Bacterial Toxins
This section reorganises the toxin-producing organisms already covered across bacteriology by toxin mechanism rather than by organism, since seeing the same functional categories recur across unrelated bacteria is the fastest route to genuinely understanding, rather than simply memorising, toxin biology.
A-B Toxins
A-B toxins have a two-component structure: the B, binding, subunit binds a specific host cell surface receptor and mediates entry into the cell; the A, active, subunit is the enzymatically active component, typically transferred into the cytoplasm, where it disrupts a specific host cell process.
Diphtheria toxin, from Corynebacterium diphtheriae, has an A subunit that ADP-ribosylates elongation factor 2, halting host protein synthesis.
Cholera toxin, from Vibrio cholerae, has an A subunit that ADP-ribosylates a G-protein, causing persistent adenylate cyclase activation, a sustained rise in cAMP, and massive chloride and water efflux into the gut lumen.
Shiga toxin, from Shigella dysenteriae type 1, and the structurally and functionally identical toxin of enterohaemorrhagic E. coli, has an A subunit that is an N-glycosidase, cleaving host ribosomal RNA and halting protein synthesis, with particular toxicity to renal glomerular endothelial cells, the mechanistic basis of haemolytic uraemic syndrome.
Tetanospasmin, from Clostridium tetani, travels retrogradely along motor neuron axons to the spinal cord, then blocks release of the inhibitory neurotransmitters glycine and GABA, producing spastic paralysis.
Botulinum toxin, from Clostridium botulinum, cleaves SNARE proteins at the neuromuscular junction, blocking acetylcholine release, producing flaccid paralysis, the mechanistic and clinical opposite of tetanospasmin despite both being A-B neurotoxins acting on the nervous system.
Pertussis toxin, from Bordetella pertussis, ADP-ribosylates a G-protein, disrupting host cell signalling and contributing to lymphocytosis and impaired local immune clearance.
Pseudomonas exotoxin A, from Pseudomonas aeruginosa, inhibits protein synthesis via the same EF-2 ADP-ribosylation mechanism as diphtheria toxin, a structurally distinct toxin converging on an identical molecular target, worth recognising as a direct parallel.
Neurotoxins
A functional subset of the A-B toxins above specifically targets the nervous system, warranting explicit grouping given their shared target organ despite opposite mechanisms: tetanospasmin, inhibitory neurotransmitter blockade, spastic paralysis, and botulinum toxin, excitatory neurotransmitter blockade, flaccid paralysis, are the two defining examples.
Enterotoxins
Enterotoxins act specifically on intestinal epithelium to produce diarrhoeal disease, a functional category overlapping with, but distinct from, the A-B toxin structural category, since some enterotoxins are A-B toxins, such as cholera toxin, while others are not.
Cholera toxin is, an A-B toxin. Staphylococcus aureus enterotoxins are preformed, heat-stable toxins ingested directly in contaminated food, acting rapidly, one to six hours, and also functioning as superantigens, producing the vomiting-predominant presentation of staphylococcal food poisoning.
Bacillus cereus produces both a heat-stable emetic toxin, preformed, rapid onset, mechanistically related in its superantigen-like emetic action to staphylococcal enterotoxin, and a heat-labile diarrhoeal enterotoxin, produced in vivo, later onset.
Clostridium perfringens enterotoxin is a heat-labile toxin distinct from the organism's alpha toxin, produced in the intestine after ingestion of large numbers of vegetative cells, causing a milder, later-onset diarrhoeal illness.
E. coli heat-labile and heat-stable enterotoxins, in ETEC, show the heat-labile toxin being structurally and mechanistically closely related to cholera toxin, also an A-B toxin acting via adenylate cyclase and cAMP, while the heat-stable toxin acts via a distinct guanylate cyclase and cGMP-mediated pathway.
Cytotoxins
Cytotoxins cause direct cell damage or death, a broad functional category encompassing several distinct mechanisms.
Membrane-damaging toxins are pore-forming or membrane-degrading toxins causing direct cytolysis, including S. aureus alpha-toxin and Panton-Valentine leukocidin, streptolysin O, from S. pyogenes, and Clostridium perfringens alpha toxin, a phospholipase or lecithinase, the principal mediator of gas gangrene's extensive tissue necrosis.
Toxin B, from Clostridioides difficile, is a glucosylating cytotoxin inactivating Rho-family GTPases, disrupting the actin cytoskeleton of colonic epithelial cells, paired with Toxin A, functioning predominantly as an enterotoxin, illustrating that a single organism's toxin repertoire can span more than one functional category.
Listeriolysin O, from Listeria monocytogenes, is a pore-forming toxin, though its primary functional role is phagosomal escape enabling intracellular survival, rather than direct extracellular cytotoxicity, distinguishing its purpose from the other membrane-damaging toxins listed here.
Superantigens
Superantigens are a distinct and mechanistically unusual functional category: rather than acting enzymatically on a specific intracellular target, they bind directly and simultaneously to MHC class II, on antigen-presenting cells, and the T cell receptor, on T cells, bridging the two outside the receptor's normal, highly specific antigen-binding groove.
This nonspecific bridging activates a very large proportion of the T cell population, up to 20 percent or more, compared to the typically much smaller than 0.01 percent activated by a conventional, specific antigen, producing massive, nonspecific cytokine release, a cytokine storm, rather than a normal, targeted adaptive immune response.
S. aureus toxic shock syndrome toxin-1, TSST-1, is the classic cause of staphylococcal toxic shock syndrome, historically associated with prolonged tampon use, also occurring with wound and surgical site infection.
S. aureus enterotoxins also function as superantigens in addition to their gastrointestinal enterotoxin action, illustrating the same dual-category point made for C. difficile toxin B above.
Streptococcal pyrogenic exotoxins, from S. pyogenes, are responsible for scarlet fever and streptococcal toxic shock syndrome, the streptococcal parallel to staphylococcal toxic shock syndrome.
