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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




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

5. Nomenclature:

a. _: fungal toxin
b. _: affects nervous system
c. _: affects GI system
d. _: lyses RBCs

6. Exotoxins can be good _ targets.

a. proteins
b. smaller
c. >1
d. better

a. Mycotoxin
b. Neurotoxin
c. Enterotoxin
d. Hemolysin

6. vaccine



1. 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. _

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
e. Shigella
f. Clostridium perfringens
g. Vibrio cholerae

a. GI
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

b. Killing

c. superantigens

d. tight junction
signal transduction

a. diarrheal

b. morbidity

c. Children

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.

1. potent

2. Clostridium botulinum
Clostridium tetani

3. spastic

4. proteolytic

synaptic vesicle docking
neurotransmitter release

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
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:

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 _.

a. positive

a. soil

b. Foodborne botulism

a. E
persists longer inside the neuron

b. A

c. heat-resistance


Clostridium botulinum:

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
don't need

b. GI tract
made in vivo

c. GI tract
toxin production

d. botulinum toxin
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
flaccid paralysis

botulinum toxin



Clostridium botulinum:


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 _.
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"):

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).

a. positive

b. Staphylococcus aureus

c. E. coli

d. lecithinase

2. WBCs

3. membrane


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 _.

1. ADP-ribosylation

a. Pseudomonas

b. Diphtheria

c. nonfunctional
shuts down

2. ribosomes

a. Shiga


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:


- 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



a. Exotoxin A

b. Enzymes (proteases, elastase)

c. Leucocidin

d. Phospholipase C

e. Endotoxin

f. Capsule (slime layer / biofilms)

g. Pili


Pseudomonas aeruginosa:

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 _.

a. ubiquitous

b. epithelium
wounds, surgical incisions, burns
cystic fibrosis

a. Opportunisic

b. WBCs

c. shock

d. mortality

e. cystic fibrosis
iv lines


Pseudomonas aeruginosa:


i) _: keep wound clean. In hospitals, keep patient's room clean; keep iv. lines and catheters _.

ii) Vaccine?

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.

i) Sanitation/hygiene
to a minimum

ii) No vaccine available.

iii) topical

i) shock

ii) very

iii) antibiotics


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)
• Aztreonam
• Gentamicin, Amikacin, Tobramycin
• Ciprofloxacin, Levofloxacin
• Polymyxins (colistin)

• resistance
• quinolones or aztreonam
• "antipseudomonal"
• combinations



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

2. positives

3. cytokines
TNF and IL-1


Conventional antigen:

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



1) (Small subset of T cells respond / Massive T cell response)

2) (Desirable release of cytokines like IL-2 / Excess release of IL-2, etc.)

3) (Strong release of TNF and other proinflammatory cytokines / T cell : B cell interactions)

4) (Shock, fever / Antibody formation)

1) Massive T cell response

2) Excess release of IL-2, etc.

3) Strong release of TNF and other proinflammatory cytokines

4) Shock, fever