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)
List some protein toxins used effectively as vaccine Ags
- tetanus toxin
- diphtheria toxin
- clostridial toxins
- pasteurella osteolytic toxin (atrophic rhinitis)
- Apx 1, 2, 3
- Anthrax toxin
- Pre-existing neutralising anti-toxin Ab activity can protect against disease.
Name 3 types of mycotoxins (fungal toxins)
- toadstool poisoning
- ingestion of plant pathogenic fungi (ergotism)
- ingestion of moulded feed (mycotoxicosis)
Outline toadstool poisoning
- death cap = Anmanita phalloides (olive-green-yellow cap, lethal to dogs)
Outline ergotism or ergot poisoning
- ergots are little black structures
- size variable (small-large)
- Sclerotium forms in grass and cereal (the ergots are the sclerotium which is mycelium bound together)
- scelrotium overwinters in soil
- in spring, the ergot germinates –> mushroom structures sprount –> produce sexual spores (ASCOSPORES) inside the perithecium –> windborne transmission –> these infect the floret –> ovary colonised by fungus –> conidiospores (asexual spores) produced from mycelium in the growing ovary –> honeydew exudes from infected floret and attracts flies which then spread to other florets.
- good warm spring encourages spread of conidiospores
- the grain is replaced by a sclerotium of compacted mycelium (the ergot)
Pathophysiology of ergot poisoning
- ergot contains vasoactive alkaloids such as ergotamine
- ingestion of the ergot leads to constriction of arterioles in the extremities –> gangrene and lameness, also convulsions
- hallucinations and pain (humans)
Define mycotoxicosis. Example?
= toxins produced in feed which has been moulded after harvest (e.g. aflatoxins)
What is Turkey X disease?
- previously unknown
- then 1960, many turkey poults affected
- traced to imported groundnut meal form Brazil which had been produced from moulded nuts
- toxin found, attributed to Aspergiluus flavus (aflatoxin)
- the toxin fluoresces - blue or green (B1 or G1)
Outline dx and tx of mycotoxicosis
- TX: no antidotes, no neutralising substances, no Ab
- Dx: detection of toxin in feed relatively easy
Effects and prevalence of mycotoxicosis
- PREVALENCE: acute aflatoxin poisoning now rare but chronic poisoning continuing, young animals most susceptible
- EFFECTS: liver damage, tumours, teratogenic
What are tichothecenes?
- another mycotoxin
- grain moulded with Fusarium sp. in fields
- -> alimentary toxic aleukia in humans
What is zearlanone?
- another mycotoxin
- aka Oestrogenic factor, F-2
- found in pigs
- traced to mouldy grain
What are Ochratoxins?
- found in pigs in Denmark
- causes nephritis
- Ochratoxin A from Aspergillus ochraceus in Danish barley
- coffee beans may be contaminated with Ochratosins
Type of toxin produced by fungus Aspergillus flavus
Aflatoxin B1
Type of toxin produced by fungus Aspergillus versicolor
Sterigmatocystin
Type of toxin produced by fungus Penicillium viridcatum
Ochratoxin
Type of toxin produced by fungus Fusarium sporotrichoides
Trichothecenes (T-2)
Type of toxin produced by fungus Fusarium graminearum
Zearalanone
