Biology subjects

Maier, J.

Publications and source records attributed to Maier, J..

14 recordsLinked to original sources

bioRxiv2026

Volatile organic compounds of L. enzymogenes LEC suppress the growth of fungal and oomycete pathogens and modify the cell physiology of Rhizoctonia solani

Lysobacter enzymogenes LEC is a plant disease-suppressive bacterium. To obtain a more comprehensive understanding of its biocontrol activity and to identify further potential application methods, we investigated the function of its volatile organic compounds (VOCs). VOC activity was assessed in vitro using split-plate assays with eight different fungal and oomycete isolates and in planta against Pseudoperonospora cubensis on cucumber plants. The volatilomes of LEC and the less active L. enzymogenes DSM2043 were analysed by GC-MS analyses. Further, the effects of VOCs on cell physiology of Rhizoctonia solani were analyzed by fluorescence and transmission electron microscopy. The strongest inhibition of LEC VOCs was observed for Phytophthora infestans (94%) and Phoma lingam (83%), while inhibitions were lower for Rhizoctonia solani (42%) and Alternaria spp. (24% and 29%) and not detectable for two Fusarium isolates. VOC exposure also significantly reduced downy mildew caused by P. cubensis on cucumber plants (39%), although this effect was locally restricted to the leaf directly above the VOC source. In R. solani, VOC exposure reduced nuclei abundance and increased lipid accumulation. GC MS analyses revealed distinct volatile profiles between LEC and L. enzymogenes DSM2043 and identified ketones, such as 2-dodecanone and undecanone as candidate bioactive compounds, which is in agreement with previous findings. Our results demonstrate broad-spectrum VOC-mediated biocontrol activity, and thereby provide a more comprehensive understanding of its biocontrol activity and highlight new ways for potential applications of LEC.

microbiology↗

bioRxiv2026

Dual-Layer Serological Encoding: Integrating Pathogen-Derived and Host-Reactive Peptide Signatures Reveals Complementary Dimensions of HIV Immune Response

Serological diagnostics traditionally rely on pathogen-derived antigens to detect infection-specific antibody responses. Chronic infections also induce systemic immune remodeling that may be reflected in global antibody reactivity patterns beyond antigen specificity. Here we evaluate a dual-layer serological framework combining HIV-derived peptides with a host-derived peptide library designed to capture distributed antibody reactivity patterns. Using strict nested cross-validation in a cohort of 105 individuals, pathogen-derived 12-mer peptides achieved high classification performance with an AUC of 0.891, whereas the 10-mer host-based peptide library alone yielded moderate but statistically significant discrimination with an AUC of 0.805. Integration via regularized stacking resulted in only a modest additive improvement, reaching an AUC of 0.897, indicating partial redundancy in diagnostic ranking. In contrast, entropy and inequality analyses revealed substantial immune repertoire restructuring in HIV-positive individuals, characterized by reduced Shannon entropy and significant correlations between classifier probability and repertoire concentration. These findings support a dual-layer model of serology in which the integration of pathogen-derived and host-derived peptides into a meta model encode antigen specificity, whereas host-reactive signatures reflect systemic immune topology. Distinguishing diagnostic ranking from immune-state encoding provides a conceptual framework for multi-layer serological diagnostics.

immunology↗

bioRxiv2026

High-density peptide arrays detect tuberculosis through immune remodeling, not only antigen recognition alone

Serological diagnostics for tuberculosis rely on pathogen-derived antigens to detect infection-specific antibodies. Whether chronic TB infection also reshapes the global topology of the antibody repertoire remains largely unexplored. Here we profile serum antibody binding across 6,936 peptides in 105 individuals from three countries using two complementary libraries: Mycobacterium tuberculosis peptides (TBC) and a resemblance-ranking library representing the human self-proteome (RRL). We construct a five-dimensional immune state vector from distributional binding properties and map individual sera into an immune phase space. A remodeling classifier achieves virtually identical performance on pathogen-derived and host-derived peptides (AUC 0.63-0.73), demonstrating that the diagnostic signal arises from global repertoire restructuring rather than antigen-specific recognition. HIV co-infection partially masks this signal; restricting analysis to HIV-negative individuals increases AUC to 0.73 (permutation p = 0.005) and enables detection of smear-negative TB (AUC = 0.83, specificity 0.95 with three peptides). Phase-space projections reveal that TB severity maps onto a continuous remodeling gradient, with smear-negative patients occupying intermediate positions between healthy controls and smear-positive cases. These findings position high-density peptide arrays as sensors of antibody repertoire topology, enabling detection of chronic immune states beyond antigen-specific recognition.

immunology↗

bioRxiv2026

TrIdent - An R package to automate transductomics analysis of virus-like particle mediated DNA mobilization

BackgroundTransduction is a form of horizontal gene transfer in which bacterial DNA is packaged and transferred by virus-like particles (VLPs). Transductomics is a sequencing-based method used to detect DNA carried by VLPs. During transductomics analysis, reads from a samples ultra-purified VLPs are mapped to metagenomic contigs assembled from the same samples whole-community. The read mapping produces coverage patterns that require a time-consuming manual inspection and classification process which makes the methods use unfeasible for datasets with many samples. ResultsWe developed a novel algorithm, TrIdent (Transduction Identification), that uses pattern-matching to automate the transductomics data analysis and that is available as an R package (https://jlmaier12.github.io/TrIdent/). There is no software equivalent to TrIdent so we compared TrIdents classifications of transductomics datasets to classifications made by human classifiers. TrIdents classifications were generally comparable to the manual classifications on a previously generated, manually classified transductomics dataset. When applied to newly generated transductomics data from the murine microbiota, TrIdent agreed with two independent human classifiers as much as the two independent human classifications agreed with each other. TrIdent classified transductomics datasets in a fraction of the time needed by human classifiers, and the classifications produced by TrIdent are fully reproducible. We used TrIdent to explore three murine gut transductomes and found that bacterial DNA associated with the Oscillospiraceae and Turicibacteraceae families was highly enriched in the DNA packaged by VLPs as compared to the whole community metagenomes. ConclusionsThe TrIdent software is a more accessible, more efficient, and more reproducible alternative to the manual inspection of read coverage patterns previously required for transductomics data analysis. To demonstrate the application of TrIdent, we analyzed transductomics datasets from murine fecal pellets and showed that specific low abundance bacterial families appear to be heavily involved in transduction.

genomics↗

bioRxiv2024

Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages

BackgroundBacteriophages (phages) and bacteria within the gut microbiome persist in long-term stable coexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employ a variety of mechanisms to evade phage infection, while phages rely on counterstrategies to overcome these defences. Among the most abundant phages in the gut are the crAss-like phages that infect members of the Bacteroidales, in particular Bacteroides. In this study, we explored some of the mechanisms enabling the co-existence of four phage-Bacteroidales host pairs in vitro using a multi-omics approach (transcriptomics, proteomics and metabolomics). These included three Bacteroides species paired with three crAss-like phages (Bacteroides intestinalis and {phi}crAss001, Bacteroides xylanisolvens and {phi}crAss002, and an acapsular mutant of Bacteroides thetaiotaomicron with DAC15), and Parabacteroides distasonis paired with the siphovirus {phi}PDS1. ResultsWe show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechanism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternative resistance mechanisms, while potentially less efficient than CPS phase variation, can be activated to support bacterial survival by regulating gene expression and resulting in metabolic adaptations, particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phase variation, enable bacterial populations to persist in the presence of phages, and vice versa. An acapsular variant of B. thetaiotaomicron demonstrated broader transcriptomic, proteomic, and metabolomic changes, supporting the involvement of additional resistance mechanisms beyond CPS variation. ConclusionsThis study advances our understanding of long-term phage-host interaction, offering insights into the long-term persistence of crAss-like phages and extending these observations to other phages, such as {phi}PDS1. Knowledge of the complexities of phage-bacteria interactions is essential for designing effective phage therapies and improving human health through targeted microbiome interventions.

microbiology↗

bioRxiv2024

Dietary protein source strongly alters gut microbiota composition and function

The source of protein in a persons diet affects their total life expectancy. However, the mechanisms by which dietary protein sources differentially impact human health and life expectancy are poorly understood. Dietary choices have major impacts on the composition and function of the intestinal microbiota that ultimately modulate host health. This raises the possibility that health outcomes based on dietary protein sources might be driven by interactions between dietary protein and the gut microbiota. In this study, we determined the effects of seven different sources of dietary protein on the gut microbiota of mice using an integrated metagenomics-metaproteomics approach. The protein abundances measured by metaproteomics can provide microbial species abundances, and evidence for the molecular phenotype of microbiota members because measured proteins indicate the metabolic and physiological processes used by a microbial community. We showed that dietary protein source significantly altered the species composition and overall function of the gut microbiota. Different dietary protein sources led to changes in the abundance of microbial proteins involved in the degradation of amino acids and the degradation of glycosylations conjugated to dietary protein. In particular, brown rice and egg white protein increased the abundance of amino acid degrading enzymes. Egg white protein increased the abundance of bacteria and proteins usually associated with the degradation of the intestinal mucus barrier. These results show that dietary protein sources can change the gut microbiotas metabolism, which could have major implications in the context of gut microbiota mediated diseases.

microbiology↗

bioRxiv2024

Pseudo-pac site sequences used by phage P22 in generalized transduction of Salmonella

Salmonella enterica Serovar Typhimurium (Salmonella) and its bacteriophage P22 are a model system for the study of horizontal gene transfer by generalized transduction. Typically, the P22 DNA packaging machinery initiates packaging when a short sequence of DNA, known as the pac site, is recognized on the P22 genome. However, sequences similar to the pac site in the host genome, called pseudo-pac sites, lead to erroneous packaging and subsequent generalized transduction of Salmonella DNA. While the general genomic locations of the Salmonella pseudo-pac sites are known, the sequences themselves have not been determined. We used visualization of P22 sequencing reads mapped to host Salmonella genomes to define regions of generalized transduction initiation and the likely locations of pseudo-pac sites. We searched each genome region for the sequence with the highest similarity to the P22 pac site and aligned the resulting sequences. We built a regular expression (sequence match pattern) from the alignment and used it to search the genomes of two P22-susceptible Salmonella strains-LT2 and 14028S- for sequence matches. The final regular expression successfully identified pseudo-pac sites in both LT2 and 14028S that correspond with generalized transduction initiation sites in mapped read coverages. The pseudo-pac site sequences identified in this study can be used to predict locations of generalized transduction in other P22-susceptible hosts or to initiate generalized transduction at specific locations in P22-susceptible hosts with genetic engineering. Furthermore, the bioinformatics approach used to identify the Salmonella pseudo-pac sites in this study could be applied to other phage-host systems. ImportanceBacteriophage P22 has been a genetic tool and a key model for the study of generalized transduction in Salmonella since the 1950s, yet certain components of the generalized transduction molecular mechanism remain unknown. Specifically, the locations and sequences of pseudo-pac sites, hypothesized to facilitate packaging of Salmonella DNA by P22, to date have not been determined. In this study, we identified the specific locations and sequences of the pseudo-pac sites frequently recognized by P22 in Salmonella genomes. The identification of highly efficient pseudo-pac sites in Salmonella provides fundamental insights into the sequence specificity necessary for P22 pac site recognition and opens the door to more targeted use of generalized transduction with P22.

microbiology↗

bioRxiv2024

PPIscreenML: Structure-based screening for protein-protein interactions using AlphaFold

Protein-protein interactions underlie nearly all cellular processes. With the advent of protein structure prediction methods such as AlphaFold2 (AF2), models of specific protein pairs can be built extremely accurately in most cases. However, determining the relevance of a given protein pair remains an open question. It is presently unclear how to use best structure-based tools to infer whether a pair of candidate proteins indeed interact with one another: ideally, one might even use such information to screen amongst candidate pairings to build up protein interaction networks. Whereas methods for evaluating quality of modeled protein complexes have been co-opted for determining which pairings interact (e.g., pDockQ and iPTM), there have been no rigorously benchmarked methods for this task. Here we introduce PPIscreenML, a classification model trained to distinguish AF2 models of interacting protein pairs from AF2 models of compelling decoy pairings. We find that PPIscreenML out-performs methods such as pDockQ and iPTM for this task, and further that PPIscreenML exhibits impressive performance when identifying which ligand/receptor pairings engage one another across the structurally conserved tumor necrosis factor superfamily (TNFSF). Analysis of benchmark results using complexes not seen in PPIscreenML development strongly suggest that the model generalizes beyond training data, making it broadly applicable for identifying new protein complexes based on structural models built with AF2.

bioinformatics↗

bioRxiv2023

Near chromosome-level and highly repetitive genome assembly of the snake pipefish Entelurus aequoreus (Syngnathiformes: Syngnathidae)

The snake pipefish, Entelurus aequoreus (Linnaeus, 1758), is a slender, up to 60 cm long, northern Atlantic fish that dwells in open seagrass habitats and has recently expanded its distribution range. The snake pipefish is part of the family Syngnathidae (seahorses and pipefish) that has undergone several characteristic morphological changes, such as loss of pelvic fins and elongated snout. Here, we present a highly contiguous, near chromosome-scale genome of the snake pipefish assembled as part of a university masters course. The final assembly has a length of 1.6 Gbp in 7,391 scaffolds, a scaffold and contig N50 of 62.3 Mbp and 45.0 Mbp and L50 of 12 and 14, respectively. The largest 28 scaffolds (>21 Mbp) span 89.7% of the assembly length. A BUSCO completeness score of 94.1% and a mapping rate above 98% suggest a high assembly completeness. Repetitive elements cover 74.93% of the genome, one of the highest proportions so far identified in vertebrate genomes. Demographic modeling using the PSMC framework indicates a peak in effective population size (50 - 100 kya) during the last interglacial period and suggests that the species might largely benefit from warmer water conditions, as seen today. Our updated snake pipefish assembly forms an important foundation for further analysis of the morphological and molecular changes unique to the family Syngnathidae.

genomics↗

bioRxiv2023

Interaction of GAT1 with sodium ions: from efficient recruitment to stabilisation of substrate and conformation

The human GABA transporter (GAT1) is a membrane transporter that mediates the reuptake of the neurotransmitter GABA from the synaptic cleft into neurons and glial cells. Dysregulation of the transport cycle has been associated with epilepsy and neuropsychiatric disorders, highlighting the crucial role of the transporter in maintaining homeostasis of brain GABA levels. GAT1 is a secondary active transporter that couples the movement of substrate to the simultaneous transport of sodium and chloride ions along their electrochemical gradients. Using MD simulations, we identified a novel sodium recruiting site at the entrance to the outer vestibule, which attracts positively charged ions and increases the local sodium concentration, thereby indirectly increasing sodium affinity. Mutations of negatively charged residues at the recruiting site slowed the binding kinetics, while experimental data revealed a change in sodium dependency of GABA uptake and a reduction of sodium affinity. Simulation showed that sodium displays a higher affinity for the sodium binding site NA2, which plays a role in stabilisation of the outward-open conformation. We directly show that the presence of a sodium ion bound to NA2 increases the stability of the closed inner gate and restrains motions of TM5. We find that sodium is only weakly bound to NA1 in the absence of GABA, while the presence of the substrate strengthens the interaction due to the completed ion coordinating shell, explaining cooperativity between GABA and sodium.

molecular biology↗

bioRxiv2023

Quantitative description of the phase separation behavior of the multivalent SLP65-CIN85 complex

Biomolecular condensates play a major role in cell compartmentalization, besides membrane-enclosed organelles. The multivalent SLP65 and CIN85 proteins are downstream B cell receptor (BCR)-signaling effectors, required for a proper immune response. Both proteins phase separate together with vesicles to form pre-signaling clusters. Within this tripartite system, six PRMs of SLP65 interact promiscuously with three SH3 domains of the CIN85 monomer, establishing 18 individual SH3-PRM interactions whose individual dissociation constants we determined. Based on these 18 dissociation constants, we measured the phase separation properties of the natural SLP65/CIN85 system as well as designer constructs that emphasize the strongest SH3/PRM interactions. By modelling these various SLP65/CIN85 constructs with the program LASSI (LAttice simulation engine for Sticker and Spacer Interactions) we reproduced the observed phase separation properties. In addition, LASSI revealed a deviation in the experimental measurement, which was independently identified as a previously unknown intramolecular interaction. Thus, thermodynamic properties of the individual PRM/SH3 interactions allow to model the phase separation behavior of the SLP65/CIN85 system faithfully.

biophysics↗

bioRxiv2022

Structural basis of organic cation transporter-3 inhibition

Organic cation transporters (OCTs) facilitate the translocation of catecholamines and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 [A] resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.

pharmacology and toxicology↗

bioRxiv2022

Classifying the activity states of small vertebrates using automated VHF telemetry

O_LIThe most basic behavioural states of animals can be described as active or passive. However, while high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which the automated VHF radio-tracking of small vertebrates fitted with lightweight transmitters (< 0.2 g) is used to distinguish between active and passive behavioural states. C_LIO_LIA dataset containing > 3 million VHF signals was used to train and test a random forest model in the assignment of either active or passive behaviour to individuals from two forest-dwelling bat species (Myotis bechsteinii (n = 50) and Nyctalus leisleri (n = 20)). The applicability of the model to other taxonomic groups was demonstrated by recording and classifying the behaviour of a tagged bird and by simulating the effect of different types of vertebrate activity with the help of humans carrying transmitters. The random forest model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F-score 0.96-0.98). C_LIO_LIThe utility of the model in tackling ecologically relevant questions was demonstrated in a study of the differences in the daily activity patterns of the two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night-time activity of M. bechsteinii was relatively constant. These results show that significant differences in the timing of species activity according to ecological preferences or seasonality can be distinguished using our method. C_LIO_LIOur approach enables the assignment of VHF signal patterns to fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radio-tracking method, we provide the trained random forest models together with an R-package that includes all necessary data-processing functionalities. In combination with state-of-the-art open-source automated radio-tracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation. C_LI

animal behavior and cognition↗

bioRxiv2019

Geldanamycin inhibits Jumonji histone lysine demethylase KDM4 and targets chimeric transcription factor PAX3-FOXO1

Histone lysine demethylases (KDMs) are emerging as therapeutic targets in cancer. Development of potent KDM inhibitors may provide additional options for epigenomics-oriented therapies. Using a Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) functional demethylation assay, in combination with a high-content immunofluorescence imaging phenotypic screen, Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance mass spectrometry (MALDI-FTICR MS) and Amplified Luminescent Proximity Homogeneous Assay (ALPHA), we identified geldanamycin, an inhibitor of heat shock protein 90 (Hsp90), as a novel inhibitor of JmjC-domain containing demethylases such as KDM4B. We further found that geldanamycin can destabilize the PAX3-FOXO1 fusion oncoprotein, an Hsp90 client, which is a driver of clinically unfavorable alveolar rhabdomyosarcoma (aRMS). We then hypothesized that dual inhibition of PAX3-FOXO1 and epigenetic modifiers of aRMS would have synergistic antitumor activity. We repurposed the geldanamycin analog 17-DMAG to target aRMS and found that 17-DMAG significantly delays tumor growth, extends survival in xenograft mouse models, and inhibits expression of PAX3-FOXO1 targets and multiple oncogenic pathways including MYC, E2F and NOTCH. In addition, the combination of 17-DMAG with conventional chemotherapy or the bromodomain inhibitor JQ1 significantly enhances therapeutic efficacy. In summary, we have identified geldanamycin and 17-DMAG as dual KDM/Hsp90 inhibitors and 17-DMAG is efficacious against PAX3-FOXO1-driven rhabdomyosarcoma.

cancer biology↗