Biology subjects

Otto, C.

Publications and source records attributed to Otto, C..

8 recordsLinked to original sources

bioRxiv2026

Serial acquisition of virulence determinants and aminoglycoside resistance by the emerging Streptococcus agalactiae sequence type 1010 lineage

Based on recent epidemiologic studies, Streptococcus agalactiae (Group B Streptococcus; GBS) sequence type (ST) 1010 is an emerging lineage now identified in multiple countries. We report the phylogenetic and genomic characteristics of a set of 55 GBS sequence type (ST) 1010 strains, as well as two newly described single-locus variants of ST1010. A core genome phylogeny suggests that ST1010 is closely related to both ST452 and the hypervirulent clonal complex (CC) 17 GBS lineage. Notably, we demonstrate that genes encoding two virulence determinants previously described as specific to CC17 GBS, the HvgA adhesin and the serine-rich repeat protein Srr2, are both present in ST1010 genomes. Srr2 is shared with members of ST452. High-level gentamicin resistance (HLGR) encoded on an IS256 mobile element, previously described in a small number of ST1010 isolates, is present in a distinct ST1010 subclade encompassing the majority of ST1010 isolates. The relationship between ST452 (serotype IV), ST1010 (serotype IV), and ST17 (serotype III) strains suggests that ST17 may have arisen from a serotype IV ancestor and later acquired the type III capsule locus. Taken together, these findings clarify the phylogenetic position of ST1010 and suggest sequential acquisition of virulence determinants and HLGR prior to its international emergence. IMPACT STATEMENTST1010 GBS has emerged internationally, with colonizing and invasive isolates described in the United States, Dominican Republic, Netherlands, and Italy. Using a core genome phylogeny and targeted detection of genomic regions, we demonstrate that ST1010 shares specific virulence determinants with the CC17 hypervirulent GBS lineage and that HLGR is confined to a specific numerically dominant subclade of ST1010. Our work spotlights the importance of future epidemiologic and genomic surveillance of ST1010 and related lineages. DATA SUMMARYPublicly available genomic data were used from three previously published studies (Laycock KM et al., McGee L et al., Khan UB et al.), as well as a set of newly sequenced GBS genomes from clinical strains originating in New York City (NYC). The corresponding accession numbers and detailed information for all strains are provided in the Table.

microbiology↗

bioRxiv2026

Intrathecal antibodies cross-react with EBV BRRF2 and human antigens in multiple sclerosis

Intrathecal antibody synthesis is a hallmark of multiple sclerosis (MS). Although some intrathecally synthesized antibodies in MS are known to target viral antigens, the spectrum of their antigenic specificities remains incompletely defined. We combined proteome-wide antibody profiling by Phage ImmunoPrecipitation Sequencing (PhIP-Seq) with cross-compartment analytics (MICAR) to study intrathecal antibody synthesis at peptide resolution in paired CSF and serum samples from individuals with MS (n = 40) and non-MS controls (n = 83). While intrathecal antibody responses in MS were polyspecific and included reactivities to various viruses, we identified a subset of individuals with a convergent intrathecal antibody reactivity to a previously described motif within the Epstein-Barr virus (EBV) protein BRRF2 (BRRF2408-415). This motif-directed response showed co-reactivity with multiple CNS-expressed human antigens. In an independent cohort of n = 909 individuals with MS and n = 311 controls, including individuals with NMOSD and MOGAD, serum antibodies to BRRF2408-415 were detected in 8.36% of MS individuals and in 0.64% of non-MS controls, corresponding to an odds ratio for MS of 14.1 (95% CI: 4.4-86.04). Within MS individuals, BRRF2408-415 seropositivity was associated with increased intrathecal IgG synthesis. Cross-reactivity of antibodies to BRRF2408-415 with human targets, including TRIM71 and RTN2, was confirmed by competition ELISA and cell-based assays. Together, these data define an intrathecal EBV BRRF2-linked antibody signature with human target cross-reactivity in a subset of MS individuals. This signature identifies a highly specific serological marker in MS and may support future stratification of the heterogeneous MS spectrum.

immunology↗

bioRxiv2025

Sensitive, non-invasive detection of chronic wasting disease in wild and captive white-tailed deer using fecal volatile profiling

Chronic Wasting Disease (CWD) is a universally fatal, transmissible prion disease affecting cervids. Primarily found among deer populations in North America, the disease has spread across the continent and made forays into Europe and Asia as well. Currently, accurate methods for detecting CWD infection require post-mortem dissection of the lymph nodes and brainstem of affected animals. New, high-sensitivity methods of detecting CWD in living animals are sorely needed to help curb spread of this devastating disease in farmed and wild deer. Here, we use two-dimensional gas chromatography-mass spectrometry (GCxGC-MS) to detect volatile organic compounds (VOCs) released from the feces of white-tailed deer (WTD) for differentiation of the feces of CWD-negative and CWD-positive animals. We report four discrete VOCs in captive WTD and ten discrete VOCs in wild WTD, with which we can discriminate CWD-positive and CWD-negative samples. Additionally, we evaluate the ability to detect CWD early during disease progression, by comparing samples from the early stage of infection with samples from late stage and uninfected WTD. Our data suggest that detection of VOCs from the feces of WTD -- both in captive and wild populations -- can serve as a highly sensitive and non-invasive technique for identifying CWD infection in living animals.

microbiology↗

bioRxiv2022

Physical association of low density lipoprotein particles and extracellular vesicles unveiled by single particle analysis

Extracellular vesicles (EVs) in blood plasma are recognized as potential biomarkers for disease. Although blood plasma is easily obtainable, analysis of EVs at the single particle level is still challenging due to the biological complexity of this body fluid. Besides EVs, plasma contains different types of lipoproteins particles (LPPs), that outnumber EVs by orders of magnitude and which partially overlap in biophysical properties such as size, density and molecular makeup. Consequently, during EV isolation LPPs are often co-isolated. Furthermore, physical EV-LPP complexes have been observed in purified EV preparations. Since co-isolation or association of LPPs can impact single EV-based analysis and biomarker profiling, we investigated whether under physiological conditions LPPs and EVs can associate by using cryo-electron tomography, label-free synchronous Rayleigh and Raman scattering analysis of optically trapped particles and fluorescence-based high resolution single particle flow cytometric analysis. Furthermore, we evaluated the impact on flow cytometric analysis in the absence or presence of different types of LPPs using in vitro spike-in experiments of purified tumor cell line-derived EVs in different classes of purified human LPPs. Based on orthogonal single-particle analysis techniques we demonstrated that EV-LPP complexes can form under physiological conditions. Furthermore, we show that in fluorescence-based flow cytometric EV analysis staining of LPPs, as well as EV-LPP associations can influence EV analysis in a quantitative and qualitative manner. Our findings demonstrate that the biological colloidal matrix of the biofluid in which EVs reside impacts their buoyant density, size and/or refractive index (RI), which may have consequences for down-stream EV analysis.

cell biology↗

bioRxiv2021

Chromosome-level Thlaspi arvense genome provides new tools for translational research and for a newly domesticated cash cover crop of the cooler climates

Thlaspi arvense (field pennycress) is being domesticated as a winter annual oilseed crop capable of improving ecosystems and intensifying agricultural productivity without increasing land use. It is a selfing diploid with a short life cycle and is amenable to genetic manipulations, making it an accessible field-based model species for genetics and epigenetics. The availability of a high quality reference genome is vital for understanding pennycress physiology and for clarifying its evolutionary history within the Brassicaceae. Here, we present a chromosome-level genome assembly of var. MN106-Ref with improved gene annotation, and use it to investigate gene structure differences between two accessions (MN108 and Spring32-10) that are highly amenable to genetic transformation. We describe small RNAs, pseudogenes, and transposable elements, and highlight tissue specific expression and methylation patterns. Resequencing of forty wild accessions provides insights into genome-wide genetic variation as well as QTL regions for flowering time and a seedling color phenotype. Altogether, these data will serve as a tool for pennycress improvement in general and for translational research across the Brassicaceae.

plant biology↗

bioRxiv2021

Manipulating base quality scores enables variant calling from bisulfite sequencing alignments using conventional Bayesian approaches

Calling germline SNP variants from bisulfite-converted sequencing data poses a challenge for conventional software, which have no inherent capability to dissociate true polymorphisms from artificial mutations induced by the chemical treatment. Nevertheless, SNP data is desirable both for genotyping and to understand the DNA methylome in the context of the genetic background. The confounding effect of bisulfite conversion can be resolved by observing differences in allele counts on a per-strand basis, whereby artificial mutations are reflected by non-complementary base pairs. Herein, we present a computational pre-processing approach for adapting sequence alignment data, thus indirectly enabling downstream analysis in this manner using conventional variant calling software such as GATK or Freebayes. In comparison to specialised tools, the method represents a marked improvement in precision-sensitivity based on high-quality, published benchmark datasets for both human and model plant variants.

bioinformatics↗

bioRxiv2020

Comprehensive benchmarking of software for mapping whole genome bisulfite data: from read alignment to DNA methylation analysis

Whole genome bisulfite sequencing is currently at the forefront of epigenetic analysis, facilitating the nucleotide-level resolution of 5-methylcytosine (5mC) on a genome-wide scale. Specialised software have been developed to accommodate the unique difficulties in aligning such sequencing reads to a given reference, building on the knowledge acquired from model organisms such as human, or Arabidopsis thaliana. As the field of epigenetics expands its purview to non-model plant species, new challenges arise which bring into question the suitability of previously established tools. Herein, nine short-read aligners are evaluated: Bismark, BS-Seeker2, BSMAP, BWA-meth, ERNE-BS5, GEM3, GSNAP, Last, and segemehl. Precision-recall of simulated alignments, in comparison to real sequencing data obtained from three natural accessions, reveals on-balance that BWA-meth and BSMAP are able to make the best use of the data during mapping. The influence of difficult-to-map regions, characterised by deviations in sequencing depth over repeat annotations, is evaluated in terms of the mean absolute deviation of the resulting methylation calls in comparison to a realistic methylome. Downstream methylation analysis is responsive to the handling of multi-mapping reads relative to mapping quality (MAPQ), and potentially susceptible to bias arising from the increased sequence complexity of densely-methylated reads.

bioinformatics↗

bioRxiv2018

Functional characterization of Arabidopsis ARGONAUTE 3 in reproductive tissue

Arabidopsis encodes ten ARGONAUTE (AGO) effectors of RNA silencing, canonically loaded with either 21-22nt small RNAs (sRNA) to mediate post-transcriptional-gene-silencing (PTGS) or 24nt sRNAs to promote RNA-directed-DNA-methylation. Using full-locus constructs, we characterized the expression, biochemical properties, and possible modes of action of AGO3. Although AGO3 arose from a recent duplication at the AGO2 locus, their expression differs drastically, with AGO2 being expressed in both male and female gametes whereas AGO3 accumulates in aerial vascular terminations and specifically in chalazal seed integuments. Accordingly, AGO3 down-regulation alters gene expression in siliques. Similar to AGO2, AGO3 binds sRNAs with a strong 5-adenosine bias, but unlike most Arabidopsis AGOs - AGO2 included - it binds efficiently both 24nt and 21nt sRNAs. AGO3 immunoprecipitation experiments in siliques revealed that these sRNAs mostly correspond to genes and intergenic regions. in a manner reflecting their respective accumulation from their loci-of-origin. AGO3 localizes to the cytoplasm and co-fractionates with polysomes to possibly mediate PTGS via translation inhibition.\n\nSignificance statementThe regulation of gene expression by small RNAs is key for proper plant development and defense. Here, we characterize Arabidopsis AGO3 expression pattern, microRNA regulation and biochemical properties during sexual reproduction.

plant biology↗