Genetic Drug Resistance


Two main types of genetic drug resistance are chromosomal resistance and extrachromosomal resistance.

Chromosomal resistance

  • It evolves under the selective pressure of antibiotics that affect the bacterial population. Bacterial nucleoid mutations appear, and the selected bacterial clone becomes resistant to administered drug.
  • This is true for rifampicin resistance in tuberculosis treatment or beta-lactam resistance due to PBP-mutations. In the latter case, mutations abolish synthesis of some sensitive penicillin receptors (PBPs), thereby missing antimicrobial penicillin action.
Genetic Drug Resistance
Chromosomal resistance

Extrachromosomal resistance

  • It is encoded by plasmids and episomes – additional bacterial genetic elements. Also, temperate bacteriophages can carry genes of antibiotic resistance.
  • R-plasmids contain genes providing mono– or multi-resistance to different antibiotics and sometimes too heavy metals.
  • They can encode antibiotic-degrading enzymes, capable of destroying the antimicrobial drugs (beta-lactamases for penicillin and cephalosporin hydrolysis, acetyltransferase for chloramphenicol inactivation, enzymes that acylate different aminoglycosides, etc.)
  • This variant of resistance is under continuous evolutionary control.
  • For instance, one group of beta-lactamases is able not only to destroy penicillins and cephalosporins of first generations but also to hydrolyze 3rd generation cephalosporins (cefotaxime, ceftazidime, ceftriaxone, etc.) or monobactams (aztreonam). These enzymes are called extended-spectrum beta-lactamases.
  • A substantial amount of gram-negative bacteria are known to produce them (E. coli, K. pneumonia etc.)
Genetic Drug Resistance