Microbial toxins and mycotoxins Flashcards
2 types of microbial toxin
- endotoxin (LPS, specifically the lipid A part, hydrophobic, found in OM)
- exotoxin
How is lipid A an endotoxin?
molecular structure that is recognised by PRRs on host cells as sign of bacterial infeciton –> macrophage receptor complex (CD14, TLR4, MD2) –> release of cytokines (TNFa, IL1) –> fever, hypotension, loss of effective circulation, many pathophysiological effects
Name 7 types of exotocins
- cytolytic toxins (sometimes called haemolysins)
- enzymes
- enterotoxins
- neurotoxins
- superantigens
- ADP-ribosylation toxins
- Type 3 secretion systems
Example of cytolytic toxin
- aka sometimes haemolysins
- Streptolysin S of S. equi
- sometimes not haemolytic but still damage cells (leukocidins; e.g. Apx 3 of Actinobacillus pleuropneumoniae)
Example of enzyme exotoxin
- Phospholipase C of Clostridium perfringers (alpha toxin)
- Other protein toxins belonging to Clostridium perfringens include hyaluronidase, collagenase, protease and lipase.
Define exotoxin
= bacterial proteins, usually released during bacterial growth
Example of enterotoxin (endotoxin)
- acts in GIT
- e.g. ADP-ribosylation toxins (such as LT of E.coli which consists of 5 B subunits, 1 A subunit, similar to cholera toxin, attaches to brush border of SI cells)
How does LT cause secretory diarrhoea?
Binds cell, subunit A introduced into cell and causes Gs to convert to Gs-adp-3 (controls cAMP –> cannot control adenylate cyclase) -> overall causes increased IC [cAMP] –> Cl- channel activation –> Cl- secretion increased –> Na+ and H2O lost from tissue into lumen –> secretory diarrhoea
Action - botulinum toxin
Blocks release of Ach at synapse and NMJ –> flaccid paralysis and death
How can wild fowl suffer from botulism?
–> limber neck –> bird drowns (can’t hold head up above water). Large numbers of fowl may be affected.
Action - tetanus toxin
Blocks release of NTs for inhibitory synapses (glycine and GABA) causing uncontrolled excitatory synaptic activity –> paralysis by constant tensing of mm (tetani)
What are superantigens?
- an example of an exotoxin
- e.g. S. aureus TSST-1, a 22kDa protein
- they are immunomodulators (induce massive TC activation and cytokine release from these) –> toxin binds to invariable regions on MHC2 on APC –> normal processs of TC activation in short-circuited (i.e. no need for correct Ag to link APC and MHC2 –> inappropriate activation in a large # TCs that is many more than for a natural Ag)
What are ADP-ribosylation toxins?
= ADP-ribosyltransferases
- normally the enzyme causing addition of one/more ADP-ribose moietites to a protein
- affects cell signalling and gene regulation
- EXAMPLES: Pseudomonas exotoxin A, cholera toxin, diphtheria toxin, enterotoxins (E.coli LT)
- NAD+ donates ADP ribose to protein
CS - salmonella - and pathophysiology
- enterocyte damage –> enterocyte invasion –> bloody, mucoid diarrhoea, sometimes systemic disease (septicaemia)
- nobody has found a soluble toxin responsible for enteric damage
- MECHANISM = type 3 secretion systems (injectosome)
Outline type 3 secretion systems (injectosome) as an exotoxin
- needle-like structure in pathogenic bacteria is used as a sensory probe to detect eukaryotes and secrete proteins that help bacteria infect them
- secreted effector proteins are injected directly from bacteria into eukaryote host cell. They exert effects that help the pathogen survive and escape and immune response
- T3SS proteins are: structural, effector, chaperonins
- T2SS genes of Salmonella are laid out int he Salmonella pathogenicity island (SPI)
