5/5/2025 Notes | BIOL 412

Topic: Infection

REVIEW

  • five stages of infection

    • exposure

    • adhesion

    • invasion

    • multiplication/growth

    • disease

      • toxins

      • tissue damage

  • virulence factors: all microbial traits that enhance virulence

  • attachment mechanisms, defense against host immune response, competition for iron, etc.

OBJECTIVES

  • compare basic properties of exotoxins and endotoxins

  • describe mode of action in diphtheria toxin, tetanus toxin, and cholera toxin

SUMMARY

  • endotoxins

  • exotoxins

INTRODUCTION TO TOXINS

  • toxins are all molecules that are causative agents of disease

    • conducive to tissue damage and disease

  • different ways to use toxins

    • enhance invasion

      • Hyaluronidase breaks down hyaluronic acid (component of extracellular matrix in animal tissues)

        • ex. Streptococcus, Staphylococcus

      • collagenase breaks down collagen

        • ex. Clostridium perfringes

          • looking for anaerobic environment

    • counteract host immune response

      • fibrinolytic enzymes breaks down fibrin and triggers clotting

        • ex. Strpetococcus pyogenes

          • evades isolation via clotting and pus

    • access to nutrients

      • cytolytic exotoxins

  • two types of toxins

    • endotoxins

      • lipopolysaccharide-lipoprotein complexes

      • released on cell lysis

      • heat-stable

      • in outermembrane of gram negative

      • general mode of action and symptoms

      • moderately toxic, rarely fatal

        • high LD50

          • needs more toxin to be fatal

      • pyrogenic

      • encoded in chromosomal genes

    • exotoxins

      • proteins

      • secreted

      • heat-labile

      • gram positive or gram negative

      • specific mode of action

      • often highly toxic, sometimes fatal

        • low LD50

          • needs little toxin to be fatal

      • heat or chemical treatment may destroy toxicity

      • nonpyrogenic

      • often encoded on extrachromosomal elements or lysogenic bacteriophages

ENDOTOXINS

  • toxins resulting from lysing of gram negative cells

  • LPS protrusions from cell membrane

    • lipid A (embedded in outer membrane) is toxic region of LPS

    • plays role in lipid movement and solubility

  • less toxic than exotoxins

EXOTOXINS

  • released by the pathogen as it grows

  • three central mechanisms

    • cytolytic toxins

      • damages host cytoplasmic membrane

        • ex. hemolysis

    • superantigens

      • over-activation of adaptive and innate immune system response, resulting in tissue damage

        • ex. food poisoning from Staphylococcus aureus

    • AB toxins

AB TOXINS

  • modular proteins with two domains (A and B)

  • B domain interacts with specific cell receptor of host that activates AB protein

  • allows A protein to move into cell 99

  • A interacts with inner cell and impedes cell function

DIPHTHERIA

  • Corynebacterium diphtheriae

  • thick coating of throat mucosa

  • fever, difficulty breathing

  • 5-10% fatality rate with treatment

    • 40-50% fatality rate without treatment

  • repressor control of expression of this gene

    • activated by conditions of iron deficiency

    • associated with protophage