Inducible macrolide and lincosamide resistance in Streptomyces lividans.

Resistance to macrolide, lincosamide, and streptomgramin B type antibiotics, is widespread amongst Gram positive bacteria and is particuarly prevalent in the genus Streptomyces. The classical MLS resistance phenotype has, in a number of cases, been associated with N6,N6 dimethylation of 23S rRNA, and more specifically to methylation of the adenine residue at a position equivalent to 2058 in E. coli 23S rRNA. However, phenotypes differing from that associated with classical MLS resistance have also been reported, and this study describes the analysis of one such inducible resistance phenotype found in the non-producing organism Streptomyces lividans TK21. Two resistance genes have been isolated from S. lividans, with the aid of shotgun cloning techniques, and both have been analysed at the nucleotide level. The first, lrm, encodes a ribosomal RNA methylase of 36 KDa, that monomethylates the N6 amino group of an adenosine residue at a position equivalent to 2058 in 23S rRNA. The second resistance gene codes for a protein of 46 KDa, and though the precise function of this protein is as yet undetermined, a distant similarity does exist between this gene product and various eukaryotic UDP-glucuronosyl transferases. Transcription of lrm initiates from two promoters that lie some 253 and 377 nucleotides upstream from the translational initiation codon. The leader sequence is capable of forming a series of stable hairpin loops, and an area exists within this region that could encode a short leader peptide of 38 amino acids. It is therefore suggested that induction of lrm may be regulated by translational attenuation.