Toxins

Question 1

Which type of toxin is classically from gram (-) organisms only?

Answer 1

Endotoxin

n for negative

(toxin = lipid A = part of LPS = part of cell)

Question 2

Superantigens bind between _____ and ____, resulting in _________

What don’t superantigens require for binding?

Answer 2

• T cell receptor and MHC II on APCs
• massive stimulation of T cells (release IL-1, IL-2, TNF) and cytokine storm
• dont need an antigen!

Question 3

3 main organism-containing superantigens, the toxin(s) they produce, and the associated disease

Answer 3

1. Staphylococcus aureus:

• TSST-1: staphylococcal toxic shock syndrome
• enterotoxin: food poisoning

2. Streptococcal pyogenes:
   * Erythrogenic Toxin A and C: Scarlet Fever
3. Mycoplasma:
   * T-cell mitogens: arthritis

Question 4

4 general mechanisms of action of toxins:

Answer 4

1. directly cytolytic
2. intracellular activity
3. superantigen
4. nerve toxicity

Question 5

Action of cytolytic toxins and one important characteristic

Answer 5

• act directly on host’s plasma membrane (extracellularly) –> host cell leaks and dies
• they are NOT internalized

Question 6

What are the two types of direct cytolytic action?

Answer 6

1. non membrane damaging 2. plasma membrane disruption

Question 7

Clostridium tetani toxin (and type):

• Mechanism
• Result
• Important notes:

Answer 7

Toxin (and type):

• tetanospasm/tetanus toxin (neurotoxin)

Mechanism:

• H (heavy subunit) binds to neuronal ganglioside
• L (light subunit) blocks release of inhibitory neurotransmitters (glycine and GABA)

Result:

• tetanus- continuous motor neuron activity, uncontrolled muscle contraction, lock jaw, tetanic paralysis of respiratory muscles

Important notes:

• part of DTap vaccine (T)
• toxin gene carried on plasmid

Question 8

Clostridium botulinum toxin (and type):

• Mechanism
• Result
• Important notes:

Answer 8

Toxin (and type):

• botulinum toxin (neurotoxin)

Mechanism:

• inhibits acetylcholine release from motor neuron endplates at neuromuscular junctions

Result:

• botulism-flaccid paralysis with respiratory muscle paralysis

Important notes:

• toxin obtained by lysogenic conversion

Question 9

Vibrio cholerae toxin (and type):

• Mechanism
• Result:
• Important notes:

Answer 9

Toxin (and type): choleragen/cholera toxin (enterotoxin)

Mechanism:

• 5 B subunits bind to GM1 gangliosides on intestinal cell membrane
• 2 A subunits activate membrane associated adenylate cyclase –> converts ATP to cAMP –> induces NaCl secretion and inhibits its reabsorption

Result:

• Watery diarrhea “rice water”

Important notes:

• death by dehydration

Question 10

ETEC Toxin (and type):

• Mechanism
• Result:

Answer 10

Toxin (and type):

• heat labile toxin/LT, heat stable toxin/ST (enterotoxin-infectious diarrhea)

Mechanism:

• LT- 5 B subunits bind GM1 glanglioside on intestinal cell membranes
• 2 A subunits increase cAMP; ST-binds receptor on intestinal brush border –> activates guanylate cylase –> increase cGMP –> inhibition of NaCl resorption

Result: watery diarrhea

Question 11

EHEC Toxin (and type):

• Mechanism
• Result:
• Important notes:

Answer 11

Toxin (and type): Shiga-like toxin (enterotoxin)

Mechanism:

• 5 B subunits–binds intestinal epithelial cells
• A subunit–inhibits protein synthesis by inactivating the 60s ribosomal subunit

Result:

• kills intestinal cells –> sloughing off of dead cells –> bloody diarrhea

Important notes:

• may cause hemolytic uremic syndrome; similar to antiribosomal antibiotics

Question 12

Bacillus cereus Toxin (and type):

• Mechanism:
• Result:
• Important notes:

Answer 12

Toxin (and type):

• heat labile and heat stabile toxin (enterotoxin)

Mechanism:

• LT- increases cAMP

Result:

• LT-diarrhea and dehydration
• ST-vomiting for less than 24 hours

Important notes: endospores survive low temperature cooking

Question 13

Shigella Toxin (and type):

• Mechanism:
• Result:
• Important notes:

Answer 13

Toxin (and type): Shiga toxin (enterotoxin)

Mechanism:

• 5 B subunits–bind intestinal epithelial cells
• A subunit–inhibits protein synthesis by inactivating 60S ribosomal subunit

Result:

• Bloody diarrhea

Important notes: can cause hemolytic uremic syndrome

Question 14

Staph Aureus Toxin (and type):

• Mechanism:
• Result:
• Important notes:

Answer 14

Toxin (and type):

• 1. Heat stable toxin (enterotoxin)
• 2. Toxic shock syndrome toxin (TSST-1)

Mechanism:

• 1. xx
• 2. activates IL-1 to induce sepsis

Result:

• 1. vomiting and diarrhea
• 2. Toxic shock syndrome (fever, rash, desquamation, diarrhea, hypotension/shock)

Question 15

Strep pyogenes Group A Toxin (and type):

• Mechanism:
• Result:
• Notes:

Answer 15

Toxin (and type): pyrogenic exotoxin

Mechanism: xx

Result:

• 1. Scarlet fever (strawberry tongue, pharyngitis, widespread rash sparing face)
• 2. Toxic Shock-like Syndrome (supernatigen)
• 3. Necrotizing fascitis

Notes: obtains exotoxin from a termperate bacteriophage by lysogenic conversion

Question 16

Streptococcus pyogenes also has some important tissue invasive toxins. List the 6 and their mechanisms

Answer 16

1. M protein–in cell wall, antiphagocytic by interfering with opsonization, mimics myocin in heart so antibodies attack itself
2. Streptolysin O and S –lyse RBCs, allow them to be beta hemolytic
3. Streptokinase –activates plasminogen to lyse fibrin clotes
4. DNAases – hydrolyzes DNA
5. Hylauronidase – breaks down proteoglycans
6. NADase – hydrolyzes NAD

overall results in: tissue destruction (abscesses, skin infections, systemic infection)

Question 17

Staph aureus also has many of the Strep pyogenes’ tissue invasive toxins, in addition to these important 8. List their mechansims.

Answer 17

1. Protein A –part of cell wall, prevents opsonization and phagocytosis
2. Protease toxin – contributes to scaled skin syndrome
3. Lipases –hydrolyzes lipids
4. Penicillinase – destroys plasminogen
5. staphylokinase –activates plasminogens to lyse fibrin clots
6. leukocidin –lyses white blood cells
7. exfoliatin –epithelial cell lyses
8. factors that bind complement – cripples host complement defense

Question 18

Clostridium perfringens Toxin (and type):

• Mechanism:
• Result:

Answer 18

Toxin (and type): more than 12- most important and lethal is alpha toxin (lecithinase) (tissue invasive toxin)

Mechanism:

• lecithinase hydrolyzes lecithin in cell membranes –> cell death

Result: tissue destruction and gas gangrene

Question 19

Bacillus anthracis Toxin (and type):

• Mechanism:
• Result:
• Important notes:

Answer 19

Toxin (and type): Anthrax toxin

• 1. Edema Factor (EF)
• 2. Lethal Factor (LF) (exotoxin)
• 3. Protect Antigen (PA)

Mechanism:

• 1. A subunit–calmodulin-dependent adenylate cyclase –> increases cAMP
• 2. zinc metalloprotease that inactivates MAP kinase –> macrophage releases TNF-alpha and IL-1beta
• 3. B subunit allows entry of EF into target cell

Result:

• 1. impairs neutrophil function and causes massive edema
• 2. disrupts cell signal transduction –> death in anthrax

Important notes: all three subunits are needed for activity of this toxin

Question 20

Corynebacterium diptheriae Toxin (and type):

• Mechanism:
• Result:
• Important notes:

Answer 20

Toxin (and type): diptheria toxin (exotoxin)

Mechanism:

• B subunit binds to heart and neural tissue
• A subunit–ADP ribosylates EF2 –> inhibits translation of human mRNA into proteins

Result:

• myocarditis (heart)
• peripheral nerve palsies
• CNS effects

Important notes:

• can be considered a human antibiotic, since it inhibits protein synthesis
• part of DTap (D)

Question 21

Which type of toxin can be cytolytic?

Answer 21

exotoxin

Question 22

List one example of a toxin that is cytolytic, disrupts plasma membrane, and forms pores. What are some bacteria containing them?

Answer 22

Streptolysin O: Strep Group A, B, C, and G

o = pores

Question 23

List one example of a toxin that is cytolytic, disrupts plasma membrane, and digests membrane. What are some bacteria containing it?

Answer 23

Bacterial Phospholipases (lecithinases)

• Clostridium perfringens (alpha toxin)
• Corynebacterium (Sphinomyelinase O)
• both are lethal forms of PLP

Question 24

List two examples of a toxin that is cytolytic but NON-membrane damaging. What are some organisms containing them?

Answer 24

-hyaluronidase -collegenase Ex. Staph, Strep, Clostridia

Question 25

The one important A2B toxin

Answer 25

-Anthrax Lethal Factor (LF)

Question 26

List the three important organisms with AB5 toxins

Answer 26

1. Cholera 2. Pertussis 3. Shiga toxin

Question 27

Which organism has an AB and AB5 toxin? What is each mechanism of action?

Answer 27

Bordetella Pertussis 1. AB: activates adenylate cyclase --\> increases cAMP --\> inhibits phagocytosis by neutrophils and macrophages 2. AB5: ADP ribosylates EF-2 --\> inhibits cell protein synthesis

Question 28

What are the 6 AB toxins?

Answer 28

PB DEPT! 1. Pseudomonas exotoxin 2. Botulinum 3. Diphtheria 4. E. coli LT 5. B. pertussis 6. Tetanus

Question 29

6 toxins that affect ion regulation via cAMP or cGMP: list their associated organisms, mediator, and disease.

Answer 29

1. Pertussis Toxin: B. Pertussis, cAMP, pertussis (cough) 2. Cholera toxin: V. cholera, cAMP, cholera (diarrhea) 3. Edema factor: B. anthracis, cAMP, edema 4. Heat labile toxin: ETEC, cAMP, diarrhea 5. Heat stabile toxin: ETEC, cGMP, diarrhea 6. Perfringens enterotoxin, Clostridium perfringens, cAMP, food poisoning and diarrhea

Question 30

3 exotoxins with chromosomal carriage

Answer 30

1. Shigella toxin 2. Pertussis toxin 3. Exotoxin A of Peudomonas

Question 31

3 organisms with plasmid carriage of exotoxins

Answer 31

1. Anthrax toxins: EF, LF, PA 2. E. Coli (ETEC): LT, ST 3. Tetnospasmin of Clostridium tetanus

Question 32

4 exotoxins with lysogenic phage

Answer 32

1. Shiga-like toxin in Shigella and E. coli 2. Botulinum toxin in Clostridium botulinum 3. Cholera toxin in V. cholerae 4. Diptheria toxin in Corynebacterium diptheriae 5. Erythrogenic toxin of Strep pyogenes ABCDE

Question 33

Compare the following properties for Exotoxin vs. Endotoxin: -source -secreted from cell? -chemistry -location -toxicity:

Answer 33

Exotoxin: -source: some gram (+) and gram (-) -secreted from cell?: yes -chemistry: polypeptide -location: plasmid or bacteriophage -toxicity: high Endotoxin: -source: gram (-) outer cell membrane (LPS) -secreted from cell?: No -chemistry: Lipopolysaccharide (structural part of bacteria) -location: bacterial chromosome -toxicity: low

Question 34

Which two organisms have toxin that inactivates elongation factor 2 by ribosylation?

Answer 34

Diptheria toxin (Corynebacterium diptheriae) and Exotoxin A (Pseduomonas aeruginosa)

Question 35

Which two organisms have toxins that inactivate 60S ribosome by removing adenine from rRNA?

Answer 35

Shiga toxin (Shigella) and Shiga-like toxin (EHEC including O157:H7 strain) Only Shigella invades host cells