Toxins Flashcards
What is the definition of a toxin?
A bacterial product that either causes direct harm or triggers a destructive process
Compare and contrast endotoxins vs. exotoxins (3 points)
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
Exotoxins can appear in 2 forms, what are they?
A-B toxins of cytolytic toxins
what are exotoxins classified by?
Their site of action
what are the 4 types of exotoxins?
- Enterotoxins
- Neurotoxins
- Cytotoxins
- Pyrogenic toxins
For AB toxins, how many types are there? which subunit does what? specific or non-specific binding?
B subunit binds, A subunit has the active action
can be AB or AB5
Binding is specific
What are superantigens able to do?
able to stimulate non specific T cell proliferation leading to a significant immune response regardless of antigenic specificity
what are two examples of superantigens?
- Staphylococcus aureus TSST-1
2. Streptococcal pyrogenic exotoxins
What kinds of symptoms does LPS induce at low concentrations? At high concentrations?
Low concentration: Fever, Vasodilation, Inflammatory response
High concentration: Fever, vasodilation, DIC, hypotension, shock/death
What kind of bacteria are Clostridium species?
gram positive (although can stain gram variable), spore forming, anaerobic rods
What are the 4 Clostridium sp. we discussed and what do each of them cause?
- C. tetani: tetanus
- C. botulinum: botulism (ingestion or wound)
- C. perfringens: gangrene, food poisoning
- C. difficile: CDAD
Tetanus is most often associated with what kind of wound?
A puncture wound
What two toxins are involved in tetanus infections?
- Tetanolysin
2. Tetanospasmin
What is tetanolysin? what does it do?
Oxygen labile hemolysin
- RBC lysis
What is tetanospasmin?
Heat labile neurotoxin
What form of toxin is tetanospasmin? what is it encoded on?
plasmid encoded AB toxin
Where does tetanospasmin bind? how does it exert its effects?
- Binds to specific sialic acid receptors/glycoproteins of motor neurons
- Internalized in endosome
- Travels by retrograde axonal transport to CNS
- Blocks inhibitory impulse to motor neurons by blocking neurotransmitter release
How does tetanospasmin block the inhibitory impulse/neurotransmitters?
Inactivates proteins that regulate release of inhibitory neurotransmitters glycine & gamma-aminobutryic acid (GABA)
Is binding of the tetanus toxin reversible or irreversible?
Irreversible
What kind of paralysis does tetanus cause?
Spastic paralysis
Botulism is what kind of disease?
Neuroparalytic
What are 3 main types of botulism?
- Foodborne
- Wound botulism
- Infant botulism
How do people normally get foodborne botulism ?
ingestion of preformed botulinal toxin in contaminated food (classically associated with home canned foods that were not prepared sterilely)
What is occurring at the site of infection when people get wound botulism?
elaboration of botulinal toxin in vivo after the growth of C. botulinum in an infected wound
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…
What kind of toxin is botulinum toxin?
AB exotoxin
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
Where does the botulinum toxin bind? How is the progression similar or different to tetanus?
- Also binds specific sialic acid receptors + glycoproteins (different ones from tetanus)
- Brought in via endosome
- Remains at neuromuscular junction
- Toxin prevents release of acetylcholine at the peripheral nerve endings leading to acute flaccid paralysis
Clostridium perfringens is the causative agent of which 3 things?
- gas gangrene
- food poisoning
- Enteritis necroticans
What is enteritis necroticans?
Ischemic necrosis of the jejunum, associated with pig feasts, Alpha & Beta toxin (mainly)
What kinds of toxins does C. perfringens have?
Alpha, Beta, and Theta toxins
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
Which two toxins are the causative agents in gas gangrene?
- Alpha/Lecithinase toxin
2. Theta/perfringolysin
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
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
What kind of symptoms are caused by C. perfringens food poisoning?
generally mild, self limiting diarrhea
What is the most common cause of infectious diarrhea in hospitals?
C. difficile
What is the clinical spectrum of CDAD?
colonized to mild disease to severe disease to severe with toxic megacolon
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
How does C. difficile establish an infection?
- Vegetative cells and spores are ingested
- Cells die in stomach but spores survive
- spores germinate in the small bowel when exposed to bile salts
- Cells release toxins and adhere to the mucosa in the colon and then multiply
- will often proliferate following disruption of normal microflora
Which bacteria shares a high degree of relation with Shigella but has distinctive pathogenesis?
E. coli
What kind of bacteria are E.coli?
Gram negative, facultative, mobile rods
Most strains of E.coli cause?
Intestinal/Diarrheal disease; Diarrheagenic E.coli
Other strains of E. coli can cause?
Urinary tract infection
Neonatal meningitis
Septicemia
How many types of diarrhea producing E.coli are there? How many are toxigenic?
6, 2 are toxigenic
Which of the diarrhea causing strains of E.coli are toxigenic?
ETEC: Enterotoxigenic
EHEC: Enterohemorrhagic
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
How many organisms of ETEC E.coli do you need to cause disease?
10^8-10^10 in a healthy individual
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
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)
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)
What is another name for EHEC ?
Also called Shiga toxin producing E.coli or Verotoxogenic E.coli
What does EHEC cause?
hemorrhagic colitis (bloody diarrhea) & may lead to hemolytic urea syndrome
How do people become infected with EHEC?
contaminated food: undercooked ground beef, raw milk, unpasteurized apple juice, vegetables
What is the most common serotype of EHEC E.coli?
O157:H7 most common
Where is the shiga like toxin gene encoded?
on a bacteriophage
What type of toxin is the shiga like toxin?
AB5
Where does the shiga-like toxin bind?
glycolipid receptors (gb3), found in varying degrees in membranes of eukaryotic cells
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
What type of bacteria is Shigella?
gram negative non motile rod
What is the reservoir for Shigella?
There is none. human pathogen only
How is Shigella spread?
more often by fecal oral route and less by contaminated foods
What is the infectious dose of Shigella like compared with E. coli?
much lower, around 10-100 organisms
What kind of bacteria are Vibrio?
curved gram negative rods, highly motile, facultative anaerobes
Where is Vibrio typically found?
in salt water
What are the 3 species of Vibrio that were discussed? What do they cause?
V. cholerae = cholera
V. parahaemolyticus = gastroenteritis
V. vulnificus = cellulitis, septicemia
How is Vibrio cholera usually acquired?
from contaminated water and occasionally through contaminated food
Where is V. cholera endemic?
South East Asia, parts of Africa & S. America
What kind of toxin is the V. cholera toxin?
An AB5 toxin
Where does the cholera toxin bind?
Bind ganglioside GM1 receptors on intestinal cells
What does the binding of the cholera toxin cause?
Increase cAMP, leading to electrolytes & water secretions (watery diarrhea)
What kind of bacteria is Staph aureus?
non motile, gram positive cocci
What 4 kinds of toxins can staph aureus produce?
- Cytotoxins
- Exfoliative toxins
- Toxic shock toxins
- Enterotoxins
What kinds of cytotoxins can S. aureus produce?
alpha, beta, delta, gamma and panton-velntine leukociden
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
What is the difference between ETA and ETB?
ETA – heat stable, chromosomal
ETB – heat labile, on plasmid
How is food poisoning caused by S. aureus?
toxins present in food at time of ingestion - not live bacteria
What is the source of food contamination in S. aureus food poisoning?
the food handler
- 50% are cases of asymptomatic carriage
What is the most common enterotoxin associated with S. aureus food poisoning? Why?
Enterotoxin A
Heat stable and resistant to gastric enzymes
What % of S. aureus strains produce Enterotoxin A?
30-50%
How quickly is the onset of S. aureus food poisoning?
abrupt, about 4 hours after ingestion of food
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!!
