Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells
Khaled Khoufache* 1, Olivier Puel* 2, Nicolas Loiseau2, Marcel Delaforge3, Danièle Rivollet1, André Coste4 ,5, Catherine Cordonnier4 ,6, Estelle Escudier4 ,7, Françoise Botterel1 and Stéphane Bretagne1
1Laboratoire de Parasitologie-Mycologie, Hôpital Henri Mondor (AP-HP), Université Paris 12, and UMR BIPAR 956, Créteil, France
2Laboratoire de Pharmacologie-Toxicologie, Institut National de Recherche Agronomique, Toulouse, France
3CNRS URA 2096, CEA Saclay DSV/DBJC/SBFM, Gif sur Yvette, France
4Inserm U 492, Université Paris 12, Créteil, France
5Service d'ORL et de Chirurgie Cervicofaciale, Hôpital Henri Mondor (AP-HP) and Hôpital Intercommunal de Créteil, France
6Service d'Hématologie clinique, Hôpital Henri Mondor (AP-HP), Créteil, France
7Département de Génétique, Cytogénétique et Embryologie, Groupe Hospitalier Pitié-Salpêtrière (AP-HP), Paris, France
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. 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.
We 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.
Verruculogen 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.
BMC Microbiology 2007, 7:5. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.