@unpublished{Baumgartner2026,

title = {Host-derived bile acids drive dysbiosis by selecting bile-resistant epimerizing bacteria in inflammatory bowel disease},

author = {Maximilian Baumgartner and Franziska Schnaufer and Maeva Duquesnoy and Takahiro Asatsuma and Adrija Chakrabarty and Adrian Frick and Claudia Fuchs and Michael Gerstorfer and Patrik Hains and Thomas Köcher and Patrick Schimmel and Mauriz A. Lichtenstein and Sofia Leistl and Felix Pinter and Elena Krstevska and Thet Khaing Nyein and Christoph Högenauer and Athanasios Makristathis and Christoph Gasche and Christian Primas and Walter Reinisch and Georg E. Winter and Michael Trauner and Claudia Günther and Georg Busslinger and Gregor Gorkiewicz and Benoit Chassaing and Clarissa Campbell},

url = {http://biorxiv.org/lookup/doi/10.64898/2026.06.18.733240},

doi = {10.64898/2026.06.18.733240},

year  = {2026},

date = {2026-06-19},

urldate = {2026-06-19},

publisher = {openRxiv},

abstract = {<jats:title>Abstract</jats:title>

                <jats:p>Microbial dysbiosis is a hallmark of inflammatory bowel diseases (IBD); however, its drivers and impact on disease pathophysiology are poorly understood. Applying neural network-based feature attribution to metabolomics and metagenomics datasets from >5000 individuals, we identified epimerized host derived bile acids (BAs) produced by microbial hydroxysteroid dehydrogenases (HSDHs) as a novel hallmark of IBD-associated dysbiosis. Epimerized BAs reduce FXR activity in intestinal epithelial cells and dampen their production of FGF19, a negative feedback regulator of host-derived bile acid (HBA) production in the liver. Increased HBA levels drive colonic epithelial remodeling by impacting goblet cell maturation and select for HSDH-carrying bacteria that transform bactericidal HBA into less toxic, epimerized forms. Confirming the translational relevance of these findings, we demonstrated that high HBA levels limit fecal microbiota transplant engraftment and show that BA sequestering drugs support microbiome recovery in patients with high HBA levels. Together, we discover that elevated HBAs deplete BA-sensitive commensals and favor the growth of HSDH-encoding pathobionts that disrupt host BA feedback signaling, establishing a causal link between changes in microbial ecology and IBD pathophysiology.</jats:p>},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {unpublished}

}

@unpublished{Kralova2026,

title = {Kineochelins - a novel group of siderophores from an Antarctic bacterium},

author = {Stanislava Kralova and Peter Spacek and Johannes Gafriller and Matej Bezdicek and Viktoria Medvedcova and Joana Séneca Cardoso Da Silva and Jay Osvatic and Ulrike Grienke and Thomas Rattei and Olga N. Sekurova and Sergey B. Zotchev and Martin Zehl and Alexander Loy},

url = {http://biorxiv.org/lookup/doi/10.64898/2026.02.23.707395},

doi = {10.64898/2026.02.23.707395},

year  = {2026},

date = {2026-02-23},

urldate = {2026-02-23},

publisher = {openRxiv},

abstract = {<jats:title>Abstract</jats:title>

                <jats:sec>

                  <jats:title>Background</jats:title>

                  <jats:p>The global rise of antimicrobial resistance has intensified the search for new microbial metabolites from underexplored environments and taxonomic groups. Extreme and geographically isolated habitats, such as Antarctic terrestrial ecosystems, represent promising reservoirs of novel biosynthetic diversity, particularly among rare and difficult-to-cultivate actinomycetes, where chemical mediators are thought to play key roles in microbial persistence and interaction under resource-limited conditions.</jats:p>

                </jats:sec>

                <jats:sec>

                  <jats:title>Results</jats:title>

                  <jats:p>

                    Here, we report the characterization of kineochelins, a previously undescribed group of siderophores produced by an Antarctic isolate,

                    <jats:italic>Actinokineospora</jats:italic>

                    sp. UV203 representing difficult to cultivate actinomycetes. Structural elucidation revealed a set of closely related congener molecules with a mixed-ligand architecture consistent with metal-chelating activity. Genome mining combined with transcriptomic analysis identified the involvement of a dedicated nonribosomal peptide synthetase-encoding biosynthetic gene cluster responsible for kineochelin production. Comparative genomic analyses showed that, although kineochelin biosynthetic genes share limited homology with those of known mixed-ligand siderophores, their biosynthetic pathways differ substantially in gene content and organization, indicating a distinct evolutionary lineage. Functional characterization of kineochelins demonstrated strong and selective iron chelation, with pronounced affinity for ferric and ferrous iron. Crude culture extracts inhibited the growth of bacterial strains isolated from the same Antarctic environment, suggesting that kineochelin-associated chemistry contributes to iron-mediated competitive interactions within native microbial communities. In addition, kineochelin-enriched fractions exhibited selective inhibitory activity against the opportunistic yeast pathogen

                    <jats:italic>Nakaseomyces glabratus</jats:italic>

                    and a clinical isolate of

                    <jats:italic>Saccharomyces cerevisiae</jats:italic>

                    associated with invasive infection.

                  </jats:p>

                </jats:sec>

                <jats:sec>

                  <jats:title>Conclusions</jats:title>

                  <jats:p>Together, these findings expand the known chemical and biosynthetic diversity of the genus Actinokineospora and demonstrate that Antarctic rare actinomycetes are a valuable source of novel natural products with potential relevance for microbial ecology and biotechnology. The ecological activities of kineochelins highlight the role of iron acquisition in shaping microbial interactions in extreme environments and underscore the biotechnological potential of metabolites derived from underexplored polar microorganisms.</jats:p>

                </jats:sec>},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {unpublished}

}

@unpublished{Jelusic2025,

title = {Reduced SARS-CoV-2 infection levels and pathotype specific altered antiviral transcriptional response in IBD intestinal organoids},

author = {Barbara Jelusic and Stefan Boerno and Patrick Schimmel and Philipp Wurm and Nicole Przysiecki and Christina Watschinger and Stella Wolfgruber and Melina Hardt and Margit Anthofer and Sandra Ehmann and Sven Klages and Kurt Zatloukal and Bernd Timmermann and Alexander Moschen and Gregor Gorkiewicz},

url = {https://www.researchsquare.com/article/rs-8029502/v1},

doi = {10.21203/rs.3.rs-8029502/v1},

year  = {2025},

date = {2025-11-26},

urldate = {2025-11-26},

publisher = {Springer Science and Business Media LLC},

abstract = {<title>Abstract</title>

                <p>

                  Background

IBD is characterized by altered immune reactions and infections are thought to trigger chronic inflammation in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients with COVID-19.

Methods

We used large and small intestinal organoids from ulcerative colitis and Crohn's disease patients and controls to comparatively assess infection levels and transcriptional response of the gut epithelium during SARS-CoV-2 infection.

Results

Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD potentially counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and increased

                  <italic>IL1B</italic>

                  expression despite lower viral loads suggestive of increased epithelial stress.

Conclusions

Altogether our analysis shows that the IBD epithelium is not more prone to SARS-CoV-2 infection and that several antiviral response genes are intrinsically activated in IBD. Moreover, ulcerative colitis and Crohn's disease exhibit specific transcriptional differences which might explain the differing COVID-19 outcomes between IBD phenotypes.

                </p>},

howpublished = {Research Square},

keywords = {},

pubstate = {published},

tppubtype = {unpublished}

}

@unpublished{Glasl2025,

title = {Branched-chain amino acid assimilation promotes mixotrophy of ammonia-oxidizing archaeal sponge symbionts},

author = {Bettina Glasl and Katharina Kitzinger and Heidi M. Luter and Anton Legin and Erika Salas and Nathalie Heldwein and Katarina Damjanovic and Stefan Schuster and Marie Rutsch and Bram Vekeman and Daan R Speth and Nicole MJ Geerlings and Petra Pjevac and Joana Séneca and Margarete Watzka and Wolfgang Wanek and Michael Wagner},

url = {http://biorxiv.org/lookup/doi/10.1101/2025.09.09.672702},

doi = {10.1101/2025.09.09.672702},

year  = {2025},

date = {2025-09-09},

urldate = {2025-09-09},

publisher = {Cold Spring Harbor Laboratory},

abstract = {<jats:p>Ammonia-oxidizing archaea (AOA) frequently form symbiotic associations with marine sponges. While free-living AOA are generally considered metabolically constrained chemolithoautotrophs, sponge-associated AOA encode for a branched-chain amino acid (BCAA) transporter, suggesting mixotrophic potential. Here, we test the unusual mixotrophic lifestyle of sponge-associated AOA by tracing the assimilation of <jats:sup>13</jats:sup>C- and <jats:sup>15</jats:sup>N-labeled BCAA in the sponge holobiont Ianthella basta. We demonstrate that BCAA degradation fuels ammonia oxidation and quantify BCAA uptake at the single-cell level by combining stable isotope probing, catalyzed reporter deposition fluorescence <jats:italic>in situ</jats:italic> hybridization, and nanoscale secondary ion mass spectrometry. Our results reveal that sponge-associated AOA are mixotrophic, assimilating BCAA as an additional carbon and nitrogen source. This metabolic adaptation may modulate BCAA availability in the holobiont, potentially regulating the host's mTOR pathway. Collectively, our study reveals a novel nutritional interaction in sponge holobionts and challenges the perception of constrained metabolic capacities of AOA.</jats:p>},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {unpublished}

}

@unpublished{Lee2025b,

title = {Kinetic Plasticity of Nitrite-Oxidizing Bacteria Containing Cytoplasmic Nitrite Oxidoreductase},

author = {Ui-Ju Lee and Joo-Han Gwak and Christiana Abiola and Seongjun Lee and Jin-Sun Yu and Ok-Ja Si and Hyo Je Cho and Zhe-Xue Quan and Katharina Kitzinger and Holger Daims and Michael Wagner and Man-Young Jung and Sung-Keun Rhee},

url = {http://biorxiv.org/lookup/doi/10.1101/2025.07.31.663499},

doi = {10.1101/2025.07.31.663499},

year  = {2025},

date = {2025-07-22},

urldate = {2025-07-31},

publisher = {Cold Spring Harbor Laboratory},

abstract = {<jats:title>Abstract</jats:title> 

 <jats:p>Nitrite oxidation, the second step of nitrification, is essential to the global nitrogen cycle. Nitrite-oxidizing bacteria (NOB) are classified into two groups based on the cellular localization of their key enzyme nitrite oxidoreductase (NXR): periplasmic (pNXR) and cytoplasmic (cNXR). The use of a cNXR by NOB has been reported to be linked to a lower nitrite affinity and energy efficiency of nitrite oxidation, indicating adaptation to nitrogen-rich environments. In this study, cNXR NOB model strains demonstrated nitrite concentration-dependent shifts in optimal growth pH, a behavior not observed in pNXR NOB. <jats:italic>Nitrobacter winogradskyi</jats:italic> Nb-255 (cNXR NOB), grown at 1 mM nitrite (pH 7.5), exhibited a high nitrite affinity in terms of apparent <jats:italic>K</jats:italic> 

 <jats:sub>m</jats:sub> (25.9 μM) and a high specific affinity <jats:italic>a°</jats:italic> (440.5 l g cells<jats:sup>−1</jats:sup> h<jats:sup>−1</jats:sup>), both comparable to pNXR NOB in microrespirometry-based kinetic assays. Unexpectedly, cells pre-grown at 10 mM nitrite (pH 7.5) achieved a pNXR-like affinity at pH 5.5 without prior adaptation to acidic conditions. In contrast, pNXR NOB exhibited consistent kinetic behavior across different pH conditions. Kinetic inhibition in the presence of nitrate suggested that this plasticity is driven by a regulated interplay between nitrite uniport and nitrite/nitrate antiporter systems. Our findings indicate that <jats:italic>Nitrobacter</jats:italic> can dynamically modulate nitrite affinity in response to both nitrite concentration and pH, conferring a flexible adaptation strategy that features traits of both <jats:italic>r</jats:italic>-and <jats:italic>K</jats:italic>-strategists across a range of environmental conditions. This adaptive plasticity likely extends to other cNXR-containing NOB in response to fluctuating environmental conditions.</jats:p>},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {unpublished}

}

@unpublished{Gwak2025,

title = {Hypoosmolarity inhibits archaeal ammonia oxidation},

author = {Joo-Han Gwak and Adebisi Olabisi and Ui-Ju Lee and Christiana Abiola and Seongjun Lee and Hackwon Do and Yun Ji Choi and Jay-Jung Lee and Man-Young Jung and Nico Jehmlich and Martin Bergen and Michael Wagner and Samuel Imisi Awala and Zhe-Xue Quan and Sung-Keun Rhee},

url = {http://biorxiv.org/lookup/doi/10.1101/2025.07.07.663500},

doi = {10.1101/2025.07.07.663500},

year  = {2025},

date = {2025-07-07},

urldate = {2025-07-07},

publisher = {Cold Spring Harbor Laboratory},

abstract = {<jats:title>Abstract</jats:title> 

 <jats:p>Salinity strongly influences the physiology and distribution of nitrifying microorganisms, yet the effects of low salinity on them remain understudied. This study investigates the impact of hypoosmolarity on different groups of ammonia oxidizers in soil and lake environments, as well as in pure culture isolates. In soil microcosms amended with ammonium, at low salinity levels (∼120 μS/cm), comparable to values commonly found in pristine terrestrial and aquatic environments, the abundance of ammonia-oxidizing bacteria (AOB), dominated by <jats:italic>Nitrosomonas oligotropha</jats:italic>, significantly increased. In contrast, the growth of ammonia-oxidizing archaea (AOA), dominated by “<jats:italic>Ca.</jats:italic> Nitrosotenuis” of the <jats:italic>Nitrosopumilaceae</jats:italic> family, was stimulated by high salinity (∼760 μS/cm). In ammonium-fed lake microcosms, the abundance of AOB, dominated by <jats:italic>N. oligotropha,</jats:italic> significantly increased under both low (∼170 μS/cm) and high salinity (∼850 μS/cm) conditions. In the presence of allylthiourea, a bacterial nitrification inhibitor, AOA were sensitive to low salinity in both soil and lake microcosms. Consistently, pure culture studies revealed marked growth inhibition of AOA, especially members of <jats:italic>Nitrosopumilaceae</jats:italic>, under hypoosmolarity, unlike AOB and complete ammonia oxidizer (comammox) strains. Comparative genomic analyses with AOB and comammox, along with transcriptomic studies, suggested that the sensitivity of AOA to hypoosmolarity stress was possibly due to a lack of sophisticated osmoregulatory transport systems and their S-layer cell wall structure. Overall, this study highlights hypoosmolarity as a key factor shaping the ecological niches and distribution of ammonia oxidizers, as well as nitrification activities, in terrestrial and aquatic environments that are increasingly affected by intensified water cycles due to climate change.</jats:p>},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {unpublished}

}