetables
55
What is the most common serotype of EHEC E.coli?
O157:H7 most common
56
Where is the shiga like toxin gene encoded?
on a bacteriophage
57
What type of toxin is the shiga like toxin?
AB5
58
Where does the shiga-like toxin bind?
glycolipid receptors (gb3), found in varying degrees in membranes of eukaryotic cells
59
What does shiga like toxin target while in systemic circulation? what does this cause?
endothelial cells, causing vascular damage, bloody diarrhea, and, in some patients, a prothrombotic state that precedes the hemolytic uremic syndrome
60
What type of bacteria is Shigella?
gram negative non motile rod
61
What is the reservoir for Shigella?
There is none. human pathogen only
62
How is Shigella spread?
more often by fecal oral route and less by contaminated foods
63
What is the infectious dose of Shigella like compared with E. coli?
much lower, around 10-100 organisms
64
What kind of bacteria are Vibrio?
curved gram negative rods, highly motile, facultative anaerobes
65
Where is Vibrio typically found?
in salt water
66
What are the 3 species of Vibrio that were discussed? What do they cause?
V. cholerae = cholera V. parahaemolyticus = gastroenteritis V. vulnificus = cellulitis, septicemia
67
How is Vibrio cholera usually acquired?
from contaminated water and occasionally through contaminated food
68
Where is V. cholera endemic?
South East Asia, parts of Africa & S. America
69
What kind of toxin is the V. cholera toxin?
An AB5 toxin
70
Where does the cholera toxin bind?
Bind ganglioside GM1 receptors on intestinal cells
71
What does the binding of the cholera toxin cause?
Increase cAMP, leading to electrolytes & water secretions (watery diarrhea)
72
What kind of bacteria is Staph aureus?
non motile, gram positive cocci
73
What 4 kinds of toxins can staph aureus produce?
1. Cytotoxins 2. Exfoliative toxins 3. Toxic shock toxins 4. Enterotoxins
74
What kinds of cytotoxins can S. aureus produce?
alpha, beta, delta, gamma and panton-velntine leukociden
75
What are the 2 exfoliative toxins that S. aureus produces? What kind of action do they have ?
ETA and ETB | Serine proteases that disrupt cell adhesion structures
76
What is the difference between ETA and ETB?
ETA – heat stable, chromosomal | ETB – heat labile, on plasmid
77
How is food poisoning caused by S. aureus?
toxins present in food at time of ingestion - not live bacteria
78
What is the source of food contamination in S. aureus food poisoning?
the food handler | - 50% are cases of asymptomatic carriage
79
What is the most common enterotoxin associated with S. aureus food poisoning? Why?
Enterotoxin A Heat stable and resistant to gastric enzymes
80
What % of S. aureus strains produce Enterotoxin A?
30-50%
81
How quickly is the onset of S. aureus food poisoning?
abrupt, about 4 hours after ingestion of food
82
What are some of the symptoms of a S. aureus food poisoning episode? how long do the symptoms last?
Should resolve in about 24 hours ``` severe vomiting watery non-bloddy diahrrhea abdominal pain nausea no fever!! ```

Clinical Micro (28 decks)

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