Microbial Mechanisms of Pathogenicity

Chapter 15: Microbial Mechanisms of Pathogenicity

Microorganism Entry
  - Principal Portals of Entry:
    - Mucous membranes
    - Skin
    - Parenteral route (deposited directly into tissues)
  - ID50 (Infectious Dose): The number of microorganisms required to cause infection in 50% of a sample population; measures virulence.
  - LD50 (Lethal Dose): The amount of toxin required to kill 50% of a sample population; measures toxin potency.
Numbers of Invading Microbes:
  - Example:
    - Bacillus anthracis:
      - Skin: 10–50 endospores
      - Inhalation: 10,000–20,000 endospores
      - Ingestion: 250,000–1,000,000 endospores
Toxins:
  - LD50 Examples:
    - Botulinum toxin: 0.03 ng/kg
    - Shiga toxin: 250 ng/kg
    - Staphylococcal enterotoxin: 1350 ng/kg
Adherence Mechanisms:
  - Pathogens employ adhesins (ligands) to bind to host cells via structures like
    - Glycocalyx and Fimbriae.
  - Biofilms are formed, allowing communities of microbes to share nutrients.
Penetration of Host Defenses:
  - Capsules:
    - Glycocalyx impairing phagocytosis (e.g., Streptococcus pneumoniae, Bacillus anthracis).
  - Cell Wall Components:
    - M protein (resists phagocytosis, Streptococcus pyogenes).
    - Opa protein (attachment, Neisseria gonorrhoeae).
    - Mycolic acid (resists digestion, Mycobacterium tuberculosis).
  - Enzymes:
    - Coagulases: Coagulate fibrinogen.
    - Kinases: Digest fibrin clots.
    - Hyaluronidase: Digests polysaccharides that hold cells together.
    - Collagenase: Breaks down collagen.
    - IgA proteases: Destroy IgA antibodies.
Antigenic Variation:
- Pathogens can alter their surface proteins, making antibodies ineffective.
Mechanisms of Evasion from Phagocytosis:
  1. Production of surface proteins (Invasins) that rearrange host cytoskeleton (e.g., Shigella, Listeria).
  2. Survival in low pH environments (phagolysosome).
  3. Escape from phagosome before fusion with lysosome.
  4. Prevent fusion of the lysosome with the phagosome.
Siderophores:
- Proteins secreted to bind iron tightly, essential for bacterial survival.
Direct Damage:
- Disruption of host cell function, utilizing nutrients, and causing cell rupture through multiplication.
Production of Toxins:
  - Toxins: Substances that produce adverse effects such as fever, shocks, or organ failure.
  - Toxigenicity: The ability to produce toxins.
  - Toxemia: Presence of toxins in the bloodstream.
  - Intoxications: Presence of toxins without microbial growth.
Exotoxins:
  - Soluble proteins produced and secreted that inhibit host functions; categorized into:
    - A-B Toxins: Enzyme component (A) and binding component (B) (e.g., Diphtheria toxin).
    - Membrane-disrupting Toxins: Lyse host cells (e.g., Leukocidins, Hemolysins).
    - Superantigens: Cause intense immune responses.
    - Genotoxins: Cause DNA damage and increase cancer risk.
Endotoxins:
- Lipid A portion of LPS from gram-negative bacteria; typically causes general effects such as fever and shock.
- LAL assay used for detection.
Plasmids and Lysogeny:
- Plasmids may carry genes for pathogenicity, and lysogeny can introduce new traits to bacteria.
Cytopathic Effects of Viruses:
  - Includes:
    - Stops cell synthesis and lysosomes releasing enzymes.
    - Cell fusion, antigenic changes, and potential for cancer.
Pathogenic Properties of Other Microbes:
  - Fungi: Produce toxic metabolic products.
  - Protozoa: Cause symptoms through waste products.
  - Algae: Produce neurotoxins.
Portals of Exit:
- Key routes include respiratory, gastrointestinal, genitourinary tracts, skin, and blood (needles, arthropods).
Key Conceptual Links:
- Infection results when the balance between host defenses and pathogens favors the latter, leading to tissue damage through various mechanisms.
- Pathogens typically exit through the same portals as they utilized to enter the body, emphasizing the importance of containment in infection control.