bacteria causing damage Flashcards
until p30
BROADLY, how does bacterial infection cause damage?
either through direct bacterial action and/or as an indirect consequence of the host immune response.
what are exotoxins?
protein toxins secreted by pathogenic bacteria. they can be denatured to produce non-toxic immunogenic forms for vaccination. there are 2 broad groups - cytolysins and intracellular enzymatic toxins.
what do cytolysins do and what’s their advantage?
they interact with host cell membranes.
1 - enzymatically degrade membrane phospholipids. ie clostridium perfringens alpha-toxin.
2 - pore formation - streptococcus pneumoniae pneumolysin, strep. pyogenes streptolysin, E.coli haemolysin.
- cell lysis. at lower concs they subvert cell signal transduction with many effects inc leukotriene release or apoptosis.
- disable immune cells and assist tissue damage for bacterial spread.
what do enzymatic intracellular toxins do?
they poison host cells by specific catalytic activity
- called A-B toxins as their function depends on receptor binding and intracellularly active components.
can be single polypeptides cleaved to form catalytic fragments (diphtheria, tetanus, botulinium toxins) or multimeric (anthrax, pertussis, cholera toxins)
how do intracellular acting toxins get into host cells?
by receptor mediated endocytosis and or retrograde transport
what are the specific actions of enzymatic toxins?
1 - Adp-ribosylators of adenylate cyclase
2 - they are adenylate cylcases
3- block protein synthesis
4- glycosylate small GTPases involved in signal transduction
what enzymatic toxins are ADP ribosylators?
1 - cholera toxin, E.coli enterotoxin (labile toxin), pertussis toxin (whooping cough)
2- diphtheria toxin - targets translation elongation factor 2, so blocks protein synthesis.
what enzymatic toxins are adenylate cyclases
1 - bordatella pertussis (whooping cough), bacillus anthracis (anthrax) produce toxins that are adenylate cyclases.
what does shiga toxin do?
shiga toxin (bacterial dysentry) is a glycosylase that modifies rRNA and blocks protein synthesis.
what does clostridium difficile toxin do?
causes antibiotic associated diarrhoea. the toxins glucosylate small GTPases involved in signal transduction - causes destruction of actin cytoskeleton and tight junctions.
how does tetanus neurotoxin act as a neurotoxin?
binds a receptor on peripheral nerve membranes. A chain internaised, retrograde transport to inhibitory interneurons. the A chain cleaves synaptobrevin blocking release of inhibitory neurotransmitters. results in uncontrollable muscle contraction, spastic paralysis (death from spasms of repiratory muscles).
how does botulinum neurotoxin act?
same proteolytic action as tetanus but acts on peripheral nerves, preventing release of stimulatory neurotransmitters, resulting in flaccid paralysis.
whats the advantage of enzymatic exotoxins?
- can aid colonisation ie kill ciliated cells in whooping cough.
some less clear such as tetanus and anthrax, may aid dissemination by killing host…
some toxins are superantigens, how do they work?
bridges weakly interacting MHC class 2 and TCR by binding outside the normal antigen binding poscket. causes activation of various useless T cells.ie staphylococcal toxins in food poisining and toxic shcok syndrome. - may not be the primary function but may deflect the immune response.
acute inflammation triggered by what in some bacteria?
the lipid A component of Gram negative bacterial LPS, this is also called endotoxin. LPS is released from dead bacteria, bound by LPS-binding protein and delivered to macrophage CD14 and TLR4. triggers inflammation.
Lipid A is unique to bacteria but endotoxin overload from many bacteria deaths can cause septic shock.
