Biology subjects

Niehaus, K.

Publications and source records attributed to Niehaus, K..

6 recordsLinked to original sources

bioRxiv2026

Tuning into xanthan: A conserved yet flexible polysaccharide utilization system in Microbacterium

Bacteria encounter structurally complex extracellular polysaccharides in natural environments, yet the regulatory and evolutionary basis of their utilization remains poorly understood. Here, we isolated a soil-derived Microbacterium strain, named Microbacterium xanthanicum UB-LE1, that grows on xanthan as the sole carbon source. We dissected the genetic and regulatory architecture underlying this capability. Genome sequencing combined with transcriptomic and proteomic profiling uncovered a discrete, strongly inducible regulon associated with xanthan utilization, encoding 23 proteins with five secreted proteins and three candidate transcriptional regulators. DNA-affinity purification sequencing confirmed two regulators binding to operons within the xanthan utilization locus. Comparative genomics across the Microbacteriaceae revealed conserved and lineage-specific features of this system and supports recent acquisition and modular integration of the locus, with at least two predominant architectural variants possibly shaped by substrate availability and ecological specialization. Coordinated induction at both the transcript and protein levels, together with two experimentally validated regulators, points to tight regulatory control of complex polysaccharide degradation in Microbacterium xanthanicum UB-LE1. Together, these findings provide mechanistic and evolutionary insight into how bacteria adapt to complex extracellular carbohydrates, expand current knowledge of xanthan turnover in microbial ecosystems, and establish a framework for exploring the emergence and diversification of specialized polysaccharide utilization pathways across bacterial taxa. IMPORTANCEMicroorganisms are central drivers of carbon turnover in soils and other terrestrial ecosystems, determining the availability of nutrients and shaping microbial community structure. A significant portion of soil carbon is contained in extracellular polysaccharides, yet the pathways by which microorganisms degrade these complex polymers remain poorly understood. Xanthan, a structurally complex and widely produced microbial exopolysaccharide, represents a persistent and largely overlooked carbon pool. By dissecting the genetic, regulatory, and evolutionary basis of xanthan utilization in Microbacterium xanthanicum UB-LE1, this study advances our understanding of how soil bacteria adapt to complex extracellular carbohydrates and how substrate availability shapes the emergence and diversification of specialized metabolic pathways. Importantly, the identification of additional xanthan-active enzymes and regulatory components in M. xanthanicum UB-LE1 opens opportunities for targeted modification of xanthan structure and properties, paving the way for new biotechnological applications in food, materials, and industrial biotechnology, while linking microbial ecology to functional innovation.

microbiology↗

bioRxiv2026

Paleometabolomics reveals impacts of abiotic factors on rodent midden metabolism over the last 50,000 years.

Metabolomics and paleoecology combined can reveal how past ecosystems worked, helping us predict future changes more accurately. Pioneering studies are needed to shed light on the potential of the so-called paleometabolomics and to standardise its application. Here, we deployed an untargeted metabolomic workflow on a timeline (200 to 49,600 cal yr BP) of rodent middens that efficiently and reproducibly captured rodent midden metabolic diversity, recovering 79% of the richness detected in 15 contemporary plant species. We found that midden chemical diversity and metabolites were influenced by the midden composition, age, and environment. Variation at the metabolite level in middens could fit age, past temperature and precipitation levels with an R{superscript 2} > 88% and their plant composition. Compounds and families responding to climate variation included lipids (e.g. glycerophospholipids) and other metabolites linked to redox status such as phenolics (e.g. flavonoids, lignans). The responses of significant midden chemical indices and compounds to abiotic pressures were supported by their response in plants collected near the midden sites to temperature and soil water content across an elevation gradient. Overall, our results not only showcase paleometabolomics as a powerful tool to reconstruct past ecosystem dynamics and metabolic evolutionary trajectories, but also to uncover relevant chemical families that could serve as trackers of past -and potentially future- climate fluctuations.

ecology↗

bioRxiv2024

Study of excess manganese stress response highlights the central role of manganese exporter Mnx for holding manganese homeostasis in the cyanobacterium Synechocystis sp. PCC 6803

Cellular levels of the essential micronutrient manganese (Mn) need to be carefully balanced within narrow boarders. In cyanobacteria, sufficient Mn supply is critical for assuring the function of the oxygen-evolving complex as central part of the photosynthetic machinery. However, Mn accumulation is fatal for the cells. The reason for the observed cytotoxicity is unclear. To understand the causality behind Mn toxicity in cyanobacteria, we investigated the impact of excess Mn on physiology and global gene expression in the model organism Synechocystis sp. PCC 6803. We compared the response of the wild type and the knock-out mutant in the manganese exporter (Mnx), {Delta}mnx, which is disabled in the export of surplus Mn and thus functions as model for toxic Mn overaccumulation. While growth and pigment accumulation in {Delta}mnx was severely impaired 24 h after addition of 10-fold Mn, the wild type was not affected and thus mounted an adequate transcriptional response. RNA-seq data analysis revealed that the Mn stress transcriptomes were partly resembling an iron limitation transcriptome. However, the expression of iron limitation signature genes isiABDC was not affected by the Mn treatment, indicating that Mn excess is not accompanied by iron limitation in Synechocystis. We suggest that the Ferric uptake regulator, Fur, gets partially mismetallated under Mn excess conditions and thus interferes with an iron-dependent transcriptional response. To encounter mismetallation and other Mn-dependent problems on protein level, the cells invest into transcripts of ribosomes, proteases, and chaperones. In case of the {Delta}mnx mutant the consequences of the disability to export excess Mn from the cytosol manifest in additionally impaired energy metabolism and oxidative stress transcriptomes with fatal outcome. This study emphasizes the central importance of Mn homeostasis and the transporter Mnxs role in restoring and holding it.

microbiology↗

bioRxiv2023

Head and neck cancer cells terminally differentiate reflecting their tissue of origin: a rationale for differentiation therapies

BackgroundHuman papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have striking tumor-targeting potential. MethodsWe modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by RNA-seq and ATAC-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations. ResultsHNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem-cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue and dysplastic mucosa. Cornification was observed to frequently surround necrotic and immune-infiltrated areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators were found to activate the HNSCC cell differentiation program. ConclusionsDistinct cell differentiation states create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection.

cancer biology↗

bioRxiv2019

The small GTPase Rab11F represents a molecular marker within the secretory pathway required for the nitrogen-fixing symbiosis

The nitrogen-fixing root nodule is generally derived through a successful symbiotic interaction between legume plants and bacteria of the genus Rhizobium. A root nodule shelter hundreds of Rhizobia, which are thought to invade into the plant cells through an endocytosis-like process despite the existence of turgor pressure. Each invading Rhizobium is surrounded by the peribacteroid membrane to form the symbiosome, which results in the higher acquisition of host membrane materials. In this study, we show the localization of Rab11F, a RabA6b homolog with the large Rab-GTPase family, which was highly expressed in root nodules of Medicago sativa and M. truncatula. Rab11F-labeled organelles accumulated the membrane specific dye FM4-64 and were sensitive to Brefeldin A by forming aggregates after treatment with this drug. By co-localization with the cis-Golgi marker, GmMan1-mCherry, Rab11F-organelles formed tri-colored organelles, whereby Rab11F was located to the opposite side of GmMan1-mCherry indicating that Rab11F-labeled structures were localized within the trans-Golgi network (TGN). In root nodules, Rab11F was localized transiently at the infection thread-covering membrane on the side of infection droplets and the peribacteroid membranes. The symbiosome acquires Rab11F during the entry process and differentiation. However, the symbiosome did not recruit Rab11F after cessation of division. In conclusion, the legume plant seemed to use a specialized secretion pathway from the TGN, which was marked by Rab11F, to proliferate the symbiosome membrane.

plant biology↗

bioRxiv2018

Machine learning enables detection of early-stage colorectal cancer by whole-genome sequencing of plasma cell-free DNA

BackgroundBlood-based methods using cell-free DNA (cfDNA) are under development as an alternative to existing screening tests. However, early-stage detection of cancer using tumor-derived cfDNA has proven challenging because of the small proportion of cfDNA derived from tumor tissue in early-stage disease. A machine learning approach to discover signatures in cfDNA, potentially reflective of both tumor and non-tumor contributions, may represent a promising direction for the early detection of cancer.\n\nMethodsWhole-genome sequencing was performed on cfDNA extracted from plasma samples (N=546 colorectal cancer and 271 non-cancer controls). Reads aligning to protein-coding gene bodies were extracted, and read counts were normalized. cfDNA tumor fraction was estimated using IchorCNA. Machine learning models were trained using k-fold cross-validation and confounder-based cross-validation to assess generalization performance.\n\nResultsIn a colorectal cancer cohort heavily weighted towards early-stage cancer (80% stage I/II), we achieved a mean AUC of 0.92 (95% CI 0.91-0.93) with a mean sensitivity of 85% (95% CI 83-86%) at 85% specificity. Sensitivity generally increased with tumor stage and increasing tumor fraction. Stratification by age, sequencing batch, and institution demonstrated the impact of these confounders and provided a more accurate assessment of generalization performance.\n\nConclusionsA machine learning approach using cfDNA achieved high sensitivity and specificity in a large, predominantly early-stage, colorectal cancer cohort. The possibility of systematic technical and institution-specific biases warrants similar confounder analyses in other studies. Prospective validation of this machine learning method and evaluation of a multi-analyte approach are underway.

cancer biology↗