Journal article
Sniffing out the hypoxia volatile metabolic signature of Aspergillus fumigatus
Journal of breath research, Vol.11(3), pp.036003-036003
09/01/2017
DOI: 10.1088/1752-7163/aa7b3e
PMCID: PMC5793853
PMID: 28825403
Abstract
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 low-oxygen 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 two-dimensional 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. We assigned 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.
Details
- Title: Subtitle
- Sniffing out the hypoxia volatile metabolic signature of Aspergillus fumigatus
- Creators
- Christiaan A. Rees - Dartmouth CollegePierre-Hugues Stefanuto - University of LiègeSarah R. Beattie - Dartmouth CollegeKatherine M. Bultman - Dartmouth CollegeRobert A. Cramer - Dartmouth CollegeJane E. Hill - Dartmouth College
- Resource Type
- Journal article
- Publication Details
- Journal of breath research, Vol.11(3), pp.036003-036003
- DOI
- 10.1088/1752-7163/aa7b3e
- PMID
- 28825403
- PMCID
- PMC5793853
- NLM abbreviation
- J Breath Res
- ISSN
- 1752-7155
- eISSN
- 1752-7163
- Publisher
- IOP Publishing Ltd
- Number of pages
- 9
- Grant note
- 2R01AI081838 / National Institute of Allergy and Infectious Diseases (NIAID); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Burroughs Wellcome Fund (BWF); Burroughs Wellcome Fund Cystic Fibrosis Foundation; Italian Cystic Fibrosis Research Foundation University of Liege T32AI007519 / NIAID; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) European Union; European Commission P30GM106394 / National Institute of General Medicine Sciences (NIGMS) T32GM008704 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Burroughs Wellcome Fund
- Language
- English
- Date published
- 09/01/2017
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984353808302771
Metrics
8 Record Views