Table 1 |
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Examples of clinically relevant resistance mechanisms in major bacterial pathogens |
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Resistance mechanism |
Molecular basis |
Antibiotics affected |
Relevant clinical pathogens |
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Drug inactivation |
β-Lactamases |
β-Lactams (variable spectrum, depending on the enzyme type) |
Many Gram-positive and Gram-negative pathogens |
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Aminoglycoside-modifying enzymes |
Aminoglycosides (variable spectrum, depending on the enzyme type) |
Many Gram-positive and Gram-negative pathogens |
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Target modification |
Mutated DNA topoisomerases |
Quinolones and fluoroquinolones |
Many Gram-positive and Gram-negative pathogens |
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Mutated RNA polymerase |
Rifampin |
Staphylococcus aureus, Mycobacterium tuberculosis |
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Altered peptidoglycan (presence of D-Ala-D-Lac depsipeptide) |
Glycopeptides |
Enterococci |
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Target protection |
23S ribosomal RNA methylation by Erm methylases |
Macrolides |
Streptococci, Staphylococci, anaerobes |
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16S ribosomal RNA methylation by Arm/Rmt-like methylases |
Aminoglycosides |
Enterobacteriaceae |
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Ribosomal protection by Tet proteins |
Tetracyclines |
Many Gram-positive pathogens |
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Topoisomerase protection by Qnr proteins |
Quinolones and fluoroquinolones |
Enterobacteriaceae |
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Bypass of target function |
Production of PBP2a, which takes over the functions of other PBPs |
Most β-lactams |
Methicillin-resistant Staphylococcus aureus (MRSA) |
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Impermeability |
Loss of OprD porin |
Carbapenems |
Pseudomonas aeruginosa |
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Drug efflux |
Tet MFS-type pumps |
Tetracyclines |
Enterobacteriaceae, Staphylococci |
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Upregulation of MexAB RND-type pump |
Fluoroquinolones and most anti-pseudomonal β-lactams |
Pseudomonas aeruginosa |
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Upregulation of MexXY RND type pump |
Fluoroquinolones, aminoglycosides, cefepime and meropenem |
Pseudomonas aeruginosa |
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PBP: penicillin-binding-protein. |
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Rossolini and Thaller Genome Medicine 2010 2:15 doi:10.1186/gm136 |
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