Alteration Of Target Site - In this mechanism the binding of the drug to the target site is reduced or eliminated by alteration of the site. An example is the resistance in gram positive bacteria (typically staphyloccoci and streptococci) to macrolide (erythromycin) lincosaminide (lincomycin). In this case methylation of 23S rRNA results in erythromycin resistance.
A plasmid-determined enzyme, methylase, dimethylates two specific adenine residues in 23S rRNA of the 50S ribosomal subunit. Binding of the erythromycin-lincomycin type of antibiotic is prevented by methylation of RNA, thus making the cell resistant to high levels of the drug.
