Pathogenicity: Virulence and determinants Flashcards
What are the features of endotoxins LPS (lipopolysaccharide)? (5)
- Produced by gram negative bacteria
- Heat stable and poorly antigenic (hard to kill - even using autoclave)
- Shock, fever, 50,000 deaths in USA
- Lipid A associates with LPS binding protein (LBP) and binds to receptor CD14 in conjunction with TLR4
- Triggers signalling: cytokine release (cytokine storm), iNOS activation, inflammation
What molecule does LPS bind with to form a complex?
LBP (LPS binding protein)
Which receptors recognise LPS?
TLR4/CD14/MD2 receptor complex
What happens when the receptor complex (on macrophages and monocytes) has recognised LPS?
Activates mass production of pro-inflammatory cytokines
What is endotoxaemia?
The presence of LPS in the bloodstream which leads to cytokine storn
In what illness/disease is LPS a main driving agent?
Sepsis and septic shock
What are the 2 different types of exotoxins?
Membrane-acting toxins
Intracellular toxins
What are the actions of membrane-acting toxins?
- Enzymatic: lead to digestion/break down constituents of membrane
- Pore formation: form pores through membrane
- Perturbs signalling
Which is the most notable enzyme involved in exotoxin activity?
Phospholipase (C. albicans can produce this)
Which organism can produce pore formation?
E Coli alpha-haemolysin
What toxin is produced by enterotoxigenic E Coli (ETEC)?
ST Toxin
How does the ST toxin work?
It works by binding to the extracellular domain pf guanylylcyclase C
- molecular mimicry (similar to natural ligand guanylin).
This then activates the intracellular catalytic domain to produce cGMP.
Higher levels of cGMP then leads to exflux of Cl- and prevents influx of Na+, leading to osmotic diarrhoea.
What superantigen derives from S Aureus?
TSST-1
this causes Toxic shock syndrome due to excessive activation of T cell immune response
How do super antigens work?
They associate with the MHC class 2 receptor on antigen-presenting cell, they then cross-link this with generic V (variable)- Beta region on Y cell receptors from non-specific T cell.
This is a non-specific t cell activation
How are intracellular toxins classified?
Classified by enzymatic activity now
What are the 3 main attributes of intracellular toxins?
Bind to cell surface
Cross the membrane to gain entry
Enzymatic activity
How do intracellular toxins attack cells?
- Cell binding
- Membrane translocation
- Enzymatic activity
What 2 subunits make up AB toxins?
A fragment - active
B fragment - binding
Give 3 examples of AB toxins
diphtheria
tetanus
botulinum
What is an example of an A2B toxin (so 2 active subunits and 1 B subunit)?
Anthrax
Name 2 neurotoxins
Botulinum
Tetanus
How do neurotoxins work?
They attack signalling between nerve cells.
They do this by preventing fusion of the vesicles containing the neurotransmitters
Which enzyme do we tend to see associated with neurotoxins?
Zinc proteases
How does tetanus toxin work?
It works by preventing the release of the inhibitory transmitters, so the signal is never turned off so it is long and drawn out
