Jena, Germany
Jena, Germany

Time filter

Source Type

Brunke S.,University Hospital | Brunke S.,Hans Knoll Institute | Quintin J.,University of Strasbourg | Quintin J.,Radboud University Nijmegen | And 15 more authors.
DMM Disease Models and Mechanisms | Year: 2015

Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent ofmanyalternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictivemodel for estimating the virulence potential of C. glabratamutants in themouse fromfly survival data. As examples, we found cellwall integritymutants attenuated in flies, andmutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host. Copyright © 2015. Published by The Company of Biologists Ltd.


Bruns S.,Hans Knoll Institute | Bruns S.,Friedrich - Schiller University of Jena | Seidler M.,University of Heidelberg | Albrecht D.,Hans Knoll Institute | And 8 more authors.
Proteomics | Year: 2010

The opportunistic pathogenic mold Aspergillus fumigatus is an increasing cause of morbidity and mortality in immunocompromized and in part immunocompetent patients. A. fumigatus can grow in multicellular communities by the formation of a hyphal network encased in an extracellular matrix. Here, we describe the proteome and transcriptome of planktonic- and biofilm-grown A. fumigatus mycelium after 24 and 48 h. A biofilm- and time-dependent regulation of many proteins and genes of the primary metabolism indicates a developmental stage of the young biofilm at 24 h, which demands energy. At a matured biofilm phase, metabolic activity seems to be reduced. However, genes, which code for hydrophobins, and proteins involved in the biosynthesis of secondary metabolites were significantly upregulated. In particular, proteins of the gliotoxin secondary metabolite gene cluster were induced in biofilm cultures. This was confirmed by real-time PCR and by detection of this immunologically active mycotoxin in culture supernatants using HPLC analysis. The enhanced production of gliotoxin by in vitro formed biofilms reported here may also play a significant role under in vivo conditions. It may confer A. fumigatus protection from the host immune system and also enable its survival and persistence in chronic lung infections such as aspergilloma. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


PubMed | Hans Knoll Institute, University of Strasbourg, French National Institute for Agricultural Research, University Hospital and 3 more.
Type: Journal Article | Journal: Disease models & mechanisms | Year: 2015

Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.


PubMed | Germany 4Friedrich Schiller University, Hans Knoll Institute and Debrecen University
Type: Journal Article | Journal: Microbiology (Reading, England) | Year: 2016

The glucocorticoid betamethasone (BM) is frequently employed in clinical practice because of its anti-inflammatory and immunosuppressive properties. In this study, we investigated the effect of BM (1 and 2 mM) on the ability of Candida albicans to adhere to, invade and damage oral, intestinal or vaginal epithelial cells, as well as to elicit cytokine and chemokine release. BM at 2 mM concentration stimulated adherence of C. albicans to vaginal cells and facilitated the invasion of intestinal and vaginal epithelia without influencing the growth rate of invading C. albicans hyphae at any type of epithelia and BM concentrations tested. In addition, BM at 2 mM concentration also augmented C. albicans-initiated cell damage of oral and intestinal cells. Furthermore, BM exposure decreased IL-6 cytokine and IL-8 chemokine release from oral and vaginal epithelial cells and also IL-6 release from intestinal epithelium after infection with C. albicans. These observations suggest that high-dose applications of BM may predispose patients to various epithelial C. albicans infections.


Keller J.,Justus Liebig University | Ringseis R.,Justus Liebig University | Priebe S.,Hans Knoll Institute | Guthke R.,Hans Knoll Institute | And 2 more authors.
Nutrition and Metabolism | Year: 2011

Background: Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown. Methods. To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver. Results: Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid -oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation. Conclusion: The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis. © 2011Keller et al; licensee BioMed Central Ltd.


Barthel A.,Max Planck Institute for Chemical Ecology | Kopka I.,Hans Knoll Institute | Vogel H.,Max Planck Institute for Chemical Ecology | Zipfel P.,Hans Knoll Institute | And 3 more authors.
Proceedings of the Royal Society B: Biological Sciences | Year: 2014

Ecological immunology examines the adaptive responses of animals to pathogens in relation to other environmental factors and explores the consequences of trade-offs between investment in immune function and other life-history traits. Among species of herbivorous insects, diet breadth may vary greatly, with generalists consuming a wide variety of plant families and specialists restricted to a few species. Generalists may thus be exposed to a wider range of pathogens exerting stronger selection on the innate immune system. To examine whether this produces an increase in the robustness of the immune response, we compared larvae of the generalist herbivore Heliothis virescens and the specialist Heliothis subflexa challenged by entomopathogenic and non-pathogenic bacteria. Heliothis virescens larvae showed lower mortality, a lower number of recoverable bacteria, lower proliferation of haemocytes and higher phagocytic activity. These results indicate a higher tolerance to entomopathogenic bacteria by the generalist, which is associated with a more efficient cell-mediated immune response by mechanisms that differ between these closely related species. Our findings provide novel insights into the consequences of diet breadth and related environmental factors, which may be significant in further studies to understand the ecological forces and investment trade-offs that shape the evolution of innate immunity. © 2014 The Authors Published by the Royal Society. All rights reserved.


Iven T.,University of Würzburg | Strathmann A.,University of Würzburg | Bottner S.,University of Würzburg | Zwafink T.,University of Würzburg | And 4 more authors.
Plant Journal | Year: 2010

Expression of BZI-1ΔN, a dominant-negative form of the tobacco (Nicotiana tabacum) basic leucine zipper (bZIP) transcription factor BZI-1 leads to severe defects in pollen development which coincides with reduced transcript abundance of the stamen specific invertase gene NIN88 and decreased extracellular invertase enzymatic activity. This finding suggests a function of BZI-1 in regulating carbohydrate supply of the developing pollen. BZI-1 heterodimerises with the bZIP factors BZI-2, BZI-3 and BZI-4 in vitro and in planta. Whereas BZI-1 exhibits only weak activation properties, BZI-1/BZI-2 heterodimers strongly activate transcription. Consistently, approaches leading to reduced levels of functional BZI-1 or BZI-2 both significantly interfere with pollen development, auxin responsiveness and carbohydrate partitioning. In situ hybridisation studies for BZI-1 and BZI-2 confirmed temporal and spatial overlapping expression patterns in tapetum and pollen supporting functional cooperation of these factors during pollen development. Plants over-expressing BZI-4 produce significantly reduced amounts of intact pollen and are also impaired in NIN88 transcription and enzymatic activity. BZI-4 homodimer efficiently binds to a G-box located in the NIN88 promoter but exhibits almost no transcriptional activation capacity. As BZI-4 does not actively repress transcription, we propose that its homodimer blocks G-box mediated transcription. In summary, these data support a regulatory model in which BZI-4 homodimers and BZI-1/BZI-2 heterodimers perform opposing functions as negative or positive transcriptional regulators during pollen development. © 2010 Blackwell Publishing Ltd.


Barthel A.,Max Planck Institute for Chemical Ecology | Kopka I.,Hans Knoll Institute | Vogel H.,Max Planck Institute for Chemical Ecology | Zipfel P.,Hans Knoll Institute | And 2 more authors.
Proceedings. Biological sciences / The Royal Society | Year: 2014

Ecological immunology examines the adaptive responses of animals to pathogens in relation to other environmental factors and explores the consequences of trade-offs between investment in immune function and other life-history traits. Among species of herbivorous insects, diet breadth may vary greatly, with generalists consuming a wide variety of plant families and specialists restricted to a few species. Generalists may thus be exposed to a wider range of pathogens exerting stronger selection on the innate immune system. To examine whether this produces an increase in the robustness of the immune response, we compared larvae of the generalist herbivore Heliothis virescens and the specialist Heliothis subflexa challenged by entomopathogenic and non-pathogenic bacteria. Heliothis virescens larvae showed lower mortality, a lower number of recoverable bacteria, lower proliferation of haemocytes and higher phagocytic activity. These results indicate a higher tolerance to entomopathogenic bacteria by the generalist, which is associated with a more efficient cell-mediated immune response by mechanisms that differ between these closely related species. Our findings provide novel insights into the consequences of diet breadth and related environmental factors, which may be significant in further studies to understand the ecological forces and investment trade-offs that shape the evolution of innate immunity. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Keller J.,Justus Liebig University | Ringseis R.,Justus Liebig University | Priebe S.,Hans Knoll Institute | Guthke R.,Hans Knoll Institute | And 2 more authors.
Molecular Nutrition and Food Research | Year: 2011

Scope: Carnitine improves protein accretion, muscle mass, and protein:fat accretion in piglets. The underlying mechanisms, however, are largely unknown. Methods and results: To gain insight into mechanisms through which carnitine exerts these effects, we fed piglets either a control or a carnitine-supplemented diet, and analyzed the transcriptome in skeletal muscle. Carnitine concentrations in plasma and muscle were about four-fold higher in the carnitine group when compared to the control group. Transcript profiling revealed 211 genes to be differentially expressed in muscle by carnitine supplementation. The identified genes were mainly involved in molecular processes such as cytoskeletal protein binding, insulin-like growth factor (IGF) binding, transcription factor activity, and insulin receptor binding. Identified genes with the molecular function transcription factor activity encoded primarily transcription factors, most of which were down-regulated by carnitine, including pro-apoptotic transcription factors such as proto-oncogene c-fos, proto-oncogene c-jun and activating transcription factor 3. Furthermore, atrophy-related genes such as atrogin-1, MuRF1, and DRE1 were significantly down-regulated by carnitine. IGF signalling and insulin signalling were identified as significantly up-regulated regulatory pathways in the carnitine group. Conclusion: Carnitine may have beneficial effects on skeletal muscle mass through stimulating the anabolic IGF-1 pathway and suppressing pro-apoptotic and atrophy-related genes, which are involved in apoptosis of muscle fibers and proteolysis of muscle proteins, respectively. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


PubMed | University of Amsterdam, Hans Knoll Institute and Max Planck Institute for Chemical Ecology
Type: Journal Article | Journal: Proceedings. Biological sciences | Year: 2014

Ecological immunology examines the adaptive responses of animals to pathogens in relation to other environmental factors and explores the consequences of trade-offs between investment in immune function and other life-history traits. Among species of herbivorous insects, diet breadth may vary greatly, with generalists consuming a wide variety of plant families and specialists restricted to a few species. Generalists may thus be exposed to a wider range of pathogens exerting stronger selection on the innate immune system. To examine whether this produces an increase in the robustness of the immune response, we compared larvae of the generalist herbivore Heliothis virescens and the specialist Heliothis subflexa challenged by entomopathogenic and non-pathogenic bacteria. Heliothis virescens larvae showed lower mortality, a lower number of recoverable bacteria, lower proliferation of haemocytes and higher phagocytic activity. These results indicate a higher tolerance to entomopathogenic bacteria by the generalist, which is associated with a more efficient cell-mediated immune response by mechanisms that differ between these closely related species. Our findings provide novel insights into the consequences of diet breadth and related environmental factors, which may be significant in further studies to understand the ecological forces and investment trade-offs that shape the evolution of innate immunity.

Loading Hans Knoll Institute collaborators
Loading Hans Knoll Institute collaborators