The multidrug ABC transporter BmrC/BmrD of Bacillus subtilis is regulated via a ribosome-mediated transcriptional attenuation mechanism.
The multidrug ABC transporter BmrC/BmrD of Bacillus subtilis is regulated via a ribosome-mediated transcriptional attenuation mechanism.
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DOI：
10.1093/nar/gku832
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发表时间：
2014-10
影响因子：
14.9
通讯作者：
Denham EL
中科院分区：
文献类型：
--
作者：
Reilman E;Mars RA;van Dijl JM;Denham EL
响应抗生素压力的特定药物转运蛋白的表达是细菌多药耐药性发展的关键因素，并且代表了对人类健康的严重关注。为了更好地了解潜在的调控机制，我们解剖了革兰氏阳性模式细菌枯草芽孢杆菌的ATP结合盒（ABC）转运蛋白BmrC/BmrD的转录激活。通过使用启动子-GFP融合和活细胞阵列技术，我们证明了一个时间控制的转录激活的bmrCD基因的抗生素，靶向蛋白质合成。有趣的是，bmrCD表达只发生在后期指数和静止生长阶段，无论抗生素的挑战时间。我们表明，这是由于严格的转录控制的过渡态调节AbrB。此外，我们的研究结果表明，bmrCD基因与bmrB（yheJ），一个小的开放阅读框直接上游的bmrC，窝藏三个替代茎环结构的共转录。这些茎环显然是至关重要的抗生素诱导的bmrCD转录。重要的是，拟南芥诱导的bmrCD表达需要bmrB的翻译，这意味着BmrB作为调节前导肽。总之，我们首次证明了核糖体介导的转录衰减机制可以控制多药ABC转运蛋白的表达。
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.
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影响因子：
11.5
作者：
Li XZ;Nikaido H
通讯作者：
Nikaido H
影响因子：
11.4
作者：
DUBNAU, D
通讯作者：
DUBNAU, D
影响因子：
2.8
作者：
Doherty, Geoff P.;Fogg, Mark J.;Lewis, Peter J.
通讯作者：
Lewis, Peter J.
影响因子：
3.7
作者：
Galián C;Manon F;Dezi M;Torres C;Ebel C;Lévy D;Jault JM
通讯作者：
Jault JM
影响因子：
14.9
作者：
GRYCZAN, TJ;GRANDI, G;DUBNAU, D
通讯作者：
DUBNAU, D