Antimicrobial Resistance

Describe the principles of anti-microbial resistance

Resistance occurs when the maximal level of the agent tolerated is insufficient to inhibit growth.

Resistance can occur broadly via two mechanisms:

  • Genetic Alteration
    • Spontaneously, through mutation and subsequent natural selection of resistant organisms
    • Transferal of resistance genes from organism to organism via plasmids
  • Protein Expression
    Increasing or decreasing expression of proteins with subsequent change in efficacy of antimicrobials.


Specific mechanisms of resistance (which may be genetic alterations or changes in protein expression) include:

  • Prevent access to target
    • Decrease permeability
      • Narrowing of porin channels
        e.g. Streptococcal resistance to penicillins typically occurs by reducing access to PBPs.
      • Loss of non-essential transporter channels
        e.g. Anaerobes have no oxygen-transport channel which prevents penetration by aminoglycosides.
    • Active efflux of agent
      Increased efficiency or expression of efflux pumps. Can be:
      • Removed from cell
      • Trapped between cell wall layers
        e.g. Glycopeptide resistance in VRSA.
  • Alter antibiotic target site
    • Changes in binding site protein will increase resistance to agents with low affinity
    • Over-expression of target protein
    • Synthesis of target-protecting proteins
  • Modification or Inactivation of Drug
    • Metabolism of drug
      e.g. β-lactamases hydrolyse β-lactam rings
  • Modification of Metabolic Pathways
    • Development of metabolic pathways to bypass site of action of antibiotic
      e.g. Resistance to Trimethoprim-Sulfamethoxazole by allowing bacteria to synthesis or absorb folic acid.


  1. Harvey RA, Cornelissen CN, Fisher BD. Lippincott Illustrated Reviews: Microbiology (Lippincott Illustrated Reviews Series). 3rd Ed. LWW.
  2. CICM September/November 2008
  3. Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015 Jan;13(1):42-51. doi: 10.1038/nrmicro3380.
  4. Microrao - Mechanisms of Antimicrobial Resistance
Last updated 2019-07-18

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