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Prof Alexander Westermann

Host-pathogen-microbiota interactions

Our research and approach

The research group led by Alexander Westermann investigates molecular RNA-based mechanisms underlying the interplay between the host, invading pathogens and the host microbiota. They seek to identify potential molecules and metabolic pathways to target in diagnostics and therapeutics.

The current antibiotics crisis has highlighted the urgency of developing alternative therapeutic approaches to infectious disease. RNA-based therapies offer great potential for targeting specific enteric pathogens at species level, whilst minimizing collateral damage to the surrounding microbiota.

Alexander Westermann’s group maps the complex network of interactions between human gut microbes, the host and invading pathogens during infection processes. Their research seeks to identify and functionally characterize non-coding RNA molecules (ncRNA) and RNA-binding proteins in pathogens, the host and its microbiota to advance the development of targeted RNA-based diagnostics and therapeutics.

Their current work focuses on the transcriptome of human gut commensal Bacteroides thetaiotaomicron in the context of host niche colonization in the human colon. They are developing a sophisticated in vitro model of the human gut with cell organoids and utilizing RNA-sequencing technologies, such as Dual RNA-seq and differential RNA-seq. The group’s overarching goal is to find novel targets for the treatment and prevention of enteric infections based on RNA mechanisms.

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

2024

Improved RNA stability estimation through Bayesian modeling reveals most Salmonella transcripts have subminute half-lives

Jenniches L, Michaux C, Popella L, Reichardt S, Vogel J, Westermann AJ, Barquist L (2024)

Proceedings of the National Academy of Sciences of the United States of America 121 (14): e2308814121

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

Ryan D, Bornet E, Prezza G, Alampalli SV, Franco de Carvalho T, Felchle H, Ebbecke T, Hayward RJ, Deutschbauer AM, Barquist L, Westermann AJ (2024)

Nature Microbiology 9 (4): 1130-1144

CRISPR-based screening of small RNA modulators of bile susceptibility in Bacteroides thetaiotaomicron

Prezza G, Liao C, Reichardt S, Beisel CL, Westermann AJ (2024)

Proceedings of the National Academy of Sciences of the United States of America 121 (6): 1096

Non-professional efferocytosis of Salmonella-infected intestinal epithelial cells in the neonatal host

Zhang K, Repnik U, Diab N, Friske D, Pütz A, Bachmann AZ, Gubbi NMKP, Hensel M, Förstner KU, Westermann AJ, Dupont A, Hornef MW (2024)

The Journal of Experimental Medicine 221 (3)

Group B Streptococcus transcriptome when interacting with brain endothelial cells

Vollmuth N, Bridgers BE, Armstrong ML, Wood JF, Gildea AR, Espinal ER, Hooven TA, Barbieri G, Westermann AJ, Sauerwein T, …, Schubert-Unkmeir A, Kim BJ (2024)

Journal of Bacteriology (Online ahead of print): e0008724

CRISPR Interference-Based Functional Small RNA Genomics

Prezza G, Westermann AJ (2024)

Methods in Molecular Biology 2741: 101-116

2023

Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr

Salehi S, Zare A, Prezza G, Bader J, Schneider C, Fischer U, Meissner F, Mann M, Briese M, Sendtner M (2023)

Nature Communications 14 (1): 4158

Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria

Collias D, Vialetto E, Yu J, Co K, Almási ÉDH, Rüttiger AS, Achmedov T, Strowig T, Beisel CL (2023)

Nature Communications 14 (1): 680

RNA recording in single bacterial cells using reprogrammed tracrRNAs

Jiao C, Reckstadt C, König F, Homberger C, Yu J, Vogel J, Westermann AJ, Sharma CM, Beisel CL (2023)

Nature Biotechnology 41 (8): 1107-1116

A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection

Däullary T, Imdahl F, Dietrich O, Hepp L, Krammer T, Fey C, Neuhaus W, Metzger M, Vogel J, Westermann AJ, Saliba AE, Zdzieblo D (2023)

Gut Microbes 15 (1): 2186109

2022

TFEB induces mitochondrial itaconate synthesis to suppress bacterial growth in macrophages

Schuster EM, Epple MW, Glaser KM, Mihlan M, Lucht K, Zimmermann JA, Bremser A, Polyzou A, Obier N, Cabezas-Wallscheid N, …, Westermann AJ, Rambold AS (2022)

Nature Metabolism 4 (7): 856-866

The ambivalent role of Bacteroides in enteric infections

Bornet E, Westermann AJ (2022)

Trends in Microbiology 30 (2): 104-108

Comparative genomics provides structural and functional insights into Bacteroides RNA biology

Prezza G, Ryan D, Mädler G, Reichardt S, Barquist L, Westermann AJ (2022)

Molecular Microbiology 117 (1): 67-85

2021

SPI2 T3SS effectors facilitate enterocyte apical to basolateral transmigration of Salmonella-containing vacuoles in vivo

Fulde M, van Vorst K, Zhang K, Westermann AJ, Busche T, Huei YC, Welitschanski K, Froh I, Pägelow D, Plendl J, …, Repnik U, Hornef MW (2021)

Gut Microbes 13 (1): 1973836

Cross-species RNA-seq for deciphering host–microbe interactions

Westermann AJ, Vogel J (2021)

Nature Reviews Genetics 22 (6): 361–378

MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT

Correia Santos S, Bischler T, Westermann AJ, Vogel J (2021)

Cell Reports 34 (5): 108722

2020

A high-resolution transcriptome map identifies small RNA regulation of metabolism in the gut microbe Bacteroides thetaiotaomicron

Ryan D, Jenniches L, Reichardt S, Barquist L, Westermann AJ (2020)

Nature Communications 11 (1): 3557

Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen

Mika-Gospodorz B, Giengkam S, Westermann AJ, Wongsantichon J, Kion-Crosby W, Chuenklin S, Wang LC, Sunyakumthorn P, Sobota RM, Subbian S, …, Barquist L, Salje J (2020)

Nature Communications 11: 3363

An RNA-centric view on gut Bacteroidetes

Ryan D, Prezza G, Westermann AJ (2020)

Biological Chemistry 402 (1): 55-72

A global data-driven census of Salmonella small proteins and their potential functions in bacterial virulence

Venturini E, Svensson SL, Maaß S, Gelhausen R, Eggenhofer F, Li L, Cain AK, Parkhill J, Becher D, Backofen R, …, Westermann AJ, Vogel J (2020)

microLife 1 (1): 597

Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model

Seelbinder B, Wallstabe J, Marischen L, Weiss E, Wurster S, Page L, Löffler C, Bussemer L, Schmitt A, Wolf T, …, Schäuble S, Loeffler J (2020)

Cell Reports 33 (7): 108389

Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin

Hennessen F, Miethke M, Zaburannyi N, Loose M, Lukežic T, Bernecker S, Hüttel S, Jansen R, Schmiedel J, Fritzenwanker M, …, Herrmann J, Müller R (2020)

Antibiotics 9 (9): 619

Improved bacterial RNA-seq by Cas9-based depletion of ribosomal RNA reads

Prezza G, Heckel T, Dietrich S, Homberger C, Westermann AJ, Vogel J (2020)

RNA 26 (8): 1069-1078

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

Schulte LN, Schweinlin M, Westermann AJ, Janga H, Santos SC, Appenzeller S, Walles H, Vogel J, Metzger M (2020)

mBio 11 (1): e03348-19

2019

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

Martins Gomes SF, Westermann AJ, Sauerwein T, Hertlein T, Förstner KU, Ohlsen K, Metzger M, Shusta EV, Kim BJ, Appelt-Menzel A, Schubert-Unkmeir A (2019)

Frontiers in Microbiology 10: 1181

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

Westermann AJ, Venturini E, Sellin ME, Förstner KU, Hardt W, Vogel J (2019)

mBio 10 (1): e02504-18

2018

Salmonella persisters undermine host immune defenses during antibiotic treatment

Stapels DA, Hill PW, Westermann AJ, Fisher RA, Thurston TL, Saliba AE, Blommestein I, Vogel J, Helaine S (2018)

Science 362 (6419): 1156-1160

Toward Cell Type-Specific In Vivo Dual RNA-Seq

Frönicke L, Bronner DN, Byndloss MX, McLaughlin B, Bäumler AJ, Westermann AJ (2018)

Methods In Enzymology 612: 505-522

Regulatory RNAs in Virulence and Host-Microbe Interactions

Westermann AJ (2018)

Microbiology Spectrum 6 (4): 305-337

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

Simon LM, Karg S, Westermann AJ, Engel M, Elbehery AH, Hense B, Heinig M, Deng L, Theis FJ (2018)

GigaScience 7 (6): giy070

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

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

PLOS Genetics 14 (6): e1007401

Host-Pathogen Transcriptomics by Dual RNA-Seq

Westermann AJ, Vogel J (2018)

In: Arluison V., Valverde C. (eds) Bacterial Regulatory RNA, Methods in Molecular Biology 1737: 59-75

2017

P5SM suicide exon for regulating gene expression

Hammond MC, Westermann AJ, Qin Q (2017)

Patent (US9637750B2)

Einzelzell-RNA-Sequenzierung beleuchtet den Infektionsprozess

Saliba AE, Westermann AJ, Vogel J (2017)

BIOspektrum 23 (5): 525-528

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 AJ, Gunn JS, Vogel J (2017)

PNAS 114 (26): 6824-6829

Resolving host-pathogen interactions by dual RNA-seq

Westermann AJ, Barquist L, Vogel J (2017)

PLOS Pathogens 13 (2): e1006033

2016

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

Saliba AE, Li L, Westermann AJ, Appenzeller S, Stapels DA, Schulte LN, Helaine S, Vogel J (2016)

Nature Microbiology 2: 16206

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

Westermann AJ, Forstner KU, Amman F, Barquist L, Chao Y, Schulte LN, Muller L, Reinhardt R, Stadler PF, Vogel J (2016)

Nature 529 (7587): 496-501

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

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

PLOS Pathogens 12 (6): e1005723

Molecular phenotyping of infection-associated small non-coding RNAs

Barquist L, Westermann AJ, Vogel J (2016)

Philosophical Transactions of the Royal Society of London B: Biological Sciences 371 (1707): 20160081

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 AJ, Rotter B, Vogel J, Winter P, Kahl G (2015)

BMC Genomics 16: 323

2014

Single-cell RNA-seq: advances and future challenges

Saliba AE, Westermann AJ, Gorski SA, Vogel J (2014)

Nucleic Acids Research 42 (14): 8845-60

2013

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

Schulte LN, Westermann AJ, Vogel J (2013)

Nucleic Acids Research 41 (1): 542-53

2012

Dual RNA-seq of pathogen and host

Westermann AJ, Gorski SA, Vogel J (2012)

Nature Reviews Microbiology 10 (9): 618-30

Transgene regulation in plants by alternative splicing of a suicide exon

Hickey SF, Sridhar M, Westermann AJ, Qin Q, Vijayendra P, Liou G, Hammond MC (2012)

Nucleic Acids Research 40 (10): 4701-10

2010

Polypyrimidine tract-binding protein homologues from Arabidopsis underlie regulatory circuits based on alternative splicing and downstream control

Stauffer E, Westermann A, Wagner G, Wachter A (2010)

The Plant journal : for cell and molecular biology 64 (2): 243-55