Biology subjects

Sauer, U.

Publications and source records attributed to Sauer, U..

At least 19 recordsLinked to original sources

bioRxiv2026

Metabolic cascades drive spatial prebiotic fermentation in a defined gut consortium

Dietary fiber deficiency shifts the gut microbiota to degrade host mucus, compromising intestinal homeostasis. Mechanistically linking in vitro metabolic dynamics of fiber degradation to in vivo outcomes remains challenging due to a lack of representative model systems. Introducing spatial mucin structures to a defined Oligo-Mouse-Microbiota (OMM12) in vitro consortium allowed us to recapitulate the spatio-temporal dynamics of xylooligosaccharide (XOS) processing in gnotobiotic mice. XOS supplementation rapidly established a stable community state in vitro and in vivo across compositional, metabolic and transcriptional levels. XOS supplementation established distinct functional guilds: Bifidobacterium animalis and Blautia coccoides partitioning xylose and arabinose catabolism, whilst profiting from XOS degradation by Bacteroides caecimuris. Along the colonic axis, a spatial XOS gradient exposes Bl. coccoides's substrate preference for xylose and drives longitudinal functional adaptations. Altogether, our predictive platform proves that regional microenvironments govern prebiotic efficacy, highlighting spatial cascades as essential parameters for targeted microbiome interventions.

microbiology↗

bioRxiv2026

Crossfeeding interactions in a minimal marine chitin-degrading community

Communities of heterotrophic particle-associated marine bacteria contribute to oceanic carbon cycling through interspecies interactions that can influence polysaccharide degradation. While these interactions have been extensively studied using single natural isolates or pairwise combinations thereof, their mechanistic relevance within multispecies communities remains unclear. To address this gap, we developed MCC4, a minimal chitin-degrading bacterial community consisting of two chitin degraders and two non-degrading isolates that represent globally prevalent marine bacterial taxa. We show that the community remains stable across ten growth-dilution cycles, establishing a reproducible model for controlled multi-isolate experiments. Using transcriptomic and metabolomic analyses combined with metabolite supplementation assays, we uncovered the underlying crossfeeding network. While one degrader drives chitin degradation, the other exploits chitin monomers and chitooligomers generated by the main degrader. The two non-degraders are sustained by consuming deacetylated chitin monomers, 2-carbon compounds, nucleotides, and branched-chain amino acids, likely released by degraders. Community assembly is driven by competitive scavenging abilities, potentially complemented by specific survival strategies such as increased motility and deployment of type VI secretion systems. Despite its simplicity, MCC4 captures dynamic microbial interactions characteristic of natural marine ecosystems. It offers a tractable, reproducible framework for investigating how environmental perturbations impact community function and testing ecological theories in particle-associated marine environments.

microbiology↗

bioRxiv2026

Microbiota during early life windows orchestrates intestinal maturation and barrier formation in the offspring

There is a critical window in early life for immune development that prepares a young mammal for postnatal exposure to environmental, dietary and microbial antigens. Both the maternal microbiota and endogenous colonization have emerged as pivotal drivers in this process. Using gnotobiotic mouse models and reversible colonization to model the effects of the maternal microbiota during pregnancy compared with early life colonization on the small intestinal epithelium we show that both microbial metabolites originating from the maternal microbiota and the postnatal endogenous microbiota drive intestinal epithelial maturation by modulating epigenetic signatures. Microbiota-derived signals from both the pregnant mother and from endogenous postnatal colonisation drove the BLIMP1-guided epithelial neonatal-to-adult transition at weaning through epigenetic mechanisms and direct transcriptional effects. These microbial signals also shaped the developmental trajectory of barrier-forming tight junctional claudins in the neonatal intestine, increased aerobic respiration, and increased the gene expression of xenosensors. Thus, both maternal and endogenous microbiota derived drivers of the offspring's epigenetic and transcriptomic intestinal epithelial landscape fine-tuned the timing of epithelial maturation and augmented functional plasticity at weaning.

microbiology↗

bioRxiv2026

Negative and neutral interactions are prevalent in interactions between marine chitin degraders

Bacterial chitin degradation contributes to global carbon cycling, particularly in marine environments where it is a highly abundant polysaccharide. Despite the taxonomic diversity of co-occurring chitin-degrading bacteria, the influence of individual traits on interactions between them remains poorly understood. Here, we measured key physiological traits of seven chitin degraders and investigated how these traits shape interaction outcomes and chitin degradation in pairwise cocultures. We found mainly negative and neutral interactions among degraders, contrasting with the synergistic dynamics observed with other complex polysaccharides. However, chitin degradation was not consistently diminished. These interaction types could be attributed to the limited partitioning of degradation products, alongside variations in enzyme repertoires and attachment behaviours that help some degraders to prevail over others. Further, we showed that one degrader can strongly inhibit the growth of others, even those possessing favourable physiological traits, likely due to the secretion of inhibitory compounds. These findings extend our understanding of the breadth of interactions among primary polysaccharide degraders and their implications for the degradation process. One-sentence SummaryThe physiological traits of bacteria that degrade chitin, a highly abundant biopolymer in marine environments, promote a range of neutral and negative interactions among them.

microbiology↗

bioRxiv2026

D-gluconate drives Salmonella growth during acute and chronic infection

Monosaccharides support Salmonella enterica serovar Typhimurium colonization of the gut, yet the role of their oxidized derivatives remains understudied. Sugar acids are largely diet-independent carbon sources generated by host-driven oxidative processes, but their contribution during infection - particularly that of less oxidized aldonic and uronic acids - has not been defined. Here, we systematically assess the role of sugar acids derived from D-glucose and D-galactose in S. Typhimurium SL1344 colonization. Among D-glucose-derived acids, D-gluconate accumulated to the highest levels and was the dominant substrate supporting luminal expansion in streptomycin-pretreated mice, exceeding the more oxidized acids D-glucuronate and D-glucarate. During chronic infection, D-glucose-derived sugar acids became increasingly important for pathogen persistence. Ecological niche invasion assays identified these compounds as a principal metabolic niche, whereas D-galactose-derived acids contributed minimally. Consistent with a transient, inflammation-linked nutrient niche, sugar acid utilization pathways were similarly prevalent in Escherichia coli from individuals with and without inflammatory bowel disease. Together, these findings identify D-gluconate as a key inflammation-dependent nutrient source that fuels Enterobacteriaceae expansion in the inflamed gut.

microbiology↗

bioRxiv2025

A division of labor controls the degradation of fucoidans in the ocean

Fucoidans--complex polysaccharides produced by brown algae and diatoms--contribute to long-term carbon sequestration due to their resistance to microbial degradation1,2. While individual microbes can break down portions of these polymers3-5, it remains unclear whether complete breakdown is possible in nature and, if so, by what mechanisms. Here we show that fucoidans are degraded through synergistic interactions between specialized bacteria with conserved metabolic functions. Using metabolomic analysis of a reconstructed marine consortium, we uncovered functional guilds of bacteria that target either the sulfated fucose backbone or the side-branches of rare monomers. This division of labor leads to an unexpectedly high number of positive interactions between different degraders that enhanced degradation efficiency up to 97.1%. Despite variation in fucoidan structure across different types of algae, the metabolic functions of degraders remained conserved, enabling quantitative prediction of degradation outcomes based on community composition. Our findings suggest that the environmental turnover of complex macromolecules depends not only on individual metabolic capabilities but also on ecological interactions shaped by substrate architecture. This work provides a mechanistic framework for understanding carbon cycling in the ocean and for engineering synthetic microbial consortia to degrade recalcitrant polysaccharides.

microbiology↗

bioRxiv2025

Deep sea anaerobic microbial community couples the degradation of insoluble chitin to extracellular electron transfer

Chitin is a major structural component of arthropod exoskeletons, and an important carbon and nitrogen source in marine environments. In anoxic sediments, its degradation generates chitooligosaccharides and N-acetylglucosamine (GlcNAc), which are fermented into smaller organic molecules and oxidized anaerobically using soluble electron acceptors or insoluble ones such as metal oxides. To date, many aspects of chitin degradation in deep-sea anoxic sediments have been overlooked, including the potential coupling of insoluble chitin degradation to metal oxide reduction, the involvement of extracellular electron transfer (EET), and the spatial organization of the microorganisms involved. Using anoxic deep-sea sediments recovered from a whale fall site, we developed an innovative workflow based on electrochemical reactors, to characterize chitin degradation in these environments. Sediment samples enriched on poorly crystalline iron oxides, and subsequently transferred into an electrochemical reactor poised at +0.22 V vs SHE, showed active anodic current production when supplied with chitin, which increased 2-fold when amended with GlcNAc. Chitin reactors were dominated by Vallitalea (Firmicutes), Spirochaetota, Gammaproteobacteria and Desulfobacterota. Exoenzyme activity assays, metabolite profiling, and continued anodic current production confirmed ongoing chitin degradation linked to EET. We observed metabolic associations between chitin degraders and secondary consumers using in situ imaging (16S rRNA gene FISH coupled with BONCAT and nanoSIMS). These microbial partners, within the electrode-attached community, required close proximity to the poised electrode ([≤] 10 {micro}m) to remain metabolically active. Supporting these observations, cultured isolates of Vallitalea sp. and Trichloromonas sp. recovered from the whale fall site exhibited chitin degradation and electrochemical activity, respectively. When co-cultured in an bioelectrochemical reactor, the acetate produced by Vallitalea sp. during chitin degradation fueled Trichloromonas sp., which facilitated EET, hereby demonstrating that syntrophic interactions are used to couple anoxic chitin degradation to EET in deep-sea sediments. These findings exemplify the interspecies interactions and resource optimization occurring in hard-to-reach and largely unknown deep-sea ecosystems.

microbiology↗

bioRxiv2025

Predicting input signals of transcription factors in Escherichia coli through metabolomics and transcriptomics

The activity of bacterial transcription factors (TFs) is typically modulated through direct interactions with small molecules. However, these input signals remain unknown for most TFs, even in well-studied model bacteria. Identifying these signals typically requires tedious experiments for each TF. Here, we develop a systematic workflow for the identification of TF input signals in bacteria based on metabolomics and transcriptomics data. We inferred the activity of 173 TFs from published transcriptomics data and determined the abundance of 279 metabolites across 40 matched experimental conditions in Escherichia coli. By correlating TF activities with metabolites abundances, we successfully identified previously known TF-metabolite interactions and predicted novel TF effector metabolites for 41 TFs. To validate our predictions, we conducted in vitro assays and confirmed a predicted effector metabolite for LeuO. As a result, we established a network of 80 regulatory interactions between 71 metabolites and 41 E. coli TFs. This network includes 76 novel interactions that encompass a diverse range of chemical classes and regulatory patterns, bringing us closer to a comprehensive TF regulatory network in E. coli.

microbiology↗

bioRxiv2025

Extracellular polymeric substance degradation shapes microbial community diversity

Competition for and exchange of nutrients play crucial roles in shaping microbial community function and dynamics. Although cross-feeding of small metabolites is known to drive carbon exchange among species, the importance of self-produced extracellular polymeric substances (EPS)-- which include proteins, polysaccharides, DNA, and humic-like substances-- remains less understood. Utilizing chitin-degrading microbial isolates and natural seawater communities, we found that 4-7% of the carbon from chitin degradation is converted into EPS, accounting for nearly a quarter of the exuded carbon. Different sources of EPS were found to select for distinct microbial communities. Through enzyme assays and untargeted metabolomics, we demonstrated that secreted enzymes degrade EPS in multiple steps that influence community diversity: larger oligomers are initially utilized by specialized degraders, while the subsequent breakdown into smaller oligomers, monosaccharides, and amino acids supports non-specialized consumers. These findings highlight the role of EPS as a significant carbon source exchanged between microbes, fueling metabolically diverse populations and enriching our understanding of carbon-mediated microbial interactions.

microbiology↗

bioRxiv2025

Growth in Low Carbon Conditions Reveals Amino-Acid-Coupled Iron Uptake

Bacteria in nature encounter substrates at widely varying concentrations, yet studies of bacterial physiology have focused more on nutrient type than concentration, partly due to challenges in maintaining low concentrations. We developed a Millifluidic Continuous Culture Device (MCCD) to culture bacteria under precisely controlled nutrient conditions, including very low concentrations, in a manner suitable for proteomic analysis. Using the MCCD, we cultured Escherichia coli with a mixture of amino acids as the sole carbon source at three concentrations supporting growth rates spanning a fivefold range. Surprisingly, at the lowest concentration, cells exhibited proteomic signatures of iron shortage despite equal iron levels across conditions. We observed the uptake of labeled iron-histidine and iron-cysteine complexes, indicating that amino acids facilitated iron acquisition and that amino-acid-bound iron is bioavailable to E. coli. These findings reveal a previously unknown mechanism of bacterial iron acquisition that emerged under the flow imposed by the MCCD, which likely diluted the siderophore pool and reduced their efficacy. This work highlights the importance of studying bacterial physiology under low nutrient concentrations and demonstrates how physical conditions, such as flow, shape microbial nutrient acquisition strategies.

microbiology↗

bioRxiv2025

Bacteroidales T6SS minor Hcp subunits form heteromers recognising effectors

The type VI secretion system (T6SS) is a macromolecular protein complex found in Gram-negative bacteria that mediates intercellular antagonism. T6SSs are gut colonization factors that influence gut biodiversity. Hemolysin-coregulated proteins (Hcp) are major structural proteins in these systems. Hcp forms hexameric rings that stack to create an inner tube structure essential for translocating effector proteins into target cells. In Bacteroidales, T6SS loci encode multiple Hcp proteins with unknown function. The gut commensal Bacteroides fragilis encodes five Hcp subunits (sHcp and Hcp1-4) that have low sequence similarity. In this study, we investigated the roles of these proteins. Interaction studies showed that sHcp forms homohexamers, which is consistent with a major role of forming the bulk of the inner tube. In contrast, the less abundant minor Hcp1-4 were shown to form an interaction network involving heteromeric complexes. Biochemical analyses demonstrated that Hcp1 and Hcp2 assemble into heterohexamers and that this complex recognizes the secreted effector Bte1. Finally, we showed that Hcp modules, which are encoded in highly syntenic regions in T6SS loci of Bacteroidales, cluster with effectors. These results imply that the minor Hcps genetically cosegregate with cognate effectors, contributing to effector cassette variability. Thus, minor Hcp subunits function as recognition particles for effectors to mediate secretion, which appears to be a conserved trait in Bacteroidales T6SSs. Exploiting these features could facilitate the characterization of unknown effectors by copurifying them with their cognate Hcps. This approach may reveal new insights into bacterial interactions and the mechanisms that establish gut biodiversity.

biochemistry↗

bioRxiv2024

Competition strategies driving resource partitioning in chitin degrading communities

Resource competition strongly shapes microbial community dynamics and function. In polysaccharide-degrading communities, primary degraders secrete monomer-releasing enzymes and exploiters consume released products without investing in enzymes. By investigating competitive strategies between chitin degraders and N-acetylglucosamine (GlcNAc) exploiters, we uncover several interacting factors, including GlcNAc liberation rates, diffusive loss, and resource partitioning between competitors, which determine community viability and growth dynamics at early stages of degradation. Aside from cases involving antibiotic secretion or aggregation on particles to privatize degrading enzymes, exploiters also inhibit degraders by siphoning away limiting GlcNAc flux during early stages of particle degradation, when degraders must overcome diffusive GlcNAc loss to sustain chitinase production. Analogous to the Allee effect in population biology, these effects lead to sensitive dependences on initial species densities for a community to thrive. This study elucidates how metabolic competition at early stages of particle degradation shapes species interactions, resource partitioning, and ultimately community viability.

microbiology↗

bioRxiv2024

Selective preservation of fucose-rich oligosaccharides in the North Atlantic Ocean

The ocean has a substantial capacity to store carbon dioxide fixed via photosynthesis in dissolved organic molecules. An estimated 20% of the 660 Gt dissolved organic carbon in the ocean pool consists of structurally uncharacterized oligosaccharides, which appear to resist microbial degradation (Aluwihare et al., 1997). Current technologies lack the sensitivity and molecular resolution to identify these oligosaccharides. Here, we adapted graphitized carbon chromatography to extract and separate marine oligosaccharides for liquid chromatography high resolution mass spectrometry analysis. Using a newly-developed de novo annotation tool, we found 110 oligosaccharide structures in surface and deep ocean seawater at two distant locations in the North Atlantic Ocean. One group of the detected oligosaccharides was found only in surface seawater and consisted of larger and more abundant molecules detected by our analysis. A second group of smaller, less abundant oligosaccharides was detected in both the surface and deep ocean seawater of both sampled locations. The composition of oligosaccharides differed between the surface and deep ocean, with deep ocean samples relatively enriched in hard-to-metabolize deoxy-sugars, and xylose, amino sugars and uronic acids compared to simple hexoses. Notably the deoxy-sugar fucose constituted 35-40% of the monomers in deep-sea oligosaccharides, twice the percentage in surface ocean oligosaccharides. The ubiquity of deep ocean oligosaccharides indicates that they represent a preserved fraction of the carbohydrate pool. Their enrichment in specific monosaccharides suggests selective preservation of fucose-rich oligosaccharides in the deep ocean.

ecology↗

bioRxiv2024

Monosaccharides Drive Salmonella Gut Colonization in a Context-Dependent Manner

The carbohydrates that fuel gut colonization by S. Typhimurium are not fully known. To investigate this, we designed a quality-controlled mutant pool to probe the metabolic capabilities of this enteric pathogen. Using WISH-barcoding, we tested 35 metabolic mutants across five different mouse models, allowing us to differentiate between context-dependent and context-independent nutrient sources. Results showed that S. Typhimurium uses D-glucose, D-mannose, D-fructose, and D-galactose as context-independent carbohydrates across all models. The utilization of N-acetylglucosamine and hexuronates, on the other hand, was context-dependent. Furthermore, we showed that D-fructose is important in strain-to-strain competition between Salmonella serovars. Complementary experiments confirmed that D-glucose, D-fructose, and D-galactose are excellent niches for S. Typhimurium to exploit during colonization. Quantitative measurements revealed sufficient amounts of D-glucose and D-galactose in the murine cecum to drive S. Typhimurium colonization. Understanding these key substrates and their context-dependent use by enteric pathogens will inform the future design of probiotics and therapeutics to prevent diarrheal infections such as non-typhoidal salmonellosis.

microbiology↗

bioRxiv2024

Polysaccharide quantification using microbial enzyme cocktails

Polysaccharide quantification plays a vital role in understanding ecological and nutritional processes in microbes, plants, and animals. Traditional methods hydrolyze these large molecules into monomers, but these approaches are restricted to chemically hydrolysable polysaccharides. Enzymatic degradation is a promising alternative but typically requires the use of characterized recombinant enzymes or microbial isolates that secrete enzymes. In this study, we introduce a versatile method that employs undefined enzyme cocktails secreted by individual microbes or complex environmental microbial communities for the hydrolysis of polysaccharides. We focus on colloidal chitin and laminarin as representative polysaccharides of ecological relevance. Our results demonstrate that colloidal chitin can be effectively digested with an enzyme cocktail derived from a chitin-degrading Psychromonas sp. isolate. Utilizing a 3,5-dinitrosalicylic acid reducing sugar assay or liquid chromatography-mass spectrometry for mono- and oligomers detection, we successfully determined chitin concentrations as low as 62 mg/L and 15 mg/L, respectively. This allows for effective monitoring of microbial chitin degradation. To extend the applicability of our method, we also leveraged complex, undefined microbial communities as sources of enzyme cocktails capable of degrading laminarin. With this approach, we achieved a detection limit of 30 mg/L laminarin through the reducing sugar assay. Our findings highlight the potential of utilizing enzyme cocktails from both individual microbes and, notably, from undefined microbial communities for polysaccharide quantification. This advancement addresses limitations associated with traditional chemical hydrolysis methods.

microbiology↗

bioRxiv2023

Peroxiredoxinylation buffers the redox state of the proteome upon cellular stress

The redox state of proteins is essential for their function and guarantees cell fitness. Peroxiredoxins protect cells against oxidative stress, maintain redox homeostasis, act as chaperones and transmit hydrogen peroxide signals to redox regulators. Despite the profound structural and functional knowledge of peroxiredoxins action, information on how the different functions are concerted is still scare. Using global proteomic analyses, we show here that the yeast peroxiredoxin Tsa1 binds hundreds of proteins of essential biological processes, including protein turnover and carbohydrate metabolism. Several of these interactions are of covalent nature and failure of this peroxiredoxinylation leads to global changes in the metabolome and reduced stress resistance. Thioredoxins directly remove TSA1-formed mixed disulfide intermediates, thus expanding the role of the thioredoxin-peroxiredoxin redox cycle pair to buffer the redox state of proteins in an unprecedented way.

biochemistry↗

bioRxiv2023

Long-term history dependence of growth rates of E. coli after nutrient shifts

According to a widely accepted paradigm of microbiology, steady-state growth rates are determined solely by current growth conditions1-3 and adaptations between growth states are rapid, as recently recapitulated by simple resource allocation models4. However, even in microbes overlapping regulatory networks can yield multi-stability or long-term cellular memory. Species like Listeria monocytogenes5 and Bacillus subtilis "distinguish" distinct histories for the commitment to sporulation6, but it is unclear if these states can persist over many generations. Remarkably, studying carbon co-utilization of Escherichia coli, we found that growth rates on combinations of carbon sources can depend critically on the previous growth condition. Growing in identical conditions, we observed differences in growth rates of up to 25% and we did not observe convergence of growth rates over 15 generations. We observed this phenomenon occurs across combinations of different phosphotransferase (PTS) substrates with various gluconeogenic carbon sources and found it to depend on the transcription factor Mlc.

microbiology↗

bioRxiv2023

Overall biomass yield of multiple nutrient sources

Microorganisms utilize nutrients primarily to generate biomass and replicate. When a single nutrient source is available, the produced biomass increases linearly with the initial amount of the available nutrient. This linear trend can be predicted to high accuracy by "black box models" that consider growth as a single chemical reaction with nutrients as substrates and biomass as a product. Since natural environments typically feature multiple nutrients, we here quantify the effect of co-utilization of multiple nutrients on bacterial biomass production. First, we demonstrate a mutual effect between the metabolism of different nutrient sources where the ability to utilize one is affected by the other. Second, we show that for some nutrient combinations, the produced biomass is no longer linear to the initial amount of nutrients. These observations cannot be explained by the traditional "black box models", presumably because the metabolism of one nutrient affects another, which is not accounted for by these models. To capture these observations, we extent "black box models" to include catabolism, anabolism, and biosynthesis of biomass precursors and phenomenologically add a mutual effect between the metabolism of the nutrient sources. The expanded model qualitatively recaptures the experimental observations and, unexpectedly, predicts that the produced biomass is not only dependent on the combination of nutrient sources but also on their relative initial amounts. We validate this prediction experimentally by demonstrating how measurement of the produced biomass can be used to determine how each nutrient effects the metabolic processes of another.

microbiology↗