Abstract
BackgroundThe role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds.ResultsWe fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model.The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10-8 M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts.ConclusionVerruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined.
Highlights
The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage
The first tissue usually encountered by the inhaled conidia is the airway epithelium, and it is frequently damaged in patients at risk for invasive aspergillosis [10]
We previously studied the interactions between A. fumigatus and the respiratory epithelium using human nasal epithelium cell (HNEC) cultures [11,12]
Summary
The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. Aspergillus fumigatus is associated with many human health conditions [1] It is the most common cause of invasive aspergillosis, an opportunistic infection whose incidence increases in immunocompromised patients [2]. The first tissue usually encountered by the inhaled conidia is the airway epithelium, and it is frequently damaged in patients at risk for invasive aspergillosis [10]. We previously studied the interactions between A. fumigatus and the respiratory epithelium using human nasal epithelium cell (HNEC) cultures [11,12]. After one week of culture, the HNEC are organized in a pseudostratified epithelium with mucus and ciliated cells, very similar to the in vivo airway epithelium [12]
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