Mechanism of resistance in macrolide antibiotics

Resistance to macrolides usually results from one of four mechanisms: (1) drug efflux by an active pump mechanism (encoded by mrsA, mefA, or mefE in staphylococci, group A streptococci, or S. pneumoniae, respectively);
(2) ribosomal protection by inducible or constitutive production of methylase enzymes, mediated by expression of ermA, ermB, and ermC, which modify the ribosomal target and decrease drug binding;
(3) macrolide hydrolysis by esterases produced by Enterobacteriaceae
(4) chromosomal mutations that alter a 50S ribosomal protein (found in B. subtilis, Campylobacter spp., mycobacteria, and gram-positive cocci).

The MLSB (macrolide-lincosamide-streptogramin B) phenotype is conferred by erm genes, which encode methylases that modify the macrolide binding of the ribosome. Because macrolides, lincosamides, and type B streptogramins share the same ribosomal binding site, constitutive expression of erm confers cross-resistance to all three drug classes