Microbial Mechanisms of Pathogenicity Notes

Chapter 15: Microbial Mechanisms of Pathogenicity

Introduction to Pathogenicity

• Pathogenicity: Ability of an organism to cause disease.

• Virulence: Degree of pathogenicity - how effective a pathogen is at causing disease.

• Infection or disease occurs when the balance between host defenses and microbial mechanisms tips in favor of the microbe.

Key Concepts in Pathogenicity

• For disease to occur, microbes must:

  • Enter the host through specific portals of entry.

  • Adhere to host tissues.

  • Penetrate or evade host defenses.

  • Damage host tissues in some manner.

• Pathogens leave the host via portals of exit, often the same points of entry.

Portals of Entry

• Mucous Membranes:

  • Respiratory tract

  • Gastrointestinal tract

  • Genitourinary tract

  • Conjunctiva

• Skin: Acts as a barrier, but can be punctured.

• Parenteral Route: Directly deposited into tissues when barriers are penetrated.

• Most pathogens prefer specific portals of entry.

Quantifying Pathogenicity: ID50 and LD50

• ID50: Infectious dose for 50% of a sample population; indicates virulence (e.g., for Bacillus anthracis):

  • Skin: 10-50 endospores

  • Inhalation: 10,000-20,000 endospores

  • Ingestion: 250,000-1,000,000 endospores

• LD50: Lethal dose for 50% of a sample; measures toxicity of a toxin (e.g., Botulinum toxin: 0.03 ng/kg).

Adherence Mechanisms

• Adhering to Host Tissues: Almost all pathogens attach via mechanisms called adherins (ligands) which bind to host cell receptors. Common structures include:

  • Glycocalyx: (capsules, biofilms)

  • Fimbriae

  • Pili

Evasion of Host Defenses

• **Methods of Evasion:

  • Capsules: Prevent phagocytosis (e.g., Streptococcus pyogenes).

  • Cell Wall Components:

  • M protein: resists phagocytosis (e.g., Streptococcus pyogenes).

  • Waxy lipid (mycolic acid) helps resist digestion (e.g., Mycobacterium tuberculosis).

• Enzymes:

  • Coagulases: Coagulate fibrinogen.

  • Kinases: Digest fibrin clots.

  • Hyaluronidase: Breaks down polysaccharides that hold cells together.

  • Collagenase: Breaks down collagen.

  • IgA Proteases: Destroy IgA antibodies.

• Antigenic Variation:

  • Pathogens change surface antigens to evade detection (e.g., Trypanosoma sp., Influenza, COVID-19).

Penetration into Host Cells

• Invasins: Surface proteins produced by bacteria rearranging cytoskeleton actin to enter cells, causing membrane ruffling (e.g., Shigella sp. and Listeria sp.).

Damage to Host Cells

• Siderophores: Iron-binding proteins secreted by pathogens; essential for microbial growth, allowing bacteria to multiply inside the host.

• Toxins: Poisonous substances produced by microorganisms, with two main types:

  • Exotoxins:

  • Soluble proteins, can disrupt cellular functions (e.g., Diphtheria toxin, Shiga toxin).

  • Mechanisms include:

    • Membrane-disrupting toxins: Lyse host cells (e.g., leukocidins, hemolysins).

    • Superantigens: Cause intense immune response by provoking cytokine release.

  • Endotoxins:

  • Part of the lipopolysaccharides in the outer membrane of Gram-negative bacteria (Lipid A). Released during bacterial cell death or division, causing general systemic effects like fever and inflammation.

Comparison of Exotoxins and Endotoxins

Portals of Exit

• Pathogens often exit through the same portals as entry:

  • Respiratory Tract: Coughing, sneezing.

  • Gastrointestinal Tract: Feces, saliva.

  • Genitourinary Tract: Urine, genital secretions.

  • Skin: Casual shedding.

  • Blood: Via arthropods, needles, or syringes.