Induction of ermC methylase in the absence of macrolide antibiotics and by pseudomonic acid A.

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.