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Jun Prof Alexander Westermann

Host-pathogen-microbiota interactions

The group of Alexander Westermann focuses on investigating molecular RNA-based mechanisms that allow infecting pathogens to outcompete the resident microbiota. Their research centers on the identification and functional characterization of noncoding RNA molecules in pathogens, microbiota members and the host, to identify those RNAs that may serve as biomarkers for diagnostics or as therapeutic targets.

Our research and approach

The importance of RNA in maintaining cellular physiology by controlling gene expression in response to intrinsic and external cues has long been underestimated. Now, numerous human diseases have been linked to RNA functioning. Likewise, we now know that bacterial pathogens harness a large suite of noncoding RNA molecules to adapt to environmental stress and to precisely regulate their virulence programs. In an era of antibiotic crisis, it is essential to discover alternative combat strategies against pathogenic bacteria — ideally ones that spare the beneficial microbiota communities. The high specificity of RNA molecules provides great potential for achieving these goals.

Team members

Research projects

Bacterial infections of mammalian hosts are arguably among the most complex biological processes, often comprising a multitude of interacting organisms from different kingdoms. How do bacterial pathogens promote infection and what defense mechanisms do they have to overcome in order to colonize? What molecular mechanisms manifest the protective role of the microbiota against pathogenic attack? And what is the role of noncoding RNAs in host-microbiota-pathogen crosstalk? These and related questions are addressed in our group. Using cutting-edge RNA-sequencing-based techniques, our research centers on the identification and functional characterization of noncoding RNA molecules in the enteric pathogen Salmonella Typhimurium, the important intestinal microbiota member Bacteroides thetaiotaomicron, and the human host, to identify those RNAs that may serve as biomarkers for diagnosis or as therapeutic targets in the future. In addition to contributing to the field by the development of novel RNA-seq-based technologies for complex infection settings, we aim to increase the knowledge about functions of regulatory RNA molecules and RNA-binding proteins in bacterial pathogenesis and symbiosis, by gaining biological insights from mechanistic studies.

Publications

2020

An Advanced Human Intestinal Coculture Model Reveals Compartmentalized Host and Pathogen Strategies during Salmonella Infection

Schulte L, Schweinlin M, Westermann A, Janga H, Santos S, Appenzeller S, Walles H, Vogel J, Metzger M (2020)

MBio, 11 (1)DOI: 10.1128/mBio.03348-19

2019

Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells as a Cellular Model to Study Neisseria meningitidis Infection

Martins Gomes S, Westermann A, Sauerwein T, Hertlein T, Förstner K, Ohlsen K, Metzger M, Shusta E, Kim B, Appelt-Menzel A, Schubert-Unkmeir A (2019)

Frontiers In Microbiology, 10: 1181DOI: 10.3389/fmicb.2019.01181

The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression in Salmonella enterica Serovar Typhimurium

Westermann A, Venturini E, Sellin M, Förstner K, Hardt W, Vogel J (2019)

MBio, 10 (1): 02504-18DOI: 10.1128/mBio.02504-18

2018

Toward Cell Type-Specific In Vivo Dual RNA-Seq

Frönicke L, Bronner D, Byndloss M, McLaughlin B, Bäumler A, Westermann A (2018)

Methods In Enzymology, 612: 505-522DOI: 10.1016/bs.mie.2018.08.013

Regulatory RNAs in Virulence and Host-Microbe Interactions

Westermann A (2018)

Microbiology Spectrum, 6 (4): 305-337DOI: 10.1128/microbiolspec.RWR-0002-2017

MetaMap: an atlas of metatranscriptomic reads in human disease-related RNA-seq data

Simon L, Karg S, Westermann A, Engel M, Elbehery A, Hense B, Heinig M, Deng L, Theis F (2018)

GigaScience, 7 (6): 070DOI: 10.1093/gigascience/giy070

Salmonella persisters undermine host immune defenses during antibiotic treatment

Stapels D, Hill P, Westermann A, Fisher R, Thurston T, Saliba A, Blommestein I, Vogel J, Helaine S (2018)

Science, 362 (6419): 1156-1160DOI: 10.1126/science.aat7148

CRP-cAMP mediates silencing of Salmonella virulence at the post-transcriptional level

El Mouali Y, Gaviria-Cantin T, Sánchez-Romero M, Gibert M, Westermann A, Vogel J, Balsalobre C (2018)

PLoS Genetics, 14 (6): 10074DOI: 10.1371/journal.pgen.1007401

Host-Pathogen Transcriptomics by Dual RNA-Seq

Westermann A, Vogel J (2018)

In: Arluison V., Valverde C. (eds) Bacterial Regulatory RNA, Methods Mol Biol (Methods in Molecular Biology), 1737: 59-75DOI: 10.1007/978-1-4939-7634-8_4

2017

Einzelzell-RNA-Sequenzierung beleuchtet den Infektionsprozess

Saliba A, Westermann A, Vogel J (2017)

BIOspektrum, 23 (5): 525-528DOI: 10.1007/s12268-017-0836-y

RNA target profiles direct the discovery of virulence functions for the cold-shock proteins CspC and CspE

Michaux C, Holmqvist E, Vasicek E, Sharan M, Barquist L, Westermann A, Gunn J, Vogel J (2017)

Proceedings Of The National Academy Of Sciences Of The United States Of America, 114 (26): 6824-6829DOI: 10.1073/pnas.1620772114

Resolving host-pathogen interactions by dual RNA-seq

Westermann A, Barquist L, Vogel J (2017)

PLoS Pathogens, 13 (2): 10060

2016

An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection

Müller A, Dolowschiak T, Sellin M, Felmy B, Verbree C, Gadient S, Westermann A, Vogel J, LeibundGut-Landmann S, Hardt W (2016)

PLoS Pathogens, 12 (6): 10057DOI: 10.1371/journal.ppat.1005723

Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella

Saliba A, Li L, Westermann A, Appenzeller S, Stapels D, Schulte L, Helaine S, Vogel J (2016)

Nature Microbiology, 2: 16206DOI: 10.1038/nmicrobiol.2016.206

Molecular phenotyping of infection-associated small non-coding RNAs

Barquist L, Westermann A, Vogel J (2016)

Philosophical Transactions Of The Royal Society Of London. Series B, Biological Sciences, 371 (1707): 20160DOI: 10.1098/rstb.2016.0081

Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions

Westermann A, Forstner K, Amman F, Barquist L, Chao Y, Schulte L, Muller L, Reinhardt R, Stadler P, Vogel J (2016)

Nature, 529 (7587): 496-501DOI: 10.1038/nature16547

2015

Dual 3'Seq using deepSuperSAGE uncovers transcriptomes of interacting Salmonella enterica Typhimurium and human host cells

Afonso-Grunz F, Hoffmeier K, Müller S, Westermann A, Rotter B, Vogel J, Winter P, Kahl G (2015)

BMC Genomics, 16: 323DOI: 10.1186/s12864-015-1489-1

2014

Single-cell RNA-seq: advances and future challenges

Saliba A, Westermann A, Gorski S, Vogel J (2014)

Nucleic Acids Research, 42 (14): 8845-60DOI: 10.1093/nar/gku555

2013

Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing

Schulte L, Westermann A, Vogel J (2013)

Nucleic Acids Research, 41 (1): 542-53DOI: 10.1093/nar/gks1030

2012

Dual RNA-seq of pathogen and host

Westermann A, Gorski S, Vogel J (2012)

Nature Reviews Microbiology, 10 (9): 618-30DOI: 10.1038/nrmicro2852

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