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
