Genetic Basis of Bacterial Virulence

Genetic Basis of Bacterial Virulence

Genetic Basis of Bacterial Virulence

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Virulence Factors & Genes - Tiny Terrors' Toolkit

  • Virulence Factors: Pathogen-produced molecules enhancing disease capability. 📌 CAPTured (Capsules, Adhesins, Pili/PAIs, Toxins).
    • Types:
      • Toxins: Damage host (e.g., exotoxins, endotoxins).
      • Adhesins: Mediate attachment (e.g., pili, fimbriae).
      • Invasins: Facilitate host cell/tissue penetration.
      • Capsules: Evade phagocytosis.
      • Enzymes: Spread/damage tissues (e.g., coagulase).
  • Genetic Basis: Virulence genes located on:
    • Bacterial Chromosome
    • Plasmids
    • Bacteriophages (e.g., toxin production via lysogeny)
    • Transposons
    • Pathogenicity Islands (PAIs) Horizontal gene transfer mechanisms in bacteria

⭐ Pathogenicity islands (PAIs) are large (10-200 kb) chromosomal or plasmid regions containing multiple virulence genes, often acquired by horizontal gene transfer, and frequently associated with tRNA genes or insertion sequences.

Virulence Gene Regulation - Sneaky Switches

Bacteria control virulence genes via:

  • Environmental Signals: Host cues:
    • Temperature (e.g., Yersinia Yops at 37°C)
    • pH, osmolarity, ↓iron (diphtheria toxin)
    • Host signals
  • Two-Component Systems (TCS): Signal relay. 📌 Sir Kenneth Responds Rapidly.
    • Sensor Kinase (SK): Detects signal, autophosphorylates.
    • Response Regulator (RR): Phosphorylated by SK, alters gene expression.
  • Quorum Sensing (QS): Density-dependent.
    • Autoinducers (AIs): Acyl-homoserine lactones (AHLs - Gram-neg), Autoinducing peptides (AIPs - Gram-pos).
    • ↑Cell density → ↑AIs → Coordinated attack.

    ⭐ Quorum sensing in Pseudomonas aeruginosa (AHLs) controls biofilm and virulence factors (elastase, pyocyanin), a key anti-virulence target.

  • Global Regulators: Master switches.
    • Fur (iron), H-NS (temp/osmolarity), cAMP-CRP (glucose).

Bacterial Quorum Sensing and Two-Component Systems

Genetic Exchange & Virulence - Sharing Secrets

Horizontal Gene Transfer (HGT) enables bacteria to acquire virulence genes, Pathogenicity Islands (PAIs), & antibiotic resistance. 📌 Bacteria Get Virulent Through The Clever Conversions (Transformation, Transduction, Conjugation).

  • Transformation:
    • Uptake of naked DNA from environment.
    • Requires cell competence.
  • Transduction:
    • Bacteriophage-mediated DNA transfer.
    • Generalized: Any bacterial DNA.
    • Specialized: Specific genes adjacent to prophage site.

    ⭐ Specialized transduction is responsible for the transfer of genes encoding potent exotoxins such as diphtheria toxin (Corynebacterium diphtheriae by β-phage) and cholera toxin (Vibrio cholerae by CTXφ phage).

  • Conjugation:
    • Plasmid-mediated direct cell-to-cell DNA transfer.
    • Requires F-pilus (sex pilus).
    • Hfr (High-frequency recombination) strains transfer chromosomal genes.

Bacterial Horizontal Gene Transfer Mechanisms

Key Virulence Mechanisms - Masterminds of Mayhem

  • Toxins:
    • Exotoxins (secreted):
      • A-B type (e.g., cholera, diphtheria)
      • Membrane-damaging (e.g., hemolysins)
      • Superantigens (e.g., TSST-1, causes cytokine storm)
    • Endotoxin: LPS (Lipid A of Gram-negatives); fever, shock.
  • Adhesion: Pili/fimbriae, afimbrial adhesins for attachment.
  • Invasion: Invasins (entry), effector proteins (manipulation).
  • Secretion Systems: Deliver effectors.
    • Type III (T3SS): "Molecular syringe".
    • Type IV (T4SS - DNA/protein transfer), Type VI (T6SS - contact-dependent). Bacterial Secretion Systems and Toxin Delivery
  • Biofilms: Protective communities; ↑resistance, evasion.
  • Iron Acquisition: Siderophores (e.g., enterobactin) scavenge Fe.

⭐ Type III Secretion Systems (T3SS), found in many Gram-negative pathogens like Salmonella, Shigella, and E. coli, act like molecular syringes to inject bacterial effector proteins directly into the host cell cytoplasm, subverting host cellular functions.

High‑Yield Points - ⚡ Biggest Takeaways

  • Virulence factors like toxins and adhesins are genetically encoded.
  • Virulence genes reside on chromosomes (Pathogenicity Islands - PAIs), plasmids, or bacteriophages.
  • PAIs are large, distinct DNA segments acquired by Horizontal Gene Transfer (HGT).
  • HGT (transformation, transduction, conjugation) facilitates rapid spread of virulence.
  • Plasmids frequently carry genes for toxins (e.g., Anthrax) and antibiotic resistance.
  • Lysogenic bacteriophages transfer toxin genes (e.g., Diphtheria, Cholera, Shiga toxins).
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Practice Questions: Genetic Basis of Bacterial Virulence

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The ELISA test for virulence antigen is used to diagnose which type of Escherichia coli?

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Which 5 bacterial toxins depend on lysogeny in order to be secreted by their corresponding bacteria?_____Botulinum ToxinCholera ToxinDiphtheria ToxinShiga Toxin

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Which 5 bacterial toxins depend on lysogeny in order to be secreted by their corresponding bacteria?_____Botulinum ToxinCholera ToxinDiphtheria ToxinShiga Toxin

Group A strep Erythrogenic toxin (causes scarlet fever)

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