Table 1 Examples of clinically relevant resistance mechanisms in major bacterial pathogens
From: Coping with antibiotic resistance: contributions from genomics
Resistance mechanism | Molecular basis | Antibiotics affected | Relevant clinical pathogens |
|---|---|---|---|
Drug inactivation | β-Lactamases | β-Lactams (variable spectrum, depending on the enzyme type) | Many Gram-positive and Gram-negative pathogens |
| Â | Aminoglycoside-modifying enzymes | Aminoglycosides (variable spectrum, depending on the enzyme type) | Many Gram-positive and Gram-negative pathogens |
Target modification | Mutated DNA topoisomerases | Quinolones and fluoroquinolones | Many Gram-positive and Gram-negative pathogens |
| Â | Mutated RNA polymerase | Rifampin | Staphylococcus aureus, Mycobacterium tuberculosis |
| Â | Altered peptidoglycan (presence of D-Ala-D-Lac depsipeptide) | Glycopeptides | Enterococci |
Target protection | 23S ribosomal RNA methylation by Erm methylases | Macrolides | Streptococci, Staphylococci, anaerobes |
| Â | 16S ribosomal RNA methylation by Arm/Rmt-like methylases | Aminoglycosides | Enterobacteriaceae |
| Â | Ribosomal protection by Tet proteins | Tetracyclines | Many Gram-positive pathogens |
| Â | Topoisomerase protection by Qnr proteins | Quinolones and fluoroquinolones | Enterobacteriaceae |
Bypass of target function | Production of PBP2a, which takes over the functions of other PBPs | Most β-lactams | Methicillin-resistant Staphylococcus aureus (MRSA) |
Impermeability | Loss of OprD porin | Carbapenems | Pseudomonas aeruginosa |
Drug efflux | Tet MFS-type pumps | Tetracyclines | Enterobacteriaceae, Staphylococci |
|  | Upregulation of MexAB RND-type pump | Fluoroquinolones and most anti-pseudomonal β-lactams | Pseudomonas aeruginosa |
| Â | Upregulation of MexXY RND type pump | Fluoroquinolones, aminoglycosides, cefepime and meropenem | Pseudomonas aeruginosa |