This is the institutional Repository of the Helmholtz Centre for Infection Research in Braunschweig/Germany (HZI), the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken/Germany, the TWINCORE Zentrum für Exprerimentelle und Klinische Infektionsforschung, Hannover/Germany,Helmholtz-Institut für RNA-basierte Infektionsforschung (HIRI), Würzburg/Germany, Braunschweig Integrated Centre for Systems biology (BRICS), Centre for Structural Systems Biology (CSSB) the Study Centre Hannover, Hannover/Germany and the Centre for Individualised Infection Medicine (CiiM).

 

  • Updates to the recently introduced family Lacipirellulaceae in the phylum Planctomycetes: isolation of strains belonging to the novel genera Aeoliella, Botrimarina, Pirellulimonas and Pseudobythopirellula and the novel species Bythopirellula polymerisocia and Posidoniimonas corsicana.

    Wiegand, Sandra; Jogler, Mareike; Boedeker, Christian; Heuer, Anja; Peeters, Stijn H; Kallscheuer, Nicolai; Jetten, Mike S M; Kaster, Anne-Kristin; Rohde, Manfred; Jogler, Christian; et al. (Springer, 2020-11-05)
    Eight novel strains of the phylum Planctomycetes were isolated from different aquatic habitats. Among these habitats were the hydrothermal vent system close to Panarea Island, a public beach at Mallorca Island, the shore of Costa Brava (Spain), and three sites with brackish water in the Baltic Sea. The genome sizes of the novel strains range from 4.33 to 6.29 Mb with DNA G+C contents between 52.8 and 66.7%. All strains are mesophilic (Topt 24-30 °C) and display generation times between 17 and 94 h. All eight isolates constitute novel species of either already described or novel genera within the family Lacipirellulaceae. Two of the novel species, Posidoniimonas polymericola (type strain Pla123aT = DSM 103020T = LMG 29466T) and Bythopirellula polymerisocia (type strain Pla144T = DSM 104841T = VKM B-3442T), belong to established genera, while the other strains represent the novel genera Aeoliella gen. nov., Botrimarina gen. nov., Pirellulimonas gen. nov. and Pseudobythopirellula gen. nov. Based on our polyphasic analysis, we propose the species Aeoliella mucimassa sp. nov. (type strain Pan181T = DSM 29370T = LMG 31346T = CECT 9840T = VKM B-3426T), Botrimarina colliarenosi sp. nov. (type strain Pla108T = DSM 103355T = LMG 29803T), Botrimarina hoheduenensis sp. nov. (type strain Pla111T = DSM 103485T = STH00945T, Jena Microbial Resource Collection JMRC), Botrimarina mediterranea sp. nov. (type strain Spa11T = DSM 100745T = LMG 31350T = CECT 9852T = VKM B-3431T), Pirellulimonas nuda sp. nov. (type strain Pla175T = DSM 109594T = CECT 9871T = VKM B-3448T) and Pseudobythopirellula maris sp. nov. (type strain Mal64T = DSM 100832T = LMG 29020T).
  • Molecular Dissection of Neurodevelopmental Disorder-Causing Mutations in CYFIP2.

    Schaks, Matthias; Reinke, Michael; Witke, Walter; Rottner, Klemens; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-05-29)
    Actin remodeling is frequently regulated by antagonistic activities driving protrusion and contraction downstream of Rac and Rho small GTPases, respectively. WAVE regulatory complex (WRC), which primarily operates downstream of Rac, plays pivotal roles in neuronal morphogenesis. Recently, two independent studies described de novo mutations in the CYFIP2 subunit of WRC, which caused intellectual disability (ID) in humans. Although mutations had been proposed to effect WRC activation, no experimental evidence for this was provided. Here, we made use of CRISPR/Cas9-engineered B16-F1 cell lines that were reconstituted with ID-causing CYFIP variants in different experimental contexts. Almost all CYFIP2-derived mutations (7 out of 8) promoted WRC activation, but to variable extent and with at least two independent mechanisms. The majority of mutations occurs in a conserved WAVE-binding region, required for WRC transinhibition. One mutation is positioned closely adjacent to the Rac-binding A site and appears to ease Rac-mediated WRC activation. As opposed to these gain-of-function mutations, a truncating mutant represented a loss-of-function variant and failed to interact with WRC components. Collectively, our data show that explored CYFIP2 mutations frequently, but not always, coincide with WRC activation and suggest that normal brain development requires a delicate and precisely tuned balance of neuronal WRC activity.
  • Effect of a strict hygiene bundle for the prevention of nosocomial transmission of SARS-CoV-2 in the hospital: a practical approach from the field.

    Ambrosch, Andreas; Rockmann, Felix; Klawonn, Frank; Lampl, Benedikt; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2020-10-20)
    Background: During the novel coronavirus disease (COVID-19) pandemic it is crucial for hospitals to implement infection prevention strategies to reduce nosocomial transmission to the lowest possible number. This is all the more important because molecular tests for identifying SARS-CoV-2 infected patients are uncertain, and the resources available for them are limited. In this view, a monocentric, retrospective study with an interventional character was conducted to investigate the extent to which the introduction of a strict hygiene bundle including a general mask requirement and daily screening for suspicious patients has an impact on the SARS-CoV-2 nosocomial rate in the pandemic environment. Methods: All inpatients from a maximum care hospital in Regensburg (Bavaria) between March 1st and June 10th 2020 were included. Patient with respiratory symptoms were tested for SARS-CoV-2 at admission, patients were managed according to a standard hygiene protocol. At the end of March a strict hygiene bundle was introduced including a general mask obligation and a daily clinical screening of inpatients for respiratory symptoms. Nosocomial infection rate for COVID-19 and the risk for infection transmission estimated by the nosocomial incidence density before and after introduction the hygiene bundle were compared. The infection pressure for the hospital during the entire observational period was characterized by the infection reports in the region in relation to the number of hospitalized COVID-19 patients and the number of infected employees. Results: In fact, after the introduction of a strict hygiene bundle including a general mouth and nose protection obligation and a daily clinical screening of suspicious patients, a significant reduction of the nosocomial rate from 0.28 to 0.06 (p = 0.026) was observed. Furthermore, the risk of spreading hospital-acquired infections also decreased dramatically from 0.0007 to 0.00018 (p = 0.031; rate ratio after/before 0.25 (95%CI 0.06, 1.07) despite a slow decrease of the hospital COVID 19-prevalence and an increase of infected employees. Conclusion: The available data underline that a strict hygiene bundle seem to be associated with a decrease of nosocomial SARS-CoV-2 transmission in the pandemic situation.
  • Impact of process temperature and organic loading rate on cellulolytic/hydrolytic biofilm microbiomes during biomethanation of ryegrass silage revealed by genome-centered metagenomics and metatranscriptomics

    Maus, Irena; Klocke, Michael; Derenkó, Jaqueline; Stolze, Yvonne; Beckstette, Michael; Jost, Carsten; Wibberg, Daniel; Blom, Jochen; Henke, Christian; Willenbücher, Katharina; et al. (BMC, 2020-03-02)
    Background: Anaerobic digestion (AD) of protein-rich grass silage was performed in experimental two-stage twophase biogas reactor systems at low vs. increased organic loading rates (OLRs) under mesophilic (37 °C) and thermophilic (55 °C) temperatures. To follow the adaptive response of the biomass-attached cellulolytic/hydrolytic biofilms at increasing ammonium/ammonia contents, genome-centered metagenomics and transcriptional profiling based on metagenome assembled genomes (MAGs) were conducted. Results: In total, 78 bacterial and archaeal MAGs representing the most abundant members of the communities, and featuring defined quality criteria were selected and characterized in detail. Determination of MAG abundances under the tested conditions by mapping of the obtained metagenome sequence reads to the MAGs revealed that MAG abundance profiles were mainly shaped by the temperature but also by the OLR. However, the OLR effect was more pronounced for the mesophilic systems as compared to the thermophilic ones. In contrast, metatranscriptome mapping to MAGs subsequently normalized to MAG abundances showed that under thermophilic conditions, MAGs respond to increased OLRs by shifting their transcriptional activities mainly without adjusting their proliferation rates. This is a clear difference compared to the behavior of the microbiome under mesophilic conditions. Here, the response to increased OLRs involved adjusting of proliferation rates and corresponding transcriptional activities. The analysis led to the identification of MAGs positively responding to increased OLRs. The most outstanding MAGs in this regard, obviously well adapted to higher OLRs and/or associated conditions, were assigned to the order Clostridiales (Acetivibrio sp.) for the mesophilic biofilm and the orders Bacteroidales (Prevotella sp. and an unknown species), Lachnospirales (Herbinix sp. and Kineothrix sp.) and Clostridiales (Clostridium sp.) for the thermophilic biofilm. Genome-based metabolic reconstruction and transcriptional profiling revealed that positively responding MAGs mainly are involved in hydrolysis of grass silage, acidogenesis and / or acetogenesis. Conclusions: An integrated -omics approach enabled the identification of new AD biofilm keystone species featuring outstanding performance under stress conditions such as increased OLRs. Genome-based knowledge on the metabolic potential and transcriptional activity of responsive microbiome members will contribute to the development of improved microbiological AD management strategies for biomethanation of renewable biomass. Keywords: Metagenome assembled genomes, Integrated -omics, Polyomics, Anaerobic digestion, Biogas, Bioconversion, Microbial community structure, Methane, Metabolic activity
  • Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion.

    Damiano-Guercio, Julia; Kurzawa, Laëtitia; Mueller, Jan; Dimchev, Georgi; Schaks, Matthias; Nemethova, Maria; Pokrant, Thomas; Brühmann, Stefan; Linkner, Joern; Blanchoin, Laurent; et al. (eLife Sciences Publications, 2020-05-11)
    Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.

View more