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).

 

  • Buchwald-Hartwig versus Microwave-Assisted Amination of Chloroquinolines: En Route to the Pyoverdin Chromophore

    Seubert, Philipp; Freund, Marcel; Rudolf, Richard; Lin, Yulin; Altevogt, Luca; Bilitewski, Ursula; Baro, Angelika; Laschat, Sabine; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Thieme Verlag, 2020-07-22)
    The reaction of 2-chloro-3-nitroquinoline and a series of amines and aminoalkanoates under basic microwave-mediated conditions and Buchwald-Hartwig amination conditions is reported. The microwave irradiation favored the reaction with amines, resulting in yields up to 80%, while amino acid functionalization gave yields comparable to those of BuchwaldHartwig amination. (2R)-4-[(6,7-dimethoxy-3-nitroquinolinyl)amino]-2-hydroxybutanoate could be successfully cyclized to the pyoverdin chromophore, a subunit of siderophores.
  • Unsaturated Fatty Acids Control Biofilm Formation of and Other Gram-Positive Bacteria.

    Yuyama, Kamila Tomoko; Rohde, Manfred; Molinari, Gabriella; Stadler, Marc; Abraham, Wolf-Rainer; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-11-08)
    Infections involving biofilms are difficult to treat due to increased resistances against antibiotics and the immune system. Hence, there is an urgent demand for novel drugs against biofilm infections. During our search for novel biofilm inhibitors from fungi, we isolated linoleic acid from the ascomycete Hypoxylon fragiforme which showed biofilm inhibition of several bacteria at sub-MIC concentrations. Many fatty acids possess antimicrobial activities, but their minimum inhibitory concentrations (MIC) are high and reports on biofilm interferences are scarce. We demonstrated that not only linoleic acid but several unsaturated long-chain fatty acids inhibited biofilms at sub-MIC concentrations. The antibiofilm activity exerted by long-chain fatty acids was mainly against Gram-positive bacteria, especially against Staphylococcus aureus. Micrographs of treated S. aureus biofilms revealed a reduction in the extracellular polymeric substances, pointing to a possible mode of action of fatty acids on S. aureus biofilms. The fatty acids had a strong species specificity. Poly-unsaturated fatty acids had higher activities than saturated ones, but no obvious rule could be found for the optimal length and desaturation for maximal activity. As free fatty acids are non-toxic and ubiquitous in food, they may offer a novel tool, especially in combination with antibiotics, for the control of biofilm infections.
  • Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections.

    Gödecke, Natascha; Riedel, Jan; Herrmann, Sabrina; Behme, Sara; Rand, Ulfert; Kubsch, Tobias; Cicin-Sain, Luka; Hauser, Hansjörg; Köster, Mario; Wirth, Dagmar; et al. (Oxford Academic, 2020-11-18)
    Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained-but optionally de-activatable-expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections.
  • Expression, purification and crystal structure determination of a ferredoxin reductase from the actinobacterium Thermobifida fusca.

    Rodriguez Buitrago, Jhon Alexander; Klünemann, Thomas; Blankenfeldt, Wulf; Schallmey, Anett; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Wiley & Sons, 2020-07-28)
    he ferredoxin reductase FdR9 from Thermobifida fusca, a member of the oxygenase-coupled NADH-dependent ferredoxin reductase (FNR) family, catalyses electron transfer from NADH to its physiological electron acceptor ferredoxin. It forms part of a putative three-component cytochrome P450 monooxygenase system in T. fusca comprising CYP222A1 and the [3Fe-4S]-cluster ferredoxin Fdx8 as well as FdR9. Here, FdR9 was overexpressed and purified and its crystal structure was determined at 1.9 Å resolution. The overall structure of FdR9 is similar to those of other members of the FNR family and is composed of an FAD-binding domain, an NAD-binding domain and a C-terminal domain. Activity measurements with FdR9 confirmed a strong preference for NADH as the cofactor. Comparison of the FAD- and NAD-binding domains of FdR9 with those of other ferredoxin reductases revealed the presence of conserved sequence motifs in the FAD-binding domain as well as several highly conserved residues involved in FAD and NAD cofactor binding. Moreover, the NAD-binding site of FdR9 contains a modified Rossmann-fold motif, GxSxxS, instead of the classical GxGxxG motif.
  • Patient satisfaction & use of health care: a cross-sectional study of asylum seekers in the Freiburg initial reception centre.

    Bockey, Annabelle J; Janda, Aleš; Braun, Cornelia; Müller, Anne-Maria; Stete, Katarina; Kern, Winfried V; Rieg, Siegbert R; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2020-08-03)
    Background: In response to a high number of incoming asylum seekers and refugees (AS&R) in Germany, initial reception centres were established to provide immediate shelter, food and health support. This study evaluates the satisfaction with and use of the health care available at the Freiburg initial reception centre (FIRC) where an integrated health care facility (ICF) was set up in 2015. Methods: We assessed use and satisfaction with health services available to resident AS&R within and outside the FIRC in a cross-sectional design. Data were collected in 2017 using a questionnaire with both open and closed ended items. Results: The majority of 102 included participants were young (mean age 24.2; 95%CI 22.9-25.5, range 18-43) males (93%), from Sub-Saharan Africa (92%). High use frequencies were reported from returning patients of the ICF; with 56% fortnightly use and 19% daily use reported. The summary of satisfaction scores indicated that 84% (CI95 76-89%) of respondents were satisfied with the ICF. Multivariate analysis showed female gender and non-English speaking as risk factors for low satisfaction. Outside the FIRC, the satisfaction scores indicated that 60% of participants (95%CI 50-69%) were satisfied with the health care received. Conclusion: Our study shows that AS&R residing in the FIRC are generally satisfied with the services at the ICF, though strategies to enhance care for females and non-English speakers should be implemented. Satisfaction with health care outside of the FIRC was not as high, indicating the need to improve quality of care and linkage to regular health care services.

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