Now showing items 21-40 of 3886

    • Quo vadis clinical diagnostic microbiology?

      Haag, Sara; Häussler, Susanne; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2021-07-26)
      No abstract available
    • Reaching the Unreachable: Strategies for HCV Eradication in Patients With Refractory Opioid Addiction-A Real-world Experience.

      Sandmann, Lisa; Deppe, Julian; Beier, Christoph; Ohlendorf, Valerie; Schneider, Julia; Wedemeyer, Heiner; Wedegärtner, Felix; Cornberg, Markus; Maasoumy, Benjamin; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (2021-06-17)
    • Immune Responses to Pandemic H1N1 Influenza Virus Infection in Pigs Vaccinated with a Conserved Hemagglutinin HA1 Peptide Adjuvanted with CAF01 or CDA/αGalCerMPEG.

      López-Serrano, Sergi; Cordoba, Lorena; Pérez-Maillo, Mónica; Pleguezuelos, Patricia; Remarque, Edmond J; Ebensen, Thomas; Guzmán, Carlos A; Christensen, Dennis; Segalés, Joaquim; Darji, Ayub; et al. (MDPI, 2021-07-06)
      This study aimed to evaluate the immune response and protection correlates against influenza virus (IV) infection in pigs vaccinated with the novel NG34 HA1 vaccine candidate adjuvanted with either CAF®01 or CDA/αGalCerMPEG (αGCM). Two groups of six pigs each were vaccinated intramuscularly twice with either NG34 + CAF®01 or NG34 + CDA/αGCM. As controls, groups of animals (n = 6 or 4) either non-vaccinated or vaccinated with human seasonal trivalent influenza vaccine or NG34 + Freund's adjuvant were included in the study. All animal groups were challenged with the 2009 pandemic (pdm09) strain of H1N1 (total amount of 7 × 106 TCID50/mL) via intranasal and endotracheal routes 21 days after second vaccination. Reduced consolidated lung lesions were observed both on days three and seven post-challenge in the animals vaccinated with NG34 + CAF®01, whereas higher variability with relatively more severe lesions in pigs of the NG34 + CDA/αGCM group on day three post-infection. Among groups, animals vaccinated with NG34 + CDA/αGCM showed higher viral loads in the lung at seven days post infection whereas animals from NG34 + CAF®01 completely abolished virus from the lower respiratory tract. Similarly, higher IFNγ secretion and stronger IgG responses against the NG34 peptide in sera was observed in animals from the NG34 + CAF®01 group as compared to the NG34 + CDA/αGCM. NG34-vaccinated pigs with adjuvanted CAF®01 or CDA/αGCM combinations resulted in different immune responses as well as outcomes in pathology and viral shedding.
    • Pseudomonas aeruginosa PA14 produces R-bodies, extendable protein polymers with roles in host colonization and virulence.

      Wang, Bryan; Lin, Yu-Cheng; Vasquez-Rifo, Alejandro; Jo, Jeanyoung; Price-Whelan, Alexa; McDonald, Shujuan Tao; Brown, Lewis M; Sieben, Christian; Dietrich, Lars E P; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Nature, 2021-07-29)
      R-bodies are long, extendable protein polymers formed in the cytoplasm of some bacteria; they are best known for their role in killing of paramecia by bacterial endosymbionts. Pseudomonas aeruginosa PA14, an opportunistic pathogen of diverse hosts, contains genes (referred to as the reb cluster) with potential to confer production of R-bodies and that have been implicated in virulence. Here, we show that products of the PA14 reb cluster associate with R-bodies and control stochastic expression of R-body structural genes. PA14 expresses reb genes during colonization of plant and nematode hosts, and R-body production is required for full virulence in nematodes. Analyses of nematode ribosome content and immune response indicate that P. aeruginosa R-bodies act via a mechanism involving ribosome cleavage and translational inhibition. Our observations provide insight into the biology of R-body production and its consequences during P. aeruginosa infection.
    • Tbx21 and foxp3 are Epigenetically Stabilized in T-Bet Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs.

      Elfaki, Yassin; Yang, Juhao; Boehme, Julia; Schultz, Kristin; Bruder, Dunja; Falk, Christine S; Huehn, Jochen; Floess, Stefan; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2021-07-14)
      During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet- Tregs are epigenetically stabilized during IAV-induced infection in the lung.
    • Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10).

      Fushimi, Makoto; Buck, Hannes; Balbach, Melanie; Gorovyy, Anna; Ferreira, Jacob; Rossetti, Thomas; Kaur, Navpreet; Levin, Lonny R; Buck, Jochen; Quast, Jonathan; et al. (ACS, 2021-07-14)
      Soluble adenylyl cyclase (sAC) has gained attention as a potential therapeutic target given the role of this enzyme in intracellular signaling. We describe successful efforts to design improved sAC inhibitors amenable for in vivo interrogation of sAC inhibition to assess its potential therapeutic applications. This work culminated in the identification of TDI-10229 (12), which displays nanomolar inhibition of sAC in both biochemical and cellular assays and exhibits mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound.
    • RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum.

      Ponath, Falk; Tawk, Caroline; Zhu, Yan; Barquist, Lars; Faber, Franziska; Vogel, Jörg; HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany. (Nature Research, 2021-07-08)
      Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.
    • Occasional comment: Fungal identification to species-level can be challenging.

      Raja, Huzefa A; Oberlies, Nicholas H; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2021-07-14)
      [No abstract available]
    • Analysis of Bacterial Communities on North Sea Macroalgae and Characterization of the Isolated Planctomycetes gen. nov., sp. nov., sp. nov., sp. nov. and sp. nov.

      Wiegand, Sandra; Rast, Patrick; Kallscheuer, Nicolai; Jogler, Mareike; Heuer, Anja; Boedeker, Christian; Jeske, Olga; Kohn, Timo; Vollmers, John; Kaster, Anne-Kristin; et al. (MDPI, 2021-07-13)
      Planctomycetes are bacteria that were long thought to be unculturable, of low abundance, and therefore neglectable in the environment. This view changed in recent years, after it was shown that members of the phylum Planctomycetes can be abundant in many aquatic environments, e.g., in the epiphytic communities on macroalgae surfaces. Here, we analyzed three different macroalgae from the North Sea and show that Planctomycetes is the most abundant bacterial phylum on the alga Fucus sp., while it represents a minor fraction of the surface-associated bacterial community of Ulva sp. and Laminaria sp. Especially dominant within the phylum Planctomycetes were Blastopirellula sp., followed by Rhodopirellula sp., Rubripirellula sp., as well as other Pirellulaceae and Lacipirellulaceae, but also members of the OM190 lineage. Motivated by the observed abundance, we isolated four novel planctomycetal strains to expand the collection of species available as axenic cultures since access to different strains is a prerequisite to investigate the success of planctomycetes in marine environments. The isolated strains constitute four novel species belonging to one novel and three previously described genera in the order Pirellulales, class Planctomycetia, phylum Planctomycetes.
    • Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life.

      Jacobsen, Henning; Walendy-Gnirß, Kerstin; Tekin-Bubenheim, Nilgün; Kouassi, Nancy Mounogou; Ben-Batalla, Isabel; Berenbrok, Nikolaus; Wolff, Martin; Dos Reis, Vinicius Pinho; Zickler, Martin; Scholl, Lucas; et al. (Springer Nature, 2021-08-16)
      Influenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life. Offspring born to influenza A virus infected mothers are stunted in growth and more vulnerable to heterologous infections (influenza B virus and MRSA) than those born to PBS- or poly(I:C)-treated mothers. Enhanced vulnerability to infection in neonates is associated with reduced haematopoetic development and immune responses. In particular, alveolar macrophages of offspring exposed to maternal influenza have reduced capacity to clear second hit pathogens. This impaired pathogen clearance is partially reversed by adoptive transfer of alveolar macrophages from healthy offspring born to uninfected dams. These findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring.
    • Cyclofaulknamycin with the Rare Amino Acid D-capreomycidine Isolated from a Well-Characterized Strain.

      Horbal, Liliya; Stierhof, Marc; Palusczak, Anja; Eckert, Nikolas; Zapp, Josef; Luzhetskyy, Andriy N; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (MDPI, 2021-07-28)
      Targeted genome mining is an efficient method of biosynthetic gene cluster prioritization within constantly growing genome databases. Using two capreomycidine biosynthesis genes, alpha-ketoglutarate-dependent arginine beta-hydroxylase and pyridoxal-phosphate-dependent aminotransferase, we identified two types of clusters: one type containing both genes involved in the biosynthesis of the abovementioned moiety, and other clusters including only arginine hydroxylase. Detailed analysis of one of the clusters, the flk cluster from Streptomyces albus, led to the identification of a cyclic peptide that contains a rare D-capreomycidine moiety for the first time. The absence of the pyridoxal-phosphate-dependent aminotransferase gene in the flk cluster is compensated by the XNR_1347 gene in the S. albus genome, whose product is responsible for biosynthesis of the abovementioned nonproteinogenic amino acid. Herein, we report the structure of cyclofaulknamycin and the characteristics of its biosynthetic gene cluster, biosynthesis and bioactivity profile.
    • Clinical Course of Infection and Cross-Species Detection of Equine Parvovirus-Hepatitis.

      Reinecke, Birthe; Klöhn, Mara; Brüggemann, Yannick; Kinast, Volker; Todt, Daniel; Stang, Alexander; Badenhorst, Marcha; Koeppel, Katja; Guthrie, Alan; Groner, Ursula; et al. (MDPI, 2021-07-26)
      The intriguing structural complexity of molecules produced by natural organisms is uncontested. Natural scaffolds serve as an important basis for the development of molecules with broad applications, e.g., therapeutics or agrochemicals. Research in recent decades has demonstrated that by means of classic metabolite extraction from microbes only a small portion of natural products can be accessed. The use of genome mining and heterologous expression approaches represents a promising way to discover new natural compounds. In this paper we report the discovery of a novel cyclic pentapeptide called bonsecamin through the heterologous expression of a cryptic NRPS gene cluster from Streptomyces albus ssp. chlorinus NRRL B-24108 in Streptomyces albus Del14. The new compound was successfully isolated and structurally characterized using NMR. The minimal set of genes required for bonsecamin production was determined through bioinformatic analysis and gene deletion experiments. A biosynthetic route leading to the production of bonsecamin is proposed in this paper.
    • Bonsecamin: A New Cyclic Pentapeptide Discovered through Heterologous Expression of a Cryptic Gene Cluster.

      Lasch, Constanze; Stierhof, Marc; Estévez, Marta Rodríguez; Myronovskyi, Maksym; Zapp, Josef; Luzhetskyy, Andriy N; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (MDPI, 2021-07-31)
      The intriguing structural complexity of molecules produced by natural organisms is uncontested. Natural scaffolds serve as an important basis for the development of molecules with broad applications, e.g., therapeutics or agrochemicals. Research in recent decades has demonstrated that by means of classic metabolite extraction from microbes only a small portion of natural products can be accessed. The use of genome mining and heterologous expression approaches represents a promising way to discover new natural compounds. In this paper we report the discovery of a novel cyclic pentapeptide called bonsecamin through the heterologous expression of a cryptic NRPS gene cluster from Streptomyces albus ssp. chlorinus NRRL B-24108 in Streptomyces albus Del14. The new compound was successfully isolated and structurally characterized using NMR. The minimal set of genes required for bonsecamin production was determined through bioinformatic analysis and gene deletion experiments. A biosynthetic route leading to the production of bonsecamin is proposed in this paper.
    • Development of a data generator for multivariate numerical data with arbitrary correlations and distributions

      Vahldiek, Kai; Zhou, Libing; Zhu, Wenfeng; Klawonn, Frank; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (IOS Press, 2021-01-01)
      Artificial or simulated data are particularly relevant in tests and benchmarks for machine learning methods, in teaching for exercises and for setting up analysis workflows. They are relevant when real data may not be used for reasons of data protection, or when special distributions or effects should be present in the data to test certain machine learning methods. In this paper a generator for multivariate numerical data with arbitrary marginal distributions and – as far as possible – arbitrary correlations is presented. The data generator is implemented in the open source statistics software R. It can also be used for categorical variables, if data are generated separately for the corresponding characteristics of a categorical variable. Additionally, outliers can be integrated. The use of the data generator is demonstrated with a concrete example.
    • Assessing excess mortality in times of pandemics based on principal component analysis of weekly mortality data-the case of COVID-19.

      Vanella, Patrizio; Basellini, Ugofilippo; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer Nature, 2021-08-09)
      The COVID-19 outbreak has called for renewed attention to the need for sound statistical analyses to monitor mortality patterns and trends over time. Excess mortality has been suggested as the most appropriate indicator to measure the overall burden of the pandemic in terms of mortality. As such, excess mortality has received considerable interest since the outbreak of COVID-19 began. Previous approaches to estimate excess mortality are somewhat limited, as they do not include sufficiently long-term trends, correlations among different demographic and geographic groups, or autocorrelations in the mortality time series. This might lead to biased estimates of excess mortality, as random mortality fluctuations may be misinterpreted as excess mortality. We propose a novel approach that overcomes the named limitations and draws a more realistic picture of excess mortality. Our approach is based on an established forecasting model that is used in demography, namely, the Lee-Carter model. We illustrate our approach by using the weekly age- and sex-specific mortality data for 19 countries and the current COVID-19 pandemic as a case study. Our findings show evidence of considerable excess mortality during 2020 in Europe, which affects different countries, age, and sex groups heterogeneously. Our proposed model can be applied to future pandemics as well as to monitor excess mortality from specific causes of death.
    • Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of CagA.

      Knorr, Jakob; Sharafutdinov, Irshad; Fiedler, Florian; Soltan Esmaeili, Delara; Rohde, Manfred; Rottner, Klemens; Backert, Steffen; Tegtmeyer, Nicole; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2021-06-03)
      Cortactin is a well-known regulatory protein of the host actin cytoskeleton and represents an attractive target of microbial pathogens like Helicobacter pylori. H. pylori manipulates cortactin's phosphorylation status by type-IV secretion-dependent injection of its virulence protein CagA. Multiple host tyrosine kinases, like FAK, Src, and Abl, are activated during infection, but the pathway(s) involved is (are) not yet fully established. Among them, Src and Abl target CagA and stimulate tyrosine phosphorylation of the latter at its EPIYA-motifs. To investigate the role of cortactin in more detail, we generated a CRISPR/Cas9 knockout of cortactin in AGS gastric epithelial cells. Surprisingly, we found that FAK, Src, and Abl kinase activities were dramatically downregulated associated with widely diminished CagA phosphorylation in cortactin knockout cells compared to the parental control. Together, we report here a yet unrecognized cortactin-dependent signaling pathway involving FAK, Src, and Abl activation, and controlling efficient phosphorylation of injected CagA during infection. Thus, the cortactin status could serve as a potential new biomarker of gastric cancer development.
    • A simplified LC-MS/MS method for the quantification of the cardiovascular disease biomarker trimethylamine-N-oxide and its precursors

      Rox, Katharina; Rath, Silke; Pieper, Dietmar H.; Vital, Marius; Brönstrup, Mark; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier BV, 2021-03)
      Trimethylamine-N-oxide (TMAO) has emerged as a potential biomarker for atherosclerosis and the development of cardiovascular diseases (CVDs). Although several clinical studies have shown striking associations of TMAO levels with atherosclerosis and CVDs, TMAO determinations are not clinical routine yet. The current methodology relies on isotope-labeled internal standards, which adds to pre-analytical complexity and costs for the quantification of TMAO and its precursors carnitine, betaine or choline. Here, we report a liquid chromatography-tandem mass spectrometry based method that is fast (throughput up to 240 samples/day), consumes low sample volumes (e.g., from a finger prick), and does not require isotope-labeled standards. We circumvented the analytical problem posed by the presence of endogenous TMAO and its precursors in human plasma by using an artificial plasma matrix for calibration. We cross-validated the results obtained using an artificial matrix with those using mouse plasma matrix and demonstrated that TMAO, carnitine, betaine and choline were accurately quantified in ‘real-life’ human plasma samples from healthy volunteers, obtained either from a finger prick or from venous puncture. Additionally, we assessed the stability of samples stored at −20 °C and room temperature. Whereas all metabolites were stable at −20 °C, increasing concentrations of choline were determined when stored at room temperature. Our method will facilitate the establishment of TMAO as a routine clinical biomarker in hematology in order to assess the risk for CVDs development, or to monitor disease progression and intervention effects.
    • Special Issue "Adenovirus Pathogenesis".

      Arnberg, Niklas; Lenman, Annasara; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. (MDPI, 2021-06-10)
      Excerpt Note: In lieu of an abstract, this is an excerpt from the first page. Adenovirus is a common cause of disease in humans and in animals [...]
    • Leitlinienreport zur aktualisierten S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion

      Jansen, Petra Lynen; van Leeuwen, Pia; Sandmann, Lisa; Cornberg, Markus; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (Thieme, 2021-07-12)
      [No abstract available]
    • S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11)

      Cornberg, Markus; Sandmann, Lisa; Protzer, Ulrike; Niederau, Claus; Tacke, Frank; Berg, Thomas; Glebe, Dieter; Jilg, Wolfgang; Wedemeyer, Heiner; Wirth, Stefan; et al. (Thieme, 2021-07-12)
      [No abstract available]