title: Induction of ermC methylase in the absence of macrolide antibiotics and by pseudomonic acid A.
abstract: The methylase encoded by erm genes and induced by erythromycin modifies the 23S rRNA and confers resistance to macrolide-lincosamide-streptogramin B antibiotics. Induction is due to a posttranscriptional mechanism in which the inducer activates translation of methylase mRNA by binding to unmethylated (erythromycin-sensitive) ribosomes and stalling them in the leader region. It is shown in this study that pseudomonic acid A, an inhibitor of isoleucyl-tRNA synthetase, can also induce methylase synthesis. Isoleucine starvation has a similar effect on ribosomes translating the ermC leader region to cause induction of methylase synthesis. These observations support the requirements for ribosome stalling and destabilization of a stem-loop structure and demonstrate that stalling can occur without macrolide-bound ribosomes.
authors.affiliation: Anti Infective Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: S K
authors.initials: SK
authors.lastname: Kadam
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004790:Enzyme Induction; D004917:Erythromycin / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D007700:Kinetics; D008780:Methyltransferases / Q000096:biosynthesis / Q000235:genetics*; D016712:Mupirocin; D010957:Plasmids; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D004917:Erythromycin; D016712:Mupirocin; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; D001616:beta-Galactosidase