An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity

Ryan, Daniel; Bornet, Elise; Prezza, Gianluca; Alampalli, Shuba Varshini; Franco de Carvalho, Taís; Felchle, Hannah; Ebbecke, Titus; Hayward, Regan J.; Deutschbauer, Adam M.; Barquist, Lars; Westermann, Alexander J.

doi:10.1038/s41564-024-01642-9

Title: An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity

Journal Article · 24 March 2024 · Nature Microbiology

DOI: https://doi.org/10.1038/s41564-024-01642-9 · OSTI ID:2375467

^[1];

^[1]; Prezza, Gianluca ^[1]; Alampalli, Shuba Varshini ^[1];

^[1]; Felchle, Hannah ^[2]; Ebbecke, Titus ^[1]; Hayward, Regan J. ^[1];

^[3];

^[4];

^[5]

Helmholtz Centre for Infection Research, Wurzburg (Germany). Institute for RNA-based Infection Research
Helmholtz Centre for Infection Research, Wurzburg (Germany). Institute for RNA-based Infection Research; Technical Univ. of Munich (Germany)
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Helmholtz Centre for Infection Research, Wurzburg (Germany). Institute for RNA-based Infection Research; Univ. of Wurzburg (Germany); Univ. of Toronto, Mississauga, ON (Canada)
Helmholtz Centre for Infection Research, Wurzburg (Germany). Institute for RNA-based Infection Research; Univ. of Wurzburg (Germany)

Plasticity in gene expression allows bacteria to adapt to diverse environments. This is particularly relevant in the dynamic niche of the human intestinal tract; however, transcriptional networks remain largely unknown for gut-resident bacteria. Here we apply differential RNA sequencing (RNA-seq) and conventional RNA-seq to the model gut bacterium Bacteroides thetaiotaomicron to map transcriptional units and profile their expression levels across 15 in vivo-relevant growth conditions. We infer stress- and carbon source-specific transcriptional regulons and expand the annotation of small RNAs (sRNAs). Integrating this expression atlas with published transposon mutant fitness data, we predict conditionally important sRNAs. These include MasB, which downregulates tetracycline tolerance. Using MS2 affinity purification and RNA-seq, we identify a putative MasB target and assess its role in the context of the MasB-associated phenotype. These data—publicly available through the Theta-Base web browser (http://micromix.helmholtz-hiri.de/bacteroides/)—constitute a valuable resource for the microbiome community.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2375467

Journal Information:: Nature Microbiology, Journal Name: Nature Microbiology Journal Issue: 4 Vol. 9; ISSN 2058-5276

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (71)

The role of Bacteroides conjugative transposons in the dissemination of antibiotic resistance genes Whittle, G.; Shoemaker, N. B.; Salyers, A. A. Cellular and Molecular Life Sciences (CMLS), Vol. 59, Issue 12 https://doi.org/10.1007/s000180200004	journal	December 2002
Small RNAs in Bacteria and Archaea: : Who They Are, What They Do, and How They Do It Wagner, E. Gerhart H.; Romby, Pascale Advances in Genetics, Vol. 90, 133-208 https://doi.org/10.1016/bs.adgen.2015.05.001	book	January 2015
Specificity of Polysaccharide Use in Intestinal Bacteroides Species Determines Diet-Induced Microbiota Alterations Sonnenburg, Erica D.; Zheng, Hongjun; Joglekar, Payal Cell, Vol. 141, Issue 7 https://doi.org/10.1016/j.cell.2010.05.005	journal	June 2010
MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT Correia Santos, Sara; Bischler, Thorsten; Westermann, Alexander J. Cell Reports, Vol. 34, Issue 5 https://doi.org/10.1016/j.celrep.2021.108722	journal	February 2021
Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments Liu, Hualan; Shiver, Anthony L.; Price, Morgan N. Cell Reports, Vol. 34, Issue 9 https://doi.org/10.1016/j.celrep.2021.108789	journal	March 2021
Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization Kennedy, Megan S.; Zhang, Manjing; DeLeon, Orlando Cell Reports, Vol. 42, Issue 8 https://doi.org/10.1016/j.celrep.2023.113009	journal	August 2023
Mucosal Glycan Foraging Enhances Fitness and Transmission of a Saccharolytic Human Gut Bacterial Symbiont Martens, Eric C.; Chiang, Herbert C.; Gordon, Jeffrey I. Cell Host & Microbe, Vol. 4, Issue 5 https://doi.org/10.1016/j.chom.2008.09.007	journal	November 2008
Molecular Chaperones in Pathogen Virulence: Emerging New Targets for Therapy Neckers, Len; Tatu, Utpal Cell Host & Microbe, Vol. 4, Issue 6 https://doi.org/10.1016/j.chom.2008.10.011	journal	December 2008
Identifying Genetic Determinants Needed to Establish a Human Gut Symbiont in Its Habitat Goodman, Andrew L.; McNulty, Nathan P.; Zhao, Yue Cell Host & Microbe, Vol. 6, Issue 3 https://doi.org/10.1016/j.chom.2009.08.003	journal	September 2009
An Infection-Relevant Transcriptomic Compendium for Salmonella enterica Serovar Typhimurium Kröger, Carsten; Colgan, Aoife; Srikumar, Shabarinath Cell Host & Microbe, Vol. 14, Issue 6 https://doi.org/10.1016/j.chom.2013.11.010	journal	December 2013
A Subset of Polysaccharide Capsules in the Human Symbiont Bacteroides thetaiotaomicron Promote Increased Competitive Fitness in the Mouse Gut Porter, Nathan T.; Canales, Pablo; Peterson, Daniel A. Cell Host & Microbe, Vol. 22, Issue 4 https://doi.org/10.1016/j.chom.2017.08.020	journal	October 2017
The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut Schofield, Whitman B.; Zimmermann-Kogadeeva, Maria; Zimmermann, Michael Cell Host & Microbe, Vol. 24, Issue 1 https://doi.org/10.1016/j.chom.2018.06.002	journal	July 2018
Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation Becattini, Simone; Sorbara, Matthew T.; Kim, Sohn G. Cell Host & Microbe, Vol. 29, Issue 3 https://doi.org/10.1016/j.chom.2021.01.003	journal	March 2021
Differential RNA-seq: the approach behind and the biological insight gained Sharma, Cynthia M.; Vogel, Jörg Current Opinion in Microbiology, Vol. 19 https://doi.org/10.1016/j.mib.2014.06.010	journal	June 2014
Starch Catabolism by a Prominent Human Gut Symbiont Is Directed by the Recognition of Amylose Helices Koropatkin, Nicole M.; Martens, Eric C.; Gordon, Jeffrey I. Structure, Vol. 16, Issue 7 https://doi.org/10.1016/j.str.2008.03.017	journal	July 2008
The ambivalent role of Bacteroides in enteric infections Bornet, Elise; Westermann, Alexander J. Trends in Microbiology, Vol. 30, Issue 2 https://doi.org/10.1016/j.tim.2021.11.009	journal	February 2022
Identification of unknown RNA partners using MAPS Lalaouna, David; Prévost, Karine; Eyraud, Alex Methods, Vol. 117 https://doi.org/10.1016/j.ymeth.2016.11.011	journal	March 2017
Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism Cuskin, Fiona; Lowe, Elisabeth C.; Temple, Max J. Nature, Vol. 517, Issue 7533 https://doi.org/10.1038/nature13995	journal	January 2015
Normalization of RNA-seq data using factor analysis of control genes or samples Risso, Davide; Ngai, John; Speed, Terence P. Nature Biotechnology, Vol. 32, Issue 9 https://doi.org/10.1038/nbt.2931	journal	August 2014
The outer mucus layer hosts a distinct intestinal microbial niche Li, Hai; Limenitakis, Julien P.; Fuhrer, Tobias Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms9292	journal	September 2015
NIH Image to ImageJ: 25 years of image analysis Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W. Nature Methods, Vol. 9, Issue 7 https://doi.org/10.1038/nmeth.2089	journal	June 2012
An insider's perspective: Bacteroides as a window into the microbiome Wexler, Aaron G.; Goodman, Andrew L. Nature Microbiology, Vol. 2, Issue 5 https://doi.org/10.1038/nmicrobiol.2017.26	journal	April 2017
A high-resolution transcriptome map identifies small RNA regulation of metabolism in the gut microbe Bacteroides thetaiotaomicron Ryan, Daniel; Jenniches, Laura; Reichardt, Sarah Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-17348-5	journal	July 2020
Complex N-glycan breakdown by gut Bacteroides involves an extensive enzymatic apparatus encoded by multiple co-regulated genetic loci Briliūtė, Justina; Urbanowicz, Paulina A.; Luis, Ana S. Nature Microbiology, Vol. 4, Issue 9 https://doi.org/10.1038/s41564-019-0466-x	journal	June 2019
Spatially distinct physiology of Bacteroides fragilis within the proximal colon of gnotobiotic mice Donaldson, Gregory P.; Chou, Wen-Chi; Manson, Abigail L. Nature Microbiology, Vol. 5, Issue 5 https://doi.org/10.1038/s41564-020-0683-3	journal	March 2020
Phase-variable capsular polysaccharides and lipoproteins modify bacteriophage susceptibility in Bacteroides thetaiotaomicron Porter, Nathan T.; Hryckowian, Andrew J.; Merrill, Bryan D. Nature Microbiology, Vol. 5, Issue 9 https://doi.org/10.1038/s41564-020-0746-5	journal	June 2020
Sulfated glycan recognition by carbohydrate sulfatases of the human gut microbiota Luis, Ana S.; Baslé, Arnaud; Byrne, Dominic P. Nature Chemical Biology, Vol. 18, Issue 8 https://doi.org/10.1038/s41589-022-01039-x	journal	June 2022
Clustergrammer, a web-based heatmap visualization and analysis tool for high-dimensional biological data Fernandez, Nicolas F.; Gundersen, Gregory W.; Rahman, Adeeb Scientific Data, Vol. 4, Issue 1 https://doi.org/10.1038/sdata.2017.151	journal	October 2017
Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica: Global gene expression profiling of intracellular Salmonella Eriksson, Sofia; Lucchini, Sacha; Thompson, Arthur Molecular Microbiology, Vol. 47, Issue 1 https://doi.org/10.1046/j.1365-2958.2003.03313.x	journal	December 2002
A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism Sonnenburg, E. D.; Sonnenburg, J. L.; Manchester, J. K. Proceedings of the National Academy of Sciences, Vol. 103, Issue 23 https://doi.org/10.1073/pnas.0603249103	journal	May 2006
Bacteroides thetaiotaomicron uses a widespread extracellular DNase to promote bile-dependent biofilm formation Béchon, Nathalie; Mihajlovic, Jovana; Lopes, Anne-Aurélie Proceedings of the National Academy of Sciences, Vol. 119, Issue 7 https://doi.org/10.1073/pnas.2111228119	journal	February 2022
Coordinate Regulation of Glycan Degradation and Polysaccharide Capsule Biosynthesis by a Prominent Human Gut Symbiont Martens, Eric C.; Roth, Robyn; Heuser, John E. Journal of Biological Chemistry, Vol. 284, Issue 27 https://doi.org/10.1074/jbc.M109.008094	journal	July 2009
Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine Singhal, Rashi; Shah, Yatrik M. Journal of Biological Chemistry, Vol. 295, Issue 30 https://doi.org/10.1074/jbc.REV120.011188	journal	July 2020
Dietary sugars silence the master regulator of carbohydrate utilization in human gut Bacteroides species Pearce, Victoria H.; Groisman, Eduardo A.; Townsend, Guy E. Gut Microbes, Vol. 15, Issue 1 https://doi.org/10.1080/19490976.2023.2221484	journal	June 2023
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Robinson, M. D.; McCarthy, D. J.; Smyth, G. K. Bioinformatics, Vol. 26, Issue 1 https://doi.org/10.1093/bioinformatics/btp616	journal	November 2009
READemption—a tool for the computational analysis of deep-sequencing–based transcriptome data Förstner, Konrad U.; Vogel, Jörg; Sharma, Cynthia M. Bioinformatics, Vol. 30, Issue 23 https://doi.org/10.1093/bioinformatics/btu533	journal	August 2014
ANNOgesic: a Swiss army knife for the RNA-seq based annotation of bacterial/archaeal genomes Yu, Sung-Huan; Vogel, Jörg; Förstner, Konrad U. GigaScience, Vol. 7, Issue 9 https://doi.org/10.1093/gigascience/giy096	journal	August 2018
Translational control and target recognition by Escherichia coli small RNAs in vivo Urban, Johannes H.; Vogel, Jörg Nucleic Acids Research, Vol. 35, Issue 3 https://doi.org/10.1093/nar/gkl1040	journal	January 2007
Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation McCarthy, Davis J.; Chen, Yunshun; Smyth, Gordon K. Nucleic Acids Research, Vol. 40, Issue 10 https://doi.org/10.1093/nar/gks042	journal	January 2012
BSRD: a repository for bacterial small regulatory RNA Li, Lei; Huang, Dandan; Cheung, Man Kit Nucleic Acids Research, Vol. 41, Issue D1 https://doi.org/10.1093/nar/gks1264	journal	November 2012
CopraRNA and IntaRNA: predicting small RNA targets, networks and interaction domains Wright, Patrick R.; Georg, Jens; Mann, Martin Nucleic Acids Research, Vol. 42, Issue W1 https://doi.org/10.1093/nar/gku359	journal	May 2014
PULDB: the expanded database of Polysaccharide Utilization Loci Terrapon, Nicolas; Lombard, Vincent; Drula, Élodie Nucleic Acids Research, Vol. 46, Issue D1 https://doi.org/10.1093/nar/gkx1022	journal	October 2017
IntaRNA 2.0: enhanced and customizable prediction of RNA–RNA interactions Mann, Martin; Wright, Patrick R.; Backofen, Rolf Nucleic Acids Research, Vol. 45, Issue W1 https://doi.org/10.1093/nar/gkx279	journal	May 2017
eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses Huerta-Cepas, Jaime; Szklarczyk, Damian; Heller, Davide Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky1085	journal	November 2018
Loss of Bacteroides thetaiotaomicron bile acid altering enzymes impact bacterial fitness and the global metabolic transcriptome McMillan, Arthur S.; Foley, Matthew H.; Perkins, Caroline E. https://doi.org/10.1101/2023.06.27.546749	journal	June 2023
Superfolder GFP reporters validate diverse new mRNA targets of the classic porin regulator, MicF RNA Corcoran, Colin P.; Podkaminski, Dimitri; Papenfort, Kai Molecular Microbiology, Vol. 84, Issue 3 https://doi.org/10.1111/j.1365-2958.2012.08031.x	journal	March 2012
Comparative genomics provides structural and functional insights into Bacteroides RNA biology Prezza, Gianluca; Ryan, Daniel; Mädler, Gohar Molecular Microbiology, Vol. 117, Issue 1 https://doi.org/10.1111/mmi.14793	journal	August 2021
A Genomic View of the Human-Bacteroides thetaiotaomicron Symbiosis Xu, J. Science, Vol. 299, Issue 5615 https://doi.org/10.1126/science.1080029	journal	March 2003
Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides Wu, Meng; McNulty, Nathan P.; Rodionov, Dmitry A. Science, Vol. 350, Issue 6256 https://doi.org/10.1126/science.aac5992	journal	October 2015
Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut Jiang, Xiaofang; Hall, A. Brantley; Arthur, Timothy D. Science, Vol. 363, Issue 6423 https://doi.org/10.1126/science.aau5238	journal	January 2019
Defining the Bacteroides Ribosomal Binding Site Wegmann, Udo; Horn, Nikki; Carding, Simon R. Applied and Environmental Microbiology, Vol. 79, Issue 6 https://doi.org/10.1128/AEM.03086-12	journal	March 2013
cis -Encoded Small RNAs, a Conserved Mechanism for Repression of Polysaccharide Utilization in Bacteroides Cao, Yanlu; Förstner, Konrad U.; Vogel, Jörg Journal of Bacteriology, Vol. 198, Issue 18 https://doi.org/10.1128/JB.00381-16	journal	September 2016
Genetic Manipulation of Wild Human Gut Bacteroides Bencivenga-Barry, Natasha A.; Lim, Bentley; Herrera, Carmen M. Journal of Bacteriology, Vol. 202, Issue 3 https://doi.org/10.1128/JB.00544-19	journal	November 2019
Polysaccharide Utilization Loci: Fueling Microbial Communities Grondin, Julie M.; Tamura, Kazune; Déjean, Guillaume Journal of Bacteriology, Vol. 199, Issue 15 https://doi.org/10.1128/JB.00860-16	journal	January 2017
The Small RNA RteR Inhibits Transfer of the Bacteroides Conjugative Transposon CTnDOT Waters, Jillian L.; Salyers, Abigail A. Journal of Bacteriology, Vol. 194, Issue 19 https://doi.org/10.1128/JB.00941-12	journal	October 2012
New Regulatory Gene That Contributes to Control of Bacteroides thetaiotaomicron Starch Utilization Genes Cho, Kyu Hong; Cho, Diedre; Wang, Gui-Rong Journal of Bacteriology, Vol. 183, Issue 24 https://doi.org/10.1128/JB.183.24.7198-7205.2001	journal	December 2001
Effect of regulatory protein levels on utilization of starch by Bacteroides thetaiotaomicron. D'Elia, J. N.; Salyers, A. A. Journal of bacteriology, Vol. 178, Issue 24 https://doi.org/10.1128/jb.178.24.7180-7186.1996	journal	January 1996
Characterization of four outer membrane proteins that play a role in utilization of starch by Bacteroides thetaiotaomicron Reeves, A. R.; Wang, G. R.; Salyers, A. A. Journal of Bacteriology, Vol. 179, Issue 3 https://doi.org/10.1128/jb.179.3.643-649.1997	journal	February 1997
Erratum for Townsend et al., “A Master Regulator of Bacteroides thetaiotaomicron Gut Colonization Controls Carbohydrate Utilization and an Alternative Protein Synthesis Factor” Townsend, Guy E.; Han, Weiwei; Schwalm, Nathan D. mBio, Vol. 11, Issue 2 https://doi.org/10.1128/mBio.00301-20	journal	April 2020
Rapid Quantification of Mutant Fitness in Diverse Bacteria by Sequencing Randomly Bar-Coded Transposons Wetmore, Kelly M.; Price, Morgan N.; Waters, Robert J. mBio, Vol. 6, Issue 3, Article No. e00306-15 https://doi.org/10.1128/mBio.00306-15	journal	May 2015
Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron Schwalm, Nathan D.; Townsend, Guy E.; Groisman, Eduardo A. mBio, Vol. 7, Issue 5 https://doi.org/10.1128/mBio.01342-16	journal	October 2016
Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs Nugent, S. G. Gut, Vol. 48, Issue 4 https://doi.org/10.1136/gut.48.4.571	journal	April 2001
The Critical Roles of Polysaccharides in Gut Microbial Ecology and Physiology Porter, Nathan T.; Martens, Eric C. Annual Review of Microbiology, Vol. 71, Issue 1 https://doi.org/10.1146/annurev-micro-102215-095316	journal	September 2017
How deep is deep enough for RNA-Seq profiling of bacterial transcriptomes? Haas, Brian J.; Chin, Melissa; Nusbaum, Chad BMC Genomics, Vol. 13, Issue 1 https://doi.org/10.1186/1471-2164-13-734	journal	January 2012
RegPrecise 3.0 – A resource for genome-scale exploration of transcriptional regulation in bacteria Novichkov, Pavel S.; Kazakov, Alexey E.; Ravcheev, Dmitry A. BMC Genomics, Vol. 14, Issue 1 https://doi.org/10.1186/1471-2164-14-745	journal	January 2013
ViennaRNA Package 2.0 Lorenz, Ronny; Bernhart, Stephan H.; Höner zu Siederdissen, Christian Algorithms for Molecular Biology, Vol. 6, Issue 1 https://doi.org/10.1186/1748-7188-6-26	journal	November 2011
JBrowse 2: a modular genome browser with views of synteny and structural variation Diesh, Colin; Stevens, Garrett J.; Xie, Peter Genome Biology, Vol. 24, Issue 1 https://doi.org/10.1186/s13059-023-02914-z	journal	April 2023
Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts Martens, Eric C.; Lowe, Elisabeth C.; Chiang, Herbert PLoS Biology, Vol. 9, Issue 12 https://doi.org/10.1371/journal.pbio.1001221	journal	December 2011
An RNA-centric view on gut Bacteroidetes Ryan, Daniel; Prezza, Gianluca; Westermann, Alexander J. Biological Chemistry, Vol. 402, Issue 1 https://doi.org/10.1515/hsz-2020-0230	journal	September 2020
Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity Han, Weiwei; Peng, Bee‐Zen; Wang, Chunyan The EMBO Journal, Vol. 42, Issue 2 https://doi.org/10.15252/embj.2022112372	journal	December 2022
A selective gut bacterial bile salt hydrolase alters host metabolism Yao, Lina; Seaton, Sarah Craven; Ndousse-Fetter, Sula eLife, Vol. 7 https://doi.org/10.7554/eLife.37182	journal	July 2018

Similar Records

Construction and characterization of a genome-scale ordered mutant collection of Bacteroides thetaiotaomicron

Journal Article · 2022 · BMC Biology · OSTI ID:2470821

Arjes, Heidi A.; Sun, Jiawei; Liu, Hualan; +13 more

Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization

Journal Article · 2023 · Cell Reports · OSTI ID:2375001

Kennedy, Megan S.; Zhang, Manjing; DeLeon, Orlando; +13 more

Cloning and expression in Escherichia coli of a gene coding for a chondroitin lyase from Bacteroides thetaiotaomicron

Journal Article · 1985 · J. Bacteriol.; (United States) · OSTI ID:5448903

Guthrie, E P; Shoemaker, N B; Salyers, A A

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
biochemistry
microbiology

Title: An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity

Citation Formats

References (71)

Similar Records

Related Subjects