THE MACROLIDE-LINCOSAMIDE-STREPTOGRAMIN-B RESISTANCE PHENOTYPES CHARACTERIZED BY USING A SPECIFICALLY DELETED, ANTIBIOTIC-SENSITIVE STRAIN OF STREPTOMYCES-LIVIDANS

Genes conferring resistance to macrolide, lincosamide, and streptogram in B (MLS) antibiotics via ribosomal modification are widespread in ba cteria, including clinical isolates and MLS-producing actinomycetes, S uch erm-type genes encode enzymes that mono- or dimethylate residue A- 2058 of 23S rRNA. The different phenotypes resulting from monomethylat ion (MLS-I phenotype, conferred by erm type I genes) or dimethylation (MLS-II phenotype due to erm type II genes) have been characterized by introducing tlrD or ermE, respectively, into an MLS-sensitive derivat ive of Streptomyces lividans TK21, This strain (designated OS456) was generated by specific replacement of the endogenous resistance genes I rm and mgt. The MLS-I phenotype is characterized by high-level resista nce to lincomycin with only marginal resistance to macrolides such as chalcomycin or tylosin, whereas the MLS-II phenotype involves high-lev el resistance to all MLS drugs. Mono- and dimethylated ribosomes were introduced into a cell-free protein-synthesizing system prepared from S. lividans and compared,vith unmodified particles in their response t o antibiotics. There was no simple correlation between the relative po tencies of MLS drugs at the level of the target site (i.e., the riboso me) and their antibacterial activities expressed as MICs.