Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics

Abstract

Inducible resistance to lincomycin and macrolides in Streptomyces lividans TK21 results from expression of two linked genes: lrm, encoding a ribosomal RNA methyltransferase that confers high-level resistance to lincomycin with lower levels of resistance to macrolides, and mgt, encoding a glycosyl transferase that specifically inactivates macrolides using UDP-glucose as cofactor. The lrm and mgt genes have been cloned and sequenced. The deduced lrm product is a 26-kDa protein with much similarity to other ribosomal RNA methyltransferases, such as the carB, tlrA and ermE products, whereas the mgt product (predicted to be 42 kDa) resembles a eukaryotic glycosyl transferase. Macrolides that induce the lrm-mgt gene pair are substrates for inactivation by the mgt product, and the lrm product confers ribosomal resistance to such inducers.