Flashcards in M32: Exotoxins Deck (21)
1. What are toxins?
Molecules that have the capacity to _ or _ when administered in (large / small) quantities.
2. Who makes toxins?
many _, some _ and _ (rotavirus?)
3. 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
fungi and parasites
LPS or LOS
4. 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
a. _: fungal toxin
b. _: affects nervous system
c. _: affects GI system
d. _: lyses RBCs
6. Exotoxins can be good _ targets.
1. Examples of enterotoxin producers:
a. _ (makes emetic and diarrheal enterotoxins)
c. _ (toxins A and B).
d. _: heat-labile and heat stable enterotoxins, Shiga toxin
e. Some _ isolates: Shiga toxin
2. 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
f. Clostridium perfringens
g. Vibrio cholerae
diarrhea and abdominal cramps
3. 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)
4. 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
d. tight junction
d. fecal-oral route
e. restoration of fluid/electrolyte balances
1. Bacterial neurotoxins are the most _ toxins known! For example, these are ~100,000 times more _ than sarin gas.
2. The two most important bacteria producing neurotoxins are _ and _.
3. Tetanus is a (flaccid / spastic) paralysis, while botulism is a (flaccid / spastic) paralysis.
4. 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 _
5. Botulinum toxins are now used clinically to treat a wide variety of conditions such as
_, as well as for _ purposes.
2. Clostridium botulinum
synaptic vesicle docking
5. inappropriate muscle contractions
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
v) spastic paralysis
i) neuromuscular junction
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.
2. 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.
3. 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.
4. 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 _.
b. Foodborne botulism
persists longer inside the neuron
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
b. GI tract
made in vivo
c. GI tract
d. botulinum toxin
e. bioterrorism / biowarfare
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.
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 _.
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 _.
i) home-prepared (smoked or canned) foods
iii) heat-labile neurotoxin
iv) A vaccine is available for special use.
Membrane active toxins ("hemolysins"):
1. 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
2. Many "hemolysins" affect _ as well as _.
3. Most hemolysins disrupt _ function, either by forming _ (e.g., S. aureus a toxin) or by _ action (e.g., C. perfringens a toxin).
b. Staphylococcus aureus
c. E. coli
Toxins that Inhibit Mammalian Protein Synthesis:
1. 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 _.
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.
- Gram-(positive / negative), (aerobic / anaerobic), (motile / non-motile) _.
- Often make _ pigments (fluorescein and pyocyanin).
- Grow (slowly / rapidly).
- Highly _ resistant.
- Very hardy.
- Oxidase-(positive / negative).
- Primarily an (intracellular / extracellular) pathogen.
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
a. Exotoxin A
b. Enzymes (proteases, elastase)
d. Phospholipase C
f. Capsule (slime layer / biofilms)
Transmission and reservoirs:
a. P. aeruginosa is _ in the environment
b. This bacterium usually can't penetrate the _, so it mainly causes diseases through (3). _ factors (e.g., use of catheters) also assist entry. Host defenses important (e.g., _ infections).
a. _ pathogen:
b. In healthy people, _ can resist disease.
c. Septicemic infections often involve _.
d. Diseases often with high _ rates.
e. Particularly important for _ infections, _ infections and patients with _ (UTIs) and _.
wounds, surgical incisions, burns
e. cystic fibrosis
i) _: keep wound clean. In hospitals, keep patient's room clean; keep iv. lines and catheters _.
iii) Use _ agents (such as _) on wounds to prevent infection.
i) Supportive therapy for _.
ii) P. aeruginosa (very / not very) antibiotic resistant.
iii) Should use _ specifically effective against this pathogen.
to a minimum
ii) No vaccine available.
Drugs with some activity against Pseudomonas aeruginosa:
• _, _
• _, _ (not other 3rd generation cephalosporins)
• _, _, _ (not Ertapenem)
• _, _, _
• _, _
• _ (colistin)
• There is significant _ of P. aeruginosa even to these agents.
• 50% of UPMC strains are resistant to _ or _
• 20% of UPMC strains are resistant to other "_" drugs
• May need to use _ of antibiotics for serious infections.
• Piperacillin, Ticarcillin
• Cefepime, Ceftazidime (not other 3rd generation cephalosporins)
• Imipenem, Meropenem, Doripenem (not Ertapenem)
• Gentamicin, Amikacin, Tobramycin
• Ciprofloxacin, Levofloxacin
• Polymyxins (colistin)
• quinolones or aztreonam
1. Examples include _, _, and _ (involved in scarlet fever).
2. Provide a way for Gram-(positives / negatives) to induce shock, fever, etc.
3. Lead to massive production of _, such as _ and _, that cause systemic effects such as shock.
1. toxic shock syndrome toxin, staphylococcal enterotoxin and streptococcal erythrogenic toxins
TNF and IL-1
1) (Small subset of T cells respond / Massive T cell response)
2) (Desirable release of cytokines like IL-2 / Excess release of IL-2, et.c)
3) (Strong release of TNF and other proinflammatory cytokines / T cell : B cell interactions)
4) (Shock, fever / Antibody formation)
1) Small subset of T cells respond
2) Desirable release of cytokines like IL-2
3) T cell : B cell interactions
4) Antibody formation