Bacterial strategies for host damage Flashcards
Why are toxins so well studied?
They are the first virulence factor to be identified
Many toxins are excreted or released so relarivly easy to isolate, purify and characterise
Why are toxins beneficial for the bacteria?
Can kill neutrophils and macrophages
protect bacteria from the phagocytic cells might clear them
What are endo and exo toxins?
Endotoxins are components of the cell wall e.g. Lipids or LPS
Exotoxins are secreted proteins and peptides
What is Botulinum, where is it found, what are the benefits to Clostridium botulium?
Botulism- Food borne disease-paralysis-respiratory collapse
Spores in food- hard to see benefit to bacterial growth for pathogen that does not colonise the host
Benefit to Clostridium botulium in environmental habitat
- Possibly regulates cellular or phage functions or cell-cell signalling
- Harm to human can be seen as accidental
Gram negative: Endotoxins such as LPS, what are its components?
Polysaccharide O-chain: activation of host complement, serological specificity
Outer core and inner core: structural link
Lipid A: endotoxic activity
What is the interaction between LPS and host’s macrphages?
Binding of LPS (a specific type of PAMP) to the PRR results in the activation of a signalling pathway
the signalling pathway causes the transcription factor NF-kB to enter the nucleus
NF-kB initiates the transcrption and eventual secretion of the cytokines IL-8 IL-1 and TNF-a
What is Type I toxin?
Superantigen
Bypasses the normal antigen presentation by binding to class II MHC on APC and to non-specific regions of the T-cell ANTIGEN RECEPTOR
Activate T-cells at order of magnitude above antigen specific activation, resulting in massive cytokine release
Usual T-cell activation 1 in 10,000 cells activated—> activation of sAG is 1 in 5
Excess tissye damage by cytokines
Give an example of a Type I toxin.
Stapgylococci entertoxin B
Excess cytokine production asa a result of sAG binding
Leads to spesis and shock
What is Type II toxins?
Membrane disrupting toxins form channels in the membrane causing osmotic pressure of the host cell cytoplasm resuling in cell lysis
Pore forming toxins tend to be highly helical in their water -souble state and form pore in membranes using helices
Give an example of pore forming toxins.
Staphylococcus aureus, myobacterium tuberculosis
Clostridial a-toxin Zinc-dependent phospholipase
What is Type III toxins?
Simplest types of A-B toxin is synthesised as a single polypeptide which has one binding B and one enzymatic A domain
Phage with toxin gene creates A-B toxin
A-B bind to cell surface receptor causeing an Endosome
B causes translocation across the mebrane releasing A.
A has modifications of the target
What is the activity of Cholera entertoxin? (Cholera)
Ribosylation of G-proteins stimulate adenylate cyclase and increases cAMP in cells of the GI tract, causing secretion of water and electrolytes.
What is the activity of Diphtheria toxin? (Diphtheria)
Ribosylation of elongation factor 2 leads to inhibition of protein synthesis in target cells
What is the activity of the shiga toxin? (Diarrhea)
Enzymatically cleaves rRNA resulting in inhibition of protein synthesis in susceptible cells
What is the activity of the Tentnus toxin?
Zn++ dependent protease that inhibits neurotransmission at inhibatory synapses resuling in spastic paralysis
