Publication Date:
2016-04-28
Description:
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 antibiotic-responsive 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dar, Daniel -- Shamir, Maya -- Mellin, J R -- Koutero, Mikael -- Stern-Ginossar, Noam -- Cossart, Pascale -- Sorek, Rotem -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):aad9822. doi: 10.1126/science.aad9822.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Institut Pasteur, Unite des Interactions Bacteries-Cellules, Paris, F-75015 France. INSERM, U604, Paris, F-75015 France. Institut National de la Recherche Agronomique, USC2020, Paris, F-75015 France. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. rotem.sorek@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120414" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions/genetics
;
Anti-Bacterial Agents/pharmacology
;
Bacillus subtilis/drug effects/genetics
;
Drug Resistance, Bacterial/*genetics
;
Enterococcus faecalis/drug effects
;
Gastrointestinal Microbiome/drug effects/genetics
;
*Gene Expression Regulation, Bacterial
;
Genome, Bacterial/genetics
;
Genome-Wide Association Study/*methods
;
High-Throughput Nucleotide Sequencing/*methods
;
Humans
;
Listeria monocytogenes/drug effects/genetics
;
Ribosomes/metabolism
;
Riboswitch/*genetics
;
Sequence Analysis, RNA/methods
;
*Transcription Termination, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
