Microbial Interactions (Faber lab)
Enteric infections and their clinical outcome are often associated with underlying microbial dysbiosis. Clostridioides difficile – being a leading cause of antibiotic-associated diarrhea – is a prime example. Therefore, a mechanistic understanding of virulence regulation in the context of pathogen-commensal interactions is paramount for the development of novel therapeutics.
The production of toxins and the ability to form antibiotic-resistant spores are the major virulence factors in C. difficile that contribute to significant morbidity and 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 biochemical, genetic and microbiology techniques 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 the activities of these regulators is shaped by microbial and host signals. To better understand this cross-talk, we take a bottom-up approach by studying individual pathogen-commensal interactions using microbiology, genetic, intestinal organoids/advanced tissue culture and metabolomics approaches.
Experimental work
- Fuchs M, Lamm-Schmidt V, Lenče T, Sulzer J, Bublitz A, Wackenreuter J, Gerovac M, Strowig T, Faber F
A network of small RNAs regulates sporulation initiation in C difficile.
EMBO J 2023 doi:10.15252/embj.2022112858
- Tiffany CR, Lee JY, Rogers AWL, Olsan EE, Morales P, Faber F*, Bäumler A*
The metabolic footprint of Clostridia and Erysipelotrichia reveals their role in depleting sugar alcohols in the cecum.
Microbiome 2021 doi: 10.1186/s40168-021-01123-9
- Ponath F, Tawk C, Zhu Y, Barquist L, Faber F, Vogel J
RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum.
Nature Microbiology 2021 doi: 10.1038/s41564-021-00927-7
- Fuchs M*, Lamm-Schmidt V*, Sulzer J, Ponath F, Jenniches L, Kirk JA, Fagan RP, Barquist L, Vogel J, Faber F
An RNA-centric global view of the clinically important bacterium Clostridioides difficile reveals broad activity of Hfq in a Gram-positive species.
PNAS 2021 doi:10.1073/pnas.2103579118
- Walker GT, Yang G, Tsai JY, Rodriguez JL, English BC, Faber F, Souvannaseng L, Butler BP, Tsolis RM
Malaria parasite infection compromises colonization resistance to an enteric pathogen by reducing gastric acidity.
Science Advances 2021 7:eabd6232
- Lamm-Schmidt V, Fuchs M, Sulzer J, Gerovac M, Hör J, Dersch P, Vogel J, Faber F
Grad-seq identifies KhpB as a global RNA-binding protein in Clostridioides difficile that regulates toxin production.
microLife 2021 uqab004:10.1093/femsml/uqab004
- Saedtler M, Förtig N, Ohlsen K, Faber F, Masota N, Kowalick K, Holzgrabe U, Meinel L
Anti-bacterial anacardic acid derivatives.
ACS Infectious Diseases 2020 doi: 10.1021/acsinfecdis.9b00378
- Velazquez EM, Nguyen H, Heasley KT, Seachao CH, Gil LM, Rogers AWL, Miller BM, Rolston MR, Lopez CA, Litvak Y, Liou MJ, Faber F, Bronner DN, Tiffany CR, Byndloss MX, Byndloss AJ, Bäumler AJ
Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection.
Nature Microbiology 2019 doi:10.1038/s41564-019-0407-8
- An S, Ding Y, Faber F, Hobley L, Sá-Pessoa J
Social behaviour and making attachments: a report from the fifth ‘Young Microbiologists Symposium on Microbe Signalling, Organisation and Pathogenesis’
Microbiology 2018 doi:10.1099/mic.0.000746
- Litvak Y, Mon KKZ, Nguyen H, Chanthavixay G, Liou M, Velazquez EM, Kutter L, Alcantara MA, Byndloss MX, Tiffany CR, Walker GT, Faber F, Zhu Y, Bronner DN, Byndloss AJ, Tsolis RM, Zhou H, Bäumler AJ
Commensal Enterobacteriaceae protect against Salmonella colonization by competing for oxygen.
Cell Host & Microbe 2018 25(1):128-139.e5 doi: 10.1016/j.chom.2018.12.003
- Bronner DN, Faber F, Olsan EE, Byndloss MX, Sayed NA, Xu G, Yoo W, Kim K, Ryu S, Lebrilla CB, Bäumler AJ
Genetic ablation of butyrate utilization attenuates gastrointestinal Salmonella disease.
Cell Host & Microbe 2018 23(2):266-273
- Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA, Lokken KL, Torres TP, Byndloss AJ, Faber F, Gao Y, Litvak Y, Lopez CA, Xu G, Napoli E, Giulivi C, Tsolis RM, Revzin A, Lebrilla CB, Bäumler AJ
Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion.
Science 2017 357(6351):570-575.
- Faber F, Thiennimitr P, Spiga L, Byndloss MX, Litvak Y, Lawhon S, Andrews-Polymenis HL, Winter SE, Bäumler AJ
Respiration of microbiota-derived 1,2-propanediol drives Salmonella expansion during colitis.
PLoS Pathogens 2017 13(1):e1006129 doi: 10.1371/journal.ppat.1006129
- Elfenbein JR, Knodler LA, Schaeffer AR, Faber F, Bäumler AJ, Andrews-Polymenis HL
A Salmonella Regulator Modulates Intestinal Colonization and Use of Phosphonoacetic Acid.
Front Cell Infect Microbiol 2017 15;7:69.
- Faber F, Tran L, Byndloss MX, Lopez CA, Velazquez EM, Kerrinnes T, Nuccio SP, Wangdi T, Fiehn O, Tsolis RM, Bäumler AJ
Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion.
Nature 2016 534(7609):697-9 doi: 10.1038/nature18597
- Rivera-Chávez F, Zhang LF, Faber F, Lopez CA, Byndloss MX, Olsen EE, Xu G, Velazquez EM, Lebrilla CB, Winter SE, Bäumler AJ
Depletion of Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella.
Cell Host & Microbe 2016 19(4):443-54 doiI: 10.1016/j.chom.2016.03.004
- Mooney JP, Lokken KL, Byndloss MX, George MD, Velazquez EM, Faber F, Butler BP, Walker GT, Ali MM, Potts R, Tiffany C, Ahmer BM, Luckhart S, Tsolis RM
Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.
Scientific Reports 2015 5(5):14603
- Winter SE, Winter MG, Poon V, Keestra AM, Sterzenbach T, Faber F, Costa LF, Cassou F, Costa EA, Alves GE, Paixão TA, Santos RL, Bäumler AJ Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation.
PLoS Pathogens 2014 10(7):e1004207
- Skiebe E, de Berardinis V, Morczinek P, Kerrinnes T, Faber F, Lepka D, Hammer B, … Pfeifer Y, Wilharm G
Surface-associated motility, a common trait of clinical isolates of Acinetobacter baumannii, depends on 1,3-diaminopropane.
International Journal of Medical Microbiology 2012 302(3):117-28
- Volkmann M, Skiebe E, Kerrinnes T, Faber F, Lepka D, Pfeifer Y, Holland G, Bannert N, Wilharm G
Orbus hercynius gen. nov., sp. nov., isolated from faeces of wild boar, is most closely related to members of the orders Enterobacteriales and Pasteurellales.
International Journal of Systematic and Evolutionary Microbiology 2010 60(Pt 11):2601-5
- Wilharm G, Lepka D, Faber F, Hofmann J, Kerrinnes T, Skiebe E
A simple and rapid method of bacterial transformation.
Journal of Microbiological Methods 2010 80(2):215-6
- Kerrinnes T, Zelas Z, Streckel W, Faber F, Tietze E, Tschäpe H, Yaron S
CsrA and CsrB are required for the post-ranscriptional control of the virulence-associated effector protein AvrA of Salmonella enterica.
International Journal of Medical Microbiology 2009 299(5):333-41
- Forster G, Schwieger C, Faber F, Weber T, Blume A
Influence of poly(L:-lysine) on the structure of dipalmitoylphosphatidylglycerol/water studied by X-ray scattering.
European Biophysics Journal 2007 36(4-5):425-35
- Faber F, Gembardt F, Sun X, Mizutani S, Siems WE, Walther T
Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice.
Regulatory Peptides. 2006 136(1-3):130-7
Reviews
- Winter SE, Faber F, Bäumler AJ
Durchfallerreger und die Homöostase der Mikrobiota
Biospektrum 29, 127–129 (2023). doi: 10.1007/s12268-023-1901-3
- Olsen E, Byndloss MX, Faber F, Rivera-Chávez F, Tsolis RM, Bäumler AJ
Colonization resistance: the deconvolution of a complex trait.
Journal of Biological Chemistry 2017 292(21):8577-8581
- Faber F, Bäumler AJ
The impact of intestinal inflammation on the nutritional environment of the gut microbiota.
Immunology Letters. 2014 162(2 Pt A):48-53
