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RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior

Please always quote using this URN: urn:nbn:de:bvb:20-opus-151390
  • 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 byBackground: 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.show moreshow less

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Metadaten
Author: Henriette Irmer, Sonia Tarazona, Christoph Sasse, Patrick Olbermann, Jürgen Loeffler, Sven Krappmann, Ana Conesa, Gerhard H. Braus
URN:urn:nbn:de:bvb:20-opus-151390
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):BMC Genomics
Year of Completion:2015
Volume:16
Issue:640
Source:BMC Genomics (2015) 16:640. DOI: 10.1186/s12864-015-1853-1
DOI:https://doi.org/10.1186/s12864-015-1853-1
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Aspergillus fumigatus; Candida albicans; Saccharomyces cerevisiae; cell wall; cerebral aspergillosis; detoxification; gene expression; human pathogen; human pathogenic fungi; invasive pulmonary aspergillosis; iron homeostasis; lysine biosynthesis; mRNA-Seq; murine model; secondary metabolite gene cluster; transcriptome; virulence
Release Date:2017/10/11
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International