Biology subjects

Zinser, E.

Publications and source records attributed to Zinser, E..

3 recordsLinked to original sources

bioRxiv2026

Three catalase-peroxidases promote extended stationary phase survival of Vibrio natriegens during ecologically relevant exposures to exogenous hydrogen peroxide

Vibrio natriegens is an emerging model organism in laboratory and biotechnology research that is known for its fast growth rate and diverse metabolic capabilities. However, little is known about its response to oxidative stress. Reactive oxygen species (ROS) are ubiquitous stressors for most aerobic life and without mitigation can lead to cellular damage and sometimes death. V. natriegens is unusual amongst the Vibrio genus and Proteobacterial phylum in having three copies of katG encoding the bifunctional ROS defense enzyme catalase-peroxidase. The biological significance of having three copies of this protective gene was investigated with phylogenetics and gene inactivation studies. We determined that two of the katG copies arose recently via duplication and subsequent divergence. Analysis of single, double, and triple {Delta}katG constructs revealed each katG gene product contributes to survival during exposure to ecologically relevant concentrations of exogenous hydrogen peroxide (HOOH) under stationary phase conditions but found the genes were dispensable for HOOH resistance during exponential growth. We also demonstrated the involvement of the RpoS regulon in V. natriegens oxidative stress response in stationary phase. As an outcome of this investigation, we identified and repaired several spontaneous loss-of-function mutations of rpoS in laboratory cultures of the V. natriegens type strain ATCC 14048. Together, these results provide physiological and evolutionary insights into V. natriegens ROS response.

microbiology↗

bioRxiv2026

Glycosylated GM-CSF expands B-1b cells and B-1b plasma cells and programs them for immunosuppression

The myeloid growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) exhibits paradoxical pro- and anti-inflammatory functions, but the factors determining these divergent outcomes remain unclear. Here, we report that this functional divergence is controlled by its glycosylation. Murine recombinant fully glycosylated GM-CSF (rgGM-CSF) specifically induces immunosuppressive cell types, whereas its recombinant non-glycosylated counterpart (rngGM-CSF) promotes effector immune cells. Using single-cell ATAC-sequencing and flow cytometry, we show that rgGM-CSF has a previously unrecognized ability to effectively expand IL-10+ LAG-3+ PD-L1+ B-1b plasma cells (PCs) with immunosuppressive properties and self reactive natural IgM secretion. Although rgGM-CSF also promotes the expansion of hematopoietic stem and progenitor cells (HSPCs) and monocytic myeloid-derived suppressor cells (M-MDSCs), adoptive transfer experiments demonstrate that the rgGM-CSF-induced B-1b PCs are responsible for an IL-10-dependent long-term protection in mice from experimental autoimmune-encephalomyelitis (EAE). Our data suggest that glycosylation enhances the systemic bioavailability and activity of GM-CSF and promotes the expansion of immunoregulatory cells rather than pro-inflammatory myeloid effector cells. Together, these results demonstrate that the dual activity of GM-CSF is controlled by its glycosylation, resulting in opposing immune functions. These findings support a re-evaluation of human rgGM-CSF (regramostim) as a potential therapeutic strategy for immunosuppression in transplantation and autoimmune diseases. Key pointsO_LIGlycosylated GM-CSF promotes B-1b cells and B-1b plasma cells expansion and establishes their long-term imprinting as IL-10+ LAG3+ PD-L1+ natural IgM secreting regulatory cells. C_LIO_LIAlbumin binding enhances the systemic activity of glycosylated GM-CSF in generating regulatory B-1b plasma cells. C_LIO_LIGlycosylated GM-CSF injections into mice expand M-MDSCs, but their suppressive iNOS production is only maintained short-term. C_LIO_LINon-glycosylated GM-CSF injections preferentially promote expansion of pro-inflammatory effector monocytes and neutrophils. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=179 HEIGHT=200 SRC="FIGDIR/small/703206v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1814c57org.highwire.dtl.DTLVardef@1bb0e95org.highwire.dtl.DTLVardef@1ba8011org.highwire.dtl.DTLVardef@12df69f_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Epigenome analysis of an algae-infecting giant virus reveals a unique methylation motif catalogue

DNA methylation can epigenetically alter gene expression and serve as a mechanism for genomic stabilization. Advancements in long-read sequencing technology have allowed for increased exploration into the methylation profiles of various organisms, including viruses. Studies into the Nucleocytoviricota phylum of giant dsDNA viruses have revealed unique strategies for genomic methylation. However, given the diversity across this phylum, further inquiries into specific lineages are necessary. Kratosvirus quantuckense is predicted to encode six distinct methyltransferases, which bear homology to other methyltransferases across the many clades of Nucleocytoviricota. We found that this virus methylates its own DNA with high consistency and targets up to nine different motifs for DNA adenine methylation. Methylation levels varied depending on the associated motif. Likewise, distinct motifs were enriched within unique genomic regions. Collectively this suggests that each methyltransferase targets unique DNA regions and may suggest they have varying functionality. This work reveals an array of methyltransferase activity in Kratosvirus quantuckense and begins to implicate the importance of DNA methylation to the Nucleocytoviricota infection cycle.

microbiology↗