Biology subjects

Fuchs, L.

Publications and source records attributed to Fuchs, L..

4 recordsLinked to original sources

bioRxiv2026

Gut microbiota within-host evolution enforces colonization resistance against enteric infection

Limited resource availability in the gut promotes competitive interactions between bacteria, which drive adaptive within-host evolution (1-3). While adaptive evolution of bacterial communities has been increasingly studied in the recent years (4-7), its functional implications for host physiology remain unknown. Here, we show that within-host evolution of the human commensal Enterococcus faecalis boosts colonization resistance to enteric Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. During gut colonization, E. faecalis evolves the ability to metabolize fructoselysine, an abundant Amadori rearrangement product generated by thermal food processing. The depletion of this diet-derived nutrient prevents S. Typhimurium colonization by restricting an essential resource. This protective mechanism was conserved across independent mouse colonies and arises via diverse evolutionary trajectories, including nucleotide polymorphisms, gene amplifications, and a horizontal gene transfer event. Additionally, analysis of E. faecalis isolates from human infants revealed that adaptation to fructoselysine availability occurs in a diet-dependent manner. Isolates from infants fed with fructoselysine-rich formula were able to utilize fructoselysine, whereas those from infants fed with fructoselysine-poor breast milk were not. Conclusively, our results identify an inherent microbiome-driven self-healing mechanism, wherein bacterial evolution restores colonization resistance against enteric pathogens through evolved nutrient depletion. Understanding these evolutionary dynamics will inform microbiome-targeted approaches to prevent and treat infectious diseases by harnessing adaptive bacterial metabolism.

microbiology↗

bioRxiv2025

The Gfr uptake system provides a context-dependent fitness advantage to Salmonella Typhimurium SL1344 during the initial gut colonization phase

Salmonella enterica serovar Typhimurium (S. Tm) is a major cause of foodborne diarrhea. However, in healthy individuals, the microbiota typically restricts the growth of incoming pathogens, a protective mechanism termed colonization resistance (CR). To circumvent CR, Salmonella strains can utilize private nutrients that remain untapped by the resident microbiota. However, the metabolic pathways and environmental niches promoting pathogen growth are still not completely understood. Here, we investigate the significance of the gfr operon in gut colonization of S. Tm, which is essential for the utilization of fructoselysine (FL) and glucoselysine (GL). These Amadori compounds are present in heated foods with high protein and carbohydrate contents, particularly in Western-type diets. We detected FL in both mouse chow and the intestinal tract of mice and showed that gfr mutants are attenuated during the initial phase of colonization in the murine model. Experiments in gnotobiotic mice and competition experiments with Escherichia coli suggest that gfr-dependent fitness advantage is context-dependent. We conclude that dietary Amadori products like FL can support S. Tm gut colonization, depending on the metabolic capacities of the microbiota.

microbiology↗

bioRxiv2024

Demonstrating Soft X-Ray Tomography in the lab for correlative cryogenic biological imaging using X-rays and light microscopy

Soft X-ray tomography (SXT) enables native-contrast three-dimensional (3D) imaging of fully hydrated, cryogenically preserved biological samples, revealing ultrastructural details without the need for staining, embedding, or sectioning. Traditionally available only at synchrotron facilities, recent advances in laser-driven plasma sources have led to the development of compact soft X-ray microscopes, such as the SXT-100. The SXT-100 achieves imaging resolutions down to 54 nm full-pitch, with tomograms acquired in 30 minutes to two hours. Integrated with an epifluorescence microscope, the SXT-100 facilitates correlative workflows by bridging fluorescence and electron microscopy while preserving the structural integrity of vitrified samples. We demonstrate the capabilities of the SXT-100 through various use cases, including imaging Euglena gracilis, Saccharomyces cerevisiae yeast cells, and nanoparticles in mammalian cells. The relatively short tomogram acquisition times, the virtually non-destructive nature of soft X-ray tomography, and its quantitative imaging capabilities underscore its potential as a powerful tool for advanced biological imaging. Future developments promise enhanced throughput and deeper integration with emerging correlative imaging modalities, and a wider variety of sample types including tissue.

biophysics↗

bioRxiv2019

Identification of the best index case significantly improves mutation detection rates in families with hereditary breast and ovarian cancer

To date, a disease-causing mutation can be found in 15-30% of families with hereditary breast and ovarian cancer (HBOC) and it is believed that more than half of the cases still remain unsolved. Usually it is intended to perform genetic analyses in the family member with the most severe phenotype, which, however, may not always be possible. Moreover, no standard criteria have been established to define the person who is most suitable for genetic testing within a family: the best index case. We therefore established clinical criteria to identify the best index case in HBOC and analyzed the impact on genetic testing. 130 patients who presented at our department from 2016 to 2018 were divided into two groups. In group A (N = 98) genetic analyses were performed in the best index case based on our criteria. In group B (N = 32) at least one other family member was considered a better index case. The detection rate of expected mutations was significantly higher for group A (64.3% vs. 32.0%, p = 0.034) while there was no significant difference of calculated mutation carrier risks between these groups. We conclude that the mutation detection rate in families with HBOC is notably higher after identifying the best index case for genetic testing according to the clinical selection criteria reported here.

genetics↗