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Jun Prof Franziska Faber

RNA Biology of gram-positive Bacteria (associated research group)

Our research and approach

Franziska Faber leads a research group located at the Julius-Maximilians-Universität of Würzburg and associated with HIRI. The group investigates the interplay between the enteric pathogen Clostridioides difficile and the intestinal microbiota. They seek to better understand the RNA-based mechanisms controlling virulence during these interactions. The goal is to leverage this knowledge for the development of novel RNA-based antimicrobials.

Enteric infections and their clinical outcome are often associated with underlying microbial dysbiosis, an imbalance in the microbiota. Clostridioides  difficile—a leading cause of antibiotic-associated diarrhea—is a prime example: In healthy individuals, infection with C. difficile results in asymptomatic colonization. However, after antibiotic treatment, the enteric pathogen causes a wide spectrum of diseases. Therefore, a mechanistic understanding of virulence regulation in the context of pathogen-commensal interactions is paramount for the development of novel RNA-based therapeutics.

Franziska Faber’s group addresses this goal through the molecular characterization of virulence regulation, with a focus on post-transcriptional regulation by non-coding RNAs and their cognate RNA-binding proteins. They also identify the microbial and host signals that regulate the virulence gene expression. Furthermore, the Faber group establishes antisense oligomer-based targeting of genes and pathways essential for virulence.

Their work combines technologies from the fields of RNA biology, biochemistry, metabolomics, genetics and microbiology. The overarching goal of the Faber group is to identify and functionally characterize novel RNA-based mechanisms of virulence regulation that can be exploited as therapeutic targets. 

Team members

Research projects

The production of toxins and the ability to form antibiotic-resistant spores are the major virulence factors in C. difficile. These factors contribute to significant morbidity, mortality, and to high recurrence rates in patients. Their production is tightly regulated by metabolic signals whose abundance and composition throughout the infection cycle is shaped by the gut microbial community.

In our lab, we combine deep RNA-sequencing based approaches with RNA biology, biochemical, genetic and microbiological techniques. We aim to discover and mechanistically characterize non-coding RNAs and their RNA-binding protein partners involved in virulence gene regulation.

We are also interested in how microbial and host signals shape the activities of these regulators. To better understand this cross-talk, we take a bottom-up approach by studying individual pathogen-commensal interactions. To do this, we integrate microbiological, genetic, advanced cell culture and metabolomics approaches.

The overarching goal of our research is to identify regulatory RNAs along with their regulated pathways that may be exploited as therapeutic targets in the future. Towards that goal, we are currently establishing antisense oligomer-based gene silencing in C. difficile focusing on essential genes.

Publications

2021

RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum

Ponath F, Tawk C, Zhu Y, Barquist L, Faber F, Vogel J (2021)

Nature Microbiology 6 (8): 1007-1020

Grad-seq identifies KhpB as a global RNA-binding protein in Clostridioides difficile that regulates toxin production

Lamm-Schmidt V, Fuchs M, Sulzer J, Gerovac M, Hör J, Dersch P, Vogel J, Faber F (2021)

microLife 2: 3704

Malaria parasite infection compromises colonization resistance to an enteric pathogen by reducing gastric acidity

Walker GT, Yang G, Tsai JY, Rodriguez JL, English BC, Faber F, Souvannaseng L, Butler BP, Tsolis RM (2021)

Science Advances 7 (27): 6232

The metabolic footprint of Clostridia and Erysipelotrichia reveals their role in depleting sugar alcohols in the cecum

Tiffany CR, Lee JY, Rogers AWL, Olsan EE, Morales P, Faber F, Bäumler AJ (2021)

Microbiome 9 (1): 174

An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium

Fuchs M, Lamm-Schmidt V, Sulzer J, Ponath F, Jenniches L, Kirk JA, Fagan RP, Barquist L, Vogel J, Faber F (2021)

PNAS 118 (25): 2103579

2020

Antibacterial Anacardic Acid Derivatives

Saedtler M, Förtig N, Ohlsen K, Faber F, Masota N, Kowalick K, Holzgrabe U, Meinel L (2020)

ACS Infectious Diseases 6 (7): 1674-1685

2019

Commensal Enterobacteriaceae Protect against Salmonella Colonization through Oxygen Competition

Litvak Y, Mon KKZ, Nguyen H, Chanthavixay G, Liou M, Velazquez EM, Kutter L, Alcantara MA, Byndloss MX, Tiffany CR, …, Zhou H, Bäumler AJ (2019)

Cell Host & Microbe 25 (1): 128-139

Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection

Velazquez EM, Nguyen H, Heasley KT, Saechao CH, Gil LM, Rogers AWL, Miller BM, Rolston MR, Lopez CA, Litvak Y, …, Byndloss AJ, Bäumler AJ (2019)

Nature Microbiology 4 (6): 1057-1064

2018

Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease

Bronner DN, Faber F, Olsan EE, Byndloss MX, Sayed NA, Xu G, Yoo W, Kim D, Ryu S, Lebrilla CB, Bäumler AJ (2018)

Cell Host & Microbe 23 (2): 266-273

2017

Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion

Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA, Lokken KL, Torres TP, Byndloss AJ, Faber F, Gao Y, …, Lebrilla CB, Bäumler AJ (2017)

Science 357 (6351): 570-575

Colonization resistance: The deconvolution of a complex trait

Olsan EE, Byndloss MX, Faber F, Rivera-Chávez F, Tsolis RM, Bäumler AJ (2017)

The Journal of Biological Chemistry 292 (21): 8577-8581

A Salmonella Regulator Modulates Intestinal Colonization and Use of Phosphonoacetic Acid

Elfenbein JR, Knodler LA, Schaeffer AR, Faber F, Bäumler AJ, Andrews-Polymenis HL (2017)

Frontiers in Cellular and Infection Microbiology 7: 69

Respiration of Microbiota-Derived 1,2-propanediol Drives Salmonella Expansion during Colitis

Faber F, Thiennimitr P, Spiga L, Byndloss MX, Litvak Y, Lawhon S, Andrews-Polymenis HL, Winter SE, Bäumler AJ (2017)

PLOS Pathogens 13 (1): 1006129

2016

Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella

Rivera-Chávez F, Zhang LF, Faber F, Lopez CA, Byndloss MX, Olsan EE, Xu G, Velazquez EM, Lebrilla CB, Winter SE, Bäumler AJ (2016)

Cell Host & Microbe 19 (4): 443-54

Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion

Faber F, Tran L, Byndloss MX, Lopez CA, Velazquez EM, Kerrinnes T, Nuccio SP, Wangdi T, Fiehn O, Tsolis RM, Bäumler AJ (2016)

Nature 534 (7609): 697-9

2015

Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection

Mooney JP, Lokken KL, Byndloss MX, George MD, Velazquez EM, Faber F, Butler BP, Walker GT, Ali MM, Potts R, …, Luckhart S, Tsolis RM (2015)

Scientific Reports 5: 14603

2014

The impact of intestinal inflammation on the nutritional environment of the gut microbiota

Faber F, Bäumler AJ (2014)

Immunology Letters 162 (2 Pt A): 48-53

Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation

Winter SE, Winter MG, Poon V, Keestra AM, Sterzenbach T, Faber F, Costa LF, Cassou F, Costa EA, Alves GE, …, Santos RL, Bäumler AJ (2014)

PLOS Pathogens 10 (7): 1004207

2012

Surface-associated motility, a common trait of clinical isolates of Acinetobacter baumannii, depends on 1,3-diaminopropane

Skiebe E, de Berardinis V, Morczinek P, Kerrinnes T, Faber F, Lepka D, Hammer B, Zimmermann O, Ziesing S, Wichelhaus TA, …, Pfeifer Y, Wilharm G (2012)

International Journal of Medical Microbiology 302 (3): 117-28

2010

A simple and rapid method of bacterial transformation

Wilharm G, Lepka D, Faber F, Hofmann J, Kerrinnes T, Skiebe E (2010)

Journal of Microbiological Methods 80 (2): 215-6

Orbus hercynius gen. nov., sp. nov., isolated from faeces of wild boar, is most closely related to members of the orders 'Enterobacteriales' and Pasteurellales

Volkmann M, Skiebe E, Kerrinnes T, Faber F, Lepka D, Pfeifer Y, Holland G, Bannert N, Wilharm G (2010)

International Journal of Systematic and Evolutionary Microbiology 60 (Pt 11): 2601-2605

2009

CsrA and CsrB are required for the post-transcriptional control of the virulence-associated effector protein AvrA of Salmonella enterica

Kerrinnes T, Zelas ZB, Streckel W, Faber F, Tietze E, Tschäpe H, Yaron S (2009)

International Journal of Medical Microbiology 299 (5): 333-41

2007

Influence of poly(L-lysine) on the structure of dipalmitoylphosphatidylglycerol/water dispersions studied by X-ray scattering

Förster G, Schwieger C, Faber F, Weber T, Blume A (2007)

European Biophysics Journal 36 (4-5): 425-35

2006

Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice

Faber F, Gembardt F, Sun X, Mizutani S, Siems WE, Walther T (2006)

Regulatory Peptides 136 (1-3): 130-7