PMI02-2008 Pathogenicity: Virulence determinants Flashcards
What is an endotoxin?
A lipopolysaccharide kept within the bacterial cells and only released after the destruction of the cell wall
What kind of bacteria only produces endotoxins?
Only gram negative bacteria
How do endotoxins initiate attack?
Lipid A of endotoxin binds to the LPS binding protein and binds to the CD14/TLR4/MD2 receptor complex on macrophages and dendritic cells
What signalling do endotoxins trigger?
Cytokine release (cytokine storm)
iNOS activation which releases nitric oxide
Inflammation
What is LPS composed of?
Lipid A
An inner and outer core
O-antigen
How does the look of the LPS differ if the O-antigen region is longer?
If the O-antigen region is longer then there is a smoother look
If the O-antigen region is shorter, it has a semi-rough look and the colonies will look more matte
How does toxicity differ amongst the LPS molecules?
The shorter the Lipid A chain, the more toxic the molecule
What is an exotoxin?
A toxin secreted by bacteria
How do membrane-acting toxins affect the membrane?
Enzymatic effect, where there is digestion of the membrane (phospholipase)
Pore formation which go through the cell allowing substances to ingress or egress
Detergent like action- hydrophobic phospholipid tail associates with a hydrophobic protein, causing regions in the membrane to bud away
How to pore-forming exotoxins work?
Associate with particular receptors in the surface of the membrane
After association, this leads to a polymerisation of the subunits of the pore-forming toxins
They then undergo conformational change, where they pass through the membrane structure
It allows the entry of hydrophilic molecules
What is small toxin?
A cysteine- rich peptide
How does small toxin work?
ST binds to the extracellular domain of the guanylylcyclase C receptor
It does this through molecular mimicry, which mimics the natural ligand guanylin
This results in the activation of the intracellular catalytic domain to produce cGMP
Efflux of Cl- and prevents influx of Na+, leading to osmotic diarrhoea as there is water and electrolyte loss
What do superantigens do?
Causes toxic shock syndrome due to excessive activation of T cell immune response
Superantigens associate with MHC class II on APCs
This gives non-specific activation of the T cell
Causing cytokine storm
What is an example of an intracellular toxin?
AB toxin
What is an AB toxin?
Has 2 subunits: A and B subunit
A subunit has the active toxin effect
B fragment attaches to the target regions of the cell membrane
