The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence

Efficient and highly organized regulation of transcription is fundamental to an organism's ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their regulation is crucial to determining how pathogenic bac...

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Veröffentlicht in:PLoS pathogens 2018-12, Vol.14 (12), p.e1007461-e1007461
Hauptverfasser: Warrier, Indu, Ram-Mohan, Nikhil, Zhu, Zeyu, Hazery, Ariana, Echlin, Haley, Rosch, Jason, Meyer, Michelle M, van Opijnen, Tim
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container_issue 12
container_start_page e1007461
container_title PLoS pathogens
container_volume 14
creator Warrier, Indu
Ram-Mohan, Nikhil
Zhu, Zeyu
Hazery, Ariana
Echlin, Haley
Rosch, Jason
Meyer, Michelle M
van Opijnen, Tim
description Efficient and highly organized regulation of transcription is fundamental to an organism's ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their regulation is crucial to determining how pathogenic bacteria cause disease and how they may be inhibited. In this study, we map the transcriptional landscape of the bacterial pathogen Streptococcus pneumoniae TIGR4 by applying a combination of high-throughput RNA-sequencing techniques. We successfully map 1864 high confidence transcription termination sites (TTSs), 790 high confidence transcription start sites (TSSs) (742 primary, and 48 secondary), and 1360 low confidence TSSs (74 secondary and 1286 primary) to yield a total of 2150 TSSs. Furthermore, our study reveals a complex transcriptome wherein environment-respondent alternate transcriptional units are observed within operons stemming from internal TSSs and TTSs. Additionally, we identify many putative cis-regulatory RNA elements and riboswitches within 5'-untranslated regions (5'-UTR). By integrating TSSs and TTSs with independently collected RNA-Seq datasets from a variety of conditions, we establish the response of these regulators to changes in growth conditions and validate several of them. Furthermore, to demonstrate the importance of ribo-regulation by 5'-UTR elements for in vivo virulence, we show that the pyrR regulatory element is essential for survival, successful colonization and infection in mice suggesting that such RNA elements are potential drug targets. Importantly, we show that our approach of combining high-throughput sequencing with in vivo experiments can reconstruct a global understanding of regulation, but also pave the way for discovery of compounds that target (ribo-)regulators to mitigate virulence and antibiotic resistance.
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subjects Acids
Animals
Antibiotic resistance
Antibiotics
Bioinformatics
Biology
Biology and Life Sciences
Colonization
Drug resistance
Gene expression
Gene regulation
Gene sequencing
Genes, Bacterial - genetics
Genomes
Genomics
Growth conditions
High-Throughput Nucleotide Sequencing
Infectious diseases
Mapping
Medicine and Health Sciences
Mice
Next-generation sequencing
Operon - genetics
Operons
Pathogens
Proteins
Research and analysis methods
Ribonucleic acid
Riboswitches
RNA
RNA sequencing
Streptococcus
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - genetics
Streptococcus pneumoniae - pathogenicity
Transcription termination
Transcription, Genetic
Virulence
Virulence - genetics
title The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence
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