Lecture 31

1. Damage-Response Framework

  • Purpose: This model explains microbial pathogenesis as a balance between pathogen virulence and host response.

  • Trade-Offs: Pathogens must balance host exploitation with transmission potential; too much damage can reduce host survival, impacting pathogen spread.

2. Evolution of Bacterial Pathogens

  • Selection Pressure: Pathogens face natural selection pressures, with mutations that enhance survival being favored.

  • Patho-Adaptation: Bacteria can acquire virulence factors quickly through:

    • High Mutation Rates: Bacterial replication enzymes are error-prone, increasing mutation rates.

    • Horizontal Gene Transfer (HGT): Acquisition of genes from other bacteria, often via:

      • Transformation: Uptake of environmental DNA.

      • Pathogenicity Islands (PAIs): Large gene clusters gained through HGT that provide new pathogenic traits (e.g., Salmonella SPI-1 and SPI-2 islands for host invasion and survival).

3. Evolution of Viral Pathogens

  • High Mutation Rates:

    • RNA viruses, such as HIV and Influenza, have error-prone replication enzymes (e.g., reverse transcriptase), leading to rapid genetic changes.

    • Mutation rates vary:

      • HIV: ~1 mutation every 7,000 base pairs.

      • Norovirus: ~1 mutation per genome replication cycle.

  • Rapid Replication: Viruses replicate within hours, creating large populations quickly, allowing rapid mutation accumulation and evolution.

  • Gene Swapping (HGT): Viruses infecting the same cell can exchange genetic material, as seen in influenza, which can result in major antigenic changes and contribute to pandemics.

4. Antigenic Drift vs. Antigenic Shift

  • Antigenic Drift: Gradual mutations in viral antigens (common in influenza), leading to reduced immune recognition over time.

  • Antigenic Shift: Major genetic recombination events (often due to HGT), resulting in new viral strains that can cause widespread outbreaks.

5. Immune System Adaptation to Pathogen Evolution

  • VDJ Recombination: This process in immune cells generates a diverse array of antibodies and T-cell receptors, allowing the immune system to recognize a vast number of pathogens.

  • Therapeutics: Advances in understanding pathogen evolution guide vaccine and antiviral development to stay ahead of rapidly evolving pathogens.