Antimicrobial Resistance and Mechanisms of Resistance

Main Therapeutic Tools

  • Antimicrobials are vital in human and veterinary medicine for treating bacterial infectious diseases.

Antimicrobial Resistance (AMR)

  • Over the past 50 years, misuse and overuse of antimicrobials have led to the emergence of resistant bacterial strains.
  • Resistant pathogens in animals can affect public health, particularly through foodborne transmission.
  • AMR is a critical priority in public health due to its widespread impact.

Mechanisms of Antimicrobial Resistance

  • Bacteria develop resistance through several mechanisms:
    • Genetic Mutation
    • Destruction or Inactivation
    • Efflux
Selection Pressure
  • Natural selection plays a significant role where resistant bacteria survive in the presence of antimicrobials, leading to a shift in bacterial populations over time.
  • Continuous antimicrobial usage can result in reduced effectiveness for previously treatable infections.
Genetic Mutation
  • DNA mutations can alter the target enzyme of antimicrobials, making them ineffective.
  • Example: Fluoroquinolones target DNA gyrase; mutations can prevent binding and allow DNA replication despite the presence of the drug.
Destruction or Inactivation
  • Certain bacteria can produce enzymes that degrade or modify antimicrobials before reaching the target site, rendering them ineffective.
Efflux
  • Bacteria can use efflux pumps to expel antimicrobials from inside the cell.
  • Antimicrobial enters through channel (aporin) but is exported back out by the efflux pump, preventing accumulation necessary for cell death.

Genetic Transfer of Resistance

  • Bacteria can share resistant genes through:
    • Conjugation
    • Involves plasmids (circular DNA that replicates independently).
    • A pilus forms between two cells, allowing plasmid transfer and conferring resistance.
    • Transformation
    • Involves uptake of naked DNA released from lysed bacteria.
    • This DNA may contain resistance genes, providing a survival advantage.
    • Transduction
    • Bacteriophages transport DNA between bacteria during infection.
    • Bacterial DNA may be incorporated into phage DNA and spread to other bacteria during their lifecycle.