Biology subjects

Moser, D.

Publications and source records attributed to Moser, D..

10 recordsLinked to original sources

bioRxiv2026

A membrane-anchored inhibitor of papain-like cysteine proteases promotes Pseudomonas root colonization

Pseudomonas species, spanning both beneficial and pathogenic lifestyles, possess conserved mechanisms to modulate plant immunity. Nevertheless, the mechanisms by which commensal bacteria establish and maintain host colonization remain poorly understood. Here, we report the characterization of a Pseudomonas chagasin-like protease inhibitor (Cpi1), conserved across pseudomonads representing a novel class of membrane-anchored PLCP inhibitor. Unlike previously described secreted protease inhibitors, P. putida Cpi1 is a lipoprotein localized to the bacterial surface and outer membrane vesicles (OMVs), positioning it to selectively inhibit immune-related papain-like cysteine proteases (PLCPs) during host interactions. Functional assays demonstrated inhibition of maize PLCP activity in the nanomolar range, while cpi1 deletion and chagasin motif mutants exhibited significantly impaired early root colonization, particularly in the meristematic and elongation zones. Besides, lack of cpi1 resulted in an altered structure of a maize root-associated synthetic community. We hypothesize that, Cpi1 may protect critical bacterial surface proteins from cleavage by inhibiting plant proteases and thereby modulate the release of MAMPs, dampening host immune responses. Moreover, the release of Cpi1 via OMVs could further extend its function within the root periphery and the apoplast. Together, our results uncover a conserved, membrane-anchored mechanism among pseudomonads for subverting plant immunity and establishing host-microbe interactions.

microbiology↗

bioRxiv2025

The native human glomerulus features a slit diaphragmresembling a densely interwoven fishnet

The slit diaphragm (SD), a core element of the glomerular filtration barrier, is essential for renal filtration and disrupted in all forms of glomerulopathy. Using cryo-electron tomography of human kidney tissue, we resolved the near-native SD architecture at unprecedented resolution. The SD comprises crisscrossing strands intersecting at [~]90{degrees}, forming a fishnet-like lattice across the [~]44 nm space between podocyte foot processes. An atomic model based on the Nephrin-Neph1 heterodimer reveals [~]9 nm spacing in humans, compared with 12.3 nm in mice and 15 nm in Drosophila. Our data establish the SD as a conserved fishnet-like assembly from invertebrates to mammals, with the tighter human lattice likely conferring enhanced permselectivity.

physiology↗

bioRxiv2025

The slit diaphragm in Drosophila features a bi-layered, fishnet-like architecture

The kidney filters large volumes of blood plasma, relying on the glomerulus for the filtration. The slit diaphragm, a critical component of the glomerulus, is formed between podocytes by the immunoglobulin domain proteins nephrin and Neph1. The molecular architecture of the slit diaphragm has remained elusive for decades. Using cryo-electron tomography on focused ion beam-milled Drosophila nephrocytes, an invertebrate podocyte model, we show that the slit diaphragm adopts a fishnet-like pattern. Comparison of hundreds of slit diaphragm segments reveals that it is bi-layered and highly periodic. Based on the cryo-electron tomography map, we propose four possible models for the arrangement of the Drosophila nephrin ortholog (Sns), and the Drosophila Neph1 ortholog (Kirre), the main components of the slit diaphragm in Drosophila. In each model, precise and consistent homo- and heterophilic interactions between crossing immunoglobulin domains of Sns and Kirre become apparent, with immediate implications for the stability and the assembly of the slit diaphragm. Cryo-electron tomography shows that sns silencing disrupts this fishnet pattern, linking this directly to Drosophila nephrin. After Rab5 silencing, causing Sns mistrafficking and ectopic SD formation, the fishnet pattern appears ectopically as well. Our findings align with observations applying cryo-electron tomography to podocytes in mice, indicating that the molecular architecture is evolutionarily conserved across animals. This highlights the value of the nephrocyte as a podocyte model and establishes a crucial link between the architecture of the slit diaphragm and its function.

biophysics↗

bioRxiv2024

Camera Paths, Modeling, and Image Processing Tools for ArtiaX

The enhancement of biomolecular image analysis and data interpretation is significantly improved through the application of advanced visualization techniques. Numerous visualization packages are currently available, spanning a broad spectrum of applications. Recently, we have extended the capabilities of UCSF ChimeraX to address the specific demands of cryo-electron tomography. Here, we introduce the evolution of our existing plugin, ArtiaX, designed to generate models that facilitate particle selection, define camera recording paths, and execute particle selection routines. In particular, diverse models can be generated and populated with putative particle positions and orientations. A specifically tailored coarse grained algorithm was developed to rectify overlaps, as encountered in template matching, employing a rapid and efficient approach. In addition, models can be used to drive the camera position, thereby simplifying the process of movie creation. The plugin incorporates fundamental image filtering options for the on-the-fly analysis of tomographic data and also provides compatibility of particle lists with RELION-5 star files. Collectively, this update of ArtiaX comprehensively encompasses essential tools for the analysis and visualization of electron tomograms. It retains its hallmark attributes of speed, reliability, and user-friendliness, fostering seamless human-machine interaction.

bioinformatics↗

bioRxiv2024

Carbon Dioxide Controls Fungal Fitness and Skin Tropism of Candida auris

The pronounced skin tropism and pan-antifungal resistance traits of the fungal pathogen Candida auris stand out as a serious health threat. Here, we show that a carbonic sensing pathway (CSP) promotes development of resistance to amphotericin B through a reactive oxygen species (ROS) response, as well as ectopic cell wall and membrane lipid homeostasis. Mechanistically, the transcription factor Rca1 acts in cooperation with Efg1 to control the expression and activity of the carbonic anhydrase Nce103 as a key effector component. The conversion of carbon dioxide to bicarbonate provides a direct link to energy metabolism, facilitating colonization and growth on skin tissues. Native mouse and human skin models unequivocally show that the CSP is essential for maintaining skin tropism as well as fungal fitness. Curiously, upon ablation of Rca1 and Efg1, C. auris debilitates efficient growth on native skin. Collectively, our findings highlight critical roles of the CSP in C. auris skin tropism and antifungal drug resistance. The work suggests therapeutic options for disrupting skin colonization and thus preventing infections. Highlights{checkmark} Proteo-transcriptomics links a carbonic sensing pathway (CSP) to C. auris multidrug resistance {checkmark}The Nce103 carbonic anhydrase controls drug resistance as a key component of the CSP {checkmark}The transcription factors Rca1 and Efg1 control Nce103 and link CSP with C. auris skin tropism {checkmark}CSP acts through ectopic ROS response, cell wall architecture and membrane lipid function {checkmark}CSP is required for C. auris fitness and efficient growth and colonization of skin tissues Result contents{checkmark} Integrated omics reveals multidrug-resistant mechanisms in C. auris {checkmark}CO2-sensing controls amphotericin B resistance (AMBR) traits through Rca1 and Efg1 {checkmark}The carbonic anhydrase Nce103 governs susceptibility to amphotericin B {checkmark}The CSP influences AMBR by maintaining reactive oxygen species homeostasis {checkmark}The CSP controls AMBR via cell membrane and cell wall remodelling {checkmark}The CSP regulates fungal fitness through controlling energy metabolism {checkmark}C. auris requires the CSP for skin colonization

microbiology↗

bioRxiv2022

Maize phytocytokines and microbial-patterns trigger antagonistic features in co-incidence with wounding and fungal pathogens

Phytocytokines are signalling peptides that activate immune responses and alarm bystander cells of danger. The pathways of phytocytokine perception and activation are thought to be shared between exogenous danger signals such as microbe-associated molecular patterns (MAMPs) and endogenous, passively released, damage-associated molecular patterns (DAMPs). However, downstream responses triggered by danger molecules and their effect in plant survival is still largely unknown. Here, we have identified three biologically active maize orthologues of phytocytokines previously described in other plants. The maize phytocytokines show common features with MAMPs, including the induction of immune related genes and activation of papain-like cysteine proteases. In contrast to MAMPs, the phytocytokines do not promote cell death in the presence of wounding. In infection assays with fungal pathogens of two different life styles we found that phytocytokines affect the development of disease symptoms, likely due to the activation of phytohormonal pathways. Collectively, our results show that phytocytokines and MAMPs trigger unique and antagonistic features of immunity. We propose a model in which phytocytokines activate immune responses partially similar to MAMPs but in contrast to microbial signals, they act as danger and survival molecules to the surrounding cells. Future studies will focus on the components determining the divergence of signalling outputs upon phytocytokine activation.

plant biology↗

bioRxiv2021

Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo

ObjectiveRecording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes. ApproachWe report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-m-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e., grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse for in vivo recordings of freely behaving animals. Main resultsProbes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiological in vivo recordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone. SignificanceThe innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-m-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.

neuroscience↗

bioRxiv2021

Capacity of countries to reduce biological invasions

The extent and impacts of biological invasions on biodiversity are largely shaped by an array of socio-ecological predictors, which exhibit high variation among countries. Yet a global synthetic perspective of how these factors vary across countries is currently lacking. Here, we investigate how a set of five socio-ecological predictors (Governance, Trade, Environmental Performance, Lifestyle and Education, Innovation) explain i) country-level established alien species (EAS) richness of eight taxonomic groups, and ii) country capacity to prevent and manage biological invasions and their impacts. Trade and Governance together best predicted the average EAS richness, increasing variance explained by up to 54% compared to models based on climatic and spatial variables only. Country-level EAS richness increased strongly with Trade, whereas high level of Governance resulted in lower EAS richness. Historical (1996) levels of Governance and Trade better explained response variables than current (2015) levels. Thus, our results reveal a historical legacy of these two predictors with profound implications for the future of biological invasions. We therefore used Governance and Trade to define a two-dimensional socio-economic space in which the position of a country captures its capacity to address issues of biological invasions. Our results provide novel insights into the complex relationship between socio-ecological predictors and biological invasions. Further, we highlight the need for designing better policies and management measures for alien species, and for integrating biological invasions in global environmental scenarios.

ecology↗

bioRxiv2019

A global perspective on microbial diversity in the terrestrial deep subsurface

While recent efforts to catalogue Earths microbial diversity have focused upon surface and marine habitats, 12% to 20% of Earths bacterial and archaeal biomass is suggested to inhabit the terrestrial deep subsurface, compared to [~]1.8% in the deep subseafloor 1-3. Metagenomic studies of the terrestrial deep subsurface have yielded a trove of divergent and functionally important microbiomes from a range of localities 4-6. However, a wider perspective of microbial diversity and its relationship to environmental conditions within the terrestrial deep subsurface is still required. Here, we show the diversity of bacterial communities in deep subsurface groundwater is controlled by aquifer lithology globally, by using 16S rRNA gene datasets collected across five countries on two continents and from fifteen rock types over the past decade. Furthermore, our meta-analysis reveals that terrestrial deep subsurface microbiota are dominated by Betaproteobacteria, Gammaproteobacteria and Firmicutes, likely as a function of the diverse metabolic strategies of these taxa. Despite this similarity, evidence was found not only for aquifer-specific microbial communities, but also for a common small consortium of prevalent Betaproteobacteria and Gammaproteobacterial OTUs across the localities. This finding implies a core terrestrial deep subsurface community, irrespective of aquifer lithology, that may play an important role in colonising and sustaining microbial habitats in the deep terrestrial subsurface. An in-silico contamination-aware approach to analysing this dataset underscores the importance of downstream methods for assuring that robust conclusions can be reached from deep subsurface-derived sequencing data. Understanding the global panorama of microbial diversity and ecological dynamics in the deep terrestrial subsurface provides a first step towards understanding the role of microbes in global subsurface element and nutrient cycling.

microbiology↗

bioRxiv2017

Solagigasbacteria: Lone genomic giants among the uncultured bacterial phyla

Recent advances in single-cell genomic and metagenomic techniques have facilitated the discovery of numerous previously unknown, deep branches of the tree of life that lack cultured representatives. Many of these candidate phyla are composed of microorganisms with minimalistic, streamlined genomes lacking some core metabolic pathways, which may contribute to their resistance to growth in pure culture. Here we analyzed single-cell genomes and metagenome bins to show that the \"Candidate phylum SPAM\" represents an interesting exception, by having large genomes (6-8 Mbps), high GC content (66%-71%), and the potential for a versatile, mixotrophic metabolism. We also observed an unusually high genomic heterogeneity among individual SPAM cells in the studied samples. These features may have contributed to the limited recovery of sequences of this candidate phylum in prior metagenomic studies. Based on these observations, we propose renaming SPAM to \"Candidate phylum Solagigasbacteria\". Current evidence suggests that Solagigasbacteria are distributed globally in diverse terrestrial ecosystems, including soils, the rhizosphere, volcanic mud, oil wells, aquifers and the deep subsurface, with no reports from marine environments to date.

microbiology↗