Microbial and Fungal Toxins Flashcards
WHat 2 types of microbial toxin exist?
> Endotoxin (LPS) - part of the outermembrane of G- bacteria - Lipid A part specifically (O some chains largely irrelevant) - heat stable - hydrophobic > exotoxins - secreted or released on lysis - proteins(so heat labile)
How is LPS toxic?
- molecular structure recognised by PRRs on macrophages etc. as a sign of bacterial infection
- macrophage receptors ocmplexes CD14, TLR4, MD2 cause release of cytokines TNFa[tumour necrosis factor], IL-1
- > fever, hypotension, and other pathophysiological effects
Give 7 examples of exotoxins
- cytolytic toxins
- enzymes
- enterotoxins
- neurotoxins
- superantigens
- ADP-ribosylation toxins
- Type 3 secretion systems
Give an examples of cytolytic toxins
- Heamolysins eg Streptolysin S (Strep equi)
- leukocidins e.g. APXIII of a. pleuropneumoniae
Give examples of enzymes
- phospholipase C of Clostridium. perfringens (alpha toxin)
- hyaluronidase
- collagenase
- protease
- lipase
e.g.. of enterotoxins
- act in the GIT
- ADP-ribosylation toxins - Latbile enterotoxin (LT) of E. COli (similar to cholera toxin, attaches brush border of SI cells, -> secretion of CL- (+ therefore Na+) -> secretory D+ via cAMP and G protein receptors)
eg. of neurotoxin
> Botulinum toxin
- blocks release of ACh at synapse and NMJ -> flaccid paralysis and death
- often source is a dead and rotting small animal in a bale of silage
wild fowl also get botulism (“limber neck”)
Tetanus toxin
- blocks release of NTs for inhibitory synapses (GABA and glycine)
- uncontrolled exitatory synaptic activity
Why is botulism a public health risk?
Gets into milk
What are super antigens?
- eg. staph aureus TSST-1
- immunomodulators, induce massive T-cell activation and cytokine release
- toxin binds to invariable regions on MHC Class 2 on APC
- > short circuiting of the normal T cell activation pathway
What are ribose transferases?
- add one/more ADP-ribose moieties to a protein
- affect cell signalling and gender regulation
- toxicity of cholera toxin, diphtheria toxin and enterotoxins
- may types of exotoxin act this way eg. pertussis toxin, pseudomonas exotoxin A, diptheria, cholera, E.Coli LT
Outline the pathogenesis of salmonella. Clinical signs?
- > bloody mucoid D+ +- septicaemia
- Type 3 secretion systems (Injectosomes)
- needle like structure used as sensory probe to detect eukaryotic cells and then secret proteins into cells
- exert effects that help pathogen to survive and evade the immune response (uptake into host cell blebosome) initiate apoptosis of host cell
- T3SS proteins = structural proteins (syringe) efector proteins (contents) and chaperonins (protectors) contained in the Salmonella Pathogenicity Island
Egs. of toxins used as vaccine agents
> neutrolising Ab production to the toxoid (formalin treated toxin)
- tetanus
- diptheria
- clostridial
- pasteurella osteolytic tocin (atrophic rhinitis)
- APX1,2,3
- Anthrax toxin
3 classes of mycotoxin?
- toadstool poisoning
- ingestion of plant pathogenic fungi (ergotism)
- ingestion of mouldy feed (mycotoxicosis)
What colour is amanita phalloides? COmmon name?
Orange
- death cap
What is ergotism? Clinical signs
- ergot poisoning
- sclerotium forms in grass and cereal
- ergots contain vasoactive alkaloids (eg. ergotamine)
- ingestion -> constriction of arterioles in extremitis -> gangrene and lameness, convulsions, halucinations and pain
Outline the lifecycle of ergot
eg. claviceps purpurea
- sclerotium overwinters in soil
- in spring, ergot germinates -> tiny toadstools produce sexual spores (ascospores) inside the perithecium
- ascospores infect the floret of wheat etc (ovary colonised by the fungus)
- conidiospores (asexual spores) produced from mycelium
- honeydew exudes from infected floret, attracting flies
- conidiospres SPREAD TO OTHER FLORETS (warm spring encourages spread)
- grain replaced by compacted mycelium (ergot)
What is mycotoxicsosis? eg? How can this be identified?
- toxins produced in feed moulded after harvest
> eg. AFLAtoxin (not alfa)
-> turkey X disease d/t aspergillus flavus (hence afla) - fluoresces blue or green
-eg. also aspergillus fumigatus (sporing heads with conidiospores)
> trichothecenes - grain moulded with fusarium sp. in the field
-> alimentary toxis aleukia in humans
> zearalonone - oestrogenic factor
- pigs, mouldy grain
> ochratoxins - Denmark, pigs
- nephritis
- coffee beans?
How common is aflatoxin poisoning? Clinical signs/path?
Now rare, young animals most susceptible
-> liver damage, tumours and teratogenic
What toxin does aspergillus flavus produce?
Aflatoxin B1
What toxin does aspergillus versicolorproduce?
Sterigmatocystin
What toxin does penicillum viridicatum produce?
Ochratoxin
What toxin does fusarium sporotrichoides produce?
Trichothecens (T-2)
What toxin does fusarium graminearum produce?
Zearalonone
