Mechanisms of Antibiotic Resistance

Selection pressure

  • Exposure to antibiotics in the environment encourages resistance as small numbers of ‘resistant mutants’ will survive whilst susceptible organisms die off
  • Particularly likely to happen in the gut of someone taking antibiotics or in bacteria in a hospital environment

How bacteria aquire resistance

  • The ability to become resistant to an antibiotic is the result of a change in the bacterial DNA
  • Can occur by 2 mechanisms:

Genetic mutation

  • Misreading of DNA
  • Bacteria reproduce rapidly - lots of scope for misreading

Transfer of bacterial DNA

  • Transformation: when bacteria die and the cells break apart, ‘free-floating’ DNA released into surrounding environment may be ‘scavenged’ by other bacteria and incorporated into DNA - the DNA may contain genes for antibiotic resistance
  • Conjugation: replication and transfer of plasmid DNA - plasmid DNA may contain genes for resistance
  • Transduction: bacterial DNA transferred from one bacterium to the other inside a virus that infects bacteria (bacteriophages)

Mechanisms of resistance

Altered binding site

  • A change in bacterial DNA can cause a change in the gene product which is the target of the antibiotic

Destruction of antibiotic

  • Bacteria may possess genes which code for enzymes that chemically degrade or inactivate the antibiotic
  • β -lactamases and cephalosporinases target and disrupt the β-lactam ring of the antibiotics
  • ESBLs: enzymes that inactive almost all penicillins and cephalosporins
    • Produced by some Gram-negative bacteria

Increased efflux

  • Efflux pumps actively export antibiotics out of the bacterial cell
  • Genetic change may increase the rate of efflux - antibiotic pumped back out of the cell before it has time to act

Empirical antibiotics for infection

  • Staph aureus: flucloxacillin IV
  • Staph epidermidis: vancomycin IV
  • Strep pyrogenes: doxycycline
  • Gram negatives: clindamycin
  • Anaerobes: metronidazole, cotriomazol