Molecular cloning and characterization of two lincomycin‐resistance genes, ImrA and ImrB, from Streptomyces lincolnensls 78–11

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Abstract
Two different lincomycin‐resistance determinants (ImrA and ImrB) from Streptomyces lincolnensis 78–11 were cloned in Streptomyces lividans 66 TK23. The gene ImrA was localized on a 2.16 kb fragment, the determined nucleotide sequence of which encoded a single open reading frame 1446 bp long. Analysis of the deduced amino acid sequence suggested the presence of 12 membrane‐spanning domains and showed significant similarities to the methylenomycin‐resistance protein (Mmr) from Streptomyces coelicolor, the QacA protein from Staphylococcus aureus, and several tetracycline‐resistance proteins from both Gram‐positive and Gram‐negative bacteria, as well as to some sugar‐transport proteins from Escherichia coli. The ImrB gene was actively expressed from a 2.7 kb fragment. An open reading frame of 837 bp could be localized which encoded a protein that was significantly similar to 23S rRNA adenine(2058)‐N‐methyltransferases conferring macrolide—lincosamide—streptogramin resistance. LmrB also had putative rRNA methyltransferase activity since lincomycin resistance of ribosomes was induced in ImrB‐containing strains. Surprisingly, both enzymes, LmrA and LmrB, had a substrate specificity restricted to lincomycin and did not cause resistance to other lincosamides such as celesticetin and clindamycin, or to macrolides.