Toxins Flashcards
Which type of toxin is classically from gram (-) organisms only?
Endotoxin
n for negative
(toxin = lipid A = part of LPS = part of cell)
Superantigens bind between _____ and ____, resulting in _________
What don’t superantigens require for binding?
- 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!
3 main organism-containing superantigens, the toxin(s) they produce, and the associated disease
- Staphylococcus aureus:
- TSST-1: staphylococcal toxic shock syndrome
- enterotoxin: food poisoning
- Streptococcal pyogenes:
* Erythrogenic Toxin A and C: Scarlet Fever - Mycoplasma:
* T-cell mitogens: arthritis
4 general mechanisms of action of toxins:
- directly cytolytic
- intracellular activity
- superantigen
- nerve toxicity
Action of cytolytic toxins and one important characteristic
- act directly on host’s plasma membrane (extracellularly) –> host cell leaks and dies
- they are NOT internalized
What are the two types of direct cytolytic action?
- non membrane damaging 2. plasma membrane disruption
Clostridium tetani toxin (and type):
- Mechanism
- Result
- Important notes:
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
Clostridium botulinum toxin (and type):
- Mechanism
- Result
- Important notes:
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
Vibrio cholerae toxin (and type):
- Mechanism
- Result:
- Important notes:
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
ETEC Toxin (and type):
- Mechanism
- Result:
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
EHEC Toxin (and type):
- Mechanism
- Result:
- Important notes:
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
Bacillus cereus Toxin (and type):
- Mechanism:
- Result:
- Important notes:
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
Shigella Toxin (and type):
- Mechanism:
- Result:
- Important notes:
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
Staph Aureus Toxin (and type):
- Mechanism:
- Result:
- Important notes:
Toxin (and type):
- Heat stable toxin (enterotoxin)
- Toxic shock syndrome toxin (TSST-1)
Mechanism:
- xx
- activates IL-1 to induce sepsis
Result:
- vomiting and diarrhea
- Toxic shock syndrome (fever, rash, desquamation, diarrhea, hypotension/shock)
Strep pyogenes Group A Toxin (and type):
- Mechanism:
- Result:
- Notes:
Toxin (and type): pyrogenic exotoxin
Mechanism: xx
Result:
- Scarlet fever (strawberry tongue, pharyngitis, widespread rash sparing face)
- Toxic Shock-like Syndrome (supernatigen)
- Necrotizing fascitis
Notes: obtains exotoxin from a termperate bacteriophage by lysogenic conversion
Streptococcus pyogenes also has some important tissue invasive toxins. List the 6 and their mechanisms
- M protein–in cell wall, antiphagocytic by interfering with opsonization, mimics myocin in heart so antibodies attack itself
- Streptolysin O and S –lyse RBCs, allow them to be beta hemolytic
- Streptokinase –activates plasminogen to lyse fibrin clotes
- DNAases – hydrolyzes DNA
- Hylauronidase – breaks down proteoglycans
- NADase – hydrolyzes NAD
overall results in: tissue destruction (abscesses, skin infections, systemic infection)
Staph aureus also has many of the Strep pyogenes’ tissue invasive toxins, in addition to these important 8. List their mechansims.
- Protein A –part of cell wall, prevents opsonization and phagocytosis
- Protease toxin – contributes to scaled skin syndrome
- Lipases –hydrolyzes lipids
- Penicillinase – destroys plasminogen
- staphylokinase –activates plasminogens to lyse fibrin clots
- leukocidin –lyses white blood cells
- exfoliatin –epithelial cell lyses
- factors that bind complement – cripples host complement defense
Clostridium perfringens Toxin (and type):
- Mechanism:
- Result:
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
Bacillus anthracis Toxin (and type):
- Mechanism:
- Result:
- Important notes:
Toxin (and type): Anthrax toxin
- Edema Factor (EF)
- Lethal Factor (LF) (exotoxin)
- Protect Antigen (PA)
Mechanism:
- A subunit–calmodulin-dependent adenylate cyclase –> increases cAMP
- zinc metalloprotease that inactivates MAP kinase –> macrophage releases TNF-alpha and IL-1beta
- B subunit allows entry of EF into target cell
Result:
- impairs neutrophil function and causes massive edema
- disrupts cell signal transduction –> death in anthrax
Important notes: all three subunits are needed for activity of this toxin
Corynebacterium diptheriae Toxin (and type):
- Mechanism:
- Result:
- Important notes:
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)
Which type of toxin can be cytolytic?
exotoxin
List one example of a toxin that is cytolytic, disrupts plasma membrane, and forms pores. What are some bacteria containing them?
Streptolysin O: Strep Group A, B, C, and G
o = pores
List one example of a toxin that is cytolytic, disrupts plasma membrane, and digests membrane. What are some bacteria containing it?
Bacterial Phospholipases (lecithinases)
- Clostridium perfringens (alpha toxin)
- Corynebacterium (Sphinomyelinase O)
- both are lethal forms of PLP
List two examples of a toxin that is cytolytic but NON-membrane damaging. What are some organisms containing them?
-hyaluronidase -collegenase Ex. Staph, Strep, Clostridia
The one important A2B toxin
-Anthrax Lethal Factor (LF)
List the three important organisms with AB5 toxins
- Cholera 2. Pertussis 3. Shiga toxin
Which organism has an AB and AB5 toxin? What is each mechanism of action?
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
What are the 6 AB toxins?
PB DEPT! 1. Pseudomonas exotoxin 2. Botulinum 3. Diphtheria 4. E. coli LT 5. B. pertussis 6. Tetanus
6 toxins that affect ion regulation via cAMP or cGMP: list their associated organisms, mediator, and disease.
- 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
3 exotoxins with chromosomal carriage
- Shigella toxin 2. Pertussis toxin 3. Exotoxin A of Peudomonas
3 organisms with plasmid carriage of exotoxins
- Anthrax toxins: EF, LF, PA 2. E. Coli (ETEC): LT, ST 3. Tetnospasmin of Clostridium tetanus
4 exotoxins with lysogenic phage
- 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
Compare the following properties for Exotoxin vs. Endotoxin: -source -secreted from cell? -chemistry -location -toxicity:
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
Which two organisms have toxin that inactivates elongation factor 2 by ribosylation?
Diptheria toxin (Corynebacterium diptheriae) and Exotoxin A (Pseduomonas aeruginosa)
Which two organisms have toxins that inactivate 60S ribosome by removing adenine from rRNA?
Shiga toxin (Shigella) and Shiga-like toxin (EHEC including O157:H7 strain) Only Shigella invades host cells
