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.
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