An integrated transcriptomics–functional genomics approach reveals a small RNA that modulates Bacteroides thetaiotaomicron sensitivity to tetracyclines
Daniel Ryan,Elise Bornet,Gianluca Prezza,Shuba Varshini Alampalli,Taís Franco de Carvalho,Hannah Felchle,Titus Ebbecke,Regan J. Hayward,Adam M. Deutschbauer,Lars Barquist,Alexander J. Westermann +10 more
TLDR
In this paper , the authors map transcriptional units and profile their expression levels in Bacteroides thetaiotaomicron over a suite of 15 defined experimental conditions that are relevant in vivo, such as variation of temperature, pH, and oxygen tension, exposure to antibiotic stress, and growth on simple carbohydrates or on host mucin derived glycans.Abstract:
Gene expression plasticity allows bacteria to adapt to diverse environments, tie their metabolism to available nutrients, and cope with stress. This is particularly relevant in a niche as dynamic and hostile as the human intestinal tract, yet transcriptional networks remain largely unknown in gut Bacteroides spp. Here, we map transcriptional units and profile their expression levels in Bacteroides thetaiotaomicron over a suite of 15 defined experimental conditions that are relevant in vivo, such as variation of temperature, pH, and oxygen tension, exposure to antibiotic stress, and growth on simple carbohydrates or on host mucin-derived glycans. Thereby, we infer stress- and carbon source-specific transcriptional regulons, including conditional expression of capsular polysaccharides and polysaccharide utilization loci, and expand the annotation of small regulatory RNAs (sRNAs) in this organism. Integrating this comprehensive expression atlas with transposon mutant fitness data, we identify conditionally important sRNAs. One example is MasB, whose inactivation led to increased bacterial tolerance of tetracyclines. Using MS2 affinity purification coupled with RNA sequencing, we predict targets of this sRNA and discuss their potential role in the context of the MasB-associated phenotype. Together, this transcriptomic compendium in combination with functional sRNA genomics—publicly available through a new iteration of the ‘Theta-Base’ web browser (www.helmholtz-hiri.de/en/datasets/bacteroides-v2)—constitutes a valuable resource for the microbiome and sRNA research communities alike.read more
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A CRISPR-based genetic screen in Bacteroides thetaiotaomicron reveals a small RNA modulator of bile susceptibility
TL;DR: In this article , the authors established CRISPR interference in the abundant microbiota member Bacteroides thetaiotaomicron for genome-wide sRNA screens by assessing the abundance of different protospacer-adjacent motifs and identifying the Prevotella bryantii B14 Cas12a as a suitable nuclease.
Journal ArticleDOI
Dietary sugars silence the master regulator of carbohydrate utilization in human gut Bacteroides species
TL;DR: In this article , it was shown that diets rich in fructose and glucose can reduce the fitness and abundance of a human gut symbiont, Bacteroides thetaiotaomicron, by silencing the production of a critical intestinal colonization protein via its mRNA leader through an unknown mechanism.
References
More filters
Journal ArticleDOI
NIH Image to ImageJ: 25 years of image analysis
TL;DR: The origins, challenges and solutions of NIH Image and ImageJ software are discussed, and how their history can serve to advise and inform other software projects.
Journal ArticleDOI
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.
TL;DR: EdgeR as mentioned in this paper is a Bioconductor software package for examining differential expression of replicated count data, which uses an overdispersed Poisson model to account for both biological and technical variability and empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference.
Journal ArticleDOI
Highly accurate protein structure prediction with AlphaFold
John M. Jumper,Richard O. Evans,Alexander Pritzel,Tim Green,Michael Figurnov,Olaf Ronneberger,Kathryn Tunyasuvunakool,Russell Bates,Augustin Žídek,Anna Potapenko,Alex Bridgland,Clemens Meyer,Simon A. A. Kohl,Andrew J. Ballard,Andrew Cowie,Bernardino Romera-Paredes,Stanislav Nikolov,R. D. Jain,Jonas Adler,Trevor Back,Stig Petersen,David Reiman,Ellen Clancy,Michal Zielinski,Martin Steinegger,Michalina Pacholska,Tamas Berghammer,Sebastian Bodenstein,David L. Silver,Oriol Vinyals,Andrew W. Senior,Koray Kavukcuoglu,Pushmeet Kohli,Demis Hassabis +33 more
TL;DR: For example, AlphaFold as mentioned in this paper predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture. But the accuracy is limited by the fact that no homologous structure is available.
Journal ArticleDOI
Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation
TL;DR: A flexible statistical framework is developed for the analysis of read counts from RNA-Seq gene expression studies, and parallel computational approaches are developed to make non-linear model fitting faster and more reliable, making the application of GLMs to genomic data more convenient and practical.
Journal ArticleDOI
Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance
Ian Chopra,Marilyn C. Roberts +1 more
TL;DR: Changing the use of tetracyclines in human and animal health as well as in food production is needed if this class of broad-spectrum antimicrobials through the present century is to continue to be used.
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