| Title: | Sniffing out the hypoxia volatile metabolic signature of Aspergillus fumigatus |
| Author(s): | Rees CA; Stefanuto PH; Beattie SR; Bultman KM; Cramer RA; Hill JE; |
| Address: | "Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, United States of America" |
| ISSN/ISBN: | 1752-7163 (Electronic) 1752-7155 (Print) 1752-7155 (Linking) |
| 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" |
| Keywords: | "Adaptation, Physiological Aspergillus fumigatus/growth & development/*metabolism Breath Tests/*methods Gas Chromatography-Mass Spectrometry Humans Hypoxia/*metabolism *Metabolome Principal Component Analysis Volatile Organic Compounds/*metabolism;" |
| Notes: | "MedlineRees, Christiaan A Stefanuto, Pierre-Hugues Beattie, Sarah R Bultman, Katherine M Cramer, Robert A Hill, Jane E eng P30 GM106394/GM/NIGMS NIH HHS/ R01 AI081838/AI/NIAID NIH HHS/ T32 AI007519/AI/NIAID NIH HHS/ T32 GM008704/GM/NIGMS NIH HHS/ T32 LM012204/LM/NLM NIH HHS/ England 2017/08/22 J Breath Res. 2017 Aug 21; 11(3):036003. doi: 10.1088/1752-7163/aa7b3e" |
