[en] Invasive aspergillosis (IA) is a life-threatening infectious disease caused by fungi from the genus
Aspergillus, with an associated mortality as high as 90% in certain populations. IA-associated
pulmonary lesions are characteristically depleted in oxygen relative to normal lung tissue, and it has
been shown that the most common causal agent of IA, Aspergillus fumigatus, must respond to lowoxygen
environments for pathogenesis and disease progression. Previous studies have demonstrated
marked alterations to the Aspergillus fumigatus transcriptome in response to low-oxygen environments
that induce a ‘hypoxia response’. Consequently, we hypothesized that these transcriptomic
changes would alter the volatile metabolome and generate a volatile hypoxia signature. In the present
study, we analyzed the volatile molecules produced by A. fumigatus in both oxygen replete (normoxia)
and depleted (hypoxia) environments via headspace solid-phase micro-extraction coupled to twodimensional
gas chromatography-time-of-flight mass spectrometry. Using the machine learning
algorithm random forest, we identified 19 volatile molecules that were discriminatory between the
four growth conditions assessed in this study (i.e., early hypoxia (1 h), late hypoxia (8 h), early
normoxia (1 h), and late normoxia (8 h)), as well as a set of 19 that were discriminatory between late
hypoxia cultures and all other growth conditions in aggregate. Nine molecules were common to both
comparisons, while the remaining 20 were specific to only one of two.Weassigned putative
identifications to 13 molecules, of which six were most highly abundant in late hypoxia cultures.
Previously acquired transcriptomic data identified putative biochemical pathways induced in hypoxia
conditions that plausibly account for the production of a subset of these molecules, including
2,3-butanedione and 3-hydroxy-2-butanone. These two molecules may represent a novel hypoxia
fitness pathway in A. fumigatus, and could be useful in the detection of hypoxia-associated A.
fumigatus lesions that develop in established IA infections.
Disciplines :
Microbiology
Author, co-author :
Rees, Christiaan A; Dartmouth College > Geisel School of Medicine
Stefanuto, Pierre-Hugues ; Université de Liège > Département de chimie (sciences) > Chimie analytique, organique et biologique
Beattie, Sarah R; Dartmouth College > Geisel School of Medicine
Bultman, Katherine M; Dartmouth College > Geisel School of Medicine
Cramer, Robert A; Dartmouth College > Geisel School of Medicine
Hill, Jane E; Dartmouth College > Thayer School of Engineering
Language :
English
Title :
Sniffing out the hypoxia volatile metabolic signature of Aspergillus fumigatus
Publication date :
June 2017
Journal title :
Journal of Breath Research
ISSN :
1752-7155
eISSN :
1752-7163
Publisher :
IOPScience, Bristol, United Kingdom
Volume :
036003
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 600405 - BEIPD - Be International Post-Doc - Euregio and Greater Region
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