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Weigel, C.

Publications and source records attributed to Weigel, C..

7 recordsLinked to original sources

Cytokine signaling regulates multiple stages of gammaherpesvirus infection in myeloid cells

The gammaherpesviruses, including Epstein-Barr Virus and Kaposis Sarcoma-associated Herpesvirus, establish lifelong infections by maintaining a balance between lytic and latent infection states. How this balance is regulated in myeloid cells, an important but understudied cell type that can achieve both infection states, remains unclear. Using the murine gammaherpesvirus 68 (MHV68) model, we show that IFNg; and IL-4 reciprocally regulate lytic infection in macrophages in a time- and JAK/STAT signaling dependent-manner, with basal JAK/STAT signaling further restricting lytic infection. Using a combination of MHV68 reporter viruses, cellular and molecular techniques, we demonstrate that IFNg blocks lytic replication through at least two distinct mechanisms, restricting delivery to or stability of the viral genome in the nucleus and potently restricting lytic cycle progression downstream of the immediate-early viral transactivator, RTA. These findings define specific points during lytic infection where IFNg; to enforce restricted, latent-like infection in myeloid cells.

immunology↗

Directional Matching of Swimming Polarity Provides a Competitive Advantage During Bacterial Magneto-Aerotaxis

BackgroundMagnetotactic bacteria (MTB) utilize magnetosomes to align passively with Earths magnetic field. Magnetic alignment, coupled with flagellar motility and aerotaxis, enables MTB to perform magneto-aerotaxis--a strategy that constrains their movement to a one-dimensional trajectory along geomagnetic field lines, optimizing their search for low-oxygen niches in aquatic environments. Beyond axially constrained movement, environmental MTB isolates exhibit a hemispherically determined swimming polarity--favoring either magnetic north or south--that has been suggested to facilitate descent into oxygen-depleted zones. However, a direct quantitative evaluation of how matching swimming polarity influences navigation toward low-oxygen environments has remained elusive. Here, we employed microcapillary assays to assess the functional significance of polar magneto-aerotaxis in the model organism Magnetospirillum gryphiswaldense. ResultsWe found that a magnetic field configuration matching the predominant swimming polarity of the population results in an up to 4-fold increased peak intensity of the aerotactic band compared to populations with non-matching polarity. Competition assays using fluorescently labeled north- and south-seeking populations confirmed that congruence between swimming polarity and magnetic field orientation markedly improves aerotactic band formation in oxygen gradients. Alongside our main findings, we noted biomagnetism-independent phototactic responses integrated with aerotaxis, driving collective unidirectional migration along the oxygen gradient. ConclusionsOur results provide direct evidence that matching swimming polarity with the magnetic field confers a clear advantage in navigating oxygen gradients. These findings reinforce the role of the geomagnetic field in shaping MTB behavior and highlight the adaptive value of magnetotactic swimming polarity in environmental navigation.

microbiology↗

Dual chormosomal origins of replication (oriC) in the genomes of the Halomonadaceae - a prediction study

Chromosome replication is a key process in the bacterial cell cycle. Most, but not all, bacteria follow the "Replicon Model" for the initiation step: Their genomes encode an initiator and contain a replicator locus at which the initiator acts as activator. The single chromosomes of the model organisms E. coli and B. subtilis each contain one dnaA gene encoding the initiator protein DnaA, and one replication origin, oriC. The single chromosome of P. aeruginosa is the only exception known to date that contains two functional replication origins, oriC1 and oriC2. Since a preliminary study indicated that this unusual dualorigin configuration is also found in other Pseudomonadaceae, it seemed interesting to examine whether it can also be predicted for the Halomonadaceae, a sister clade of the Pseudomonadaceae. Here I show that of 163 Halomonadaceae genomes with an annotated dnaA gene, 23 have a single predicted origin, oriC2, and 138 have dual predicted origins, oriC1 and oriC2, with the genomic localizations of both corresponding to those in the P. aeruginosa genome. The distribution of species/strains with single or dual predicted oriC{middle dot}s in the taxogenomic tree of the Halomonadaceae suggests that a demise of oriC1 or its "downgrading" occurred repeatedly during their diversification. Experimental studies of chromosome replication in individual species/strains of the Halomonadaceae, and likewise computational cell cycle simulations, can benefit from taking the single/dual origin predictions presented here into account.

molecular biology↗

The Kocurious case of Noodlococcus: genomic insights into Kocuria rhizophila from characterisation of a laboratory contaminant

The laboratory contaminant Noodlococcus was named for its coccoid cells and unusual colony morphology, which resembled a pile of noodles. Along with laboratory characterisation and electron microscopy, we generated a complete Noodlococcus genome sequence using Illumina and Oxford Nanopore data. The genome consisted of a single, circular, 2732108 bp chromosome that shared 97.5% Average Nucleotide Identity (ANI) with the Kocuria rhizophila type strain TA68. We identified genomic features involved in replication (oriC), carotenoid synthesis (crt), and genome defence (CRISPR-Cas), and discovered four novel mobile elements (ISKrh4-7). Despite its environmental ubiquity and relevance to food production, bioremediation, and human medicine, there have been few genomic studies of the Kocuria genus. We conducted a comparative, phylogenetic, and pangenomic examination of all 257 publicly available Kocuria genomes, with a particular focus on the 56 that were identified as K. rhizophila. We found that there are two phylogenetically distinct clades of K. rhizophila, with within-clade ANI values of 96.7-100.0% and between-clade values of 89.5-90.4%. The second clade, which we refer to as K. pseudorhizophila, exhibited ANI values of <95% relative to TA68 and constitutes a separate species. Delineation of the two clades would be consistent with the rest of the genus, where all other species satisfy the 95% ANI threshold criteria. Differences in the K. rhizophila and K. pseudorhizophila pangenomes likely reflect phenotypic as well as evolutionary divergence. This distinction is relevant to clinical and industrial settings, as strains and genomes from both clades are currently used interchangeably, which may lead to reproducibility issues and phenotype-genotype discordance. Investigating an innocuous laboratory contaminant has therefore provided useful insights into the understudied species K. rhizophila, prompting an unexpected reassessment of its taxonomy. Impact statementBacterial genome sequence databases are dominated by a relatively small number of medically relevant genera, while most of the global bacterial populations diversity is largely uncharacterised. Kocuria is a widespread bacterial genus with industrial and medical relevance. Despite its ubiquity, only 22 complete and 235 draft Kocuria genomes were publicly available at the outset of this study. Our phylogenetic and pangenomic examination of all available Kocuria genomes was the first for this genus, providing insights into its diversity and taxonomy. Most notably, we found that Kocuria rhizophila is comprised of two clades that are sufficiently divergent to constitute different species, but are frequently used interchangeably in experimental and genomic research. The complete, high-quality Noodlococcus genome generated and characterised here can serve as a reference for true K. rhizophila, particularly while there is only a draft genome sequence available for type strain TA68. Data summarySequencing reads and the assembled Noodlococcus genome are available from NBCI BioProject accession PRJNA835814 and BioSample accession SAMN28111796. The complete sequence of the Noodlococcus chromosome can be found in the GenBank nucleotide database under accession number CP097204.1. Entries for the novel insertion sequences ISKrh4 to ISKrh7 can be found in the ISFinder database (https://isfinder.biotoul.fr).

genomics↗

Uncontrolled CD21low age-associated and B1 B cell accumulation caused by failure of an EGR2/3 tolerance checkpoint

CD21low age-associated or atypical memory B cells, enriched for autoantibodies and poised for plasma cell differentiation, accumulate in large numbers in chronic infections, autoimmune disease and immunodeficiency, posing the question of what checkpoints normally oppose their excessive accumulation. Here, we reveal a critical role for the calcium-NFAT-regulated transcription factors EGR2 and EGR3. In the absence of EGR2 and EGR3 within B cells, CD21low and B1 B cells accumulate and circulate in young mice in numbers 10-20 times greater than normal, over-express a large set of EGR2 ChIP-seq target genes including known drivers of plasma cell differentiation and under-express drivers of follicular germinal centers. Most follicular B cells constitutively express Egr2 proportionally to surface IgM down-regulation by self-antigens, and EGR2/3 deficiency abolishes this characteristic anergy response. These results define a key transcriptional checkpoint repressing CD21low B cell formation and inform how NFATC1 or EGR2 mutations promote B1 cell-derived chronic lymphocytic leukemias.

immunology↗

Neuroglia Infection by Rabies Virus after Anterograde Virus Spread in Peripheral Neurons

The highly neurotropic rabies virus (RABV) enters peripheral neurons at axon termini and requires long distance axonal transport and trans-synaptic spread between neurons for the infection of the central nervous system (CNS). Whereas laboratory strains are almost exclusively detected in neurons, recent 3D imaging of field RABV-infected brains revealed an remarkably high proportion of infected astroglia, indicating that in contrast to attenuated lab strains highly virulent field viruses are able to suppress astrocyte mediated innate immune responses and virus elimination pathways. While fundamental for CNS invasion, in vivo field RABV spread and tropism in peripheral tissues is understudied. Here, we used three-dimensional light sheet and confocal laser scanning microscopy to investigate the in vivo distribution patterns of a field RABV clone in cleared high-volume tissue samples after infection via a natural (intramuscular; hind leg) and an artificial (intracranial) inoculation route. Immunostaining of virus and host markers provided a comprehensive overview of RABV infection in the CNS and peripheral nerves after centripetal and centrifugal virus spread. Importantly, we identified non-neuronal,axon-ensheathing neuroglia (Schwann cells, SCs) in peripheral nerves of the hind leg and facial regions as a target cell population of field RABV. This suggest that virus release from axons and infected SCs is part of the RABV in vivo cycle and may affect RABV-related demyelination of peripheral neurons and local innate immune responses. Detection of RABV in axon surrounding myelinating SCs after i.c. infection further provided evidence for anterograde spread of RABV, highlighting that RABV axonal transport and spread of infectious virus in peripheral nerves is not exclusively retrograde. Our data support a new model in which, comparable to CNS neuroglia, SC infection in peripheral nerves suppresses glia-mediated innate immunity and delays antiviral host responses required for successful transport from the peripheral infection sites to the brain.

microbiology↗

γBOriS: Identification of Origins of Replication in Gammaproteobacteria using Motif-based Machine Learning

The biology of bacterial cells is, in general, based on the information encoded on circular chromosomes. Regulation of chromosome replication is an essential process which mostly takes place at the origin of replication (oriC). Identification of high numbers of oriC is a prerequisite to enable systematic studies that could lead to insights of oriC functioning as well as novel drug targets for antibiotic development. Current methods for identyfing oriC sequences rely on chromosome-wide nucleotide disparities and are therefore limited to fully sequenced genomes, leaving a superabundance of genomic fragments unstudied. Here, we present{gamma} BOriS (Gammaproteobacterial oriC Searcher), which accurately identifies oriC sequences on gammaproteobacterial chromosomal fragments by employing motif-based DNA classification. Using{gamma} BOriS, we created BOriS DB, which currently contains 25,827 oriC sequences from 1,217 species, thus making it the largest available database for oriC sequences to date.

bioinformatics↗