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Drug-modifying
enzymes
(e.g., - lactamases,
aminoglycosidemodifying enzymes)
Altered
drug
targets
(e.g., PBPs
ribosomes,
DNA gyrase)
Altered
uptake or
accumulation of
drug
(e.g., altered porins,
membrane
efflux pumps)
N-acetylmuramic acid
pentapeptide
D-ala-D-ala
A subunit is added
to the growing chain
Transpeptidase (PBP) forms a 5-glycine bridge between peptides
Transpeptidase, or PBP
(orange sunburst)
is bound by beta-lactam antibiotic (light blue)
and its activity is inhibited
(turns gray)
Overexpression of
Beta-lactamases
Beta-lactamases
(dark orange)
Beta-lactamase activity
Vancomycin-intermediate S. aureus
Production of excessive cell wall; the antibiotic cannot keep up
MRSA
vancomycin MIC = 2 g/ml
VISA
vancomycin MIC =8 g/ml
MRSA
VISA
V
D-ala-D-ala
Vancomycin is
unable to bind
to the D-ala-Dlactate structure
D-ala-D-lactate
DNA
alpha-strep pbp
Alpha-strep
S. pneumoniae
transformation
alpha-strep pbp
Outer membrane
Cell wall
(peptidoglycan)
Inner membrane
Cytoplasm
Bacterium