Table 1

Examples of clinically relevant resistance mechanisms in major bacterial pathogens

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

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

Mutated RNA polymerase

Rifampin

Staphylococcus aureus, Mycobacterium tuberculosis

Altered peptidoglycan (presence of D-Ala-D-Lac depsipeptide)

Glycopeptides

Enterococci

Target protection

23S ribosomal RNA methylation by Erm methylases

Macrolides

Streptococci, Staphylococci, anaerobes

16S ribosomal RNA methylation by Arm/Rmt-like methylases

Aminoglycosides

Enterobacteriaceae

Ribosomal protection by Tet proteins

Tetracyclines

Many Gram-positive pathogens

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

Upregulation of MexXY RND type pump

Fluoroquinolones, aminoglycosides, cefepime and meropenem

Pseudomonas aeruginosa


PBP: penicillin-binding-protein.

Rossolini and Thaller Genome Medicine 2010 2:15   doi:10.1186/gm136