Reilman, E., Mars, R. A. T., van Dijl, J. M. and Denham, Emma (2014) The multidrug ABC transporter BmrC/BmrD of Bacillus subtilis is regulated via a ribosome-mediated transcriptional attenuation mechanism. Nucleic Acids Research, 42 (18). pp. 11393-11407. doi:10.1093/nar/gku832 ISSN 0305-1048.

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Abstract

Expression of particular drug transporters in response to antibiotic pressure is a critical element in the development of bacterial multidrug resistance, and represents a serious concern for human health. To obtain a better understanding of underlying regulatory mechanisms, we have dissected the transcriptional activation of the ATP-binding cassette (ABC) transporter BmrC/BmrD of the Gram-positive model bacterium Bacillus subtilis. By using promoter-GFP fusions and live cell array technology, we demonstrate a temporally controlled transcriptional activation of the bmrCD genes in response to antibiotics that target protein synthesis. Intriguingly, bmrCD expression only occurs during the late-exponential and stationary growth stages, irrespective of the timing of the antibiotic challenge. We show that this is due to tight transcriptional control by the transition state regulator AbrB. Moreover, our results show that the bmrCD genes are co-transcribed with bmrB (yheJ), a small open reading frame immediately upstream of bmrC that harbors three alternative stem-loop structures. These stem-loops are apparently crucial for antibiotic-induced bmrCD transcription. Importantly, the antibiotic-induced bmrCD expression requires translation of bmrB, which implies that BmrB serves as a regulatory leader peptide. Altogether, we demonstrate for the first time that a ribosome-mediated transcriptional attenuation mechanism can control the expression of a multidrug ABC transporter.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology Q Science > QR Microbiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Drug resistance in microorganisms, ATP-binding cassette transporters, Bacillus subtilis, Antibiotics, Peptides
Journal or Publication Title:	Nucleic Acids Research
Publisher:	Oxford University Press
ISSN:	0305-1048
Official Date:	October 2014
Dates:	Date Event October 2014 Published 12 September 2014 Available 1 September 2014 Accepted 23 November 2013 Submitted
Volume:	42
Number:	18
Page Range:	pp. 11393-11407
DOI:	10.1093/nar/gku832
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	13 January 2017
Date of first compliant Open Access:	16 January 2017
Funder:	Rijksuniversiteit te Groningen [University of Groningen], European Commission (EC), Systems Biology of Microorganisms (SysMO), Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Netherlands Organisation for Scientific Research] (NWO)
Grant number:	LSHG-CT-2006-037469, 24409 (EC), BACELL SysMO2 (SysMO)

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