STEPTRACKERMICROBIOLOGY + PHARMACOLOGY | BACTERIAL BASICS | HIGH-YIELD REVIEW

Exotoxins

Secreted protein toxins grouped by what they do to the host cell — learn the mechanism once and the disease follows.

FOCUS ON
Inhibit protein synthesis: diphtheria & exotoxin A (ADP-ribosylate EF-2), Shiga & Shiga-like (cleave 60S rRNA → HUS). ↑ cAMP: cholera, heat-labile LT (Gs on), pertussis (Gi off), anthrax edema factor (adenylyl cyclase). Neurotoxins: tetanus (blocks GABA/glycine release → spasm) and botulinum (blocks ACh → flaccid paralysis) both cleave SNARE proteins. Lysins: α-toxin of C perfringens (lecithinase), streptolysin O. Exotoxins → toxoid vaccines.
TOXIN · ORGANISM
MECHANISM
DISEASE · EFFECT
CLUE
Diphtheria toxin
C diphtheriae (β-prophage)
ADP-ribosylates EF-2 → stops protein synthesis
Pseudomembranous pharyngitis, "bull neck", myocarditis, neuropathy
Toxoid vaccine (DTaP) · antitoxin
Exotoxin A
Pseudomonas
ADP-ribosylates EF-2
Tissue necrosis in burns, pneumonia
Same target as diphtheria
Shiga toxin · Shiga-like toxin
Shigella · EHEC O157:H7
Cleaves adenine from 28S rRNA of 60S subunit → cell death
Bloody diarrhea; endothelial damage → HUS (more with EHEC)
Antibiotics may worsen EHEC HUS
Cholera toxin
Vibrio cholerae
ADP-ribosylates Gs → permanently on → ↑ cAMP → Cl⁻ and water out
Profuse rice-water diarrhea
Oral rehydration (glucose–Na⁺ cotransport intact)
Heat-labile / heat-stable toxins
ETEC
LT: ↑ cAMP (like cholera) · ST: ↑ cGMP
Traveler's watery diarrhea
LT ≈ cholera toxin (cAMP) · ST ≈ guanylate cyclase (cGMP)
Pertussis toxin
Bordetella pertussis
ADP-ribosylates Gi → inhibitory signal lost → ↑ cAMP
Whooping cough; lymphocytosis (impaired homing), ↓ phagocytosis
Acellular pertussis vaccine
Edema factor
Bacillus anthracis
Is itself an adenylyl cyclase → ↑ cAMP
Edema in cutaneous anthrax
Lethal factor = MAPK-kinase protease; protective antigen = entry
Tetanospasmin
Clostridium tetani
Retrograde to spinal cord → cleaves synaptobrevin in Renshaw cells → ↓ GABA/glycine
Spastic paralysis, trismus, risus sardonicus, opisthotonos
Antitoxin (TIG), toxoid, benzodiazepines, debridement
Botulinum toxin
Clostridium botulinum
Cleaves SNAREs at neuromuscular junction → ↓ ACh release
Descending flaccid paralysis, diplopia, dysphagia; infant "floppy baby" (honey)
Preformed toxin in adults (canned food) · spores in infants
α-Toxin (lecithinase)
Clostridium perfringens
Phospholipase C degrades membranes
Gas gangrene (myonecrosis), hemolysis
Double zone of hemolysis on blood agar
Streptolysin O
S pyogenes
Pore-forming hemolysin (oxygen-labile)
β-hemolysis
Antibodies (ASO) mark recent strep infection
Toxins A and B
Clostridioides difficile
Glucosylate Rho GTPases → actin disruption, enterocyte death
Pseudomembranous colitis
Stool toxin PCR/EIA

Mechanism — tetanus vs botulism

Tetanus toxinTravels retrograde to CNS
→
Blocks inhibitory interneurons(GABA, glycine)
→
Spastic paralysisLockjaw
Botulinum toxinStays at NMJ
→
Blocks ACh release
→
Flaccid paralysisDescending, cranial first

Both are zinc proteases that cleave SNARE proteins — the location decides the opposite pictures.

Toxins grouped by target

TARGET
TOXINS
RESULT
EF-2
Diphtheria, exotoxin A
No protein synthesis
60S rRNA
Shiga, Shiga-like
No protein synthesis, HUS
Gs (on)
Cholera, LT
↑ cAMP, watery diarrhea
Gi (off)
Pertussis
↑ cAMP
SNAREs
Tetanus, botulinum
Blocked neurotransmission
Membranes
α-toxin, streptolysin O
Lysis

How it's tested

COMMON CONFUSIONDiphtheria and Pseudomonas exotoxin A act on EF-2; Shiga toxins act on ribosomal RNA. Both stop protein synthesis.
THE TRAPInfant botulism comes from ingested spores (honey, soil) that make toxin in the gut; adult foodborne botulism comes from preformed toxin.
YOUR APPROACHSymptom (diarrhea type, paralysis type, membrane, necrosis) → host target → toxin → organism.

If you see… think…

Grey pseudomembrane, bull neck, myocarditis → diphtheria toxin (EF-2)
Rice-water stools after seafood/flood water → cholera toxin (Gs)
Bloody diarrhea then anemia, thrombocytopenia, renal failure → Shiga-like toxin (HUS)
Lockjaw after a puncture wound → tetanospasmin
Descending paralysis after home-canned food → botulinum toxin
Floppy infant after honey → infant botulism
Crepitus and myonecrosis after deep wound → C perfringens α-toxin
Paroxysmal cough with lymphocytosis → pertussis toxin (Gi)
Toxin that is an adenylyl cyclase → anthrax edema factor
Toxin raising cGMP → ETEC heat-stable toxin