Toxins Flashcards
toxins (2)
- kill cells
- alter host-cell functions without killing cells directly
type I toxins
- act extracellularly
type II toxins (3)
- act on the cell membrane and destroy cell membrane
- cytolytic
- can be enzymatic or non-enzymatic
type III toxins
- classical A/B toxins
cytolytic
- damage to membranes usually causes host cell lysis or death
type II toxins: non-enzymatic (2)
- form large pores/channels in membrane
- cholesterol-dependent cytolysins
type II toxins: how are non-enzymatic pores formed (2)
- toxin monomers can bind cholesterol and assemble on surface to form a pre-pore and then insert
- toxin monomer binds cholesterol and inserts into membrane, triggering monomers to bind and form a large pore
why does cell/phagosome lysis occur after non-enzymatic pore formation
- water enters the cell/phagosome which causes swelling
non-enzymatic type II toxin examples (2)
- streptolysin O
- listeriolysin O (LLO)
how does LLO function as a type II, non-enzymatic toxin (2)
- change in pH causes conformational change in the protein
- change allows toxin to insert into phagosome membrane
type II toxins: enzymatic damage (3)
- caused by phospholipases
- enzyme removes polar head groups from phospholipid (PlcC activity)
- causes damage to the membrane, and instability leads to lysis
what is an examples of a type II, enzymatic toxin and how does it function (2)
- PlcC (phospholipase C)
- removes polar head groups from phospholipids
what do type III toxins do (2)
- alter metabolism of the host cell
- exploit or subvert normal host cell processes
what are A/B toxins (2)
- B is the Binding component of the toxin
- A is the enzymatically Active component of the toxin that binds to target inside host
what kinds of toxins are A/B toxins (5)
- toxins that target protein synthesis
- toxins that alter signal transduction
- toxins that alter actin polymerization
- neurotoxins
- anthrax toxins
A/B toxin: forms of B component (3)
- single unit that binds to receptor
- multi-meric structure that is preformed
- mulit-meric structure that forms on the membrane
what is diptheria toxins general effect
- targets protein synthesis
what bacteria produces diptheria toxin
- corynebacterium diptheriae bacteria that are lysogenic for “beta” phage
what kind of toxin is diptheria toxin
- A/B toxin
when is diptheria toxin produced
- only produced under low iron conditions
diptheria toxin: mechanism of escape into cytosol (7)
- B subunit binds to its receptor, HB-EGF
- entire toxin is taken up by the cell
- toxin is found in the endosome and pH begins to drop
- change in conformation in both A and B subunit
- B subunit forms a pore in the endosome membrane
- A subunit translocates through pore into cytosol as its disulfide bond is reduced, releasing A from B
- A is now in the cytosol
diptheria toxin: mechanism of intoxication (3)
- ADP ribosylation
“A” catalyzes transfer of ADP-ribose from NAD to the target, changing the structure/function of the target (EF-2)
steps in ADP-ribosylation (3)
- toxin deprotonates target
- causes target to undergo a nucleophilic attach on NAD
- one bond breaks and a group on NAD is removed, while another bond forms and attaches ADP-ribose from NAD to target
why does diptheria toxin cause cell death (4)
- target for ADP-ribosylation is elongation factor 2 (EF2)
- EF-2 activity stops due to modification
- protein synthesis stops as the ribosomes are unable to accept new tRNAs at their A sites
- the cell dies
what is the role of EF2
- translocation of the peptide from the A site on the ribosome to the P site on the ribosome
what bacteria produces shiga toxin
enterohemorrhagic E. coli
what are the symptoms caused by shiga toxin (3)
- diarrheal diseases (dysentery)
- kidney failure
- hemolytic uremic syndrome, which can be fatal
what kind of toxin is the shiga toxin and what is the general structure (2)
- A/B toxin
- 1 A subunit, 5 B subunits
what is the receptor for shiga toxin B subunits (2)
- gangliosides, which are glycolipids
- specifically gb3 and gb4
gb3
- ganglioside glycolipid present in glomeruli of infants and not adults
what is shiga toxins general effect
- inhibition of protein synthesis
how does the shiga toxin A subunit enter the host cytosol (4)
- B subunits bind to gb3/gb4
- toxin is taken up and trafficked to the ER by retrograde transport
- disulfide bonds holding AB5 are reduced
- A subunit is translocated through Sec translocon to the cytosol
what is the shiga toxin A subunit
- N-glycosidase
shiga toxin: mechanism of intoxication (4)
- A subunit (N-glycosidase) cleaves adenine from 28S ribosomal RNA (found in ribosome)
- inhibits binding of amino-acyl tRNA to “A” site in the ribosome
- protein synthesis is inhibited
- cell dies
