Flashcards in microbial toxins Deck (21):
What is an exotoxin?
A soluble toxin which is secreted from the bacterial cell into the environment
What are the typre of exotoxins?
Mmebrane bamageing toxins, intracellular toxins, toxins that act from the cell surface and toxins that interfere with the immune response
What types of toxins are membrane damaging toxins?
Toxins that enzymatically damage the membranes
Toxins with detergent like effect
What types of toxins are intracellular toxins?
AB family toxins and toxins injected through type III and IV secretion
What types of toxins Act from the cell surface?
What are toxins that interfere with the immune response?
Complement inhibitors, Ig proteases etc
What are AB family toxins?
These are proteins which consist of two subunits and A or active unit which has enzymatic activity and a B unit which has binding affinity for certain residues on the host cell surface mediating internalization of the complex
Examples of these toxins are Diptheria toxin, tetanus toxin and botulin toxin
What are AB5 Toxins?
These are a subfamily of AB toxins where there is one A subunit for every 5B subunits and includes toxins like cholera toxin, pretussiss toxin, E. coli heat laible toxin and shiga toxin
How does uptake and trafficking of AB toxins occur?
The B subunit will bind to a receptor causing endocytosis mediated uptake
As the endosome formed by this process matures it will undergo a maturation process where there is a change in pH this can trigger a conformational change in some proteins causing dissociation of the A subunit this may leave at the endosome or be recognized as a damaged or misfolded protein causing it to be trafficked to the ER where it is released into the cytosol
What are toxins that have the A subunit enter the cytosol at the endosome?
Diptheria toxin, clostridial neurotoxins and anthrax
What are toxins that have the A subunit enter the cytosol at the ER?
Shiga toxin, cholera toxin, pertussis toxin and pseudomonas exotoxin A
How does cholera toxin function?
The B subunit of this complex binds GM1 ganglioside receptor on intestinal epithelial cells
The A subunit is an ADP ribosyl-transferase that ADP-ribosylates the Galpha subunit of stimulatory G proteins leading to a constant activation of adenylate cyclase increasing levels of cAMP activating PKA, this activates CFTR leading to active CL- secretion and osomotic loss of Na and water causing rice water diarrhoea with no blood or immune cells found in the feces as the damage is purely osmotic
What is heat-laible toxin of E. coli?>
This is a toxin with a very similar mechanism to that of cholera but has a milder effect typically causing travellers disease
What is Pertussis toxin?
This is produced by bordetella pertussis which is a gram negative aerobic coccobacillus which colonizing the respiratory tract and causes whooping cough
The B subunit of this toxin binds to lactosylceramide which is a glycolipid on ciliated respiratory cells
The A subunit is a n ADP-ribosyltransferase that modifies the a-subunit of inhibitory G proteins which prevent down regulation of adenylate cyclase which leads to an increase in cAMP and therefore interference with cell signalling which can prevent transcription of chemokines preventing neutrophil chemotaxis
What is Shiga toxin?
This is produced by shigella dysenteriae which is a gram negative enterobacterium
the B subunit of this toxin binds to glycophospholipids Gb3 receptor on mucosal epithelial cells
The A subunit this is an enzyme with N-glycosidase activity which can remove one adenine from ribosomal 28S rRNA resulting in an inhibition of protein synthesis which induces cytokine production due to ribotoxic stress
This contributes to inflammation of the colonic mucosa
What are the disease symptoms caused by shiga toxin?
Fever, fatigue, anorexia, malaise, watery diarrhoea with more severe cases developing into haemorrhagic colitis with bloody diarrhoea and 10% of patients will develophemolytic uremic syndrome where shigella toxin internalises into renal glomeruli causing endothelial damage and blood vessel occlusion which can lead to acute renal failure and haemolytic anemia
What is anthrax toxin?
This is produced by Bacillus anthracis a gram positive spore forming coccus where infections can occur with spores through cuts, inhalation or ingestion of contaminated meat
The B subunit is protective antigen and binds to receptors on many different cell types cleaved by furin proteases, P63 fragment
There are two different A subunits oedema factor (which is a Ca and calmodulin-dependent adenylate cyclase leading to cAMP increase influencing water-homeostasis, cell-signalling and macrophage function) and lethal factor (Zn-depedent endoprotease which cleaves mitogen activated protein kinase kinases leading to apoptosis
These toxins act on blood endothelial cells and macrophages and dendritic cells
What is diphtheria toxin?
This is secreted by corynebacterium diphtheria a gram positive facultative anaerobic bacterium
This is as very toxin which is produced as a single protein with 2 domains which is cleaved to produce two subunits
The B subunit binds the herapin-binding EGF-like growth factor precursor on a variety of cells
The A subunit ADP-ribosylates the eukaryotic elongation factor 2 (Eef-2) which results in inhibition of protein synthesis
What is clostridial neurotoxin?
The B subunit of this toxin binds to ganglioside receptors no motoneurons
The A subunit has a Zn-dependent endopeptidase activity and cleaves several proteins involved in vesicle/membrane fusion and neurotransmitter release
What is botulinum toxin?
This blocks Ach release in motoneuron resulting in paralysis of musculoskeletal and respiratory muscles this has a very high mortality if left untreated with most toxic proteins known with 1 microgram killing a human