1. Adherence & Colonization

• Pili/Fimbriae: Glycoprotein rods for attachment.
  • Type 1 fimbriae (E. coli): Attach to mannose on uroepithelium → UTI.
  • P fimbriae (E. coli): Associated w/ pyelonephritis.
  • Type IV pili (N. gonorrhoeae): Antigenic variation, attachment.

2. Immune Evasion

• Capsule: Polysaccharide layer; prevents phagocytosis.
  • Key Organisms (SHiNE SKiS): S. pneumoniae, H. influenzae type b, N. meningitidis, E. coli, S. almonella, K. lebsiella, Group B S. trep.
  • Clinical: Asplenic patients at high risk. Vaccines often target capsules.
• Protein A (S. aureus): Binds Fc region of IgG → prevents opsonization.
• M Protein (S. pyogenes): Antiphagocytic; mimics host myosin → rheumatic fever.
• IgA Protease (SHiN): Cleaves IgA, allows mucosal colonization. Secreted by S. pneumoniae, H. influenzae, N. eisseria.
• Antigenic Variation: Alter surface proteins to evade Abs (e.g., Neisseria, Borrelia).

3. Toxins

• Endotoxin (Gram-Negative ONLY):
  • Lipid A component of LPS → released on cell lysis.
  • Binds CD14 on macrophages → massive release of TNF-α, IL-1, IL-6.
  • Causes: Fever, hypotension/shock, DIC.
• Exotoxins (Gram +/-): Secreted proteins.
  • Inhibit Protein Synthesis:
    • Diphtheria Toxin (C. diphtheriae) & Exotoxin A (P. aeruginosa): Inactivate Elongation Factor 2 (EF-2) via ADP-ribosylation.
  • Increase Fluid Secretion:
    • Cholera Toxin (V. cholerae) & LT (ETEC): Overactivate Gs → ↑cAMP → watery, secretory diarrhea.
    • ST (ETEC): Overactivates guanylate cyclase → ↑cGMP.
  • Inhibit Neurotransmitter Release:
    • Tetanus Toxin (C. tetani): Cleaves SNAREs → blocks release of inhibitory NTs (GABA, glycine) → spastic paralysis.
    • Botulinum Toxin (C. botulinum): Cleaves SNAREs → blocks release of ACh at NMJ → flaccid paralysis.
  • Cleave Ribosomes:
    • Shiga Toxin (Shigella) & Shiga-like Toxin (EHEC): Inactivate 60S ribosome → inhibit protein synthesis → bloody diarrhea, HUS.
  • Superantigens:
    • TSST-1 (S. aureus) & Pyrogenic Exotoxin A (S. pyogenes): Cross-link MHC-II to TCR → massive, non-specific T-cell activation → cytokine storm, shock.

4. Spreading Factors (Extracellular Enzymes)

• Coagulase (S. aureus): Converts fibrinogen to fibrin → forms protective clot.
• Streptokinase (S. pyogenes) & Staphylokinase (S. aureus): Activates plasmin → degrades clots → promotes spread.
• Hyaluronidase (S. pyogenes, S. aureus, C. perfringens): Degrades connective tissue hyaluronic acid → "spreading factor."