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Antimicrobial Agents and Chemotherapy, May 2008, p. 1782-1789, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01376-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Yu-Hong Min,^1, Ae-Ran Kwon,² Eun-Jeong Yoon,¹ Mi-Ja Shim,³ and Eung-Chil Choi^1*

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742,¹ Department of Herbal Skin Care, Daegu Haany University, Gyeongsan 712-715,² Department of Life Science, The University of Seoul, Seoul 130-743, South Korea³

Received 25 October 2007/ Returned for modification 14 January 2008/ Accepted 16 February 2008

Translational attenuation has been proposed to be the mechanism by which the erm(B) gene is induced. Here, we report genetic and biochemical evidence, obtained by using erythromycin as the inducing antibiotic, that supports this hypothesis. We also show that erythromycin increases the level of the erm(B) transcript by stalling the ribosome on the leader mRNA and thereby facilitating the 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 at 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 by 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.

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* Corresponding author. Mailing address: College of Pharmacy, Seoul National University, San 56-1, Shillim-9 dong, Kwanak-gu, Seoul 151-742, South Korea. Phone: 82-2-880-7874. Fax: 82-2-872-1795. E-mail: ecchoi{at}snu.ac.kr

Published ahead of print on 25 February 2008.

Present address: Department of Herbal Skin Care, Daegu Haany University, Gyeongsan 712-715, South Korea.

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Antimicrobial Agents and Chemotherapy, May 2008, p. 1782-1789, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01376-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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