Publications

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Publications in peer reviewed journals

12 Publications found
  • Peripheral blood vessels are a niche for blood-borne meningococci.

    Capel E, Barnier JP, Zomer AL, Bole-Feysot C, Nussbaumer T, Jamet A, Lécuyer H, Euphrasie D, Virion Z, Frapy E, Pélissier P, Join-Lambert O, Rattei T, Bourdoulous S, Nassif X, Coureuil M
    2017 - Virulence, in press

    Abstract: 

    Neisseria meningitidis is the causative agent of cerebrospinal meningitis and that of a rapidly progressing fatal septic shock known as purpura fulminans. Meningococcemia is characterized by bacterial adhesion to human endothelial cells of the microvessels. Host specificity has hampered studies on the role of blood vessels colonization in N. meningitidis associated pathogenesis. In this work, using a humanized model of SCID mice allowing the study of bacterial adhesion to human cells in an in vivo context we demonstrate that meningococcal colonization of human blood vessels is a prerequisite to the establishment of sepsis and lethality. To identify the molecular pathways involved in bacterial virulence, we performed transposon insertion site sequencing (Tn-seq) in vivo. Our results demonstrate that 36% of the genes that are important for growth in the blood of mice are dispensable when bacteria colonize human blood vessels, suggesting that human endothelial cells lining the blood vessels are feeding niches for N. meningitidis in vivo. Altogether, our work proposes a new paradigm for meningococcal virulence in which colonization of blood vessels is associated with metabolic adaptation and sustained bacteremia responsible for sepsis and subsequent lethality.

  • The desert plant Phoenix dactylifera closes stomata via nitrate-regulated SLAC1 anion channel.

    Müller HM, Schäfer N, Bauer H, Geiger D, Lautner S, Fromm J, Riederer M, Bueno A, Nussbaumer T, Mayer K, Alquraishi SA, Alfarhan AH, Neher E, Al-Rasheid KAS, Ache P, Hedrich R
    2017 - New Phytol., in press

    Abstract: 

    Date palm Phoenix dactylifera is a desert crop well adapted to survive and produce fruits under extreme drought and heat. How are palms under such harsh environmental conditions able to limit transpirational water loss? Here, we analysed the cuticular waxes, stomata structure and function, and molecular biology of guard cells from P. dactylifera. To understand the stomatal response to the water stress phytohormone of the desert plant, we cloned the major elements necessary for guard cell fast abscisic acid (ABA) signalling and reconstituted this ABA signalosome in Xenopus oocytes. The PhoenixSLAC1-type anion channel is regulated by ABA kinase PdOST1. Energy-dispersive X-ray analysis (EDXA) demonstrated that date palm guard cells release chloride during stomatal closure. However, in Cl(-) medium, PdOST1 did not activate the desert plant anion channel PdSLAC1 per se. Only when nitrate was present at the extracellular face of the anion channel did the OST1-gated PdSLAC1 open, thus enabling chloride release. In the presence of nitrate, ABA enhanced and accelerated stomatal closure. Our findings indicate that, in date palm, the guard cell osmotic motor driving stomatal closure uses nitrate as the signal to open the major anion channel SLAC1. This initiates guard cell depolarization and the release of anions together with potassium.

  • Time-course expression QTL atlas of the global transcriptional response of wheat to Fusarium graminearum.

    Samad-Zamini M, Schweiger W, Nussbaumer T, Mayer KF, Buerstmayr H
    2017 - Plant Biotechnol. J., in press

    Abstract: 

    Fusarium head blight is a devastating disease of small grain cereals such as bread wheat (Triticum aestivum). The pathogen switches from a biotrophic to a nectrotrophic lifestyle in course of disease development forcing its host to adapt its defence strategies. Using a genetical genomics approach we illustrate genome-wide reconfigurations of genetic control over transcript abundances between two decisive time points after inoculation with the causative pathogen Fusarium graminearum. Whole transcriptome measurements have been recorded for 163 lines of a wheat doubled haploid population segregating for several resistance genes yielding 15 552 at 30 hours and 15 888 eQTL at 50 hours after inoculation. The genetic map saturated with transcript abundance-derived markers identified of a novel QTL on chromosome 6A, besides the previously reported QTL Fhb1 and Qfhs.ifa-5A. We find a highly different distribution of eQTL between time points with about 40% of eQTL being unique for the respective assessed time points. But also for more than 20% of genes governed by eQTL at either time point genetic control changes in time. These changes are reflected in the dynamic compositions of three major regulatory hotspots on chromosomes 2B, 4A and 5A. In particular control of defence-related biological mechanisms concentrated in the hotspot at 4A shift to hotspot 2B as the disease progresses. Hotspots do not colocalize with phenotypic QTL and within their intervals no higher than expected number of eQTL was detected. Thus, resistance conferred by either QTL is mediated by few or single genes. This article is protected by copyright. All rights reserved.

  • Natural haplotypes of FLM non-coding sequences fine-tune flowering time in ambient spring temperatures in Arabidopsis.

    Lutz U, Nussbaumer T, Spannagl M, Diener J, Mayer KF, Schwechheimer C
    2017 - Elife, in press

    Abstract: 

    Cool ambient temperatures are major cues determining flowering time in spring. The mechanisms promoting or delaying flowering in response to ambient temperature changes are only beginning to be understood. In Arabidopsis thaliana, FLOWERING LOCUS M (FLM) regulates flowering in the ambient temperature range and FLM is transcribed and alternatively spliced in a temperature-dependent manner. We identify polymorphic promoter and intronic sequences required for FLM expression and splicing. In transgenic experiments covering 69% of the available sequence variation in two distinct sites, we show that variation in the abundance of the FLM-ß splice form strictly correlate (R2 = 0.94) with flowering time over an extended vegetative period. The FLM polymorphisms lead to changes in FLM expression (PRO2+) but may also affect FLM intron 1 splicing (INT6+). This information could serve to buffer the anticipated negative effects on agricultural systems and flowering that may occur during climate change.

  • PGSB/MIPS PlantsDB Database Framework for the Integration and Analysis of Plant Genome Data.

    Spannagl M, Nussbaumer T, Bader K, Gundlach H, Mayer KF
    2017 - Methods Mol. Biol., 33-44

    Abstract: 

    Plant Genome and Systems Biology (PGSB), formerly Munich Institute for Protein Sequences (MIPS) PlantsDB, is a database framework for the integration and analysis of plant genome data, developed and maintained for more than a decade now. Major components of that framework are genome databases and analysis resources focusing on individual (reference) genomes providing flexible and intuitive access to data. Another main focus is the integration of genomes from both model and crop plants to form a scaffold for comparative genomics, assisted by specialized tools such as the CrowsNest viewer to explore conserved gene order (synteny). Data exchange and integrated search functionality with/over many plant genome databases is provided within the transPLANT project.

  • Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization.

    Capel E, Zomer AL, Nussbaumer T, Bole C, Izac B, Frapy E, Meyer J, Bouzinba-Ségard H, Bille E, Jamet A, Cavau A, Letourneur F, Bourdoulous S, Rattei T, Nassif X, Coureuil M
    2016 - mBio, 4: in press

    Abstract: 

    Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia, affecting infants and adults worldwide. N. meningitidis is also a common inhabitant of the human nasopharynx and, as such, is highly adapted to its niche. During bacteremia, N. meningitidis gains access to the blood compartment, where it adheres to endothelial cells of blood vessels and causes dramatic vascular damage. Colonization of the nasopharyngeal niche and communication with the different human cell types is a major issue of the N. meningitidis life cycle that is poorly understood. Here, highly saturated random transposon insertion libraries of N. meningitidis were engineered, and the fitness of mutations during routine growth and that of colonization of endothelial and epithelial cells in a flow device were assessed in a transposon insertion site sequencing (Tn-seq) analysis. This allowed the identification of genes essential for bacterial growth and genes specifically required for host cell colonization. In addition, after having identified the small noncoding RNAs (sRNAs) located in intergenic regions, the phenotypes associated with mutations in those sRNAs were defined. A total of 383 genes and 8 intergenic regions containing sRNA candidates were identified to be essential for growth, while 288 genes and 33 intergenic regions containing sRNA candidates were found to be specifically required for host cell colonization.
    Meningococcal meningitis is a common cause of meningitis in infants and adults. Neisseria meningitidis (meningococcus) is also a commensal bacterium of the nasopharynx and is carried by 3 to 30% of healthy humans. Under some unknown circumstances, N. meningitidis is able to invade the bloodstream and cause either meningitis or a fatal septicemia known as purpura fulminans. The onset of symptoms is sudden, and death can follow within hours. Although many meningococcal virulence factors have been identified, the mechanisms that allow the bacterium to switch from the commensal to pathogen state remain unknown. Therefore, we used a Tn-seq strategy coupled to high-throughput DNA sequencing technologies to find genes for proteins used by N. meningitidis to specifically colonize epithelial cells and primary brain endothelial cells. We identified 383 genes and 8 intergenic regions containing sRNAs essential for growth and 288 genes and 33 intergenic regions containing sRNAs required specifically for host cell colonization.

  • Suppressed recombination and unique candidate genes in the divergent haplotype encoding Fhb1, a major Fusarium head blight resistance locus in wheat.

    Schweiger W, Steiner B, Vautrin S, Nussbaumer T, Siegwart G, Zamini M, Jungreithmeier F, Gratl V, Lemmens M, Mayer KF, Bérgès H, Adam G, Buerstmayr H
    2016 - Theor. Appl. Genet., 8: 1607-23

    Abstract: 

    Fine mapping and sequencing revealed 28 genes in the non-recombining haplotype containing Fhb1 . Of these, only a GDSL lipase gene shows a pathogen-dependent expression pattern. Fhb1 is a prominent Fusarium head blight resistance locus of wheat, which has been successfully introgressed in adapted breeding material, where it confers a significant increase in overall resistance to the causal pathogen Fusarium graminearum and the fungal virulence factor and mycotoxin deoxynivalenol. The Fhb1 region has been resolved for the susceptible wheat reference genotype Chinese Spring, yet the causal gene itself has not been identified in resistant cultivars. Here, we report the establishment of a 1 Mb contig embracing Fhb1 in the donor line CM-82036. Sequencing revealed that the region of Fhb1 deviates from the Chinese Spring reference in DNA size and gene content, which explains the repressed recombination at the locus in the performed fine mapping. Differences in genes expression between near-isogenic lines segregating for Fhb1 challenged with F. graminearum or treated with mock were investigated in a time-course experiment by RNA sequencing. Several candidate genes were identified, including a pathogen-responsive GDSL lipase absent in susceptible lines. The sequence of the Fhb1 region, the resulting list of candidate genes, and near-diagnostic KASP markers for Fhb1 constitute a valuable resource for breeding and further studies aiming to identify the gene(s) responsible for F. graminearum and deoxynivalenol resistance.

  • EffectiveDB-updates and novel features for a better annotation of bacterial secreted proteins and Type III, IV, VI secretion systems.

    Eichinger V, Nussbaumer T, Platzer A, Jehl MA, Arnold R, Rattei T
    2016 - Nucleic Acids Res., D669-74

    Abstract: 

    Protein secretion systems play a key role in the interaction of bacteria and hosts. EffectiveDB (http://effectivedb.org) contains pre-calculated predictions of bacterial secreted proteins and of intact secretion systems. Here we describe a major update of the database, which was previously featured in the NAR Database Issue. EffectiveDB bundles various tools to recognize Type III secretion signals, conserved binding sites of Type III chaperones, Type IV secretion peptides, eukaryotic-like domains and subcellular targeting signals in the host. Beyond the analysis of arbitrary protein sequence collections, the new release of EffectiveDB also provides a 'genome-mode', in which protein sequences from nearly complete genomes or metagenomic bins can be screened for the presence of three important secretion systems (Type III, IV, VI). EffectiveDB contains pre-calculated predictions for currently 1677 bacterial genomes from the EggNOG 4.0 database and for additional bacterial genomes from NCBI RefSeq. The new, user-friendly and informative web portal offers a submission tool for running the EffectiveDB prediction tools on user-provided data.

  • Examining the transcriptional response in wheat Fhb1 near-isogenic lines to Fusarium graminearum infection and deoxynivalenol treatment

    Hofstad AN, Nussbaumer T, Akhunov E, Shin S, Kugler KG, Kistler HC, Mayer KFX, Muehlbauer GJ
    2015 - The plant genome, in press

    Abstract: 

    Fusarium Head Blight (FHB) is a disease caused predominantly by the fungal pathogen
    Fusarium graminearum that affects wheat and other small grain cereals and can lead to severe
    yield loss and reduction in grain quality. Trichothecene mycotoxins, such as deoxynivalenol
    (DON), accumulate during infection and increase pathogen virulence and decrease grain quality.
    The Fhb1 locus on wheat chromosome 3BS confers type II resistance to FHB, resistance to the
    spread of infection on the spike, and has been associated with resistance to DON accumulation.
    To gain a better genetic understanding of the functional role of Fhb1 and resistance/susceptibility
    to FHB, we examined DON and ergosterol accumulation, FHB resistance, and the whole genome
    transcriptomic response using RNA-seq in a near-isogenic line (NIL) pair carrying the resistant
    and susceptible allele for Fhb1 during F. graminearum infection and DON treatment. Our results
    provide a gene expression atlas for the resistant and susceptible wheat-F. graminearum
    interaction. The DON concentration and transcriptomic results show that the rachis is a key
    location for conferring type II resistance. In addition, the wheat transcriptome analysis revealed a
    set of Fhb1-responsive genes that may play a role in resistance, and a set of DON-responsive
    genes that may play a role in trichothecene resistance. Transcriptomic results from the pathogen
    show that the F. graminearum genome responds differently to the host level of resistance. The
    results of this study extend our understanding of host and pathogen responses in the wheat-F.
    graminearum interaction.

  • Assessing the barley genome zipper and genomic resources for breeding purposes

    Silvar C, Martis M, Nussbaumer T, Haag N, Rauser R, Keilwagen J, Korzun V, Mayer K, Ordon F, Perovic D
    2015 - The plant genome, in press

    Abstract: 

    The aim of this study was to estimate the accuracy and convergence of newly developed barley genomic resources, primarily GenomeZipper (GZ) and POPulation SEQuencing (POPSEQ), at the genome-wide level and to assess their usefulness in applied barley breeding by analysing seven known loci. Comparison of barley GenomeZipper and POPSEQ maps to a newly developed consensus genetic map constructed with data from thirteen individual linkage maps yielded an accuracy of 97.8% (GenomeZipper) and 99.3% (POPSEQ), respectively, regarding the chromosome assignment. The percentage of agreement in marker position indicates that on average only 3.7% GenomeZipper and 0.7% POPSEQ positions are not in accordance with their cM coordinates in the consensus map. The fine scale comparison involved seven genetic regions on chromosomes 1H, 2H, 4H, 6H and 7H, harboring major genes and quantitative trait loci (QTL) for disease resistance. In total, 179 GZ loci were analyzed and 64 polymorphic markers were developed. Entirely, 89.1% of these were allocated within the targeted intervals and 84.2% followed the predicted order. Forty-four markers showed a match to a POPSEQ-anchored contig, the percentage of collinearity being 93.2% on average. Forty-four markers allowed the identification of twenty-five fingerprinted contigs (FPC) and a more clear delimitation of the physical regions containing the traits of interest. Our results demonstrate that an increase in marker density of barley maps by using new genomic data significantly improves the accuracy of GenomeZipper. In addition, the combination of different barley genomic resources can be considered as a powerful tool to accelerate barley breeding.

  • PGSB PlantsDB: updates to the database framework for comparative plant genome research

    Spannagl M, Nussbaumer T, Bader KC, Martis MM, Seidel M, Kugler KG, Gundlach H and Mayer KFX
    2015 - Nucleic acids research, in press

    Abstract: 

    PGSB (Plant Genome and Systems Biology: formerly MIPS) PlantsDB (http://pgsb.helmholtz-muenchen.de/plant/index.jsp) is a database framework for the comparative analysis and visualization of plant genome data. The resource has been updated with new data sets and types as well as specialized tools and interfaces to address user demands for intuitive access to complex plant genome data. In its latest incarnation, we have re-worked both the layout and navigation structure and implemented new keyword search options and a new BLAST sequence search functionality. Actively involved in corresponding sequencing consortia, PlantsDB has dedicated special efforts to the integration and visualization of complex triticeae genome data, especially for barley, wheat and rye. We enhanced CrowsNest, a tool to visualize syntenic relationships between genomes, with data from the wheat sub-genome progenitor Aegilops tauschii and added functionality to the PGSB RNASeqExpressionBrowser. GenomeZipper results were integrated for the genomes of barley, rye, wheat and perennial ryegrass and interactive access is granted through PlantsDB interfaces. Data exchange and cross-linking between PlantsDB and other plant genome databases is stimulated by the transPLANT project (http://transplantdb.eu/).

  • Joint Transcriptomic and Metabolomic Analyses Reveal Changes in the Primary Metabolism and Imbalances in the Subgenome Orchestration in the Bread Wheat Molecular Response to Fusarium graminearum.

    Nussbaumer T, Warth B, Sharma S, Ametz C, Bueschl C, Parich A, Pfeifer M, Siegwart G, Steiner B, Lemmens M, Schuhmacher R, Buerstmayr H, Mayer KF, Kugler K, Schweiger W
    2015 - G3 (Bethesda), in press

    Abstract: 

    Fusarium head blight is a prevalent disease of bread wheat (Triticum aestivum L. ), which leads to considerable losses in yield and quality. Quantitative resistance to the causative fungus Fusarium graminearum is yet poorly understood. We integrated transcriptomics and metabolomics data to dissect the molecular response to the fungus and its main virulence factor, the toxin deoxynivalenol in near-isogenic lines segregating for two resistance quantitative trait loci, Fhb1 and Qfhs.ifa-5A. The data sets portrait rearrangements in the primary metabolism and the translational machinery to counter the fungus and the effects of the toxin and highlight distinct changes in the metabolism of glutamate in lines carrying Qfhs.ifa-5A. These observations are possibly due to the activity of two amino acid permeases located in the QTL confidence interval, which may contribute to increased pathogen endurance. Mapping to the highly resolved region of Fhb1 reduced the list of candidates to few genes that are specifically expressed in presence of the QTL and in response to the pathogen, which include a receptor-like protein kinase, a protein kinase, and an E3 ubiquitin-protein ligase. On a genome-scale level the individual subgenomes of hexaploid wheat contribute differentially to defense: Especially the D subgenome exhibited a pronounced response to the pathogen and contributed significantly to the overall defense response.

Book chapters and other publications

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