group leader: PD Dr. Steinmann

Recent Submissions

  • Six Heterocyclic Metabolites from the Myxobacterium Labilithrix luteola.

    Mulwa, Lucky S; Jansen, Rolf; Praditya, Dimas F; Mohr, Kathrin I; Wink, Joachim; Steinmann, Eike; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-02-28)
    Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] (1) and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (2), were isolated from the myxobacteriumLabilithrixluteola(DSM 27648T). Additionally, four metabolites3,4,5and6already known from other sources were obtained. Their structures were elucidated from high resolution electrospray ionisation mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data and their relative configuration was assigned based on nuclear Overhauser effect (NOE) and vicinal ¹H-NMR coupling data. The compounds where tested for biological activities; labindoles A (1) and B (2) exhibited significant activity against Hepatitis C Virus, 9H-carbazole (3), 3-chloro-9H-carbazole (4) and 4-hydroxymethyl-quinoline (5) showed antifungal activities. Moreover, compound3had weak to moderate antibacterial activities, while labindoles A (1) and B (2) were devoid of significant antifungal and antibacterial effects.
  • Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.

    Rupcic, Zeljka; Rascher, Monique; Kanaki, Sae; Köster, Reinhard W; Stadler, Marc; Wittstein, Kathrin; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-03-06)
    Basidiomycetes of the genusHericiumare among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as established more recently) brain-derived neurotrophic factor (BDNF) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom (Hericium erinaceus) strain and a strain of the rare species,Hericium flagellum(synonymH. alpestre). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act onBDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well onNGFexpression, which is consistent with the literature.
  • Virucidal efficacy of peracetic acid for instrument disinfection.

    Becker, Britta; Brill, Florian H H; Todt, Daniel; Steinmann, Eike; Lenz, Johannes; Paulmann, Dajana; Bischoff, Birte; Steinmann, Jochen; TwinCore, Zentrum für experimentelle und klinische Infektionsforschng GmbH, Feodor-Lynen-Str.7, 30625 Hannover, Germany. (2017)
    Various peracetic-acid (PAA)-based products for processing flexible endoscopes on the market are often based on a two-component system including a cleaning step before the addition of PAA as disinfectant. The peracetic acid concentrations in these formulations from different manufacturers are ranging from 400 to 1500 ppm (part per million). These products are used at temperatures between 20 °C and 37 °C. Since information on the virus-inactivating properties of peracetic acid at different concentrations and temperature is missing, it was the aim of the study to evaluate peracetic acid solutions against test viruses using the quantitative suspension test, EN 14476. In addition, further studies were performed with the recently established European pre norm (prEN 17111:2017) describing a carrier assay for simulating practical conditions using frosted glass.
  • Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys.

    Walter, Stephanie; Rasche, Andrea; Moreira-Soto, Andrés; Pfaender, Stephanie; Bletsa, Magda; Corman, Victor Max; Aguilar-Setien, Alvaro; García-Lacy, Fernando; Hans, Aymeric; Todt, Daniel; Schuler, Gerhard; Shnaiderman-Torban, Anat; Steinman, Amir; Roncoroni, Cristina; Veneziano, Vincenzo; Rusenova, Nikolina; Sandev, Nikolay; Rusenov, Anton; Zapryanova, Dimitrinka; García-Bocanegra, Ignacio; Jores, Joerg; Carluccio, Augusto; Veronesi, Maria Cristina; Cavalleri, Jessika M V; Drosten, Christian; Lemey, Philippe; Steinmann, Eike; Drexler, Jan Felix; TwinCore, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7, 30625 Hannover, Germany. (2017-01-01)
    The hepatitis C virus (HCV) is a major human pathogen. Genetically related viruses in animals suggest a zoonotic origin of HCV. The closest relative of HCV is found in horses (termed equine hepacivirus [EqHV]). However, low EqHV genetic diversity implies relatively recent acquisition of EqHV by horses, making a derivation of HCV from EqHV unlikely. To unravel the EqHV evolutionary history within equid sister species, we analyzed 829 donkeys and 53 mules sampled in nine European, Asian, African, and American countries by molecular and serologic tools for EqHV infection. Antibodies were found in 278 animals (31.5%), and viral RNA was found in 3 animals (0.3%), all of which were simultaneously seropositive. A low RNA prevalence in spite of high seroprevalence suggests a predominance of acute infection, a possible difference from the mostly chronic hepacivirus infection pattern seen in horses and humans. Limitation of transmission due to short courses of infection may explain the existence of entirely seronegative groups of animals. Donkey and horse EqHV strains were paraphyletic and 97.5 to 98.2% identical in their translated polyprotein sequences, making virus/host cospeciation unlikely. Evolutionary reconstructions supported host switches of EqHV between horses and donkeys without the involvement of adaptive evolution. Global admixture of donkey and horse hepaciviruses was compatible with anthropogenic alterations of EqHV ecology. In summary, our findings do not support EqHV as the origin of the significantly more diversified HCV. Identification of a host system with predominantly acute hepacivirus infection may enable new insights into the chronic infection pattern associated with HCV.
  • Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure.

    Pfaender, Stephanie; Walter, Stephanie; Todt, Daniel; Behrendt, Patrick; Doerrbecker, Juliane; Wölk, Benno; Engelmann, Michael; Gravemann, Ute; Seltsam, Axel; Steinmann, Joerg; Burbelo, Peter D; Klawonn, Frank; Feige, Karsten; Pietschmann, Thomas; Cavalleri, Jessika-M V; Steinmann, Eike; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. (2015-09)
    The recent discovery of hepatitis C virus (HCV)-related viruses in different animal species has raised new speculations regarding the origin of HCV and the possibility of a zoonotic source responsible for the endemic HCV transmission. As a consequence, these new findings prompt questions regarding the potential for cross-species transmissions of hepaciviruses. The closest relatives to HCV discovered to date are the non-primate hepaciviruses (NPHVs), which have been described to infect horses. To evaluate the risk of a potential zoonotic transmission, we analysed NPHV RNA and antibodies in humans with occupational exposure to horses in comparison with a low-risk group. Both groups were negative for NPHV RNA, even though low seroreactivities against various NPHV antigens could be detected irrespective of the group. In conclusion, we did not observe evidence of NPHV transmission between horses and humans.
  • Tracking HCV protease population diversity during transmission and susceptibility of founder populations to antiviral therapy.

    Khera, Tanvi; Todt, Daniel; Vercauteren, Koen; McClure, C Patrick; Verhoye, Lieven; Farhoudi, Ali; Bhuju, Sabin; Geffers, Robert; Baumert, Thomas F; Steinmann, Eike; Meuleman, Philip; Pietschmann, Thomas; Brown, Richard J P; Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany. (2017-03)
    Due to the highly restricted species-tropism of Hepatitis C virus (HCV) a limited number of animal models exist for pre-clinical evaluation of vaccines and antiviral compounds. The human-liver chimeric mouse model allows heterologous challenge with clinically relevant strains derived from patients. However, to date, the transmission and longitudinal evolution of founder viral populations in this model have not been characterized in-depth using state-of-the-art sequencing technologies. Focusing on NS3 protease encoding region of the viral genome, mutant spectra in a donor inoculum and individual recipient mice were determined via Illumina sequencing and compared, to determine the effects of transmission on founder viral population complexity. In all transmissions, a genetic bottleneck was observed, although diverse viral populations were transmitted in each case. A low frequency cloud of mutations (<1%) was detectable in the donor inoculum and recipient mice, with single nucleotide variants (SNVs) > 1% restricted to a subset of nucleotides. The population of SNVs >1% was reduced upon transmission while the low frequency SNV cloud remained stable. Fixation of multiple identical synonymous substitutions was apparent in independent transmissions, and no evidence for reversion of T-cell epitopes was observed. In addition, susceptibility of founder populations to antiviral therapy was assessed. Animals were treated with protease inhibitor (PI) monotherapy to track resistance associated substitution (RAS) emergence. Longitudinal analyses revealed a decline in population diversity under therapy, with no detectable RAS >1% prior to therapy commencement. Despite inoculation from a common source and identical therapeutic regimens, unique RAS emergence profiles were identified in different hosts prior to and during therapeutic failure, with complex mutational signatures at protease residues 155, 156 and 168 detected. Together these analyses track viral population complexity at high-resolution in the human-liver chimeric mouse model post-transmission and under therapeutic intervention, revealing novel insights into the evolutionary processes which shape viral protease population composition at various critical stages of the viral life-cycle.
  • Virucidal Activity of World Health Organization-Recommended Formulations Against Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses.

    Siddharta, Anindya; Pfaender, Stephanie; Vielle, Nathalie Jane; Dijkman, Ronald; Friesland, Martina; Becker, Britta; Yang, Jaewon; Engelmann, Michael; Todt, Daniel; Windisch, Marc P; Brill, Florian H; Steinmann, Joerg; Steinmann, Jochen; Becker, Stephan; Alves, Marco P; Pietschmann, Thomas; Eickmann, Markus; Thiel, Volker; Steinmann, Eike; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung gmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany. (2017-03-15)
    The World Health Organization (WHO) published 2 alcohol-based formulations to be used in healthcare settings and for outbreak-associated infections, but inactivation efficacies of these products have not been determined against (re-)emerging viruses. In this study, we evaluated the virucidal activity of these WHO products in a comparative analysis. Zika virus (ZIKV), Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) as (re-)emerging viral pathogens and other enveloped viruses could be efficiently inactivated by both WHO formulations, implicating their use in healthcare systems and viral outbreak situations.
  • Prevention strategies for blood-borne viruses-in the Era of vaccines, direct acting antivirals and antiretroviral therapy.

    Pfaender, Stephanie; von Hahn, Thomas; Steinmann, Joerg; Ciesek, Sandra; Steinmann, Eike; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-09)
    Blood-borne viruses, such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and the facultative blood-borne hepatitis E virus, are considered a major public health problem given that they are accountable for millions of deaths each year. Treatment options, including effective vaccine design, development of antiviral strategies and the implementation of antiretroviral therapy have improved substantially over the last couple of years and contribute to successful treatment and prevention of these infectious diseases. In this review, we summarise the current knowledge and concepts in prevention of transmission of these blood-borne viruses.
  • Biofilm formation of the black yeast-like fungus Exophiala dermatitidis and its susceptibility to antiinfective agents.

    Kirchhoff, Lisa; Olsowski, Maike; Zilmans, Katrin; Dittmer, Silke; Haase, Gerhard; Sedlacek, Ludwig; Steinmann, Eike; Buer, Jan; Rath, Peter-Michael; Steinmann, Joerg; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2017-02-17)
    Various fungi have the ability to colonize surfaces and to form biofilms. Fungal biofilm-associated infections are frequently refractory to targeted treatment because of resistance to antifungal drugs. One fungus that frequently colonises the respiratory tract of cystic fibrosis (CF) patients is the opportunistic black yeast-like fungus Exophiala dermatitidis. We investigated the biofilm-forming ability of E. dermatitidis and its susceptibility to various antiinfective agents and natural compounds. We tested 58 E. dermatitidis isolates with a biofilm assay based on crystal violet staining. In addition, we used three isolates to examine the antibiofilm activity of voriconazole, micafungin, colistin, farnesol, and the plant derivatives 1,2,3,4,6-penta-O-galloyl-b-D-glucopyranose (PGG) and epigallocatechin-3-gallate (EGCG) with an XTT reduction assay. We analysed the effect of the agents on cell to surface adhesion, biofilm formation, and the mature biofilm. The biofilms were also investigated by confocal laser scan microscopy. We found that E. dermatitidis builds biofilm in a strain-specific manner. Invasive E. dermatitidis isolates form most biomass in biofilm. The antiinfective agents and the natural compounds exhibited poor antibiofilm activity. The greatest impact of the compounds was detected when they were added prior cell adhesion. These findings suggest that prevention may be more effective than treatment of biofilm-associated E. dermatitidis infections.
  • Successful retreatment of a patient with chronic hepatitis C genotype 2k/1b virus with ombitasvir/paritaprevir/ritonavir plus dasabuvir.

    Todt, Daniel; Schlevogt, Bernhard; Deterding, Katja; Grundhoff, Adam; Manns, Michael P; Wedemeyer, Heiner; Fischer, Nicole; Cornberg, Markus; Steinmann, Eike; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2017-01-18)
  • In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome.

    Todt, Daniel; Gisa, Anett; Radonic, Aleksandar; Nitsche, Andreas; Behrendt, Patrick; Suneetha, Pothakamuri Venkata; Pischke, Sven; Bremer, Birgit; Brown, Richard J P; Manns, Michael P; Cornberg, Markus; Bock, C Thomas; Steinmann, Eike; Wedemeyer, Heiner; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-10)
    Hepatitis E virus (HEV) infection can take chronic courses in immunocompromised patients potentially leading to liver cirrhosis and liver failure. Ribavirin (RBV) is currently the only treatment option for many patients, but treatment failure can occur which has been associated with the appearance of a distinct HEV polymerase mutant (G1634R). Here, we performed a detailed analysis of HEV viral intrahost evolution during chronic hepatitis E infections.
  • Apolipoprotein E polymorphisms and their protective effect on hepatitis E virus replication.

    Weller, Romy; Todt, Daniel; Engelmann, Michael; Friesland, Martina; Wedemeyer, Heiner; Pietschmann, Thomas; Steinmann, Eike; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-12)
  • Acute and chronic infections with nonprimate hepacivirus in young horses.

    Gather, Theresa; Walter, Stephanie; Pfaender, Stephanie; Todt, Daniel; Feige, Karsten; Steinmann, Eike; Cavalleri, Jessika M V; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-09-22)
    The recently discovered nonprimate hepacivirus (NPHV) naturally infects horses and is the closest known homolog of hepatitis C virus to date. Within a follow-up study acute field infections were monitored in four young Thoroughbred horses until the ages of 12-13 months. Serum samples were analyzed for the presence of NPHV RNA and anti-NPHV NS3 antibodies and liver specific parameters were evaluated. The four young horses were not able to clear infection, but remained chronically infected for the entire monitored time period despite the presence of NPHV specific antibodies.
  • Inactivation of Zika virus in human breast milk by prolonged storage or pasteurization.

    Pfaender, Stephanie; Vielle, Nathalie J; Ebert, Nadine; Steinmann, Eike; Alves, Marco P; Thiel, Volker; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-11-23)
    Zika virus infection during pregnancy poses a serious risk for pregnant women as it can cause severe birth defects. Even though the virus is mainly transmitted via mosquitos, human-to-human transmission has been described. Infectious viral particles have been detected in breast milk of infected women which raised concerns regarding the safety of breastfeeding in areas of Zika virus transmission or in case of a suspected or confirmed Zika virus infection. In this study, we show that Zika virus is effectively inactivated in human breast milk after prolonged storage or upon pasteurization of milk.
  • Inactivation of HCV and HIV by microwave: a novel approach for prevention of virus transmission among people who inject drugs.

    Siddharta, Anindya; Pfaender, Stephanie; Malassa, Angelina; Doerrbecker, Juliane; Anggakusuma; Engelmann, Michael; Nugraha, Boya; Steinmann, Joerg; Todt, Daniel; Vondran, Florian W R; Mateu-Gelabert, Pedro; Goffinet, Christine; Steinmann, Eike (2016-11-18)
    Hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1) transmissions among people who inject drugs (PWID) continue to pose a challenging global health problem. Here, we aimed to analyse a universally applicable inactivation procedure, namely microwave irradiation, as a safe and effective method to reduce the risk of viral transmission. The exposure of HCV from different genotypes to microwave irradiation resulted in a significant reduction of viral infectivity. Furthermore, microwave irradiation reduced viral infectivity of HIV-1 and of HCV/HIV-1 suspensions indicating that this inactivation may be effective at preventing co-infections. To translate microwave irradiation as prevention method to used drug preparation equipment, we could further show that HCV as well as HIV-1 infectivity could be abrogated in syringes and filters. This study demonstrates the power of microwave irradiation for the reduction of viral transmission and establishment of this safety strategy could help reduce the transmission of blood-borne viruses.
  • Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations.

    Todt, Daniel; Walter, Stephanie; Brown, Richard J P; Steinmann, Eike; TWINCORE, Centre for experimental and clinical infection research GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany. (2016-10-13)
    Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.
  • Emergence of linezolid- and vancomycin-resistant Enterococcus faecium in a department for hematologic stem cell transplantation.

    Krull, M; Klare, I; Ross, B; Trenschel, R; Beelen, D W; Todt, D; Steinmann, E; Buer, J; Rath, P-M; Steinmann, J; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016)
    Prevalence of vancomycin-resistant enterococci has increased in Germany. Here, we report the cluster of linezolid- and vancomycin-resistant Enterococcus faecium (LVRE) in a German department for hematologic stem cell transplantation (HSCT).
  • Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells.

    Drave, S A; Debing, Y; Walter, S; Todt, D; Engelmann, M; Friesland, M; Wedemeyer, H; Neyts, J; Behrendt, P; Steinmann, E; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-07)
    Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra- and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection.
  • Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria.

    Klotz, Ulrike; Schmidt, Dirk; Willinger, Birgit; Steinmann, Eike; Buer, Jan; Rath, Peter-Michael; Steinmann, Joerg; Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany. (2016-05)
    Echinocandin resistance in Candida glabrata is emerging and is associated with the presence of FKS mutations. In this study, we analysed the antifungal susceptibility, presence of FKS mutations and clonality of C. glabrata blood culture isolates from two hospitals in Germany and Austria. Susceptibility testing of 64 C. glabrata bloodstream isolates from two university hospitals was performed with broth microdilution method according to EUCAST. In addition, all isolates were screened for FKS mutations. Molecular fingerprinting was performed by microsatellite PCR with three separate primer pairs and semiautomated repetitive sequenced-based PCR (rep-PCR). One C. glabrata isolate from Germany (1.5%) was echinocandin resistant, with a corresponding mutation in FKS2 gene hot spot 1. The discriminatory power of microsatellite PCR was higher than that of rep-PCR (Simpson Index of 0.94 vs. 0.88); microsatellite PCR created 31 separate genotypes, whereas rep-PCR created 17. Predominant genotypes or clusters of isolates from Germany and Austria were present, with no epidemiological evidence of nosocomial transmissions. Although we found a low incidence of echinocandin resistance in C. glabrata in our settings, further surveillance projects in central Europe are warranted for monitoring future epidemiological trends. The genetic population structure of C. glabrata demonstrates overrepresented geographical clusters.
  • Frequent presence of hepaci and pegiviruses in commercial equine serum pools.

    Postel, Alexander; Cavalleri, Jessika-M V; Pfaender, Stephanie; Walter, Stephanie; Steinmann, E; Fischer, Nicole; Feige, Karsten; Haas, Ludwig; Becher, Paul; Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hanover and the Helmholtz Centre for Infection Research, Hanover, Germany. (2016-01-15)
    Novel viruses belonging to the genera Hepacivirus and Pegivirus have recently been discovered in horses and other animal species. Viral genomes of non-primate hepaciviruses (NPHV), equine pegivirus 1 (EPgV 1) and Theiler's disease associated virus (TDAV) were detected in a horse serum routinely used for cell culture propagation in our laboratory. Therefore, a study was carried out to further investigate the presence of these human Hepatitis C virus (HCV) related viruses in equine serum based products used in veterinary medicine and for research and to characterize the viral genomes. Without exception all commercially available equine sera purchased for cell culture propagation (n=6) were tested positive for NPHV, EPgV 1 or TDAV genomes by qRT-PCR. Molecular analyses of one single commercial horse serum from Europe confirmed multiple viral genomes, including two TDAV genomes significantly different from the only published TDAV sequence. Furthermore, multiple batches of horse serum pools (n=35) collected for manufacturing of biological products turned out to be positive for NPHV and EPgV 1 genomes. Nevertheless, the final commercial products (n=9) were exclusively tested qRT-PCR negative. Field samples (n=119) obtained from two premises located in the same region as the donor horses were analyzed, demonstrating the frequent presence of NPHV and EPgV 1, but the absence of TDAV genomes. The presence of NPHV, EPgV 1 and TDAV in commercial equine sera and serum based products could have considerable consequences for biosecurity and may also bias the outcome of research studies conducted with related viruses.

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