M32: Exotoxins Flashcards
- What are toxins?
Molecules that have the capacity to _ or _ when administered in (large / small) quantities.
- Who makes toxins?
many _, some _ and _ (rotavirus?)
- The two major types of bacterial toxins include:
Endotoxin: part of Gram-(positive / negative) bacterial cell (_ or _), very heat-(stable / labile)
Exotoxin: _, usually heat-(stable / labile)
injure or kill
small
bacteria
fungi and parasites
negative
LPS or LOS
stable
secreted
labile
- Characteristics of bacterial exotoxins include:
a. Most are _
b. Active in (greater / smaller) amounts than endotoxin
c. One bacterial cell can make (1 / >1) toxin
d. Gram-positive bacteria are generally (better / worse) toxin producers, but there are some (good / poor) toxin-producing Gram-negatives
- Nomenclature:
a. _: fungal toxin
b. _: affects nervous system
c. _: affects GI system
d. _: lyses RBCs
- Exotoxins can be good _ targets.
a. proteins
b. smaller
c. >1
d. better
good
a. Mycotoxin
b. Neurotoxin
c. Enterotoxin
d. Hemolysin
- vaccine
Enterotoxins:
- Examples of enterotoxin producers:
a. _ (makes emetic and diarrheal enterotoxins)
b. _
c. _ (toxins A and B).
d. _: heat-labile and heat stable enterotoxins, Shiga toxin
e. Some _ isolates: Shiga toxin
f. _
g. _
- What are the effects of enterotoxins?
a. Mainly _ effects such as _ and _ (some also cause _).
a. Bacillus cereus
b. Staphylococcus aureus
c. Clostridium difficile
d. E. coli
e. Shigella
f. Clostridium perfringens
g. Vibrio cholerae
a. GI
diarrhea and abdominal cramps
vomiting
Enterotoxins:
- Enterotoxin actions can include:
a. Altering intestinal _ levels (e.g., cholera toxin, LT of ETEC increase cAMP; ST of ETEC increases cGMP)
b. _ cells (e.g. Shiga toxin)
c. Acting as _ to induce an _ response (e.g. S. aureus enterotoxins)
d. Affecting _ permeability by inducing _ changes (e.g. C. difficile toxins) - What is the importance of enterotoxin-producing for human disease?
a. These bacteria are responsible for many _ diseases.
b. In the USA, these bacteria cause mostly _ but in developing countries are an important cause of _.
c. _ are most at risk.
d. These bacteria are usually transmitted via the _.
e. Treatment varies according to disease, but always involves _.
a. cyclic nucleotide
b. Killing
c. superantigens
inflammatory
d. tight junction
signal transduction
a. diarrheal
b. morbidity
death
c. Children
d. fecal-oral route
e. restoration of fluid/electrolyte balances
Neurotoxins:
- Bacterial neurotoxins are the most _ toxins known! For example, these are ~100,000 times more _ than sarin gas.
- The two most important bacteria producing neurotoxins are _ and _.
- Tetanus is a (flaccid / spastic) paralysis, while botulism is a (flaccid / spastic) paralysis.
- Molecular Action of botulinum and tetanus toxins involve highly specific _ activity.
These toxins cleave neuronal proteins involved in _. This prevents synaptic vesicle docking and inhibition of _
- Botulinum toxins are now used clinically to treat a wide variety of conditions such as
_, as well as for _ purposes.
- potent
lethal - Clostridium botulinum
Clostridium tetani - spastic
flaccid - proteolytic
synaptic vesicle docking
neurotransmitter release
- inappropriate muscle contractions
cosmetic
What are the differences in action between tetanus and botulinum neurotoxins?
a. Tetanus toxin:
i) Works on _ in _ (travels up motor neuron into the _).
ii) Blocks release of _ (e.g., glycine).
iii) Results in _.
iv) Motor neuron constantly excites _.
v) Result is _!
b. Botulinum toxin:
i) Acts at _
ii) Blocks release of _ (excitatory neurotransmitter)
iii) Without acetylcholine, muscles do not _.
iv) Result is _.
i) CNS in spinal cord, CNS
ii) inhibitory neurotransmitters
iii) constant stimulation of the motor neuron
iv) muscle
v) spastic paralysis
i) neuromuscular junction
ii) acetylcholine
iii) contract
iv) Flaccid Paralysis
Case Study: A 42 year-old oil company executive visits operations on the North Slope of Alaska. While there, he is invited to a Native American/Eskimo dinner prepared by workers. At the dinner he enjoys traditional foods, including home-prepared smoked fish. The next day he develops “double vision” (diplopia) and swallowing problems. He is admitted to a nearby clinic. He shows a normal leukocyte count. Urinalysis and chest x-ray appear normal. That day, three other people who also attended the dinner are also admitted with similar symptoms.
The disease progresses to a descending paralysis. Thirty-two hours after admission, the patient suffers a cardiopulmonary arrest but is resuscitated. Despite repeated efforts, spontaneous respiration cannot be maintained and he is placed on a mechanical respirator. He dies the next day.
Cause: _
Clostridium botulinum
Clostridium botulinum:
- Biology of Clostridium botulinum
a. Organism is a Gram-(positive / negative) (aerobic / anaerobic), (spore-forming / non-spore-forming) _.
Eight types (A-G) have been recognized on basis of the botulinum toxin serotype they produce. New type H just discovered in 2013.
- Reservoirs and Transmission:
a. C. botulinum is found in _ throughout the world.
b. In the USA, _ is associated with home-prepared foods, particularly common in Alaska. - Virulence factors:
a. Botulinum toxin (all 9 serotypes cause similar symptoms except type _ also often causes vomiting). Type _ toxin causes most serious illness because it _.
b. Botulinum toxins are class _ select agents.
c. Spores: the ability to form spores gives _ to the organism. However, the toxin is _.
a. positive
anaerobic
spore-forming
rod
a. soil
b. Foodborne botulism
a. E
A
persists longer inside the neuron
b. A
c. heat-resistance
heat-sensitive
Clostridium botulinum:
Entry:
a. Classical foodborne botulism: acquired by _. This is often an _ (i.e., viable bacteria (need / don’t need) to be present in the body to become ill)
b. Infant botulism: now most common form of botulism in USA. Newborns _ is colonized by C. botulinum and the toxin is then _ (i.e., this is an infection).
c. Adult infant botulism: _ of adult is colonized by C. botulinum after _ have disrupted normal flora. In vivo _.
d. Wound botulism: _ produced by C. botulinum growing in _. In vivo _.
e. Class A select agent: _ / _.
a. ingestion of contaminated foods
intoxication
don’t need
b. GI tract
made in vivo
c. GI tract
antibiotics
toxin production
d. botulinum toxin
wound
toxin production
e. bioterrorism / biowarfare
Clostridium botulinum:
a. Symptoms: _, _ difficulties, followed by descending _, _ problems and other difficulties. Often infants with infant botulism first present with _.
b. All symptoms due to _. Naturally has a high _ rate.
c. Relatively (common / rare) in USA.
double vision swallowing flaccid paralysis breathing constipation
botulinum toxin
fatality
rare
Clostridium botulinum:
Treatment
i) _ antitoxin
ii) _ therapy
iii) With proper therapy, fatality rate can be (raised / lowered)
iv) If recovery occurs (can be a slow process), there are usually no long-term _.
Prevention:
i) Often follows ingestion of _. Prepare these foods carefully.
ii) Don’t feed infants _.
iii) Heating at 80°C for 30 min (or ~5 min of boiling) will inactivate this _.
iv) Vaccine?
i) Botulinum
ii) Supportive
iii) lowered
iv) sequelae
i) home-prepared (smoked or canned) foods
ii) honey
iii) heat-labile neurotoxin
iv) A vaccine is available for special use.
Membrane active toxins (“hemolysins”):
- What bacteria produce hemolysins:
a. Most Gram-(positive / negative) pathogens produce a _-dependent _, e.g., Streptolysin O, Listerolysin O
b. _ makes a toxin
c. Uropathogenic _ often make a hemolysin.
d. C. perfringens a toxin is a _ that may also activate endogenous _
e. Many others - Many “hemolysins” affect _ as well as _.
- Most hemolysins disrupt _ function, either by forming _ (e.g., S. aureus a toxin) or by _ action (e.g., C. perfringens a toxin).
a. positive
cholesterol
cytolysin
b. Staphylococcus aureus
c. E. coli
d. lecithinase
phospholipases
- WBCs
RBCs - membrane
pores
enzymatic
Toxins that Inhibit Mammalian Protein Synthesis:
- Toxins catalyzing an _ of Elongation Factor _:
EF-2 + NAD -> ADPR-EF2 + nicotinamide
a. _ exotoxin A
b. _ toxin
c. Result is EF-2 is (functional / nonfunctional), so protein synthesis _ and mammalian cells _.
2. Toxins that block protein synthesis by inactivating _.
a. _ toxin (made by EHEC and some Shigella) removes one base from one _ subunit; the _ no longer functions and protein synthesis _.
- ADP-ribosylation
2
a. Pseudomonas
b. Diphtheria
c. nonfunctional
shuts down
die
- ribosomes
a. Shiga
rRNA
ribosome
stops
Case study: An 18 year old female is involved in a serious automobile accident where she suffers serious burns on extensive regions of her body. A few days after she is admitted to the hospital, the attending physician notices a greenish discoloration on the burn dressing. Within a few hours she develops a high fever (40°C) and chills. Her blood pressure drops and she has a high WBC count. Microscopy and blood cultures identify a Gram-negative rod that is an obligate aerobe. The patient is started on ampicillin and later switched to ceftriaxone but does not respond. She soon dies from sepsis.
Cause: _
Pseudomonas aeruginosa
Pseudomonas aeruginosa:
Characteristics
- Gram-(positive / negative), (aerobic / anaerobic), (motile / non-motile) _.
- Often make _ pigments (fluorescein and pyocyanin).
- Grow (slowly / rapidly).
- Highly _ resistant.
- Very hardy.
- Oxidase-(positive / negative).
- Opportunistic?
- Primarily an (intracellular / extracellular) pathogen.
Virulence Factors
a. : causes necrosis
b. _ (, _): cause tissue damage.
c. _: inhibits/kills WBCs
d. _: hemolysin, affects WBCs
e. : promotes shock, relatively weak compared to others.
f. _ ( / _): antiphagocytic, important for making biofilms that contribute to cystic fibrosis, can interfere with antibiotic action.
g. _: adhesion
negative
aerobic
motile
rod
blue-green rapidly antibiotic positive yes extracellular
a. Exotoxin A
b. Enzymes (proteases, elastase)
c. Leucocidin
d. Phospholipase C
e. Endotoxin
f. Capsule (slime layer / biofilms)
g. Pili
