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Antimicrob. Agents Chemother. doi:10.1128/AAC.01376-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Translational Attenuation and mRNA Stabilization as Induction Mechanisms of erm(B) by Erythromycin

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Department of Herbal Skin Care, Daegu Haany University, Gyeongsan 712-715, Department of Life Science, The University of Seoul, Seoul 130-743, Korea

^* To whom correspondence should be addressed. Email: ecchoi{at}snu.ac.kr.

	Abstract

Translational attenuation has been proposed to be the mechanism by which the erm(B) gene is induced. Here, we report genetic and biochemical evidence to support this hypothesis using erythromycin as the inducing antibiotic. We show also that erythromycin increases the level of the erm(B) transcript by stalling the ribosome on the leader mRNA and thereby facilitating stabilization and processing of the mRNA. Erythromycin-induced mRNA stabilization and processing were observed with an ochre stop at codons 11 to 13 of the leader, but not with an ochre stop codon 10. This suggests that erythromycin does not stall the ribosome before codon 11 of the leader reaches the aminoacyl site. Secondary structure analyses of the erm(B) transcripts using in vitro and in vivo chemical probing techniques identified conformational changes in the transcripts that result from induction by erythromycin. These findings demonstrate that stalling of erythromycin-bound ribosomes at leader codon 11 causes the refolding of mRNA into a conformation in which the translational initiation site for the structural gene is unmasked and renders erm(B) translationally active.