Translational Attenuation: The Regulation of Bacterial Resistance to the Macrolide-Lincosamide-Streptogramin B Antibiotic

Abstract

The regulation of ermC is described in detail as an example of regulation on the level of translation. ermC specifies a ribosomal RNA methylase which confers resistance to the macrolide-lincosamide-streptogramin B group of antibiotics. Synthesis of the ermC gene product is induced by erythromycin, a macrolide antibiotic. Stimulation of methylase synthesis is mediated by binding of erythromycin to an unmethylated ribosome. The translational attenuation model, supported by sequencing data and by mutational analysis, proposes that binding of erythromycin causes stalling of a ribosome during translation of a “leader peptide”, resulting in isomerization of the ermC transcript from an inactive to an active conformer. The ermC system is analogous to the transcriptional attenuation systems described for certain biosynthetic operons. ermC is unique in that interaction with a small molecule inducer mediates regulation on the translational level. However, it is but one example of nontranscriptional-level control of protein synthesis. Other systems are discussed in which control is also exerted through alterations of RNA conformation and an attempt is made to understand ermC in this more general context. Finally, other positive examples of translational attenuation are presented.