STEPTRACKERMICROBIOLOGY + IMMUNOLOGY | BACTERIAL BASICS | HIGH-YIELD REVIEW

Endotoxin, Superantigens & Virulence Factors

How bacteria trigger shock, overstimulate T cells, escape antibodies and stick to tissue — the molecules behind the drama.

FOCUS ON
Endotoxin = LPS lipid A of gram-negatives → TLR4/CD14 → IL-1, IL-6, TNF-α, NO → fever, hypotension, DIC; heat-stable, poorly antigenic, no toxoid. Superantigens (TSST-1, staph enterotoxins, SpeA) cross-link MHC II and the TCR Vβ outside the antigen groove → polyclonal T-cell activation → cytokine storm. Escape tools: protein A (binds IgG Fc), IgA protease, M protein.
FACTOR
MECHANISM
ORGANISMS
CLINICAL EFFECT
Endotoxin (lipid A)
Released when gram-negatives lyse; binds CD14/TLR4 on macrophages → cytokines; activates complement (C3a, C5a) and tissue factor
All gram-negatives (E coli, Neisseria, Pseudomonas…)
Fever, hypotension, DIC, septic shock · meningococcemia (Waterhouse-Friderichsen)
Toxic shock syndrome toxin-1
Superantigen: MHC II + TCR Vβ cross-link
S aureus (tampons, nasal packing, wounds)
Fever, diffuse rash, desquamation of palms/soles, hypotension, multiorgan failure
Staph enterotoxins
Preformed, heat-stable superantigens
S aureus (custard, mayonnaise, deli meat)
Vomiting 2–6 h after eating
Erythrogenic toxin (SpeA)
Superantigen
S pyogenes
Scarlet fever, streptococcal toxic shock
Exfoliative toxin
Cleaves desmoglein 1
S aureus
Staphylococcal scalded skin syndrome
Protein A
Binds Fc of IgG → blocks opsonization and complement
S aureus
Used in labs to bind antibodies
IgA protease
Cleaves mucosal IgA
S pneumoniae, H influenzae type b, Neisseria
Mucosal colonization
M protein
Antiphagocytic; molecular mimicry with cardiac myosin
S pyogenes
Rheumatic fever
Type III secretion system
"Injectisome" delivers toxins directly into host cells
Pseudomonas, Salmonella, Shigella, E coli, Yersinia
—
Biofilm
Extracellular matrix protects from drugs and immunity
S epidermidis, Pseudomonas, viridans strep
Catheters, prostheses, valves, CF lungs
Antigenic variation
Changes surface proteins to escape antibodies
Neisseria (pili), Borrelia recurrentis, Trypanosoma brucei, influenza, HIV
Repeated infections, no lasting immunity
Siderophores, urease, catalase
Steal iron · raise pH · break H₂O₂
Many · Proteus, H pylori, Klebsiella, Nocardia · catalase ⁺ organisms
Catalase ⁺ organisms infect CGD patients

Mechanism — endotoxin to septic shock

Gram-negative lysisLipid A released
→
CD14 / TLR4Macrophage
→
IL-1, TNF-α, IL-6Fever
→
NO → vasodilationHypotension
→
Tissue factorDIC

Complement activation adds C3a/C5a (edema, neutrophil recruitment).

Exotoxin vs endotoxin

FEATURE
EXOTOXIN
ENDOTOXIN
Source
Secreted by gram + and −
Outer membrane of gram −
Chemistry
Protein (polypeptide)
Lipid A (LPS)
Heat
Mostly labile (staph enterotoxin stable)
Stable
Toxicity
High (tiny doses)
Lower
Vaccine
Toxoids
None
Genes
Often plasmid/phage
Chromosome

How it's tested

COMMON CONFUSIONSuperantigens skip antigen processing — they bind outside the peptide groove, activating up to 20% of all T cells.
THE TRAPAntibiotics can transiently worsen gram-negative sepsis by lysing bacteria and releasing more LPS.
YOUR APPROACHShock + gram-negative → endotoxin; shock + rash + desquamation → superantigen; recurrent infection → escape factor.

If you see… think…

Fever, rash, desquamation, hypotension after tampon use → TSST-1
Vomiting within hours of a potluck → preformed staph enterotoxin
Septic shock with DIC from a gram-negative → lipid A (endotoxin)
Receptor for endotoxin → CD14 / TLR4
Protein binding IgG Fc on S aureus → protein A
Enzyme shared by pneumococcus, H influenzae and Neisseria → IgA protease
Molecular mimicry causing rheumatic fever → M protein
Infected catheter with biofilm → S epidermidis
Recurrent gonorrhea despite past infection → pilin antigenic variation
Toxin with no toxoid vaccine → endotoxin