Antibiotics

Resistance Genes

Gene Products

Mechanisms of Resistance

β-Lactams

blaZ

β-Lactamase

Enzymatic hydrolysis of β-lactam nucleus

mecA

PBP2a

Reduced affinity for PBP

Glycopeptides

GISA: unknown

Altered peptidoglycan

Trapping of vancomycin in the cell wall

VRSA: vanA

D-Ala-D-Lac

Synthesis of dipeptide with reduced affinity for vancomycin

Quinolones

parC

ParC (or GrlA) component of topoisomerase IV

Mutations in the QRDR region,

reducing the affinity of enzyme-DNA complex for quinolones

gyrA or gyrB

GyrA or GyrB components of gyrase

Aminoglycosides (e.g., gentamycin)

Aminoglycoside-modifying enzymes (eg, aac, aph)

Acetyltransferase,

phosphotransferase

Acetylating and/or

phosphorylating enzymes

modify aminoglycosides

Trimethoprim-sulfamethoxazole

(TMP-SMZ)

Sulfonamide: sulA

Dihydropteroate synthase

Overproduction of p-aminobenzoic

acid by the enzyme

TMP: dfrB

DHFR

Reduced affinity for DHFR

Tetracyclines

Tetracycline, doxycycline and minocycline: tetM

Ribosome protection protein

Binding to the ribosome and

chasing the drug from its binding site

Tetracycline: tetK

Efflux protein

Efflux pump

Erythromycin

msrA

Efflux protein

Efflux pump

erm (A, C)

Ribosomal methylase

(constitutive or inducible)

Alteration of 23S rRNA

Clindamycin

erm (A, C)

Ribosomal methylase

(constitutive or inducible)

Alteration of 23S rRNA

Linezolid

cfr

Ribosomal methyltransferase

Methylation of the 23S rRNA that

interferes with ribosomal binding

Daptomycin

mprF

Lysylphosphatidylglycerol

synthetase (LPG) synthetase

Increasing: synthesis of total LPG, outer LPG translocation and positive net charges on cell membrane