The Volatome of Aspergillus fumigatus

Abstract

bEarly detection of invasive aspergillosis is absolutely required for efficient therapy of this fungal infection. The identification of fungal volatiles in patient breath can be an alternative for the detection of Aspergillus fumigatus that still remains problematic. In this work, we investigated the production of volatile organic compounds (VOCs) by A. fumigatus in vitro, and we show that volatile production depends on the nutritional environment. A. fumigatus produces a multiplicity of VOCs, predominantly terpenes and related compounds. The production of sesquiterpenoid compounds was found to be strongly induced by increased iron concentrations and certain drugs, i.e., pravastatin. Terpenes that were always detectable in large amounts were ␣-pinene, camphene, and limonene, as well as sesquiterpenes, identified as ␣-bergamotene and ␤-trans-bergamotene. Other substance classes that were found to be present in the volatome, such as 1-octen-3-ol, 3-octanone, and pyrazines, were found only under specific growth conditions. Drugs that interfere with the terpene biosynthesis pathway influenced the composition of the fungal volatome, and most notably, a block of sesquiterpene biosynthesis by the bisphosphonate alendronate fundamentally changed the VOC composition. Using deletion mutants, we also show that a terpene cyclase and a putative kaurene synthase are essential for the synthesis of volatile terpenes by A. fumigatus. The present analysis of in vitro volatile production by A. fumigatus suggests that VOCs may be used in the diagnosis of infections caused by this fungus.A spergillus fumigatus is an opportunistic fungal pathogen that causes life-threatening invasive pulmonary infections (invasive aspergillosis [IA]) among immunocompromised patients. A sensitive, rapid, and accurate diagnostic assay for invasive aspergillosis is required to successfully fight this fungal infection (1). It has recently been proposed that the detection of volatiles can be used for the diagnosis of pulmonary infections (2, 3) and lung cancer (4, 5). Several aspergilli, including A. flavus, A. ustus, and A. versicolor, have been identified within the scope of environmental studies, where room air was analyzed to detect fungal pollution in houses (6-8). 2-Pentylfuran (2-PF) was detected in the breath of patients with A. fumigatus infection (9). It was shown that A. fumigatus produces farnesene when grown in vitro (10), and the use of terpene volatiles for the detection of IA has recently been proposed (11). However, the spectrum of volatile organic compounds (VOCs) produced by A. fumigatus and their synthesis have been poorly described. In this work, we characterized the patterns of volatile terpenes produced in vitro by A. fumigatus during growth under saprophytic conditions. In addition, the molecular pathways responsible for the synthesis of terpenoid volatiles were defined. MATERIALS AND METHODS Strains.Aspergillus fumigatus strain FGSC A1163 (ϭ DAL ϭ CBS144.89) was used for wild type strain-based experiments. Gene deletions were obta...

Detection of Airway Colonization by Aspergillus fumigatus by Use of Electronic Nose Technology in Patients with Cystic Fibrosis

“…This biomarker was demonstrated to be exhaled by patients and to be produced by A. fumigatus in vitro (46,47). Similarly, recent GC-MS and gas chromatography-solidphase microextraction studies of A. fumigatus in vitro and in vivo demonstrated other candidate VOCs for IA, such as monoterpenes and sesquiterpenes (18,48). Last, the current study strengthens the suggestion that eNose technology can detect such a distinct profile of metabolites produced by A. fumigatus in vivo by means of exhaled breath analysis.…”

Arabidopsis thalianaas Bioindicator of Fungal VOCs in Indoor Air

“…The focus previously has been put on improving agricultural yields by increasing plant growth through direct stimulation of the plant and/or reductions in the incidence of plant disease [31]. Volatile detection has been used as an indirect marker to indicate the presence of Aspergillus species and other molds in indoor environments of stored agricultural crops [4]. To our knowledge, this report is the first to show that VOCs from A. versicolor can have an impact on plant growth and seed germination.…”

“…Industrial processes also lead to the production of anthropogenic volatiles that are important as environmental pollutants, impacting the atmosphere and having harmful effects on biological systems. In recent years, increasing number of reports demonstrate that microbe-derived VOCs in the indoor environment are a major contributor to poor air quality, contamination, and adverse health effects [345]. Particularly, molds in damp indoor environment have been associated with negative impacts on air quality in the build environment and ineffective ventilation has been shown to cause significant accumulation of fungal VOCs [6].…”

“…VOCs emitted by members of the genus Aspergillus have been used as indirect biomarkers to detect fungi in the food supply, human disease, and the built environment [4161718]. Aspergillus species are ubiquitous in terrestrial ecosystems and their spores are common in soil and air.…”

The current status of avian aspergillosis diagnoses: Veterinary practice to novel research avenues

“…Several Aspergillus metabolites are volatile organic compounds (VOCs) that can be detected in the breath of patients with pulmonary aspergillosis . Breath collection is noninvasive and is an ideal sample collection method for critically sick patients.…”