title: Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts.
abstract: 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.
authors: Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, 07747 Jena, Germany Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, 07745 Jena, Germany sascha.brunke@leibniz-hki.de.
authors: Sascha
authors: S
authors: Brunke
authors: Equipe Fondation Recherche Médicale, Unité Propre de Recherche 9022 du Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Moléculaire et Cellulaire (IBMC), Université de Strasbourg, 67084 Strasbourg, France.
authors: Jessica
authors: J
authors: Quintin
authors: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, 07745 Jena, Germany.
authors: Lydia
authors: L
authors: Kasper
authors: Research Group Microbial Immunology, Hans Knöll Institute, 07745 Jena, Germany Friedrich Schiller University, 07743 Jena, Germany.
authors: Ilse D
authors: ID
authors: Jacobsen
authors: Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, 07747 Jena, Germany Institute for Clinical Chemistry and Laboratory Medicine, Jena University Hospital, 07747 Jena, Germany.
authors: Martin E
authors: ME
authors: Richter
authors: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology, 70569 Stuttgart, Germany.
authors: Ekkehard
authors: E
authors: Hiller
authors: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University Vienna, 1030 Vienna, Austria.
authors: Tobias
authors: T
authors: Schwarzmüller
authors: Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, Département Génomes et Génétique, 75015 Paris, France INRA, USC2019, 75015 Paris, France.
authors: Christophe
authors: C
authors: d'Enfert
authors: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University Vienna, 1030 Vienna, Austria.
authors: Karl
authors: K
authors: Kuchler
authors: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology, 70569 Stuttgart, Germany.
authors: Steffen
authors: S
authors: Rupp
authors: Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, 07747 Jena, Germany Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, 07745 Jena, Germany Friedrich Schiller University, 07743 Jena, Germany.
authors: Bernhard
authors: B
authors: Hube
authors: Equipe Fondation Recherche Médicale, Unité Propre de Recherche 9022 du Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Moléculaire et Cellulaire (IBMC), Université de Strasbourg, 67084 Strasbourg, France.
authors: Dominique
authors: D
authors: Ferrandon
mesh_terms: D000818:Animals; D041221:Candida glabrata / Q000472:pathogenicity; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000382:microbiology*; D063990:Gene Ontology; D006801:Humans; D016015:Logistic Models; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D009181:Mycoses / Q000382:microbiology; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D014774:Virulence
keywords: Alternative infection models; Candida glabrata; Drosophila melanogaster; Fungal virulence factors; Mutant library; Signature-tagged mutagenesis