TY  - JOUR
A1  - Irmer, Henriette
A1  - Tarazona, Sonia
A1  - Sasse, Christoph
A1  - Olbermann, Patrick
A1  - Loeffler, Jürgen
A1  - Krappmann, Sven
A1  - Conesa, Ana
A1  - Braus, Gerhard H.
T1  - RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior
JF  - BMC Genomics
N2  - 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.
KW  - Saccharomyces cerevisiae
KW  - cerebral aspergillosis
KW  - gene expression
KW  - Aspergillus fumigatus
KW  - iron homeostasis
KW  - invasive pulmonary aspergillosis
KW  - Candida albicans
KW  - cell wall
KW  - lysine biosynthesis
KW  - human pathogen
KW  - murine model
KW  - virulence
KW  - mRNA-Seq
KW  - transcriptome
KW  - human pathogenic fungi
KW  - secondary metabolite gene cluster
KW  - detoxification
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151390
VL  - 16
IS  - 640
ER  -