title: RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior.
abstract: BACKGROUND
  Invasive aspergillosis is started after germination of Aspergillus fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. Low fungaemia indicates that fungal elements do not reside in the bloodstream for long.
  
  
  RESULTS
  We analyzed whether blood represents a hostile environment to which the physiology of A. fumigatus has to adapt. An in vitro model of A. fumigatus infection was established by incubating mycelium in blood. Our model allowed to discern the changes of the gene expression profile of A. fumigatus at various stages of the infection. The majority of described virulence factors that are connected to pulmonary infections appeared not to be activated during the blood phase. Three active processes were identified that presumably help the fungus to survive the blood environment in an advanced phase of the infection: iron homeostasis, secondary metabolism, and the formation of detoxifying enzymes.
  
  
  CONCLUSIONS
  We propose that A. fumigatus is hardly able to propagate in blood. After an early stage of sensing the environment, virtually all uptake mechanisms and energy-consuming metabolic pathways are shut-down. The fungus appears to adapt by trans-differentiation into a resting mycelial stage. This might reflect the harsh conditions in blood where A. fumigatus cannot take up sufficient nutrients to establish self-defense mechanisms combined with significant growth.
authors: Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Grisebachstraße 8, D-37077, Göttingen, Germany. hirmer@gwdg.de.
authors: Henriette
authors: H
authors: Irmer
authors: Genomics of Gene Expression Lab, Prince Felipe Research Center, Av. Eduardo Primo Yufera 3, 46012, Valencia, Spain. starazona@cipf.es.
authors: Sonia
authors: S
authors: Tarazona
authors: Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Grisebachstraße 8, D-37077, Göttingen, Germany. csasse1@gwdg.de.
authors: Christoph
authors: C
authors: Sasse
authors: Research Center for Infectious Diseases, Julius-Maximilians University Würzburg, Würzburg, Germany. patrick.olbermann@gmx.de.
authors: Patrick
authors: P
authors: Olbermann
authors: Laboratory WÜ4i, Medical Clinic and Policlinic II, University Clinic Würzburg, Würzburg, Germany. Loeffler_J@ukw.de.
authors: Jürgen
authors: J
authors: Loeffler
authors: Research Center for Infectious Diseases, Julius-Maximilians University Würzburg, Würzburg, Germany. sven.krappmann@uk-erlangen.de.|Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinik Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. sven.krappmann@uk-erlangen.de.
authors: Sven
authors: S
authors: Krappmann
authors: Genomics of Gene Expression Lab, Prince Felipe Research Center, Av. Eduardo Primo Yufera 3, 46012, Valencia, Spain. aconesa@cipf.es.|Department of Microbiology and Cell Science, Institute for Food and Agricultura Sciences, University of Florida at Gainesville, Gainesville, FL, USA. aconesa@cipf.es.
authors: Ana
authors: A
authors: Conesa
authors: Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Grisebachstraße 8, D-37077, Göttingen, Germany. gbraus@gwdg.de.
authors: Gerhard H
authors: GH
authors: Braus
mesh_terms: D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D001692:Biological Transport; D002453:Cell Cycle / Q000235:genetics; D004734:Energy Metabolism; D016469:Fungemia; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D012331:RNA, Fungal / Q000235:genetics*; D017423:Sequence Analysis, RNA; D013997:Time Factors; D059467:Transcriptome; D014774:Virulence / Q000235:genetics
chemical_list: D012331:RNA, Fungal