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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.
Staphylococcus aureus is an opportunistic and versatile pathogen that can cause several diseases, which range from acute and destructive, to chronic and difficult-to-treat infections
Bettina Löffler; Lorena Tuchscherr. Staphylococcus aureus Toxins: Promoter or Handicap during Infection? Toxins 2021, 13, 287 .
AMA StyleBettina Löffler, Lorena Tuchscherr. Staphylococcus aureus Toxins: Promoter or Handicap during Infection? Toxins. 2021; 13 (4):287.
Chicago/Turabian StyleBettina Löffler; Lorena Tuchscherr. 2021. "Staphylococcus aureus Toxins: Promoter or Handicap during Infection?" Toxins 13, no. 4: 287.
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.
Human beings are exposed to microorganisms every day. Among those, diverse commensals and potential pathogens including Staphylococcus aureus (S. aureus) compose a significant part of the respiratory tract microbiota. Remarkably, bacterial colonization is supposed to affect the outcome of viral respiratory tract infections, including those caused by influenza viruses (IV). Since 30% of the world’s population is already colonized with S. aureus that can develop metabolically inactive dormant phenotypes and seasonal IV circulate every year, super-infections are likely to occur. Although IV and S. aureus super-infections are widely described in the literature, the interactions of these pathogens with each other and the host cell are only scarcely understood. Especially, the effect of quasi-dormant bacterial subpopulations on IV infections is barely investigated. In the present study, we aimed to investigate the impact of S. aureus small colony variants on the cell intrinsic immune response during a subsequent IV infection in vitro. In fact, we observed a significant impact on the regulation of pro-inflammatory factors, contributing to a synergistic effect on cell intrinsic innate immune response and induction of harmful cell death. Interestingly, the cytopathic effect, which was observed in presence of both pathogens, was not due to an increased pathogen load.
Janine J. Wilden; Eike R. Hrincius; Silke Niemann; Yvonne Boergeling; Bettina Löffler; Stephan Ludwig; Christina Ehrhardt. Impact of Staphylococcus aureus Small Colony Variants on Human Lung Epithelial Cells with Subsequent Influenza Virus Infection. Microorganisms 2020, 8, 1998 .
AMA StyleJanine J. Wilden, Eike R. Hrincius, Silke Niemann, Yvonne Boergeling, Bettina Löffler, Stephan Ludwig, Christina Ehrhardt. Impact of Staphylococcus aureus Small Colony Variants on Human Lung Epithelial Cells with Subsequent Influenza Virus Infection. Microorganisms. 2020; 8 (12):1998.
Chicago/Turabian StyleJanine J. Wilden; Eike R. Hrincius; Silke Niemann; Yvonne Boergeling; Bettina Löffler; Stephan Ludwig; Christina Ehrhardt. 2020. "Impact of Staphylococcus aureus Small Colony Variants on Human Lung Epithelial Cells with Subsequent Influenza Virus Infection." Microorganisms 8, no. 12: 1998.
Background Healthcare workers (HCWs) are at particular risk to acquire SARS-CoV-2 infections. Aim The objectives of this study were to compare SARS-CoV-2 IgG seroprevalence and compliance to wear personal protective equipment (PPE) between HCWs working within (high-risk) or outside (intermediate-risk) units treating suspected or confirmed COVID-19 patients. In addition, administration staff (low-risk) was included. Materials Co-HCW is a prospective cohort study among employees at the Jena University Hospital, Germany. Since 16th March 2020, 50 SARS-CoV-2 inpatients and 73 outpatients were treated in our hospital. Mandatory masking was implemented on 20th March 2020. We here evaluated seroprevalence using two IgG detecting immunoassays, assessed COVID-19 exposure, clinical symptoms and compliance to wear PPE. Findings Between 19th May and 19th June 2020 we analysed 660 employees [out of 3,228; 20.4%]. Eighteen participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Among them, 13 (72.2%) were not aware of direct COVID-19 exposure and 9 (50.0%) did not report any clinical symptoms. We observed no evidence for an association between seroprevalence and risk area (high-risk: 2 of 137 HCWs (1.5%), intermediate-risk: 10 of 343 HCWs (2.9%), low-risk: 6 of 180 administration employees (3.3%); p=0.574). Reported compliance to wear PPE differed (p Conclusion No evidence for higher seroprevalence against SARS-CoV-2 in HCWs working in high-risk COVID-19 areas could be observed, probably due to high compliance to wear PPE. Compared to administration employees, we observed no additional risk to acquire SARS-CoV-2 infections by patient care.
Christina Bahrs; Aurelia Kimmig; Sebastian Weis; Juliane Ankert; Stefan Hagel; Jens Maschmann; Andreas Stallmach; Andrea Steiner; Michael Bauer; Wilhelm Behringer; Miriam Kesselmeier; Cora Richert; Florian Zepf; Martin Walter; André Scherag; Michael Kiehntopf; Bettina Loeffler; Mathias W. Pletz. Seroprevalence of SARS CoV-2 antibodies in healthcare workers and administration employees: a prospective surveillance study at a 1,400-bed university hospital in Germany. 2020, 1 .
AMA StyleChristina Bahrs, Aurelia Kimmig, Sebastian Weis, Juliane Ankert, Stefan Hagel, Jens Maschmann, Andreas Stallmach, Andrea Steiner, Michael Bauer, Wilhelm Behringer, Miriam Kesselmeier, Cora Richert, Florian Zepf, Martin Walter, André Scherag, Michael Kiehntopf, Bettina Loeffler, Mathias W. Pletz. Seroprevalence of SARS CoV-2 antibodies in healthcare workers and administration employees: a prospective surveillance study at a 1,400-bed university hospital in Germany. . 2020; ():1.
Chicago/Turabian StyleChristina Bahrs; Aurelia Kimmig; Sebastian Weis; Juliane Ankert; Stefan Hagel; Jens Maschmann; Andreas Stallmach; Andrea Steiner; Michael Bauer; Wilhelm Behringer; Miriam Kesselmeier; Cora Richert; Florian Zepf; Martin Walter; André Scherag; Michael Kiehntopf; Bettina Loeffler; Mathias W. Pletz. 2020. "Seroprevalence of SARS CoV-2 antibodies in healthcare workers and administration employees: a prospective surveillance study at a 1,400-bed university hospital in Germany." , no. : 1.
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.
BackgroundDue to the substantial proportion of asymptomatic and mild courses many SARS-CoV-2 infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed at determining and characterizing the rate of SARS-CoV-2 infections and the resulting immunity in a defined population.MethodsCoNAN is a population-based cohort study in the previously quarantined community Neustadt-am-Rennsteig, Germany six weeks after a SARS-CoV-2 outbreak with 49 cases identified by PCR screening of all 883 inhabitants. The primary objective of the study was to assess SARS-CoV-2 antibody seroconversion rate using six different IgG detecting immunoassays. Secondary objectives of the study were: i.) to determine the rate of seroconversion in children; ii.) to determine potential risk factors for symptomatic vs. asymptomatic Covid19 courses; iii.) to investigate the rate of virus persistence.FindingsWe enrolled 626 participants (71% of the community population). All actual SARS-CoV-2 PCR tests were negative; while a total of 8·4% (52 of 620 tested) had antibodies against SARS-CoV-2 in at least two independent tests. Twenty of the antibody positive participants had previously a positive SARS-CoV-2 PCR. On the contrary, of those 38 participants with SARS-CoV-2 infection, only 20 (52·6%) were antibody positive.InterpretationSeveral antibody tests conducted six weeks after an outbreak of SARS-CoV-2 did not detect all previously PCR-positive tested individuals. Cautious evaluation of antibody testing strategies to assess immunity against the infection is warranted.FundingCoNAN was funded by the Thuringian Ministry for Economic Affairs, Science and Digital Society (TMWWDG).
Sebastian Weis; André Scherag; Michael Baier; Michael Kiehntopf; Thomas Kamradt; Steffi Kolanos; Juliane Ankert; Stefan Gloeckner; Oliwia Makarewicz; Stefan Hagel; Christina Bahrs; Aurelia Kimmig; Hans Proquitté; Joel Guerra; Bettina Loeffler; Mathias W. Pletz; CoNAN study group.. Seroprevalence of SARS-CoV-2 antibodies in an entirely PCR-sampled and quarantined community after a COVID-19 outbreak - the CoNAN study. 2020, 1 .
AMA StyleSebastian Weis, André Scherag, Michael Baier, Michael Kiehntopf, Thomas Kamradt, Steffi Kolanos, Juliane Ankert, Stefan Gloeckner, Oliwia Makarewicz, Stefan Hagel, Christina Bahrs, Aurelia Kimmig, Hans Proquitté, Joel Guerra, Bettina Loeffler, Mathias W. Pletz, CoNAN study group.. Seroprevalence of SARS-CoV-2 antibodies in an entirely PCR-sampled and quarantined community after a COVID-19 outbreak - the CoNAN study. . 2020; ():1.
Chicago/Turabian StyleSebastian Weis; André Scherag; Michael Baier; Michael Kiehntopf; Thomas Kamradt; Steffi Kolanos; Juliane Ankert; Stefan Gloeckner; Oliwia Makarewicz; Stefan Hagel; Christina Bahrs; Aurelia Kimmig; Hans Proquitté; Joel Guerra; Bettina Loeffler; Mathias W. Pletz; CoNAN study group.. 2020. "Seroprevalence of SARS-CoV-2 antibodies in an entirely PCR-sampled and quarantined community after a COVID-19 outbreak - the CoNAN study." , 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.
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.
Massive neutrophil infiltration is an early key event in infectious inflammation, accompanied by chemotactic leukotriene (LT)B4 generation. LTB4 biosynthesis is mediated by 5-lipoxygenase (5-LOX), but which pathogenic factors cause 5-LOX activation during bacterial infections is elusive. Here, we reveal staphylococcal exotoxins as 5-LOX activators. Conditioned medium of wild-type Staphylococcus aureus but not of exotoxin-deficient strains induced 5-LOX activation in transfected HEK293 cells. Two different staphylococcal exotoxins mimicked the effects of S. aureus-conditioned medium: (1) the pore-forming toxin α-hemolysin and (2) amphipathic α-helical phenol-soluble modulin (PSM) peptides. Interestingly, in human neutrophils, 5-LOX activation was exclusively evoked by PSMs, which was prevented by the selective FPR2/ALX receptor antagonist WRW4. 5-LOX activation by PSMs was confirmed in vivo as LT formation in infected paws of mice was impaired in response to PSM-deficient S. aureus. Conclusively, exotoxins from S. aureus are potent pathogenic factors that activate 5-LOX and induce LT formation in neutrophils.
Erik Romp; Vandana Arakandy; Jana Fischer; Christiane Wolz; Anke Siegmund; Bettina Löffler; Lorena Tuchscherr; Oliver Werz; Ulrike Garscha. Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis. Cellular and Molecular Life Sciences 2019, 77, 3841 -3858.
AMA StyleErik Romp, Vandana Arakandy, Jana Fischer, Christiane Wolz, Anke Siegmund, Bettina Löffler, Lorena Tuchscherr, Oliver Werz, Ulrike Garscha. Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis. Cellular and Molecular Life Sciences. 2019; 77 (19):3841-3858.
Chicago/Turabian StyleErik Romp; Vandana Arakandy; Jana Fischer; Christiane Wolz; Anke Siegmund; Bettina Löffler; Lorena Tuchscherr; Oliver Werz; Ulrike Garscha. 2019. "Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis." Cellular and Molecular Life Sciences 77, no. 19: 3841-3858.
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.
Matthias Karrasch; Jennifer Geraci; Svea Sachse; Jürgen Rödel; Bettina Löffler; Michael Bauer; Daniel Thomas-Rüddel; Stefan Hagel; René Aschenbach; Frank Bloos. Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis. Clinical Chemistry and Laboratory Medicine (CCLM) 2018, 56, e207 -e209.
AMA StyleMatthias Karrasch, Jennifer Geraci, Svea Sachse, Jürgen Rödel, Bettina Löffler, Michael Bauer, Daniel Thomas-Rüddel, Stefan Hagel, René Aschenbach, Frank Bloos. Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis. Clinical Chemistry and Laboratory Medicine (CCLM). 2018; 56 (8):e207-e209.
Chicago/Turabian StyleMatthias Karrasch; Jennifer Geraci; Svea Sachse; Jürgen Rödel; Bettina Löffler; Michael Bauer; Daniel Thomas-Rüddel; Stefan Hagel; René Aschenbach; Frank Bloos. 2018. "Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis." Clinical Chemistry and Laboratory Medicine (CCLM) 56, no. 8: e207-e209.
Real-time fluorescent efflux assays are commonly used for measuring the efflux of bacterial pumps. Here we describe an optimized protocol for the NorA efflux pump in S. aureus using DiOC instead of ethidium bromide. Glucose and sodium formate were tested as energy carriers. This novel method is fast and reproducible.
Saskia Zimmermann; Lorena Tuchscherr; Jürgen Rödel; Bettina Löffler; Jürgen A. Bohnert. Optimized efflux assay for the NorA multidrug efflux pump in Staphylococcus aureus. Journal of Microbiological Methods 2017, 142, 39 -40.
AMA StyleSaskia Zimmermann, Lorena Tuchscherr, Jürgen Rödel, Bettina Löffler, Jürgen A. Bohnert. Optimized efflux assay for the NorA multidrug efflux pump in Staphylococcus aureus. Journal of Microbiological Methods. 2017; 142 ():39-40.
Chicago/Turabian StyleSaskia Zimmermann; Lorena Tuchscherr; Jürgen Rödel; Bettina Löffler; Jürgen A. Bohnert. 2017. "Optimized efflux assay for the NorA multidrug efflux pump in Staphylococcus aureus." Journal of Microbiological Methods 142, no. : 39-40.
Diabetes mellitus repräsentiert weltweit ein zunehmendes Gesundheitsproblem, das viele Komplikationen einschließt. Die diabetische Fußulzeration (DFU) stellt eine schwer zu therapierende und kostenintensive Komplikation dar. In Folge können sich Infektionen schnell etablieren und sich zu chronischen Infektionen entwickeln. Dies wird durch die verminderte Immunantwort der Patienten aufgrund des Diabetes begünstigt. Pathogene Keime wie S. aureus, aber auch wenig virulente Keime wie Corynebacterium ssp. werden als ätiologische Auslöser nachgewiesen. Die Fähigkeiten dieser Erreger, den Knochen zu infizieren und darin zu persistieren, sind vielfältig und liegen im Fokus vieler Forschergruppen. Entscheidend für den Heilungsprozess ist das erfolgreiche Zusammenspiel von antibiotischen und chirurgischen Maßnahmen, die unter anderem sowohl eine Wundsanierung als auch eine Revaskularisierung einschließen. Das Ziel ist es, die Anzahl der DFU und die dadurch bedingten Infektionen und Amputationen zu reduzieren. World wide, diabetes mellitus is a major public health problem, which is the consequence of changing lifestyles, often accompanied by a lack of exercise and poor eating habits. Diabetic foot ulceration is a difficult to treat and cost-intensive complication. Consequently, infections occur very quickly. This is favoured by the reduced immune response of diabetic patients, as well as by neuropathy and ischemia. Pathogenic bacteria like S. aureus but also less virulent bacteria like Corynebacterium sp. are found as causative agents. The virulence strategies of the pathogens to infect and persist in bones are the subject of many research groups. The interplay of adequate antibiotic therapy and surgical treatment comprising debridement, revascularization and tissue reconstruction, is crucial for healing. The aim is to reduce the number of DFUs and the involved amputations.
Svea Sachse; Martin Rindert; Olaf Bach; Wolfram Kluge; Bettina Löffler. Staphylococcus aureus bei Diabetes: persistierende Fußulzerationen. OP-JOURNAL 2017, 33, 173 -177.
AMA StyleSvea Sachse, Martin Rindert, Olaf Bach, Wolfram Kluge, Bettina Löffler. Staphylococcus aureus bei Diabetes: persistierende Fußulzerationen. OP-JOURNAL. 2017; 33 (2):173-177.
Chicago/Turabian StyleSvea Sachse; Martin Rindert; Olaf Bach; Wolfram Kluge; Bettina Löffler. 2017. "Staphylococcus aureus bei Diabetes: persistierende Fußulzerationen." OP-JOURNAL 33, no. 2: 173-177.
Staphylococcus aureus is a major pathogen causing bone infections that can become chronic and difficult to treat. Recently, we described the mechanism employed by S. aureus to switch to small colony variants (SCVs) and trigger intracellular bacterial persistence through the global stress regulator SigB. Here, we studied the role of SigB in the formation of chronic osteomyelitis. We used a murine hematogenous osteomyelitis model, where the mice were infected via the tail vein and subsequently developed chronic osteomyelitis. Mice were infected with S. aureus LS1, LS1ΔsigB and LS1ΔsigB complemented and kidney and bone tissues were analyzed six weeks after infection. S. aureus LS1ΔsigB formed a high rate of abscesses in kidneys, but the bacterial loads and the weight loss of the animals were lower in comparison with animals infected with the wild type and the complemented strain, indicating a more rapid and efficient bacterial clearing by the host immune system. Moreover, the sigB-mutant was not able to form SCV phenotypes either in kidney or in bone tissue. Our results demonstrate that staphylococcal SigB is important to avoid bacterial elimination by the host immune response, establish a bone infection and mediate bacterial adaptation (SCV-formation) for persistent infections
Lorena Tuchscherr; Jennifer Geraci; Bettina Löffler. Staphylococcus aureus Regulator Sigma B is Important to Develop Chronic Infections in Hematogenous Murine Osteomyelitis Model. Pathogens 2017, 6, 31 .
AMA StyleLorena Tuchscherr, Jennifer Geraci, Bettina Löffler. Staphylococcus aureus Regulator Sigma B is Important to Develop Chronic Infections in Hematogenous Murine Osteomyelitis Model. Pathogens. 2017; 6 (3):31.
Chicago/Turabian StyleLorena Tuchscherr; Jennifer Geraci; Bettina Löffler. 2017. "Staphylococcus aureus Regulator Sigma B is Important to Develop Chronic Infections in Hematogenous Murine Osteomyelitis Model." Pathogens 6, no. 3: 31.
Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence. Cardiac 4D PC CMR images were acquired at 9.4 T in healthy mice using the proposed self-gated radial center-out UTE acquisition scheme (TE/TR of 0.5 ms/3.1 ms) and a standard Cartesian 4D PC imaging sequence (TE/TR of 2.1 ms/5.0 ms) with a four-point Hadamard flow encoding scheme. To validate the proposed UTE flow imaging technique, experiments on a flow phantom with variable pump rates were performed. The anatomical images and flow velocity maps of the proposed 4D PC UTE technique showed reduced artifacts and an improved SNR (left ventricular cavity (LV): 8.9 ± 2.5, myocardium (MC): 15.7 ± 1.9) compared to those obtained using a typical Cartesian FLASH sequence (LV: 5.6 ± 1.2, MC: 10.1 ± 1.4) that was used as a reference. With both sequences comparable flow velocities were obtained in the flow phantom as well as in the ascending aorta (UTE: 132.8 ± 18.3 cm/s, FLASH: 134.7 ± 13.4 cm/s) and pulmonary artery (UTE: 78.5 ± 15.4 cm/s, FLASH: 86.6 ± 6.2 cm/s) of the animals. Self-gated navigator signals derived from information of the oversampled k-space center were successfully extracted for all animals with a higher gating efficiency of time spent on acquiring gated data versus total measurement time (UTE: 61.8 ± 11.5%, FLASH: 48.5 ± 4.9%). The proposed self-gated 4D PC UTE sequence enables robust and accurate flow velocity mapping of the mouse heart in vivo at high magnetic fields. At the same time SNR, gating efficiency, flow artifacts and image quality all improved compared to the images obtained using the well-established, ECG-triggered, 4D PC FLASH sequence.
M. Krämer; A. G. Motaal; K-H. Herrmann; B. Löffler; J. R. Reichenbach; Gustav Strijkers; V. Hoerr. Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging. Journal of Cardiovascular Magnetic Resonance 2017, 19, 39 .
AMA StyleM. Krämer, A. G. Motaal, K-H. Herrmann, B. Löffler, J. R. Reichenbach, Gustav Strijkers, V. Hoerr. Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging. Journal of Cardiovascular Magnetic Resonance. 2017; 19 (1):39.
Chicago/Turabian StyleM. Krämer; A. G. Motaal; K-H. Herrmann; B. Löffler; J. R. Reichenbach; Gustav Strijkers; V. Hoerr. 2017. "Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging." Journal of Cardiovascular Magnetic Resonance 19, no. 1: 39.
Staphylococcus aureus causes very serious infections of vascular grafts. Knowledge of the molecular mechanisms of this disease is largely lacking because of the absence of representable models. Therefore, the aim of this study was to set up a mouse model of vascular graft infections that closely mimics the human situation. A catheter was inserted into the right carotid artery of mice, which acted as a vascular graft. Mice were infected i.v. using 8 different S. aureus strains, and development of the infection was followed up. Although all strains had varying abilities to form biofilm in vitro and different levels of virulence in mice, they all caused biofilm formation on the grafts. This graft infection was monitored using magnetic resonance imaging (MRI) and F-fluordeoxyglucose positron emission tomography (FDG-PET). MRI allowed the quantification of blood flow through the arteries, which was decreased in the catheter after infection. FDG-PET revealed high inflammation levels at the site of the catheter after infection. This model closely resembles the situation in patients, which is characterized by a tight interplay between pathogen and host, and can therefore be used for the testing of novel treatment, diagnosis, and prevention strategies. In addition, combining MRI and PET with microscopic techniques provides an appropriate way to characterize the course of these infections and to precisely analyze biofilm development.
Hélène Van de Vyver; Philipp R. Bovenkamp; Verena Hoerr; Katrin Schwegmann; Lorena Tuchscherr; Silke Niemann; Laura Kursawe; Christina Grosse; Annette Moter; Uwe Hansen; Ute Neugebauer; Michael T. Kuhlmann; Georg Peters; Sven Hermann; Bettina Löffler. A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection. The American Journal of Pathology 2017, 187, 268 -279.
AMA StyleHélène Van de Vyver, Philipp R. Bovenkamp, Verena Hoerr, Katrin Schwegmann, Lorena Tuchscherr, Silke Niemann, Laura Kursawe, Christina Grosse, Annette Moter, Uwe Hansen, Ute Neugebauer, Michael T. Kuhlmann, Georg Peters, Sven Hermann, Bettina Löffler. A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection. The American Journal of Pathology. 2017; 187 (2):268-279.
Chicago/Turabian StyleHélène Van de Vyver; Philipp R. Bovenkamp; Verena Hoerr; Katrin Schwegmann; Lorena Tuchscherr; Silke Niemann; Laura Kursawe; Christina Grosse; Annette Moter; Uwe Hansen; Ute Neugebauer; Michael T. Kuhlmann; Georg Peters; Sven Hermann; Bettina Löffler. 2017. "A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection." The American Journal of Pathology 187, no. 2: 268-279.