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BMC Microbiol. 2007 Jan 23;7:5.

Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells.

Khoufache K, Puel O, Loiseau N, Delaforge M, Rivollet D, Coste A, Cordonnier C, Escudier E, Botterel F, Bretagne S.

Laboratoire de Parasitologie-Mycologie, Hôpital Henri Mondor (AP-HP), Université Paris 12, and UMR BIPAR 956, Créteil, France. k_khoufache@yahoo.fr  k_khoufache@yahoo.fr

BACKGROUND: 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 Aspergillus fumigatus  cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds.

RESULTS: We fractionated the organic phase of filtrate from 3-day old Aspergillus 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 Aspergillus fumigatus  isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts.

CONCLUSION: 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 Aspergillus fumigatus  on first contact with the epithelium remains to be determined.

PMID: 17244350

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