2024-03-28T21:29:33Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/3464842019-08-30T11:33:30Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Pfaender, Stephanie
author
Brinkmann, Janine
author
Todt, Daniel
author
Riebesehl, Nina
author
Steinmann, Joerg
author
Steinmann, Jochen
author
Pietschmann, Thomas
author
Steinmann, Eike
author
2015-03-01
Virus inactivation by chemical disinfectants is an important instrument for infection control in medical settings, but the mechanisms involved are poorly understood. In this study, we systematically investigated the effects of several antiviral treatments on hepatitis C virus (HCV) particles as model for enveloped viruses. Studies were performed with authentic cell culture-derived viruses, and the influence of chemical disinfectants, heat, and UV treatment on HCV was analyzed by the determination of infectious particles in a limiting-dilution assay, by quantitative reverse transcription-PCR, by core enzyme-linked immunosorbent assay, and by proteolytic protection assay. All different inactivation methods resulted in a loss of HCV infectivity by targeting different parts of the virus particle. Alcohols such as ethanol and 2-propanol did not affect the viral RNA genome integrity but disrupted the viral envelope membrane in a capsid protection assay. Heat and UV treatment of HCV particles resulted in direct damage of the viral genome since transfection of viral particle-associated RNA into permissive cells did not initiate RNA replication. In addition, heat incubation at 80°C disrupted the HCV envelope, rendering the viral capsid susceptible to proteolytic digest. This study demonstrated the molecular processes of viral inactivation of an enveloped virus and should facilitate the development of effective disinfection strategies in infection control not only against HCV but also against other enveloped viruses.
Mechanisms of methods for hepatitis C virus inactivation. 2015, 81 (5):1616-21 Appl. Environ. Microbiol.
1098-5336
25527548
10.1128/AEM.03580-14
http://hdl.handle.net/10033/346484
Applied and environmental microbiology
Mechanisms of methods for hepatitis C virus inactivation.
oai:repository.helmholtz-hzi.de:10033/3465632019-08-30T11:34:22Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Behrendt, Patrick
author
Steinmann, Eike
author
Manns, Michael P
author
Wedemeyer, Heiner
author
2014-12
Hepatitis E virus (HEV) infection has been identified as a cause of graft hepatitis in liver transplant recipients. The true frequency and clinical importance of HEV infections after liver transplantations is a matter of debate. It is proposed that consumption of HEV-contaminated undercooked meat is a main source for HEV infections in developed countries--which might also account for some hepatitis E cases after organ transplantation. However, HEV is also transmitted by transfusion of blood products, likely representing a previously underestimated risk particularly for patients in the transplant setting. HEV infection can take chronic courses in immunocompromised individuals, associated in some cases with rapid progression to cirrhosis within 1-2 years of infection. Diagnosis in transplanted patients is based on HEV RNA testing as antibody assays are not sensitive enough. Selection of immunosuppressive drugs is important as different compounds may influence viral replication and the course of liver disease. Ribavirin has antiviral activity against HEV and should be administered for at least three months in chronically infected individuals; however, treatment failure may occur. HEV infections have also been linked to a variety of extrahepatic manifestations both during and after resolution of infection. In this review we summarize the emerging data on hepatitis E with a particular focus on the importance of HEV infections for liver transplant recipients.
The impact of hepatitis E in the liver transplant setting. 2014, 61 (6):1418-29 J. Hepatol.
1600-0641
25195557
10.1016/j.jhep.2014.08.047
http://hdl.handle.net/10033/346563
Journal of hepatology
The impact of hepatitis E in the liver transplant setting.
oai:repository.helmholtz-hzi.de:10033/5928332019-08-30T11:31:23Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Stöhr, Stefanie
author
Costa, Rui
author
Sandmann, Lisa
author
Westhaus, Sandra
author
Pfaender, Stephanie
author
Anggakusuma
author
Dazert, Eva
author
Meuleman, Philip
author
Vondran, Florian W R
author
Manns, Michael P
author
Steinmann, Eike
author
von Hahn, Thomas
author
Ciesek, Sandra
author
2015-08-14
Chronically HCV-infected orthotopic liver transplantation (OLT) recipients appear to have improved outcomes when their immunosuppressive regimen includes a mammalian target of rapamycin (mTOR) inhibitor. The mechanism underlying this observation is unknown.
Host cell mTORC1 is required for HCV RNA replication. 2015: Gut
1468-3288
26276683
10.1136/gutjnl-2014-308971
http://hdl.handle.net/10033/592833
Gut
Host cell mTORC1 is required for HCV RNA replication.
oai:repository.helmholtz-hzi.de:10033/6011702019-08-30T11:33:29Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Ionidis, Georgios
author
Hübscher, Judith
author
Jack, Thomas
author
Becker, Britta
author
Bischoff, Birte
author
Todt, Daniel
author
Hodasa, Veronika
author
Brill, Florian H H
author
Steinmann, Eike
author
Steinmann, Jochen
author
2016
Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses.
Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid. 2016, 16 (1):77 BMC Infect. Dis.
1471-2334
26864562
10.1186/s12879-016-1410-9
http://hdl.handle.net/10033/601170
BMC infectious diseases
Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid.
oai:repository.helmholtz-hzi.de:10033/6034852019-08-30T11:34:48Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Pfaender, Stephanie
author
Brown, Richard Jp
author
Pietschmann, Thomas
author
Steinmann, Eike
author
2014-03
Hepatitis C virus is considered a major public health problem, infecting 2%-3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen.
Natural reservoirs for homologs of hepatitis C virus. 2014, 3 (3):e21 Emerg Microbes Infect
2222-1751
26038514
10.1038/emi.2014.19
http://hdl.handle.net/10033/603485
Emerging microbes & infections
Natural reservoirs for homologs of hepatitis C virus.
oai:repository.helmholtz-hzi.de:10033/6072262019-08-30T11:34:48Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Postel, Alexander
author
Cavalleri, Jessika-M V
author
Pfaender, Stephanie
author
Walter, Stephanie
author
Steinmann, E
author
Fischer, Nicole
author
Feige, Karsten
author
Haas, Ludwig
author
Becher, Paul
author
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.
Frequent presence of hepaci and pegiviruses in commercial equine serum pools. 2016, 182:8-14 Vet. Microbiol.
1873-2542
26711022
10.1016/j.vetmic.2015.10.032
http://hdl.handle.net/10033/607226
Veterinary microbiology
Frequent presence of hepaci and pegiviruses in commercial equine serum pools.
oai:repository.helmholtz-hzi.de:10033/6140652019-08-30T11:27:46Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Klotz, Ulrike
author
Schmidt, Dirk
author
Willinger, Birgit
author
Steinmann, Eike
author
Buer, Jan
author
Rath, Peter-Michael
author
Steinmann, Joerg
author
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.
Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria. 2016, 59 (5):312-8 Mycoses
1439-0507
26806376
10.1111/myc.12472
http://hdl.handle.net/10033/614065
Mycoses
Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria.
oai:repository.helmholtz-hzi.de:10033/6190352019-08-30T11:35:13Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Drave, S A
author
Debing, Y
author
Walter, S
author
Todt, D
author
Engelmann, M
author
Friesland, M
author
Wedemeyer, H
author
Neyts, J
author
Behrendt, P
author
Steinmann, E
author
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.
Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells. 2016, 23 (7):512-21 J. Viral Hepat.
1365-2893
26891712
10.1111/jvh.12515
http://hdl.handle.net/10033/619035
Journal of viral hepatitis
Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells.
oai:repository.helmholtz-hzi.de:10033/6205662019-08-30T11:30:58Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Krull, M
author
Klare, I
author
Ross, B
author
Trenschel, R
author
Beelen, D W
author
Todt, D
author
Steinmann, E
author
Buer, J
author
Rath, P-M
author
Steinmann, J
author
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).
Emergence of linezolid- and vancomycin-resistant Enterococcus faecium in a department for hematologic stem cell transplantation. 2016, 5:31 Antimicrob Resist Infect Control
27688876
10.1186/s13756-016-0131-6
http://hdl.handle.net/10033/620566
Antimicrobial resistance and infection control
Emergence of linezolid- and vancomycin-resistant Enterococcus faecium in a department for hematologic stem cell transplantation.
oai:repository.helmholtz-hzi.de:10033/6205842019-08-30T11:35:13Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Todt, Daniel
author
Walter, Stephanie
author
Brown, Richard J P
author
Steinmann, Eike
author
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.
Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations. 2016, 8 (10) Viruses
1999-4915
27754363
10.3390/v8100283
http://hdl.handle.net/10033/620584
Viruses
Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations.
oai:repository.helmholtz-hzi.de:10033/6206242019-08-30T11:26:42Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Siddharta, Anindya
author
Pfaender, Stephanie
author
Malassa, Angelina
author
Doerrbecker, Juliane
author
Anggakusuma
author
Engelmann, Michael
author
Nugraha, Boya
author
Steinmann, Joerg
author
Todt, Daniel
author
Vondran, Florian W R
author
Mateu-Gelabert, Pedro
author
Goffinet, Christine
author
Steinmann, Eike
author
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.
Inactivation of HCV and HIV by microwave: a novel approach for prevention of virus transmission among people who inject drugs. 2016, 6:36619 Sci Rep
2045-2322
27857152
10.1038/srep36619
http://hdl.handle.net/10033/620624
Scientific reports
Inactivation of HCV and HIV by microwave: a novel approach for prevention of virus transmission among people who inject drugs.
oai:repository.helmholtz-hzi.de:10033/6206302019-08-30T11:34:48Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Pfaender, Stephanie
author
Vielle, Nathalie J
author
Ebert, Nadine
author
Steinmann, Eike
author
Alves, Marco P
author
Thiel, Volker
author
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 Zika virus in human breast milk by prolonged storage or pasteurization. 2016, 228:58-60 Virus Res.
1872-7492
27889615
10.1016/j.virusres.2016.11.025
http://hdl.handle.net/10033/620630
Virus research
Inactivation of Zika virus in human breast milk by prolonged storage or pasteurization.
oai:repository.helmholtz-hzi.de:10033/6206642019-08-30T11:37:23Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Gather, Theresa
author
Walter, Stephanie
author
Pfaender, Stephanie
author
Todt, Daniel
author
Feige, Karsten
author
Steinmann, Eike
author
Cavalleri, Jessika M V
author
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.
Acute and chronic infections with nonprimate hepacivirus in young horses. 2016, 47 (1):97 Vet. Res.
1297-9716
27659317
10.1186/s13567-016-0381-6
http://hdl.handle.net/10033/620664
Veterinary research
Acute and chronic infections with nonprimate hepacivirus in young horses.
oai:repository.helmholtz-hzi.de:10033/6206902019-08-30T11:35:10Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Weller, Romy
author
Todt, Daniel
author
Engelmann, Michael
author
Friesland, Martina
author
Wedemeyer, Heiner
author
Pietschmann, Thomas
author
Steinmann, Eike
author
2016-12
Apolipoprotein E polymorphisms and their protective effect on hepatitis E virus replication. 2016, 64 (6):2274-2276 Hepatology
1527-3350
27541341
10.1002/hep.28788
http://hdl.handle.net/10033/620690
Hepatology (Baltimore, Md.)
Apolipoprotein E polymorphisms and their protective effect on hepatitis E virus replication.
oai:repository.helmholtz-hzi.de:10033/6208042019-08-30T11:36:32Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Todt, Daniel
author
Gisa, Anett
author
Radonic, Aleksandar
author
Nitsche, Andreas
author
Behrendt, Patrick
author
Suneetha, Pothakamuri Venkata
author
Pischke, Sven
author
Bremer, Birgit
author
Brown, Richard J P
author
Manns, Michael P
author
Cornberg, Markus
author
Bock, C Thomas
author
Steinmann, Eike
author
Wedemeyer, Heiner
author
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.
In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. 2016, 65 (10):1733-43 Gut
1468-3288
27222534
10.1136/gutjnl-2015-311000
http://hdl.handle.net/10033/620804
Gut
In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome.
oai:repository.helmholtz-hzi.de:10033/6208502019-08-30T11:34:47Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Todt, Daniel
author
Schlevogt, Bernhard
author
Deterding, Katja
author
Grundhoff, Adam
author
Manns, Michael P
author
Wedemeyer, Heiner
author
Fischer, Nicole
author
Cornberg, Markus
author
Steinmann, Eike
author
2017-01-18
Successful retreatment of a patient with chronic hepatitis C genotype 2k/1b virus with ombitasvir/paritaprevir/ritonavir plus dasabuvir. 2017 J. Antimicrob. Chemother.
1460-2091
28100444
10.1093/jac/dkw572
http://hdl.handle.net/10033/620850
The Journal of antimicrobial chemotherapy
Successful retreatment of a patient with chronic hepatitis C genotype 2k/1b virus with ombitasvir/paritaprevir/ritonavir plus dasabuvir.
oai:repository.helmholtz-hzi.de:10033/6208522019-08-30T11:35:14Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Kirchhoff, Lisa
author
Olsowski, Maike
author
Zilmans, Katrin
author
Dittmer, Silke
author
Haase, Gerhard
author
Sedlacek, Ludwig
author
Steinmann, Eike
author
Buer, Jan
author
Rath, Peter-Michael
author
Steinmann, Joerg
author
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.
Biofilm formation of the black yeast-like fungus Exophiala dermatitidis and its susceptibility to antiinfective agents. 2017, 7:42886 Sci Rep
2045-2322
28211475
10.1038/srep42886
http://hdl.handle.net/10033/620852
Scientific reports
Biofilm formation of the black yeast-like fungus Exophiala dermatitidis and its susceptibility to antiinfective agents.
oai:repository.helmholtz-hzi.de:10033/6208592019-08-30T11:29:17Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Pfaender, Stephanie
author
von Hahn, Thomas
author
Steinmann, Joerg
author
Ciesek, Sandra
author
Steinmann, Eike
author
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.
Prevention strategies for blood-borne viruses-in the Era of vaccines, direct acting antivirals and antiretroviral therapy. 2016, 26 (5):330-9 Rev. Med. Virol.
1099-1654
27185010
10.1002/rmv.1890
http://hdl.handle.net/10033/620859
Reviews in medical virology
Prevention strategies for blood-borne viruses-in the Era of vaccines, direct acting antivirals and antiretroviral therapy.
oai:repository.helmholtz-hzi.de:10033/6209732019-08-30T11:34:48Zcom_10033_620589col_10033_620590col_10033_620596
00925njm 22002777a 4500
dc
Siddharta, Anindya
author
Pfaender, Stephanie
author
Vielle, Nathalie Jane
author
Dijkman, Ronald
author
Friesland, Martina
author
Becker, Britta
author
Yang, Jaewon
author
Engelmann, Michael
author
Todt, Daniel
author
Windisch, Marc P
author
Brill, Florian H
author
Steinmann, Joerg
author
Steinmann, Jochen
author
Becker, Stephan
author
Alves, Marco P
author
Pietschmann, Thomas
author
Eickmann, Markus
author
Thiel, Volker
author
Steinmann, Eike
author
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.
Virucidal Activity of World Health Organization-Recommended Formulations Against Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses. 2017, 215 (6):902-906 J. Infect. Dis.
1537-6613
28453839
10.1093/infdis/jix046
http://hdl.handle.net/10033/620973
The Journal of infectious diseases
Virucidal Activity of World Health Organization-Recommended Formulations Against Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses.
oai:repository.helmholtz-hzi.de:10033/6210092019-08-30T11:28:51Zcom_10033_620589com_10033_620636col_10033_620590col_10033_620596col_10033_620638
00925njm 22002777a 4500
dc
Khera, Tanvi
author
Todt, Daniel
author
Vercauteren, Koen
author
McClure, C Patrick
author
Verhoye, Lieven
author
Farhoudi, Ali
author
Bhuju, Sabin
author
Geffers, Robert
author
Baumert, Thomas F
author
Steinmann, Eike
author
Meuleman, Philip
author
Pietschmann, Thomas
author
Brown, Richard J P
author
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.
Tracking HCV protease population diversity during transmission and susceptibility of founder populations to antiviral therapy. 2017, 139:129-137 Antiviral Res.
1872-9096
28062191
10.1016/j.antiviral.2017.01.001
http://hdl.handle.net/10033/621009
Antiviral research
Tracking HCV protease population diversity during transmission and susceptibility of founder populations to antiviral therapy.
oai:repository.helmholtz-hzi.de:10033/6210772019-08-30T11:36:33Zcom_10033_620589com_10033_311308col_10033_620721col_10033_620590col_10033_620596
00925njm 22002777a 4500
dc
Pfaender, Stephanie
author
Walter, Stephanie
author
Todt, Daniel
author
Behrendt, Patrick
author
Doerrbecker, Juliane
author
Wölk, Benno
author
Engelmann, Michael
author
Gravemann, Ute
author
Seltsam, Axel
author
Steinmann, Joerg
author
Burbelo, Peter D
author
Klawonn, Frank
author
Feige, Karsten
author
Pietschmann, Thomas
author
Cavalleri, Jessika-M V
author
Steinmann, Eike
author
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.
Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure. 2015, 96 (9):2636-42 J. Gen. Virol.
1465-2099
26041875
10.1099/vir.0.000208
http://hdl.handle.net/10033/621077
The Journal of general virology
Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure.
oai:repository.helmholtz-hzi.de:10033/6211592019-08-30T11:27:46Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Walter, Stephanie
author
Rasche, Andrea
author
Moreira-Soto, Andrés
author
Pfaender, Stephanie
author
Bletsa, Magda
author
Corman, Victor Max
author
Aguilar-Setien, Alvaro
author
García-Lacy, Fernando
author
Hans, Aymeric
author
Todt, Daniel
author
Schuler, Gerhard
author
Shnaiderman-Torban, Anat
author
Steinman, Amir
author
Roncoroni, Cristina
author
Veneziano, Vincenzo
author
Rusenova, Nikolina
author
Sandev, Nikolay
author
Rusenov, Anton
author
Zapryanova, Dimitrinka
author
García-Bocanegra, Ignacio
author
Jores, Joerg
author
Carluccio, Augusto
author
Veronesi, Maria Cristina
author
Cavalleri, Jessika M V
author
Drosten, Christian
author
Lemey, Philippe
author
Steinmann, Eike
author
Drexler, Jan Felix
author
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.
Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys. 2017, 91 (1) J. Virol.
1098-5514
27795428
10.1128/JVI.01711-16
http://hdl.handle.net/10033/621159
Journal of virology
Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys.
oai:repository.helmholtz-hzi.de:10033/6211862019-08-30T11:32:41Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Becker, Britta
author
Brill, Florian H H
author
Todt, Daniel
author
Steinmann, Eike
author
Lenz, Johannes
author
Paulmann, Dajana
author
Bischoff, Birte
author
Steinmann, Jochen
author
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.
Virucidal efficacy of peracetic acid for instrument disinfection. 2017, 6:114 Antimicrob Resist Infect Control
2047-2994
29177047
10.1186/s13756-017-0271-3
http://hdl.handle.net/10033/621186
Antimicrobial resistance and infection control
Virucidal efficacy of peracetic acid for instrument disinfection.
oai:repository.helmholtz-hzi.de:10033/6213282019-08-30T11:34:22Zcom_10033_620857com_10033_620589com_10033_620618col_10033_620858col_10033_620622col_10033_620596
00925njm 22002777a 4500
dc
Rupcic, Zeljka
author
Rascher, Monique
author
Kanaki, Sae
author
Köster, Reinhard W
author
Stadler, Marc
author
Wittstein, Kathrin
author
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.
Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum. 2018, 19 (3) Int J Mol Sci
1422-0067
29509661
10.3390/ijms19030740
http://hdl.handle.net/10033/621328
International journal of molecular sciences
Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.
oai:repository.helmholtz-hzi.de:10033/6213292019-08-30T11:31:23Zcom_10033_620857com_10033_620589com_10033_620618col_10033_620858col_10033_620622col_10033_620596
00925njm 22002777a 4500
dc
Mulwa, Lucky S
author
Jansen, Rolf
author
Praditya, Dimas F
author
Mohr, Kathrin I
author
Wink, Joachim
author
Steinmann, Eike
author
Stadler, Marc
author
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.
Six Heterocyclic Metabolites from the Myxobacterium Labilithrix luteola. 2018, 23 (3) Molecules
1420-3049
29495640
10.3390/molecules23030542
http://hdl.handle.net/10033/621329
Molecules (Basel, Switzerland)
Six Heterocyclic Metabolites from the Myxobacterium Labilithrix luteola.
oai:repository.helmholtz-hzi.de:10033/6214832019-08-30T11:32:38Zcom_10033_620589col_10033_620590col_10033_620596
00925njm 22002777a 4500
dc
Behrendt, Patrick
author
Perin, Paula
author
Menzel, Nicolas
author
Branda, Dominic
author
Pfaender, Stephanie
author
Alves, Marco P.
author
Thiel, Volker
author
Meulemann, Philip
author
Colpit, Che C.
author
Schang, Luis M.
author
Vondran, Florian W.R.
author
Anggakusuma
author
Manns, Michael P.
author
Steinmann, Eicke
author
Pietschmann, Thomas
author
2017-01-01
Approximately 142 million people worldwide are infected with hepatitis C virus (HCV). Although potent direct acting antivirals are available, high costs limit access to treatment. Chronic hepatitis C virus infection remains a major cause of orthotopic liver transplantation. Moreover, re-infection of the graft occurs regularly. Antivirals derived from natural sources might be an alternative and cost-effective option to complement therapy regimens for global control of hepatitis C virus infection. We tested the antiviral properties of a mixture of different Chinese herbs/roots named Zhi Bai Di Huang Wan (ZBDHW) and its individual components on HCV. One of the ZBDHW components, Penta-O-Galloyl-Glucose (PGG), was further analyzed for its mode of action in vitro, its antiviral activity in primary human hepatocytes as well as for its bioavailability and hepatotoxicity in mice. ZBDHW, its component Cortex Moutan and the compound PGG efficiently block entry of HCV of all major genotypes and also of the related flavivirus Zika virus. PGG does not disrupt HCV virion integrity and acts primarily during virus attachment. PGG shows an additive effect when combined with the well characterized HCV inhibitor Daclatasvir. Analysis of bioavailability in mice revealed plasma levels above tissue culture IC
1872-9096
28923507
10.1016/j.antiviral.2017.09.006
http://hdl.handle.net/10033/621483
Antivirals
Bioavailability
Cortex moutan
Entry inhibitor
Hepatitis C virus
Natural compounds
Penta-O-Galloyl-Glucose
Pentagalloylglucose, a highly bioavailable polyphenolic compound present in Cortex moutan, efficiently blocks hepatitis C virus entry.
oai:repository.helmholtz-hzi.de:10033/6214522019-08-30T11:28:48Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Pfaender, Stephanie
author
Helfritz, Fabian A
author
Siddharta, Anindya
author
Todt, Daniel
author
Behrendt, Patrick
author
Heyden, Julia
author
Riebesehl, Nina
author
Willmann, Wiebke
author
Steinmann, Joerg
author
Münch, Jan
author
Ciesek, Sandra
author
Steinmann, Eike
author
2018-01-01
Hepatitis C virus (HCV) is a hepatotropic, blood-borne virus, but in up to one-third of infections of the transmission route remained unidentified. Viral genome copies of HCV have been identified in several body fluids, however, non-parental transmission upon exposure to contaminated body fluids seems to be rare. Several body fluids, e.g., tears and saliva, are renowned for their antimicrobial and antiviral properties, nevertheless, HCV stability has never been systematically analyzed in those fluids.
1664-302X
29636728
10.3389/fmicb.2018.00504
http://hdl.handle.net/10033/621452
cerebrospinal fluid
contact lens solution
hepatitis C virus
infectivity
saliva
semen
tear
Environmental Stability and Infectivity of Hepatitis C Virus (HCV) in Different Human Body Fluids.
oai:repository.helmholtz-hzi.de:10033/6214782019-08-30T11:27:14Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Becker, Britta
author
Bischoff, Birte
author
Brill, Florian H H
author
Steinmann, Eike
author
Steinmann, Jochen
author
2017-01-01
The virucidal efficacy of an automated ultrasound probe disinfector (trophon® EPR) was evaluated in a three step procedure according to European and German test methods. This system uses sonicated hydrogen peroxide mist (35%) at elevated temperature (50°C) in a closed chamber with control of all parameters within a 7 minute cycle.
Methods: In the first step of examination, the peroxide solution was tested in a quantitative suspension assay according to the Guideline of Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. and Robert Koch-Institute (RKI) and in parallel with the European Norm EN 14476 with all test viruses creating a virucidal claim.
In the second step, the virucidal efficacy of the hydrogen peroxide solution was evaluated in a hard surface carrier test according to the Guideline of DVV with adenovirus, murine norovirus and parvovirus simulating practical conditions.
Finally, the efficacy was evaluated by the automated system using stainless steel carriers inoculated with test virus and positioned at different levels inside the chamber.
2196-5226
28149707
10.3205/dgkh000287
http://hdl.handle.net/10033/621478
disinfection
human papillomaviruses
trophon® EPR
ultrasound probes
virucidal efficacy
Virucidal efficacy of a sonicated hydrogen peroxide system (trophon EPR) following European and German test methods.
oai:repository.helmholtz-hzi.de:10033/6214862018-09-19T01:29:06Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Becker, Britta
author
Bischoff, Birte
author
Brill, Florian H H
author
Steinmann, Eike
author
Steinmann, Jochen
author
2017-01-01
The virucidal efficacy of an automated ultrasound probe disinfector (trophon® EPR) was evaluated in a three step procedure according to European and German test methods. This system uses sonicated hydrogen peroxide mist (35%) at elevated temperature (50°C) in a closed chamber with control of all parameters within a 7 minute cycle.
Methods: In the first step of examination, the peroxide solution was tested in a quantitative suspension assay according to the Guideline of Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. and Robert Koch-Institute (RKI) and in parallel with the European Norm EN 14476 with all test viruses creating a virucidal claim.
In the second step, the virucidal efficacy of the hydrogen peroxide solution was evaluated in a hard surface carrier test according to the Guideline of DVV with adenovirus, murine norovirus and parvovirus simulating practical conditions.
Finally, the efficacy was evaluated by the automated system using stainless steel carriers inoculated with test virus and positioned at different levels inside the chamber.
Results: A ≥4 log10 reduction of virus titre was demonstrated with all methods including carrier tests with murine norovirus, adenovirus, and parvovirus using the automated device.
Conclusion: The automated device is able to inactivate test viruses of German and European norms and can therefore claim efficacy against human pathogenic enveloped and non-enveloped viruses. This includes human papillomaviruses which form part of the complete virucidal claim.
2196-5226
28149707
10.3205/dgkh000287
http://hdl.handle.net/10033/621486
disinfection
human papillomaviruses
trophon® EPR
ultrasound probes
virucidal efficacy
Virucidal efficacy of a sonicated hydrogen peroxide system (trophon EPR) following European and German test methods.
oai:repository.helmholtz-hzi.de:10033/6215132019-08-30T11:29:45Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Seufert, R
author
Sedlacek, L
author
Kahl, B
author
Hogardt, M
author
Hamprecht, A
author
Haase, G
author
Gunzer, F
author
Haas, A
author
Grauling-Halama, S
author
MacKenzie, C R
author
Essig, A
author
Stehling, F
author
Sutharsan, S
author
Dittmer, S
author
Killengray, D
author
Schmidt, D
author
Eskandarian, N
author
Steinmann, E
author
Buer, J
author
Hagen, F
author
Meis, J F
author
Rath, P-M
author
Steinmann, J
author
2018-08-01
Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Münster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.
1460-2091
29684150
10.1093/jac/dky147
http://hdl.handle.net/10033/621513
Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany.
oai:repository.helmholtz-hzi.de:10033/6215182019-08-30T11:29:45Zcom_10033_620589col_10033_620590col_10033_620596
00925njm 22002777a 4500
dc
Todt, Daniel
author
Moeller, Nora
author
Praditya, Dimas
author
Kinast, Volker
author
Friesland, Martina
author
Engelmann, Michael
author
Verhoye, Lieven
author
Sayed, Ibrahim M
author
Behrendt, Patrick
author
Dao Thi, Viet Loan
author
Meuleman, Philip
author
Steinmann, Eike
author
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.
1872-9096
30036559
10.1016/j.antiviral.2018.07.010
http://hdl.handle.net/10033/621518
Antiviral activity
Hepatitis E virus (HEV)
Host target
Humanized mice
Replication
Silvestrol
The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo.
oai:repository.helmholtz-hzi.de:10033/6215522018-11-11T08:36:34Zcom_10033_620589col_10033_620595col_10033_620596
00925njm 22002777a 4500
dc
Franz, Sergej
author
Friesland, Martina
author
Passos, Vânia
author
Todt, Daniel
author
Simmons, Graham
author
Goffinet, Christine
author
Steinmann, Eike
author
2018-09-22
Despite increasing clinical relevance of Chikungunya virus (CHIKV) infection, caused by a rapidly emerging pathogen, recommended guidelines for its inactivation do not exist. In this study, we investigated the susceptibility of CHIKV to inactivation by heat and commercially available hand, surface, and World Health Organization-recommended disinfectants to define CHIKV prevention protocols for healthcare systems.
1537-6613
29917109
10.1093/infdis/jiy359
http://hdl.handle.net/10033/621552
Susceptibility of Chikungunya Virus to Inactivation by Heat and Commercially and World Health Organization-Recommended Biocides.
oai:repository.helmholtz-hzi.de:10033/6215562019-08-30T11:27:40Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Olsowski, Maike
author
Hoffmann, Frederike
author
Hain, Andrea
author
Kirchhoff, Lisa
author
Theegarten, Dirk
author
Todt, Daniel
author
Steinmann, Eike
author
Buer, Jan
author
Rath, Peter-Michael
author
Steinmann, Joerg
author
2018-08-24
Exophiala dermatitidis causes chromoblastomycosis, phaeohyphomycosis and fatal infections of the central nervous system of patients with Asian background. It is also found in respiratory secretions from cystic fibrosis (CF) patients. In this study a variety of E. dermatitidis strains (isolates from Asia, environmental and CF) were characterized in their pathogenicity by survival analyzes using two different invertebrate host organisms, Caenorhabditis elegans and Galleria mellonella. Furthermore, the morphological development of hyphal formation was analyzed. E. dermatitidis exhibited pathogenicity in C. elegans. The virulence varied in a strain-dependent manner, but the nematodes were a limited model to study hyphal formation. Analysis of a melanin-deficient mutant (Mel-3) indicates that melanin plays a role during virulence processes in C. elegans. The strains isolated from Asian patients exhibited significantly higher virulence in G. mellonella compared to strains from other sources. Histological analyzes also revealed a higher potential of invasive hyphal growth in strains isolated from Asian patients. Interestingly, no significant difference was found in virulence between the Mel-3 mutant and their wild type counterpart during infection in G. mellonella. In conclusion, invasive hyphal formation of E. dermatitidis was associated with increased virulence. This work is the basis for future studies concerning E. dermatitidis virulence.
2045-2322
30143674
10.1038/s41598-018-30909-5
http://hdl.handle.net/10033/621556
Exophiala dermatitidis isolates from various sources: using alternative invertebrate host organisms (Caenorhabditis elegans and Galleria mellonella) to determine virulence.
oai:repository.helmholtz-hzi.de:10033/6216172019-08-30T11:30:28Zcom_10033_311624com_10033_6839com_10033_620589col_10033_311625col_10033_620596
00925njm 22002777a 4500
dc
Khera, Tanvi
author
Behrendt, Patrick
author
Bankwitz, Dorothea
author
Brown, Richard J P
author
Todt, Daniel
author
Doepke, Mandy
author
Ghafoor Khan, Abdul
author
Schulze, Kai
author
Law, John
author
Logan, Michael
author
Hockman, Darren
author
Wong, Jason Alexander Ji-Xhin
author
Dold, Leona
author
Gonzalez-Motos, Victor
author
Spengler, Ulrich
author
Viejo-Borbolla, Abel
author
Ströh, Luisa
author
Krey, Thomas
author
Tarr, Alexander W
author
Steinmann, Eike
author
Manns, Michael P
author
Klein, Florian
author
Guzman, Carlos A
author
Marcotrigiano, Joseph
author
Houghton, Michael
author
Pietschmann, Thomas
author
2018-11-12
Induction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an HCV vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity. We created HCV variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1). Exposure of the CD81 binding site and conserved epitopes was quantified by soluble CD81 and antibody interaction and neutralization assays. E2 or E1-E2 heterodimers with mutations causing epitope exposure were used to immunize mice. Vaccine-induced antibodies were examined and compared with patient-derived antibodies. Mutant viruses bound soluble CD81 and antibodies targeting the CD81 binding site with enhanced efficacy. Mice immunized with E2 or E1E2 heterodimers incorporating these modifications mounted strong, cross-binding, and non-interfering antibodies. E2-induced antibodies neutralized the autologous virus but they were not cross-neutralizing. Viruses lacking the HVR1 and selected glycosylation sites expose the CD81 binding site and cross-neutralization antibody epitopes. Recombinant E2 proteins carrying these modifications induce strong cross-binding but not cross-neutralizing antibodies.
1600-0641
30439392
10.1016/j.jhep.2018.11.003
http://hdl.handle.net/10033/621617
Antibodies
Glycoproteins
HCV
Immunogen
Recombinant proteins
Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants.
oai:repository.helmholtz-hzi.de:10033/6216472019-08-30T11:33:54Zcom_10033_620589col_10033_620595col_10033_620596
00925njm 22002777a 4500
dc
Franz, Sergej
author
Friesland, Martina
author
Passos, Vânia
author
Todt, Daniel
author
Simmons, Graham
author
Goffinet, Christine
author
Steinmann, Eike
author
2018-09-22
Despite increasing clinical relevance of Chikungunya virus (CHIKV) infection, caused by a rapidly emerging pathogen, recommended guidelines for its inactivation do not exist. In this study, we investigated the susceptibility of CHIKV to inactivation by heat and commercially available hand, surface, and World Health Organization-recommended disinfectants to define CHIKV prevention protocols for healthcare systems.
J Infect Dis. 2018 Sep 22;218(9):1507-1510. doi: 10.1093/infdis/jiy359
1537-6613
29917109
10.1093/infdis/jiy359
http://hdl.handle.net/10033/621647
Journal of Infectious Diseases
Chikungunya virus
hand disinfection
heat inactivation
surface disinfection
World Health
Susceptibility of Chikungunya Virus to Inactivation by Heat and Commercially and World Health Organization-Recommended Biocides.
oai:repository.helmholtz-hzi.de:10033/6217452019-08-30T11:31:43Zcom_10033_620589col_10033_620590col_10033_620596
00925njm 22002777a 4500
dc
Behrendt, Patrick
author
Brüning, Janina
author
Todt, Daniel
author
Steinmann, Eike
author
2019-03-01
Hepatitis C virus (HCV) is a blood-borne virus and is most frequently transmitted through large or repeated direct percutaneous exposures to infected blood. The 2 most common exposures associated with transmission of HCV are blood transfusion and intravenous drug abuse. The association between HCV transmission and other suspected risk factors such as tattooing is more controversial. Although HCV can survive for days to weeks in suspension or on inanimate surfaces, its stability in tattooing supplies remains elusive. Here, we analyzed the influence of tattoo ink on HCV infectiousness.
Open Forum Infect Dis. 2019 Feb 13;6(3):ofz047. doi: 10.1093/ofid/ofz047. eCollection 2019 Mar.
2328-8957
30882013
10.1093/ofid/ofz047
http://hdl.handle.net/10033/621745
Open Forum Infectious diseases
hepatitis C virus
prevention
transmission
viral stability
Influence of Tattoo Ink on Hepatitis C Virus Infectiousness.
oai:repository.helmholtz-hzi.de:10033/6224272021-01-07T09:08:18Zcom_10033_620589col_10033_620596
00925njm 22002777a 4500
dc
Helfritz, Fabian A
author
Bojkova, Denisa
author
Wanders, Verena
author
Kuklinski, Nina
author
Westhaus, Sandra
author
von Horn, Charlotte
author
Rauen, Ursula
author
Gallinat, Anja
author
Baba, Hideo A
author
Skyschally, Andreas
author
Swoboda, Sandra
author
Kinast, Volker
author
Steinmann, Eike
author
Heusch, Gerd
author
Minor, Thomas
author
Meuleman, Philip
author
Paul, Andreas
author
Ciesek, Sandra
author
2018-12-01
Background: Although organ shortage is a rising problem, organs from hepatitis C virus (HCV) ribonucleic acid (RNA)-positive donors are not routinely transplanted in HCV-negative individuals. Because HCV only infects hepatocytes, other organs such as kidneys are merely contaminated with HCV via the blood. In this study, we established a protocol to reduce HCV virions during the cold ischemic time.
Methods: Standard virological assays were used to investigate the effect of antivirals, including methylene blue (MB), in different preservation solutions. Kidneys from mini pigs were contaminated with Jc1 or HCV RNA-positive human serum. Afterwards, organs were flushed with MB. Hypothermic machine perfusion was used to optimize reduction of HCV.
Results: Three different antivirals were investigated for their ability to inactivate HCV in vitro. Only MB completely inactivated HCV in the presence of all perfusion solutions. Hepatitis C virus-contaminated kidneys from mini pigs were treated with MB and hypothermic machine perfusion without any negative effect on the graft. Human liver-uPA-SCID mice did not establish HCV infection after inoculation with flow through from these kidneys.
Conclusions: This proof-of-concept study is a first step to reduce transmission of infectious HCV particles in the transplant setting and might serve as a model for other relevant pathogens.
J Infect Dis. 2018;218(11):1711-1721. doi:10.1093/infdis/jiy386.
29939277
10.1093/infdis/jiy386
http://hdl.handle.net/10033/622427
1537-6613
The Journal of infectious diseases
Methylene Blue Treatment of Grafts During Cold Ischemia Time Reduces the Risk of Hepatitis C Virus Transmission.