Molecular cloning and characterization of two lincomycin-resistance genes, lmrA and lmrB, from Streptomyces lincolnensis 78-11.
Two different lincomycin-resistance determinants (lmrA and lmrB) from Streptomyces lincolnensis 78-11 were cloned in Streptomyces lividans 66 TK23. The gene lmrA 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 lmrB 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 lmrB-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.
Zhang
H Z
HZ
Bergische Universität GH Wuppertal, Germany.
Schmidt
H
H
Piepersberg
W
W
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics; D002384:Catalysis; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000302:isolation & purification; D004352:Drug Resistance, Microbial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008034:Lincomycin / Q000494:pharmacology*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D011522:Protons; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D017385:Sequence Homology; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics*
D002352:Carrier Proteins; D004269:DNA, Bacterial; D011522:Protons; D012338:RNA, Ribosomal, 23S; D008034:Lincomycin; D008780:Methyltransferases