Bacterial toxins Flashcards
Tetanus neurotoxin
Clostridium tetani
- B chain binds to a receptor on peripheral nerve membranes. A chain is internalised and undergoes retrograde transport to the CNS
- In CNS, A chain cleaves synaptobrevin - blocking release of inhibitory NT -> uncontrollable muscle contraction, spastic paralysis (death from spasms of respiratory muscles)
Made during anaerobic growth of the pathogen in a wound. Toxin damage may aid dissemination by killing animals to generate anaerobic environment
Clostridium perfringens α toxin
Clostridium perfringens
Cytolysin. Causes enzymatic degradation of membrane phospholipids by its phospholipase activity
In food poisoning, toxins produced interact with mucosa, may be superantigens.
Botulinum neurotoxin (BoNT)
Clostridium botulinum
Produced during anaerobic growth in food (e.g home-canned foods). Absorbed from the stomach.
Same proteolytic action as TeNT (cleaves synptobrevin). But acts on peripheral nerves at the NMJ, preventing exocytosis of stimulatory NT ACh-> flaccid paralysis.
Toxins produced by Clostridium difficile
2 secreted toxins- glucosylate small GTPases involved in signal transduction -> subversion of actin cytoskeleton and disruption of tight junctions. Epithelium becomes ‘leaky’, cell destruction
Toxins produced by Bacillus anthrax
Toxin is an adenylate cyclase, mimicking the mammalian enzyme -> disturbance of cAMP levels, signalling and ion balance.
Toxin damage may aid dissemination by killing animals to generate anaerobic environment, multiply and return to
Haemolysin
E.coli
A cytolysin, induces pore formation in membranes
E.coli toxin, aka labile toxin (LT)
E.coli
A-B toxin, ADP-ribosylates adenylate cyclase -> disturbance of cAMP levels, signalling and ion balance.
Staphylococcal toxins
Function as superantigens- implicated in food poisoning and TSS.
May not be primary function of toxin, but may deflect immune response.
Toxins produced by staphylococcus aureus
Heat- & acid- stable enterotoxins that interact with gastric mucosa, thought to act as superantigens in the bloodstream.
Cholera toxin
Vibrio cholerae
CTX genes carries on a bacteriophage integrated into the bacterial chromosome, co-regulated with adhesin & other genes by a HAP signal transduction system (global regulation).
A-B toxin. Structure is AB5.
- B binds to host receptor GM1- ganglioside, uptake by receptor mediated endocytosis & retrograde transport to ER.
- Active A subunit translocated to host cell cytosol.
ADP-ribosylates Gs, fixing it in the ‘on state’ -> uncontrolled high levels of cAMP.
Increased cAMP disturbs activity of Na+ and Cl- (CFTR) membrane pumps.
Ion imbalance -> water/ electrolyte loss (12-20L/ day) into lumen
Pneumolysin
Streptococcus pneumoniae
Cytolysin: causes pore formation in membranes. Can kill macrophages (aiding immune evasion) & other target host cells.
Streptolysin
Streptococcus pyogenes
Cytolysin, induces pore formation in membranes. Kills macrophages (immune evasion) and other target host cells.
Shiga toxin
Shigella
Glycosidase that modifies rRNA. Blocks protein synthesis.
Damage caused by toxin aids transmission (faeco-oral route)
Toxins produces by Yersinia pestis
Protein toxins including injected effector proteins that subvert macrophage function to prevent engulfment.
Diptheria toxin
Corneybacterium diptheriae
A-B toxin (single polypeptide), Binds HEGF (heparin-binding epidermal growth factor) via B. A and B covalently connected by a disulphide bridge. Toxin translocates into the cell: receptor mediated endocytosis, acidification of endosome & B-dependent translocation of A across vesicle membrane into cytosol In host cytosol, disulphide bond is reduced, A released & ADP-ribosylates translation elongation factor 2 (EF-2) -> blocks protein synthesis. Gene encoding (DTX) is carried on a bacteriophage integrated into the bacterial chromosome. Controlled by bacterial TF, DtxR- represses gene expression when bound by Fe -> transcription is down regulated at high iron conc. (conc. of free iron is low in the host). Secreted following colonisation of the nasopharyngeal epithelium.
Results in intense local inflammation and damage to mucosal cells, growth of bacteria in inflammatory exudate, and formation of a pseudomembrane- occludes airway.
Can lead to irregular heartbeat, coma, death.
Damage caused by toxin aids transmission (cough droplets). ‘Toxoid’ vaccine is effective- few cases in UK, still major problem in developing world.
Pertussis toxin
Bordetella pertussis
A-B toxin, ADP-ribosylates adenylate cyclase -> disturbance of cAMP levels, signalling and ion balance.
Enzymatic exotoxins produced kill ciliated cells, aiding colonisation.
Adenylate cyclase toxin
Bordetella pertussis
Mimics the mammalian enzyme. Similar results to pertussis toxin.
Enzymatic exotoxins produced kill ciliated cells, aiding colonisation.
Vacuolating cytotoxin (VacA)
Helicobacter pylori
Causes destruction of epithelial cells - contributes to intense mucosal inflammation & ulceration.
