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Influenza virus (IV) infections are considered to cause severe diseases of the respiratory tract. Beyond mild symptoms, the infection can lead to respiratory distress syndrome and multiple organ failure. Occurrence of resistant seasonal and pandemic strains against the currently licensed antiviral medications points to the urgent need for new and amply available anti-influenza drugs. Interestingly, the virus-supportive function of the cellular phosphatidylinositol 3-kinase (PI3K) suggests that this signaling module may be a potential target for antiviral intervention. In the sense of repurposing existing drugs for new indications, we used Pictilisib, a known PI3K inhibitor to investigate its effect on IV infection, in mono-cell-culture studies as well as in a human chip model. Our results indicate that Pictilisib is a potent inhibitor of IV propagation already at early stages of infection. In a murine model of IV pneumonia, the in vitro key findings were verified, showing reduced viral titers as well as inflammatory response in the lung after delivery of Pictilisib. Our data identified Pictilisib as a promising drug candidate for anti-IV therapies that warrant further studying. These results further led to the conclusion that the repurposing of previously approved substances represents a cost-effective and efficient way for development of novel antiviral strategies.
Stefanie Deinhardt-Emmer; Laura Jäckel; Clio Häring; Sarah Böttcher; Janine Wilden; Brigitte Glück; Regine Heller; Michaela Schmidtke; Mirijam Koch; Bettina Löffler; Stephan Ludwig; Christina Ehrhardt. Inhibition of Phosphatidylinositol 3-Kinase by Pictilisib Blocks Influenza Virus Propagation in Cells and in Lungs of Infected Mice. Biomolecules 2021, 11, 808 .
AMA StyleStefanie Deinhardt-Emmer, Laura Jäckel, Clio Häring, Sarah Böttcher, Janine Wilden, Brigitte Glück, Regine Heller, Michaela Schmidtke, Mirijam Koch, Bettina Löffler, Stephan Ludwig, Christina Ehrhardt. Inhibition of Phosphatidylinositol 3-Kinase by Pictilisib Blocks Influenza Virus Propagation in Cells and in Lungs of Infected Mice. Biomolecules. 2021; 11 (6):808.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Laura Jäckel; Clio Häring; Sarah Böttcher; Janine Wilden; Brigitte Glück; Regine Heller; Michaela Schmidtke; Mirijam Koch; Bettina Löffler; Stephan Ludwig; Christina Ehrhardt. 2021. "Inhibition of Phosphatidylinositol 3-Kinase by Pictilisib Blocks Influenza Virus Propagation in Cells and in Lungs of Infected Mice." Biomolecules 11, no. 6: 808.
Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body and its correlation with tissue damage can aid in understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of the viral RNA in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the early postmortem interval (between 1.5 and 15 hr, mean: 5.6 hr) to minimize the bias due to viral RNA and tissue degradation. Very high viral loads (>104copies/ml) were detected in most patients' lungs, and the presence of intact viral particles in the lung tissue could be verified by transmission electron microscopy. Interestingly, viral RNA was detected throughout various extrapulmonary tissues and organs without visible tissue damage. The dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis that there is a maladaptive host response with viremia and multiorgan dysfunction.
Stefanie Deinhardt-Emmer; Daniel Wittschieber; Juliane Sanft; Sandra Kleemann; Stefan Elschner; Karoline Frieda Haupt; Vanessa Vau; Clio Häring; Jürgen Rödel; Andreas Henke; Christina Ehrhardt; Michael Bauer; Mike Philipp; Nikolaus Gaßler; Sandor Nietzsche; Bettina Löffler; Gita Mall. Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage. eLife 2021, 10, 1 .
AMA StyleStefanie Deinhardt-Emmer, Daniel Wittschieber, Juliane Sanft, Sandra Kleemann, Stefan Elschner, Karoline Frieda Haupt, Vanessa Vau, Clio Häring, Jürgen Rödel, Andreas Henke, Christina Ehrhardt, Michael Bauer, Mike Philipp, Nikolaus Gaßler, Sandor Nietzsche, Bettina Löffler, Gita Mall. Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage. eLife. 2021; 10 ():1.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Daniel Wittschieber; Juliane Sanft; Sandra Kleemann; Stefan Elschner; Karoline Frieda Haupt; Vanessa Vau; Clio Häring; Jürgen Rödel; Andreas Henke; Christina Ehrhardt; Michael Bauer; Mike Philipp; Nikolaus Gaßler; Sandor Nietzsche; Bettina Löffler; Gita Mall. 2021. "Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage." eLife 10, no. : 1.
Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data.
Franziska Hornung; Julia Rogal; Peter Loskill; Bettina Löffler; Stefanie Deinhardt-Emmer. The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections. International Journal of Molecular Sciences 2021, 22, 3456 .
AMA StyleFranziska Hornung, Julia Rogal, Peter Loskill, Bettina Löffler, Stefanie Deinhardt-Emmer. The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections. International Journal of Molecular Sciences. 2021; 22 (7):3456.
Chicago/Turabian StyleFranziska Hornung; Julia Rogal; Peter Loskill; Bettina Löffler; Stefanie Deinhardt-Emmer. 2021. "The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections." International Journal of Molecular Sciences 22, no. 7: 3456.
Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be asymptomatic, but they can also be accompanied by a variety of symptoms that result in mild to severe coronavirus disease-19 (COVID-19) and are sometimes associated with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human chip model composed of epithelial, endothelial, and mononuclear cells. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including interferon expression. In contrast, the adjacent endothelial layer was neither infected nor did it show productive virus replication or interferon release. With prolonged infection, both cell types were damaged, and the barrier function deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokines or components induced during infection, which further results in damage of the epithelial/endothelial barrier function and viral dissemination. IMPORTANCE SARS-CoV-2 challenges health care systems and societies worldwide in unprecedented ways. Although numerous new studies have been conducted, research to better understand the molecular pathogen-host interactions is urgently needed. For this, experimental models have to be developed and adapted. In the present study we used mono-cell culture systems, and we established a complex chip model, where epithelial and endothelial cells are cultured in close proximity. We demonstrate that epithelial cells can be infected with SARS-CoV-2, while the endothelium did not show any infection signs. Since SARS-CoV-2 is able to establish viremia, the link to thromboembolic events in severe COVID-19 courses is evident. However, whether the endothelial layer is damaged by the viral pathogens or whether other endothelial-independent homeostatic factors are induced by the virus is essential for understanding the disease development. Therefore, our study is important, as it demonstrates that the endothelial layer could not be infected by SARS-CoV-2 in our in vitro experiments, but we were able to show the destruction of the epithelial-endothelial barrier in our chip model. From our experiments, we can assume that virus-induced host factors disturbed the epithelial-endothelial barrier function and thereby promote viral spread.
Stefanie Deinhardt-Emmer; Sarah Böttcher; Clio Häring; Liane Giebeler; Andreas Henke; Roland Zell; Johannes Jungwirth; Paul M. Jordan; Oliver Werz; Franziska Hornung; Christian Brandt; Mike Marquet; Alexander S. Mosig; Mathias W. Pletz; Michael Schacke; Jürgen Rödel; Regine Heller; Sandor Nietzsche; Bettina Löffler; Christina Ehrhardt. SARS-CoV-2 Causes Severe Epithelial Inflammation and Barrier Dysfunction. Journal of Virology 2021, 95, 1 .
AMA StyleStefanie Deinhardt-Emmer, Sarah Böttcher, Clio Häring, Liane Giebeler, Andreas Henke, Roland Zell, Johannes Jungwirth, Paul M. Jordan, Oliver Werz, Franziska Hornung, Christian Brandt, Mike Marquet, Alexander S. Mosig, Mathias W. Pletz, Michael Schacke, Jürgen Rödel, Regine Heller, Sandor Nietzsche, Bettina Löffler, Christina Ehrhardt. SARS-CoV-2 Causes Severe Epithelial Inflammation and Barrier Dysfunction. Journal of Virology. 2021; 95 (10):1.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Sarah Böttcher; Clio Häring; Liane Giebeler; Andreas Henke; Roland Zell; Johannes Jungwirth; Paul M. Jordan; Oliver Werz; Franziska Hornung; Christian Brandt; Mike Marquet; Alexander S. Mosig; Mathias W. Pletz; Michael Schacke; Jürgen Rödel; Regine Heller; Sandor Nietzsche; Bettina Löffler; Christina Ehrhardt. 2021. "SARS-CoV-2 Causes Severe Epithelial Inflammation and Barrier Dysfunction." Journal of Virology 95, no. 10: 1.
From the famous 1918 H1N1 influenza to the present COVID-19 pandemic, the need for improved viral detection techniques is all too apparent. The aim of the present paper is to show that identification of individual virus particles in clinical sample materials quickly and reliably is near at hand. First of all, our team has developed techniques for identification of virions based on a modular atomic force microscopy (AFM). Furthermore, femtosecond adaptive spectroscopic techniques with enhanced resolution via coherent anti-Stokes Raman scattering (FASTER CARS) using tip-enhanced techniques markedly improves the sensitivity [M. O. Scully,et al.,Proc. Natl. Acad. Sci. U.S.A.99, 10994–11001 (2002)].
Volker Deckert; Tanja Deckert-Gaudig; Dana Cialla-May; Jürgen Popp; Roland Zell; Stefanie Deinhard-Emmer; Alexei V. Sokolov; Zhenhuan Yi; Marlan O. Scully. Laser spectroscopic technique for direct identification of a single virus I: FASTER CARS. Proceedings of the National Academy of Sciences 2020, 117, 27820 -27824.
AMA StyleVolker Deckert, Tanja Deckert-Gaudig, Dana Cialla-May, Jürgen Popp, Roland Zell, Stefanie Deinhard-Emmer, Alexei V. Sokolov, Zhenhuan Yi, Marlan O. Scully. Laser spectroscopic technique for direct identification of a single virus I: FASTER CARS. Proceedings of the National Academy of Sciences. 2020; 117 (45):27820-27824.
Chicago/Turabian StyleVolker Deckert; Tanja Deckert-Gaudig; Dana Cialla-May; Jürgen Popp; Roland Zell; Stefanie Deinhard-Emmer; Alexei V. Sokolov; Zhenhuan Yi; Marlan O. Scully. 2020. "Laser spectroscopic technique for direct identification of a single virus I: FASTER CARS." Proceedings of the National Academy of Sciences 117, no. 45: 27820-27824.
Infections with SARS-CoV-2 lead to mild to severe coronavirus disease-19 (COVID-19) with systemic symptoms. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human alveolus-on-a-chip model. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including the interferon expression. By contrast, the adjacent endothelial layer was no infected and did neither show productive virus replication or interferon release. With prolonged infection, both cell types are damaged, and the barrier function is deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokine release, which results in the damage of the alveolar barrier function and viral dissemination.
Stefanie Deinhardt-Emmer; Sarah Böttcher; Clio Häring; Liane Giebeler; Andreas Henke; Roland Zell; Franziska Hornung; Christian Brandt; Mike Marquet; Alexander S. Mosig; Mathias W Pletz; Michael Schacke; Juergen Roedel; Regine Heller; Sandor Nietzsche; Bettina Löffler; Christina Ehrhardt. SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction. 2020, 1 .
AMA StyleStefanie Deinhardt-Emmer, Sarah Böttcher, Clio Häring, Liane Giebeler, Andreas Henke, Roland Zell, Franziska Hornung, Christian Brandt, Mike Marquet, Alexander S. Mosig, Mathias W Pletz, Michael Schacke, Juergen Roedel, Regine Heller, Sandor Nietzsche, Bettina Löffler, Christina Ehrhardt. SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction. . 2020; ():1.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Sarah Böttcher; Clio Häring; Liane Giebeler; Andreas Henke; Roland Zell; Franziska Hornung; Christian Brandt; Mike Marquet; Alexander S. Mosig; Mathias W Pletz; Michael Schacke; Juergen Roedel; Regine Heller; Sandor Nietzsche; Bettina Löffler; Christina Ehrhardt. 2020. "SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction." , no. : 1.
Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body in correlation to tissue damage can help to understand SARS-CoV-2 infection. We present a detailed RNA mapping in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the (very) early postmortem interval to avoid bias due to RNA and tissue degradation. Very high viral loads were detected in the lungs of most patients and then correlated to severe tissue damage. In addition, intact viral particles could be verified in the lung tissue by transmission electron microscopy. However, viral RNA was detected throughout further extra-pulmonary tissues and organs without visible tissue damage, inflammatory and prothrombotic factors were elevated in all patients. In conclusion, the dissemination of SARS-CoV-2 RNA throughout the body supports the hypothesis of a maladaptive host response with viremia and multi-organ dysfunction.
Stefanie Deinhardt-Emmer; Daniel Wittschieber; Juliane Sanft; Sandra Kleemann; Stefan Elschner; Karoline Frieda Haupt; Vanessa Vau; Clio Häring; Jürgen Rödel; Andreas Henke; Christina Ehrhardt; Michael Bauer; Mike Philipp; Nikolaus Gaßler; Sandor Nietzsche; Bettina Löffler; Gita Mall. Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage. 2020, 1 .
AMA StyleStefanie Deinhardt-Emmer, Daniel Wittschieber, Juliane Sanft, Sandra Kleemann, Stefan Elschner, Karoline Frieda Haupt, Vanessa Vau, Clio Häring, Jürgen Rödel, Andreas Henke, Christina Ehrhardt, Michael Bauer, Mike Philipp, Nikolaus Gaßler, Sandor Nietzsche, Bettina Löffler, Gita Mall. Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage. . 2020; ():1.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Daniel Wittschieber; Juliane Sanft; Sandra Kleemann; Stefan Elschner; Karoline Frieda Haupt; Vanessa Vau; Clio Häring; Jürgen Rödel; Andreas Henke; Christina Ehrhardt; Michael Bauer; Mike Philipp; Nikolaus Gaßler; Sandor Nietzsche; Bettina Löffler; Gita Mall. 2020. "Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage." , no. : 1.
Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus aureus (S. aureus) infections affect SP-A expression. To closely reflect the situation in the lung, we used a human alveolus-on-a-chip model and a murine pneumonia model. Our results show that S. aureus can reduce extracellular levels of SP-A, most likely attributed to bacterial proteases. Mono-epithelial cell culture experiments reveal that the expression of SP-A is not directly affected by IAV or S. aureus. Yet, the mRNA expression of SP-A is strongly down-regulated by TNF-α, which is highly produced by professional phagocytes in response to bacterial infection. By using the human alveolus-on-a-chip model, we show that the down-regulation of SP-A is strongly dependent on macrophages. In a murine model of pneumonia, we can confirm that S. aureus decreases SP-A levels in vivo. These findings indicate that (I) complex interactions of epithelial and immune cells induce down-regulation of SP-A expression and (II) bacterial mono- and super-infections reduce SP-A expression in the lung, which might contribute to a severe outcome of bacterial pneumonia.
Elisabeth Schicke; Zoltán Cseresnyés; Knut Rennert; Vanessa Vau; Karoline Frieda Haupt; Franziska Hornung; Sandor Nietzsche; Fatina Swiczak; Michaela Schmidtke; Brigitte Glück; Mirijam Koch; Michael Schacke; Regine Heller; Alexander S. Mosig; Marc Thilo Figge; Christina Ehrhardt; Bettina Löffler; Stefanie Deinhardt-Emmer. Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages. Microorganisms 2020, 8, 577 .
AMA StyleElisabeth Schicke, Zoltán Cseresnyés, Knut Rennert, Vanessa Vau, Karoline Frieda Haupt, Franziska Hornung, Sandor Nietzsche, Fatina Swiczak, Michaela Schmidtke, Brigitte Glück, Mirijam Koch, Michael Schacke, Regine Heller, Alexander S. Mosig, Marc Thilo Figge, Christina Ehrhardt, Bettina Löffler, Stefanie Deinhardt-Emmer. Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages. Microorganisms. 2020; 8 (4):577.
Chicago/Turabian StyleElisabeth Schicke; Zoltán Cseresnyés; Knut Rennert; Vanessa Vau; Karoline Frieda Haupt; Franziska Hornung; Sandor Nietzsche; Fatina Swiczak; Michaela Schmidtke; Brigitte Glück; Mirijam Koch; Michael Schacke; Regine Heller; Alexander S. Mosig; Marc Thilo Figge; Christina Ehrhardt; Bettina Löffler; Stefanie Deinhardt-Emmer. 2020. "Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages." Microorganisms 8, no. 4: 577.
Pneumonia is one of the most common infectious diseases worldwide. The influenza virus (IV) can cause severe epidemics, which results in significant morbidity and mortality. Beyond the virulence of the virus itself, epidemiological data suggest that bacterial co-infections are the major cause of increased mortality. In this context, Staphylococcus aureus represents a frequent causative bacterial pathogen. Currently, available models have several limitations in the analysis of the pathogenesis of infections, e.g., some bacterial toxins strongly act in a species-specific manner. Human 2D mono-cell culture models often fail to maintain the differentiation of alveolus-specific functions. A detailed investigation of the underlying pathogenesis mechanisms requires a physiological interaction of alveolus-specific cell types. The present work aimed to establish a human in vitro alveolus model system composed of vascular and epithelial cell structures with cocultured macrophages resembling the human alveolus architecture and functions. We demonstrate that high barrier integrity maintained for up to 14 d in our model containing functional tissue-resident macrophages. We show that flow conditions and the presence of macrophages increased the barrier function. The infection of epithelial cells induced a high inflammatory response that spread to the endothelium. Although the integrity of the epithelium was not compromised by a single infection or co-infection, we demonstrated significant endothelial cell damage associated with loss of barrier function. We established a novel immune-responsive model that reflects the complex crosstalk between pathogens and host. The in vitro model allows for the monitoring of spatiotemporal spreading of the pathogens and the characterization of morphological and functional alterations attributed to infection. The alveolus-on-a-chip represents a promising platform for mechanistic studies of host-pathogen interactions and the identification of molecular and cellular targets of novel treatment strategies in pneumonia.
Stefanie Deinhardt-Emmer; Knut Rennert; Elisabeth Schicke; Zoltán Cseresnyés; Maximilian Windolph; Sandor Nietzsche; Regine Heller; Fatina Siwczak; Karoline Frieda Haupt; Swen Carlstedt; Michael Schacke; Marc Thilo Figge; Christina Ehrhardt; Bettina Loeffler; Alexander S Mosig. Co-infection with Staphylococcus aureus after primary influenza virus infection leads to damage of the endothelium in a human alveolus-on-a-chip model. Biofabrication 2020, 12, 025012 .
AMA StyleStefanie Deinhardt-Emmer, Knut Rennert, Elisabeth Schicke, Zoltán Cseresnyés, Maximilian Windolph, Sandor Nietzsche, Regine Heller, Fatina Siwczak, Karoline Frieda Haupt, Swen Carlstedt, Michael Schacke, Marc Thilo Figge, Christina Ehrhardt, Bettina Loeffler, Alexander S Mosig. Co-infection with Staphylococcus aureus after primary influenza virus infection leads to damage of the endothelium in a human alveolus-on-a-chip model. Biofabrication. 2020; 12 (2):025012.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Knut Rennert; Elisabeth Schicke; Zoltán Cseresnyés; Maximilian Windolph; Sandor Nietzsche; Regine Heller; Fatina Siwczak; Karoline Frieda Haupt; Swen Carlstedt; Michael Schacke; Marc Thilo Figge; Christina Ehrhardt; Bettina Loeffler; Alexander S Mosig. 2020. "Co-infection with Staphylococcus aureus after primary influenza virus infection leads to damage of the endothelium in a human alveolus-on-a-chip model." Biofabrication 12, no. 2: 025012.
Staphylococcus aureus is a facultative pathogenic bacterium that colonizes the nasopharyngeal area of healthy individuals, but can also induce severe infection, such as pneumonia. Pneumonia caused by mono- or superinfected S. aureus leads to high mortality rates. To establish an infection, S. aureus disposes of a wide variety of virulence factors, which can vary between clinical isolates. Our study aimed to characterize pneumonia isolates for their virulent capacity. For this, we analyzed isolates from colonization, pneumonia due to S. aureus, and pneumonia due to S. aureus/influenza virus co-infection. A total of 70 strains were analyzed for their virulence genes and the host–pathogen interaction was analyzed through functional assays in cell culture systems. Strains from pneumonia due to S. aureus mono-infection showed enhanced invasion and cytotoxicity against professional phagocytes than colonizing and co-infecting strains. This corresponded to the high presence of cytotoxic components in pneumonia strains. By contrast, strains obtained from co-infection did not exhibit these virulence characteristics and resembled strains from colonization, although they caused the highest mortality rate in patients. Taken together, our results underline the requirement of invasion and toxins to cause pneumonia due to S. aureus mono-infection, whereas in co-infection even low-virulent strains can severely aggravate pneumonia.
Stefanie Deinhardt-Emmer; Karoline Frieda Haupt; Marina Garcia-Moreno; Jennifer Geraci; Christina Forstner; Mathias Pletz; Christina Ehrhardt; Bettina Löffler. Staphylococcus aureus Pneumonia: Preceding Influenza Infection Paves the Way for Low-Virulent Strains. Toxins 2019, 11, 734 .
AMA StyleStefanie Deinhardt-Emmer, Karoline Frieda Haupt, Marina Garcia-Moreno, Jennifer Geraci, Christina Forstner, Mathias Pletz, Christina Ehrhardt, Bettina Löffler. Staphylococcus aureus Pneumonia: Preceding Influenza Infection Paves the Way for Low-Virulent Strains. Toxins. 2019; 11 (12):734.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Karoline Frieda Haupt; Marina Garcia-Moreno; Jennifer Geraci; Christina Forstner; Mathias Pletz; Christina Ehrhardt; Bettina Löffler. 2019. "Staphylococcus aureus Pneumonia: Preceding Influenza Infection Paves the Way for Low-Virulent Strains." Toxins 11, no. 12: 734.
The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.
Franziska Hufsky; Bashar Ibrahim; Sejal Modha; Martha R. J. Clokie; Stefanie Deinhardt-Emmer; Bas E. Dutilh; Samantha Lycett; Peter Simmonds; Volker Thiel; Aare Abroi; Evelien M. Adriaenssens; Marina Escalera-Zamudio; Jenna Nicole Kelly; Kevin Lamkiewicz; Lu Lu; Julian Susat; Thomas Sicheritz; David L. Robertson; Manja Marz. The Third Annual Meeting of the European Virus Bioinformatics Center. Viruses 2019, 11, 420 .
AMA StyleFranziska Hufsky, Bashar Ibrahim, Sejal Modha, Martha R. J. Clokie, Stefanie Deinhardt-Emmer, Bas E. Dutilh, Samantha Lycett, Peter Simmonds, Volker Thiel, Aare Abroi, Evelien M. Adriaenssens, Marina Escalera-Zamudio, Jenna Nicole Kelly, Kevin Lamkiewicz, Lu Lu, Julian Susat, Thomas Sicheritz, David L. Robertson, Manja Marz. The Third Annual Meeting of the European Virus Bioinformatics Center. Viruses. 2019; 11 (5):420.
Chicago/Turabian StyleFranziska Hufsky; Bashar Ibrahim; Sejal Modha; Martha R. J. Clokie; Stefanie Deinhardt-Emmer; Bas E. Dutilh; Samantha Lycett; Peter Simmonds; Volker Thiel; Aare Abroi; Evelien M. Adriaenssens; Marina Escalera-Zamudio; Jenna Nicole Kelly; Kevin Lamkiewicz; Lu Lu; Julian Susat; Thomas Sicheritz; David L. Robertson; Manja Marz. 2019. "The Third Annual Meeting of the European Virus Bioinformatics Center." Viruses 11, no. 5: 420.
Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, and from patients with endoprosthesis infection, hematogenous osteomyelitis, and sepsis. All strains were characterized by genotypic analysis, and by the expression of virulence factors. The host–pathogen interaction was studied through several functional assays in osteoblast cultures. Additionally, selected strains were tested in a murine sepsis/osteomyelitis model. We did not find characteristic bacterial features for the defined infection types; rather, a wide range in all strain collections regarding cytotoxicity and invasiveness was observed. Interestingly, all strains were able to persist and to form small colony variants (SCVs). However, the low-cytotoxicity strains survived in higher numbers, and were less efficiently cleared by the host than the highly cytotoxic strains. In summary, our results indicate that not only destructive, but also low-cytotoxicity strains are able to induce infections. The low-cytotoxicity strains can successfully survive, and are less efficiently cleared from the host than the highly cytotoxic strains, which represent a source for chronic infections. The understanding of this interplay/evolution between the host and the pathogen during infection, with specific attention towards low-cytotoxicity isolates, will help to optimize treatment strategies for invasive and therapy-refractory infection courses.
Lorena Tuchscherr; Christine Pöllath; Anke Siegmund; Stefanie Deinhardt-Emmer; Verena Hoerr; Carl-Magnus Svensson; Marc Thilo Figge; Stefan Monecke; Bettina Löffler. Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host. Toxins 2019, 11, 135 .
AMA StyleLorena Tuchscherr, Christine Pöllath, Anke Siegmund, Stefanie Deinhardt-Emmer, Verena Hoerr, Carl-Magnus Svensson, Marc Thilo Figge, Stefan Monecke, Bettina Löffler. Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host. Toxins. 2019; 11 (3):135.
Chicago/Turabian StyleLorena Tuchscherr; Christine Pöllath; Anke Siegmund; Stefanie Deinhardt-Emmer; Verena Hoerr; Carl-Magnus Svensson; Marc Thilo Figge; Stefan Monecke; Bettina Löffler. 2019. "Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host." Toxins 11, no. 3: 135.
The prevalence of nasopharyngeal colonization with Staphylococcus aureus can reach 20-30 % among the population, which can be the source for an invasive infection.The objective of this study was to investigate the prevalence of colonization among different age groups, as well as the analysis of the S. aureus strain-specific virulence patterns.For the analysis of the prevalence of colonization, groups consisting of newborns, healthy volunteers aged 5-60 years and nursing homes residents aged >80 years were examined with nasopharyngeal swabs. After S. aureus was cultured, genetic analysis and phenotypic virulence testing were performed by cell-based assays.Among 924 volunteers the overall colonization rate was approximately 30 %, with a peak in the age 5-10 years group of 49 %. Neonates and > 80-year-olds showed different distributions of clonal clusters. Overall, the strains of all age groups exhibited virulence characteristics that can contribute to infection development. In particular, the neonatal strains exhibited a high incidence of toxin genes that resulted in increased cytotoxic effects compared to the other strains tested.Colonizing strains showed a virulence profile in all age groups which can potentially lead to the establishment of an invasive infection. Consequently, decolonization measures could be considered for selected patients depending on the risk of infection.
S. Deinhardt-Emmer; S. Sachse; J. Geraci; C. Fischer; A. Kwetkat; K. Dawczynski; L. Tuchscherr; B. Löffler. Virulence patterns of Staphylococcus aureus strains from nasopharyngeal colonization. Journal of Hospital Infection 2018, 100, 309 -315.
AMA StyleS. Deinhardt-Emmer, S. Sachse, J. Geraci, C. Fischer, A. Kwetkat, K. Dawczynski, L. Tuchscherr, B. Löffler. Virulence patterns of Staphylococcus aureus strains from nasopharyngeal colonization. Journal of Hospital Infection. 2018; 100 (3):309-315.
Chicago/Turabian StyleS. Deinhardt-Emmer; S. Sachse; J. Geraci; C. Fischer; A. Kwetkat; K. Dawczynski; L. Tuchscherr; B. Löffler. 2018. "Virulence patterns of Staphylococcus aureus strains from nasopharyngeal colonization." Journal of Hospital Infection 100, no. 3: 309-315.
Staphylococcus aureus is the most frequent pathogen causing diabetic foot infections. Here, we investigated the degree of bacterial virulence required to establish invasive tissue infections in diabetic organisms. Staphylococcal isolates from diabetic and non-diabetic foot ulcers were tested for their virulence in in vitro functional assays of host cell invasion and cytotoxicity. Isolates from diabetes mellitus type I/II patients exhibited less virulence than isolates from non-diabetic patients, but were nevertheless able to establish severe infections. In some cases, non-invasive isolates were detected deep within diabetic wounds, even though the strains were non-pathogenic in cell culture models. Testing of defined isolates in murine footpad injection models revealed that both low- and high-virulent bacterial strains persisted in higher numbers in diabetic compared to non-diabetic hosts, suggesting that hyperglycemia favors bacterial survival. Additionally, the bacterial load was higher in NOD mice, which have a compromised immune system, compared to C57Bl/6 mice. Our results reveal that high as well as low-virulent staphylococcal strains are able to cause soft tissue infections and to persist in diabetic humans and mice, suggesting a reason for the frequent and endangering infections in patients with diabetes.
Lorena Tuchscherr; èva Korpos; Hélène Van De Vyver; Clais Findeisen; Salome Kherkheulidze; Anke Siegmund; Stefanie Deinhardt-Emmer; Olaf Bach; Martin Rindert; Alexander Mellmann; Cord Sunderkötter; Georg Peters; Lydia Sorokin; Bettina Löffler. Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts. International Journal of Medical Microbiology 2018, 308, 761 -769.
AMA StyleLorena Tuchscherr, èva Korpos, Hélène Van De Vyver, Clais Findeisen, Salome Kherkheulidze, Anke Siegmund, Stefanie Deinhardt-Emmer, Olaf Bach, Martin Rindert, Alexander Mellmann, Cord Sunderkötter, Georg Peters, Lydia Sorokin, Bettina Löffler. Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts. International Journal of Medical Microbiology. 2018; 308 (7):761-769.
Chicago/Turabian StyleLorena Tuchscherr; èva Korpos; Hélène Van De Vyver; Clais Findeisen; Salome Kherkheulidze; Anke Siegmund; Stefanie Deinhardt-Emmer; Olaf Bach; Martin Rindert; Alexander Mellmann; Cord Sunderkötter; Georg Peters; Lydia Sorokin; Bettina Löffler. 2018. "Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts." International Journal of Medical Microbiology 308, no. 7: 761-769.
We describe the first isolation of Mycobacterium hassiacum, a rapid-growing, partial acid-resistant mycobacterium, in a respiratory specimen from a patient with exacerbated chronic obstructive pulmonary disease. To provide therapeutic recommendation for future cases, antibiotic susceptibility testing of 3 clinical isolates was performed by broth microdilution. All strains tested showed susceptibility to clarithromycin, imipenem, ciprofloxacin, and doxycycline. The role of M hassiacum as a respiratory pathogen remains unclear and needs to be evaluated by future reports.
Stefanie Deinhardt-Emmer; Steffen Höring; Christian Mura; Doris Hillemann; Beate Hermann; Svea Sachse; Jürgen Bohnert; Bettina Löffler. First Time Isolation of Mycobacterium hassiacum From a Respiratory Sample. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 2018, 12, 1 .
AMA StyleStefanie Deinhardt-Emmer, Steffen Höring, Christian Mura, Doris Hillemann, Beate Hermann, Svea Sachse, Jürgen Bohnert, Bettina Löffler. First Time Isolation of Mycobacterium hassiacum From a Respiratory Sample. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine. 2018; 12 ():1.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Steffen Höring; Christian Mura; Doris Hillemann; Beate Hermann; Svea Sachse; Jürgen Bohnert; Bettina Löffler. 2018. "First Time Isolation of Mycobacterium hassiacum From a Respiratory Sample." Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 12, no. : 1.
Stefanie Deinhardt-Emmer; Verena Hoerr; Bettina Löffler. Vascular graft infection: a new model for treatment management? Future Microbiology 2017, 12, 651 -654.
AMA StyleStefanie Deinhardt-Emmer, Verena Hoerr, Bettina Löffler. Vascular graft infection: a new model for treatment management? Future Microbiology. 2017; 12 (8):651-654.
Chicago/Turabian StyleStefanie Deinhardt-Emmer; Verena Hoerr; Bettina Löffler. 2017. "Vascular graft infection: a new model for treatment management?" Future Microbiology 12, no. 8: 651-654.