Microbiology Pathogenicity Overview

Pathogenicity Overview

• Pathogens enter the body through specific portals, including mucous membranes (respiratory, gastrointestinal, genitourinary, conjunctiva) and skin (cuts, abrasions, hair follicles).
• The parenteral route involves direct entry into tissues via punctures, injections, or bites.

Virulence Factors

• ID50 (Infectious Dose 50): The number of pathogens needed to infect 50% of a population.
• LD50 (Lethal Dose 50): The number of pathogens needed to kill 50% of a population.
• Lower ID50/LD50 values indicate higher virulence.

Adherence Mechanisms

• Microbes adhere to host cells using adhesins, glycocalyx (e.g., capsules), fimbriae, and pili.
  • Adhesins are bacterial surface proteins that bind to host cell receptors.
  • Glycocalyx enhances adherence to surfaces, forming biofilms.
  • Fimbriae and pili are hair-like appendages enabling adherence.

Evasion of the Immune System

• Capsules: Polysaccharide or protein layers that prevent phagocytosis.
• Cell wall components:
  • Peptidoglycan can contribute to pathogenicity.
  • Mycolic acid in Mycobacteria prevents digestion within phagocytes.
  • Lipopolysaccharide (LPS) in Gram-negative bacteria triggers inflammatory responses.
• Coagulases: Cause blood clotting, hindering immune detection.
• Kinases: Break down fibrin, allowing bacterial spread.
• Hyaluronidase: Breaks down connective tissue, aiding spread.
• Collagenase: Breaks down collagen in connective tissue, aiding spread.

Antigenic Variation

• Pathogens alter their surface proteins to evade the host immune response (e.g., Influenza virus).

Internalization Mechanisms

• Some bacteria use the host cell's cytoskeleton (actin filaments) to enter cells via receptor-mediated endocytosis or phagocytosis.
• Examples include Salmonella interacting with host receptors and inducing membrane ruffling.

Avoiding Phagocytosis

• Bacteria evade phagocytes through capsules, leukocidins, preventing phagosome-lysosome fusion, or escaping from the phagosome.

Nutrient Acquisition

• Siderophores are small molecules that bind iron, helping bacteria acquire this essential nutrient for growth (e.g., E. coli).

Direct and Toxin-Mediated Damage

• Direct damage: Microbes physically damage tissues by releasing enzymes that break down tissue constituents (e.g., Streptococcus pyogenes).
• Toxin production involves exotoxins secreted by pathogenic bacteria and endotoxins, parts of Gram-negative cell walls.

Toxin Types

• Exotoxins: Protein toxins damaging or destroying host cells, often very potent (e.g., Diphtheria toxin).
• Endotoxins: Components of Gram-negative cell walls (LPS), released on bacterial death. These trigger strong inflammatory responses, potentially causing fever, shock, and death (e.g., E. coli LPS).

Mechanisms of Action

• A-B toxins: Two-part toxins (A = active, B = binding), damaging cells by disrupting cellular functions.
• Membrane-disrupting toxins: Damage host cell membranes.
• Superantigens: Cause excessive immune responses by activating large numbers of T cells.
• Genotoxins: Damage host cell DNA, leading to mutations and cancer.

Diagnostic Tools

• LAL assay: Detects endotoxins (LPS) in pharmaceuticals and medical devices using horseshoe crab blood cells.

Genetic Factors

• Plasmids: Carry genes for antibiotic resistance, virulence factors, or toxins (e.g., Shiga toxin in E. coli).
• Lysogeny: Bacteriophages integrating their DNA into the bacterial genome, potentially causing toxin production (e.g., Corynebacterium diphtheria).

Causation of Symptoms

• Fungal, protozoan, helminthic, and algal diseases’ symptoms arise from toxin production, allergic reactions, tissue invasion, parasite presence, or toxin release.

Portal of Entry vs. Exit

• Portal of entry is the site of pathogen entry into the body.
• Portal of exit is the site of pathogen exit from the body.