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), BRICS, CSSB and the Study Centre Hannover, Hannover/Germany.

 

  • Metagenomic insights into resistant starch degradation by human gut microbiota.

    Vital, Marius; Howe, Adina; Bergeron, Nathalie; Krauss, Ronald M; Jansson, Janet K; Tiedje, James M; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-09-28)
    Several studies monitoring alterations of the community structure upon resistant starch (RS) interventions are available, although comprehensive function-based analyses are lacking. Recently, a multiomics approach based on 16S rRNA gene-sequencing, metaproteomics and metabolomics on fecal samples from individuals subjected to high and low doses of type-2 RS (RS2; 48 g and 3 g/2500 kcal, respectively, daily for 2 weeks) in a cross-over intervention experiment was performed. In the present study, we did pathway-based metagenomic analyses on samples from a subset of individuals (n=12) from that study to get additional, detailed insights into the functional structure at high resolution during RS2 intervention. A mechanistic framework based on obtained results is proposed where primary degradation was governed by Firmicutes, with Ruminococcus bromii as a major taxon involved, providing fermentation substrates and increased acetate concentrations for growth of various major butyrate-producers exhibiting the enzyme butyryl-CoA:acetate CoA-transferase. H2-scavenging sulfite reducers and acetogens concurrently increased. Individual responses of gut microbiota were noted where seven of the 12 participants displayed all features of the outlined pattern, whereas four individuals showed mixed behavior and one subject was unresponsive. Intervention order did not affect the outcome emphasizing a constant substrate supply for maintaining specific functional communities.
  • Breaking the vicious cycle of antibiotic killing and regrowth of biofilm-residing .

    Müsken, Mathias; Pawar, Vinay; Schwebs, Timo; Bähre, Heike; Felgner, Sebastian; Weiss, Siegfried; Häussler, Susanne; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-10-08)
    Biofilm-residing bacteria embedded in an extracellular matrix are protected from diverse physico-chemical insults. In addition to the general recalcitrance of biofilm-bacteria, high bacterial loads in biofilm-associated infections significantly diminishes the efficacy of antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial treatment protocols, that have been established to serve the eradication of acute infections, fail to clear biofilm-associated chronic infections. In the present study, we applied automated confocal microscopy on Pseudomonas aeruginosa to monitor dynamic killing of biofilm-grown bacteria by tobramycin and colistin in real-time. We revealed that the time required for surviving bacteria to repopulate the biofilm could be taken as measure for effectiveness of the antimicrobial treatment. It depends on the: i) nature and concentration of the antibiotic, ii) duration of antibiotic treatment; iii) application as mono or combination therapy and iv) time intervals of drug administration. The vicious cycle of killing and repopulation of biofilm bacteria could also be broken in an in vivo model system by applying successive antibiotic dosages with time intervals that do not allow full reconstitution of the biofilm communities. Treatment regimens that consider the important aspects of antimicrobial killing kinetics bear the potential to improve control of biofilm regrowth. This is an important and underestimated factor that is bound to ensure sustainable treatment success of chronic infections.
  • The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo.

    Todt, Daniel; Moeller, Nora; Praditya, Dimas; Kinast, Volker; Friesland, Martina; Engelmann, Michael; Verhoye, Lieven; Sayed, Ibrahim M; Behrendt, Patrick; Dao Thi, Viet Loan; Meuleman, Philip; Steinmann, Eike; TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. (2018-09-01)
    Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients and type I interferon (IFN) has been evaluated in a few infected transplantation patients in vivo. However, no effective and specific treatments against HEV infections are currently available. In this study, we evaluated the natural compound silvestrol, isolated from the plant Aglaia foveolata, and known for its specific inhibition of the DEAD-box RNA helicase eIF4A in state-of-the-art HEV experimental model systems. Silvestrol blocked HEV replication of different subgenomic replicons in a dose-dependent manner at low nanomolar concentrations and acted additive to ribavirin (RBV). In addition, HEV p6-based full length replication and production of infectious particles was reduced in the presence of silvestrol. A pangenotypic effect of the compound was further demonstrated with primary isolates from four different human genotypes in HEV infection experiments of hepatocyte-like cells derived from human embryonic and induced pluripotent stem cells. In vivo, HEV RNA levels rapidly declined in the feces of treated mice while no effect was observed in the vehicle treated control animals. In conclusion, silvestrol could be identified as pangenotypic HEV replication inhibitor in vitro with additive effect to RBV and further demonstrated high potency in vivo. The compound therefore may be considered in future treatment strategies of chronic hepatitis E in immunocompromised patients.
  • Complete genome sequence of C130_2, a novel myovirus infecting pathogenic Escherichia coli and Shigella strains.

    Sváb, Domonkos; Falgenhauer, Linda; Rohde, Manfred; Chakraborty, Trinad; Tóth, István; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-09-20)
    The genome sequence of a novel virulent bacteriophage, named " C130_2", that is morphologically a member of the family Myoviridae is reported. The 41,775-base-pair double-stranded DNA genome of C130_2 contains 59 ORFs but exhibits overall low sequence similarity to bacteriophage genomes for which sequences are publicly available. Phylogenetic analysis indicated that C130_2 represents a new phage type. C130_2 could be propagated well on enterohemorrhagic Escherichia coli (EHEC) O157:H7 and other pathogenic E. coli strains, as well as on strains of various Shigella species.
  • Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro.

    Abeln, Markus; Borst, Kristina M; Cajic, Samanta; Thiesler, Hauke; Kats, Elina; Albers, Iris; Kuhn, Maike; Kaever, Volkhard; Rapp, Erdmann; Münster-Kühnel, Anja; Weinhold, Birgit; TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. (2017-07-04)
    The negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. In order to elucidate the impact of sialylation on differentiation processes in the absence of maternal influences, we generated mouse embryonic stem cell (mESC) lines that lack CMP-Sia synthetase (CMAS) and thereby the ability to activate Sia to CMP-Sia. Loss of CMAS activity resulted in an asialo cell surface accompanied by an increase in glycoconjugates with terminal galactosyl and oligo-LacNAc residues, as well as intracellular accumulation of free Sia. Remarkably, these changes did not impact intracellular metabolites or the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas

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