Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria

被引:249
作者
Dar, Daniel [1 ]
Shamir, Maya [1 ]
Mellin, J. R. [2 ,3 ,4 ]
Koutero, Mikael [2 ,3 ,4 ]
Stern-Ginossar, Noam [1 ]
Cossart, Pascale [2 ,3 ,4 ]
Sorek, Rotem [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[2] Inst Pasteur, Unite Interact Bacteries Cellules, F-75015 Paris, France
[3] INSERM, U604, F-75015 Paris, France
[4] INRA, USC2020, F-75015 Paris, France
基金
欧洲研究理事会; 以色列科学基金会;
关键词
CONTROLS GENE-EXPRESSION; MESSENGER-RNA STRUCTURE; BACILLUS-SUBTILIS; LISTERIA-MONOCYTOGENES; ATTENUATION; RIBOSWITCHES; ANTITERMINATION; TRANSCRIPTOMICS; TERMINATION; MECHANISM;
D O I
10.1126/science.aad9822
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Riboswitches and attenuators are cis-regulatory RNA elements, most of which control bacterial gene expression via metabolite-mediated, premature transcription termination. We developed an unbiased experimental approach for genome-wide discovery of such ribo-regulators in bacteria. We also devised an experimental platform that quantitatively measures the in vivo activity of all such regulators in parallel and enables rapid screening for ribo-regulators that respond to metabolites of choice. Using this approach, we detected numerous antibioticresponsive ribo-regulators that control antibiotic resistance genes in pathogens and in the human microbiome. Studying one such regulator in Listeria monocytogenes revealed an attenuation mechanism mediated by antibiotic-stalled ribosomes. Our results expose broad roles for conditional termination in regulating antibiotic resistance and provide a tool for discovering riboswitches and attenuators that respond to previously unknown ligands.
引用
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页数:11
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