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
