Biology subjects

Schatz, D.

Publications and source records attributed to Schatz, D..

18 recordsLinked to original sources

bioRxiv2026

Single-cell-resolved natural giant virus infections reveal conserved protist immunity

Single-cell eukaryotes (protists) are key players in microbial ecosystems. Yet, our understanding of how they interact with viruses in nature and how antiviral defenses shape these relationships remains limited. Using a single-cell multi-omics approach, we mapped associations between giant viruses and their hosts and identified active giant-virus infections in an alpine lake protist community. In naturally infected dinoflagellates, infection was accompanied by the selective induction of viperin, an ancient antiviral enzyme conserved from bacteria to humans. We also observed virus-encoded homologs of immunity-related genes whose expression correlated with viperin expression, raising the possibility of a role in viral counter-defense. These findings reveal an ecological dimension of protist immunity and provide a framework for tracing the host-virus arms race across divergent cellular lineages.

microbiology↗

bioRxiv2026

Reversible inhibition of viral life cycle in response to elevated temperature in a bloom-forming alga

Ocean warming is expected to reshape microbial interactions and community composition, with profound consequences for marine biogeochemical cycles. Host-virus dynamics are central to these processes, yet their response to elevated temperature remains poorly understood. Here, using the bloom-forming alga Gephyrocapsa huxleyi and its specific large dsDNA virus, Emiliania huxleyi virus (EhV), we show that elevated temperature withheld virion production and abolished distinct stages of the viral life cycle. Viral adsorption and early transcription remained active, whereas viral DNA replication and late gene expression were arrested, leading to an intracellular inhibition of infection. Intriguingly, this arrested infection state was reversible following prolonged heatwave conditions. Single-cell analyses revealed that reversibility of infection inhibition occurred both within a small fraction of infected cells and by reinfection by extracellular virions that remained viable during heat exposure in the extracellular milieu. Furthermore, we detected variability in infection inhibition by temperature across several host-virus pairs, suggesting that the effect of temperature is strain-specific. Our findings uncover a temperature-sensitive checkpoint in the viral life cycle, providing a mechanistic framework for understanding how marine heatwaves may reshape virus-driven mortality and carbon cycling in the ocean.

microbiology↗

bioRxiv2025

Synergy in viral-bacterial coinfection expedites algal bloom demise

Algal blooms are hotspots for diverse microbial interactions affecting bloom dynamics. Viral infections often regulate the demise of these blooms, recycling >25% of oceanic fixed carbon. Although these blooms collapse synchronously, only 10-30% of algal cells show active viral infection, suggesting additional mortality agents. Using microbial communities from natural coccolithophore blooms, we discovered that bacteria significantly enhanced virus-mediated algal mortality. We quantified this interaction using two novel metrics: the Synergy Index (SI) measuring viral-bacterial interaction strength, and the Benefit Index (BI) assessing changes in bacterial fitness. We identified Alteromonas bacteria as drivers of viral-bacterial coinfection with consistently high SI and BI. In natural communities, Alteromonas exhibited chemoattraction towards infected algal cells, leading to their enrichment in bloom demise particles. This viral-bacterial synergy represents a previously unrecognized mortality agent controlling bloom termination, modulating the balance between the carbon-recycling viral shunt and the carbon-exporting viral shuttle pathways, likely influencing global carbon cycling.

microbiology↗

bioRxiv2025

Metacaspases mediate thermotolerance of diatoms following marine heat waves

O_LIMarine heat waves (MHW) are extreme climate events characterized by elevated ocean temperatures lasting from days to months and spanning thousands of kilometers. Recent predictions show an increment in MHW frequency, duration and intensity worldwide along with climate change. Nevertheless, little is known about MHW impacts on marine microbial life and, specifically, on algal blooms. Recent studies in yeast and green algae suggested that thermotolerance is mediated by metacaspases (MC), cysteine proteases, structurally similar to caspases known to mediate programmed cell death. C_LIO_LIInitially we created a heatwave model of 72-hours that exposes the model diatom Phaeodactylum tricornutum to elevated temperature with a recovery phase that enables to capture the mechanisms underpinning such acclimation. We generated triple knock-out mutants of the PtMCA genes and identified a vital role for MC in heat-stress acclimation. C_LIO_LIPtMCA triple mutants exhibited increased sensitivity to the heatwave treatment, which induced cell death that peaked days after returning to initial temperatures. We further revealed that heatwave treatment induced accumulation of reactive oxygen species and the PtMCA mutants were hypersensitive to oxidative stress as compared to WT cells. C_LIO_LIWe propose that metacaspases have a pivotal role in diatoms acclimation to elevated temperatures a trait vital for algal survival considering climate change. C_LI

microbiology↗

bioRxiv2025

Deconstructing natural products to develop synthetic small molecule attachment inhibitors with broad spectrum antiviral activity

The continuous emergence of new viruses and the number of viruses that are each highly consequential for few people raise a need for broad spectrum antivirals. Most human and emerging viruses first attach to cellular glycosaminoglycans (GAG) or sialylated glycans (SG), a potential target for broad spectrum antivirals. Attachment to the former is through polar interactions between the negatively charged glycans and positively charged domains in virion proteins and typically inhibited by negatively charged polymers. Attachment to the latter is through specific interactions at binding pockets and inhibited by molecules that bind to these pockets. Surprisingly, EGCG inhibits viruses that attach to GAG and SG. However, it does so with widely differing potencies, is not a pharmacologically desirable molecule, and is limited by solubility. We tested whether it was possible to develop small synthetic molecules to inhibit viruses that attach to SG or GAG. We first identified the EGCG moieties responsible for the antiviral activity. The two polyhydroxylated phenyl groups were essential while the central benzopyran linker was not. We thus designed a series of gallate compounds to explore the minimal pharmacophore required for broad-spectrum antiviral activity. By exploring the linkers and number of galloyls, we identified small molecule inhibitors of herpes simplex virus 1, influenza A virus, and the coronaviruses hCoV OC43 and SARS-CoV-2. These compounds have low micromolar to submicromolar potency and no limiting cytotoxicity. These molecules are still not pharmacologically optimized and limited by solubility, but they define a minimal pharmacophore that confers broad spectrum antiviral activity. ImportanceThe SARS-CoV-2 pandemic demonstrated the importance of antivirals in managing emerging viruses. Although vaccines were successfully developed in less than two years, there was resistance to vaccination while infected or sick people were far more willing to take antivirals. It is impossible to develop antivirals specific for unknown viruses, but broad spectrum antivirals could control viral spread until more specific and potent drugs are developed. Human pathogenic and emerging viruses commonly attach to glycans, providing a target for broad spectrum antivirals. However, inhibitors of attachment to glycosaminoglycans do not typically inhibit viruses attaching to sialylated glycans, and vice-versa. We had found that EGCG has the unique property of inhibiting viruses that attach both glycans, with quite different potencies. Here, deconstructed a natural compound, EGCG, to identify the moieties responsible for its antiviral activity to then produce broad spectrum antiviral compounds against established and emerging viruses that attach to either glycan.

microbiology↗

bioRxiv2025

Mapping the transcriptional landscape of algal resistance to viral infection reveals a core expression program

O_LIAlgal blooms and their demise by viruses drive global-scale ecological processes in the ocean. These blooms form the foundation of marine food webs, regulate microbial communities, and shape biogeochemical cycles. Although algal populations are constantly infected by viruses, resistant subpopulations frequently emerge after the infection. Yet, antiviral molecular mechanisms of marine microalgae are underexplored. C_LIO_LIWe used a model system of the ubiquitous microalga Emiliania huxleyi and its giant virus, E. huxleyi virus (EhV), to study how resistant populations evolve and to identify their transcriptional programs. We generated a detailed temporal transcriptomic dataset during a viral infection, covering the stages of lysis and the recovery of a resistant subpopulation. C_LIO_LIViral infection triggered prominent transcriptome changes to support viral propagation, followed by a unique transcriptional response in resistant cells. Both infected and resistant cells highly expressed innate immune response genes, notably those with Toll/interleukin-1 receptor (TIR) domain. Additionally, resistant cells expressed genes involved in membrane-bound glycan remodeling, sphingolipid metabolism, and nutrient uptake. C_LIO_LIUsing comparative transcriptomics across diverse resistant E. huxleyi strains, we identified a core group of resistance-related genes, providing a set of gene markers to detect this rare phenotype during the host-virus arms race in algal blooms. C_LI

microbiology↗

bioRxiv2024

Mapping of the viral shunt across widespread coccolithophore blooms using metabolic biomarkers

The viral shunt is a fundamental ecosystem process which diverts the flux of organic carbon from grazers to heterotrophic microorganisms. Through the extracellular release of metabolites, lytic viral infections supply 2-10% of photosynthetically fixed carbon in the ocean for bacterial respiration. Despite its significance for the carbon cycle, we lack tools to detect the viral shunt in the natural environment and assess its ecological impact. Here, we study the use of exometabolites as biomarkers for the viral shunt by applying molecular, metabolomics, and oceanographic tools in blooms of the cosmopolitan microalga Gephyrocapsa huxleyi across the Atlantic Ocean, spanning four biogeochemical provinces between Iceland and Patagonia. We mapped the distinct metabolic footprint of its viral infections using exo- and endometabolomics approaches and detected nineteen organohalogen metabolites across the blooms, showing their global formation. Time-resolved comparison of particulate and dissolved metabolite pools during an induced mesocosm bloom indicated virocells - actively infected host cells - as the source of the halogenated metabolites. Three trichloro-iodo metabolites were present during demise of all virus-infected blooms, highlighting them as suitable metabolic biomarkers. The environmental stability of these halometabolites in the DOM pool over a few days can recapitulate viral infections at earlier stages of phytoplankton bloom succession.

ecology↗

bioRxiv2024

Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination

Somatic hypermutation (SHM) and class switch recombination (CSR) diversify immunoglobulin (Ig) genes and are initiated by the activation induced deaminase (AID), a single-stranded DNA cytidine deaminase that is thought to engage its substrate in the context of RNA polymerase II (RNAPII) transcription. Through a loss of function genetic screen, we identified numerous potential factors involved in SHM including ELOF1, a component of the RNAPII elongation complex that has been shown to function in DNA repair and transcription elongation. Loss of ELOF1 strongly compromises SHM, CSR, and AID targeting and alters RNAPII transcription by reducing RNAPII pausing downstream of transcription start sites and levels of serine 5 but not serine 2 phosphorylated RNAPII throughout transcribed genes. ELOF1 must bind to RNAPII to be a proximity partner for AID and to function in SHM and CSR. We propose that ELOF1 helps create the appropriate stalled RNAPII substrate on which AID acts. HighlightsO_LIA CRISPR knockout screen has identified numerous potential SHM factors. C_LIO_LISHM, CSR, and AID targeting are strongly compromised in the absence of ELOF1. C_LIO_LIELOF1 must interact with RNAPII to be an AID proximity partner and support AID targeting. C_LIO_LIELOF1 supports RNAPII pausing and generation of the substrate for AID action. C_LI

immunology↗

bioRxiv2024

Cathepsin X is a conserved cell death protein involved in algal response to environmental stress

Phytoplankton play a crucial role in global primary production and can form vast blooms in aquatic ecosystems. Bloom demise and the rapid turnover of phytoplankton are suggested to involve programmed cell death (PCD) induced by diverse environmental stressors. However, fundamental knowledge of the PCD molecular components in algae and protists in general remains elusive. Previously, we revealed that early oxidation in the chloroplast predicted subsequent cell death or survival in isogenic subpopulations that emerged following H2O2 treatment in the diatom Phaeodactylum tricornutum. Here, we performed transcriptome analysis of sorted sensitive oxidized cells and resilient reduced cells, to discover genes linked to their contrasting fates. By cross-comparison with a large-scale mutant screen in the green alga Chlamydomonas reinhardtii, we identified functionally relevant conserved PCD gene candidates, including the cysteine protease cathepsin X/Z (CPX). CPX mutants in P. tricornutum CPX1 and C. reinhardtii CEP12 both exhibited profound resilience to oxidative stress, supporting a conserved function in algal PCD. P. tricornutum cpx1 mutants, generated using CRISPR-Cas9, also exhibited resilience to the toxic diatom-derived infochemical cyanogen bromide. Phylogenetic and predictive structural analyses show that CPX is highly conserved in eukaryotes, and algae of the green and red lineages exhibit strong structural similarity to human cathepsin CTSZ. CPX is expressed by diverse algae across the oceans and during toxic Pseudo-nitzschia blooms, supporting its ecological importance. Elucidating PCD components in algae sheds light on the evolutionary origin of PCD in unicellular organisms, and on the cellular strategies employed by the population to cope with stressful conditions.

microbiology↗

bioRxiv2023

Homing in on the rare virosphere reveals the native host of giant viruses

Giant viruses (phylum Nucleocytoviricota) are globally distributed in aquatic ecosystems1,2. They play major roles as evolutionary drivers of eukaryotic plankton3 and regulators of global biogeochemical cycles4. Recent metagenomic studies have significantly expanded the known diversity of marine giant viruses1,5-7, but we still lack fundamental knowledge about their native hosts, thereby hindering our understanding of their lifecycle and ecological importance. Here, we aim to discover the native hosts of giant viruses using a novel, sensitive single-cell metatranscriptomic approach. By applying this approach to natural plankton communities, we unraveled an active viral infection of several giant viruses, from multiple lineages, and identified their native hosts. We identify a rare lineage of giant virus (Imitervirales-07) infecting a minute population of protists (class Katablepharidaceae) and revealed the prevalence of highly expressed viral-encoded cell-fate regulation genes in infected cells. Further examination of this host-virus dynamics in a temporal resolution suggested this giant virus controls its host population demise. Our results demonstrate how single-cell metatranscriptomics is a sensitive approach for pairing viruses with their authentic hosts and studying their ecological significance in a culture-independent manner in the marine environment.

microbiology↗

bioRxiv2022

Novel lipid biomarkers for algal resistance to viral infection in the ocean

Marine viruses play a key role in regulating phytoplankton populations, greatly affecting the biogeochemical cycling of major nutrients in the ocean. Resistance to viral infection has been reported for various phytoplankton species under laboratory conditions. Nevertheless, the occurrence of resistant cells in natural populations is underexplored due to the lack of sensitive tools to detect these rare phenotypes. Consequently, our current understanding of the ecological importance of resistance and its underlying mechanisms is limited. Here, we sought to discover lipid biomarkers for the resistance of the bloom-forming alga Emiliania huxleyi to its specific virus, E. huxleyi virus (EhV). We identified novel glycosphingolipids (GSLs) that characterize resistant E. huxleyi strains by applying an untargeted lipidomics approach. Further, we detected these lipid biomarkers in E. huxleyi isolates that were recently collected from E. huxleyi blooms and used them to detect resistant cells in the demise phase of an open ocean E. huxleyi bloom. Lastly, we show that the GSL composition of E. huxleyi cultures that recover following infection and gain resistance to the virus resembles that of resistant strains. These findings highlight the metabolic plasticity and co-evolution of the GSL biosynthetic pathway and underscore its central part in this host-virus arms race.

microbiology↗

bioRxiv2021

The ecological significance of extracellular vesicles in modulating host-virus interactions during algal blooms

Extracellular vesicles are produced by organisms from all kingdoms and serve a myriad of functions, many of which involve cell-cell signaling, especially during stress conditions and host-pathogen interactions. In the marine environment, communication between microorganisms can shape trophic level interactions and population succession, yet we know very little about the involvement of vesicles in these processes. In a previous study, we showed that vesicles produced during viral infection by the ecologically important model alga Emiliania huxleyi, could act as a pro-viral signal, by expediting infection and enhancing the half-life of the virus in the extracellular milieu. Here, we expand our laboratory findings and show the effect of vesicles on natural populations of E. huxleyi in a mesocosm setting. We profile the small-RNA (sRNA) cargo of vesicles that were produced by E. huxleyi during bloom succession, and show that vesicles applied to natural assemblages expedite viral infection and prolong the half-life of this major mortality agent of E. huxleyi. We subsequently reveal that exposure of the natural assemblage to E. huxleyi-derived vesicles modulates not only host-virus dynamics, but also other components of the microbial food webs, thus emphasizing the importance of extracellular vesicles to microbial interactions in the marine environment.

microbiology↗

bioRxiv2020

Viral infection of algal blooms leaves a halogenated footprint on the dissolved organic matter in the ocean

Algal blooms are important hotspots of primary production in the ocean, forming the basis of the marine food web and fueling the pool of dissolved organic matter (DOM)1, which is the largest global inventory of reduced carbon and a market place for metabolic exchange in the ocean2. Marine viruses are key players in controlling algal bloom demise and act as major biogeochemical drivers of nutrient cycling and metabolic fluxes by shunting algal biomass from higher trophic levels to the DOM pool, a process termed the viral shunt3,4. Nevertheless, the metabolic composition of virus-induced DOM (vDOM) in the marine environment is unknown. To decode the metabolic footprint of the viral shunt, we induced a bloom of the ecologically important alga Emiliania huxleyi in the natural environment, and followed its succession using an untargeted exometabolomics approach. Here we show that algal bloom succession induces extensive and dynamic changes in the exometabolic landscape, especially during bloom demise. By correlating to a specific viral gene marker, we discovered a set of novel chlorine-iodine-containing metabolites that were induced by viral infection and copiously released during bloom demise. We further detected several of these chloro-iodo metabolites in virus-infected open ocean blooms of E. huxleyi, supporting their use as sensitive biomarkers for virus-induced demise in the natural environment. Therefore, we propose halogenation to be a hallmark of the E. huxleyi vDOM, providing insights into the profound metabolic consequences of viral infection for the marine DOM pool.

microbiology↗

bioRxiv2020

Direct observation of RAG recombinase recruitment to chromatin and the IgH locus in live pro-B cells

The RAG1 and RAG2 proteins introduce double-strand DNA breaks at antigen-receptor loci in developing lymphocytes to initiate V(D)J recombination. How RAG proteins find the correct target locus in a vast excess of non-specific chromatin is not known. Here we measured dynamics of RAG1/RAG2 interactions with chromatin in living pro-B cells. We found that the majority of RAG1 or RAG1/RAG2 complex is in a fast 3D diffusive state, and the residual slow diffusive (bound) fraction was determined by a non-core portion of RAG1, and the PHD domain of RAG2. The RAG proteins exhibited distinct dynamics at the IgH locus. In particular, RAG2 increased the probability of RAG1 binding to IgH, a property that likely explains its non-catalytic role in V(D)J recombination. Our observations reveal how RAG finds its targets in developing B cells. One Sentence SummarySingle-molecule imaging of the RAG recombinase reveals its search strategy for chromatin, H3K4me3 and antibody gene loci in living cells.

biophysics↗

bioRxiv2019

Overprecision Increases Subsequent Surprise

Overconfident people should be surprised that they are so often wrong. Are they? Three studies examined the relationship between confidence and surprise in order to shed light on the psychology of overprecision in judgment. Participants reported ex-ante confidence in their beliefs, and after receiving accuracy feedback, they then reported ex-post surprise. Results show that more ex-ante confidence produces less ex-post surprise for correct answers; this relationship reverses for incorrect answers. However, this sensible pattern only holds for some measures of confidence; it fails for confidence-interval measures. The results can help explain the robust durability of overprecision in judgment.

animal behavior and cognition↗

bioRxiv2019

Tracking infection dynamics at single-cell level reveals highly resolved expression programs of a large virus infecting algal blooms

Nucleocytoplasmic large DNA viruses have the largest genomes among all viruses and infect diverse eukaryotes across various ecosystems, but their expression regulation and infection strategies are not well understood. We profiled single-cell transcriptomes of the worldwide-distributed microalga Emiliania huxleyi and its specific coccolithovirus responsible for massive bloom demise. Heterogeneity in viral transcript levels detected among single cells was used to reconstruct the viral transcriptional trajectory and to map cells along a continuum of infection states. This enabled identification of novel viral genetic programs, which are composed of five kinetic classes with distinct promoter elements. The infection substantially changed the host transcriptome, causing rapid shutdown of protein-encoding nuclear transcripts at the onset of infection, while the plastid and mitochondrial transcriptomes persisted to mid- and late stages, respectively. Single-cell transcriptomics thereby opens the way for tracking host-pathogen infection dynamics at high resolution within microbial communities in the marine environment.

microbiology↗

bioRxiv2018

Bacterial virulence against an oceanic bloom-forming phytoplankter is mediated by algal DMSP

Emiliania huxleyi is a bloom forming microalga that impacts the global sulfur cycle by producing large amounts of dimethylsulfoniopropionate (DMSP) and its volatile metabolic product dimethyl sulfide (DMS). Top-down regulation of E. huxleyi blooms is attributed to viruses and grazers, however, the possible involvement of algicidal bacteria in bloom demise is still elusive. We isolated from a North Atlantic E. huxleyi bloom a Roseobacter strain, Sulfitobacter D7, which exhibited algicidal effects against E. huxleyi upon co-culturing. Both the alga and the bacterium were found to co-occur during a natural E. huxleyi bloom, therefore establishing this host-pathogen system as an attractive, ecologically relevant model for studying alga-bacterium interaction in the oceans. During interaction, Sulfitobacter D7 consumed and metabolized algal DMSP to produce high amounts of methanethiol, an alternative product of DMSP catabolism. We revealed a unique strain-specific response, in which E. huxleyi strains that exuded higher amounts of DMSP were more susceptible to Sulfitobacter D7 infection. Intriguingly, exogenous application of DMSP enhanced bacterial virulence and induced susceptibility in a resistant algal strain to the bacterial pathogen. This DMSP-dependent pathogenicity was highly specific as compared to supplementation of propionate and glycerol. We propose a novel function for DMSP, in addition to its central role in mutualistic interactions, as a mediator of bacterial virulence that may regulate E. huxleyi blooms.

microbiology↗

bioRxiv2018

\"In plaque-mass spectrometry imaging\" reveals a major metabolic shift towards odd-chain fatty acid lipids induced by host-virus interactions

Tapping into the metabolic cross-talk between a host and its virus can reveal unique strategies employed during infection. Viral infection is a dynamic process that generates an evolving metabolic landscape. Gaining a continuous view into the infection process is highly challenging and is limited by current metabolomics approaches, which typically measure the average of the entire population at various stages of infection. Here, we took a novel approach to study the metabolic basis of host-virus interactions between the bloom-forming alga Emiliania huxleyi and its specific virus. We combined a classical method in virology, plaque assay, with advanced mass spectrometry imaging (MSI), an approach we termed in plaque-MSI. Taking advantage of the spatial characteristics of the plaque, we mapped the metabolic landscape induced during infection in a high spatiotemporal resolution, unfolding the infection process in a continuous manner. Further unsupervised spatially-aware clustering, combined with known lipid biomarkers, revealed a systematic metabolic shift towards lipids containing the odd-chain fatty acid pentadecanoic acid (C15:0) induced during infection. Applying in plaque-MSI might pave the way for the discovery of novel bioactive compounds that mediate the chemical arms race of host-virus interactions in diverse model systems.

microbiology↗