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


CONCLUSIONS
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.
Khoufache
Khaled
K
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>
Puel
Olivier
O
Loiseau
Nicolas
N
Delaforge
Marcel
M
Rivollet
Danièle
D
Coste
André
A
Cordonnier
Catherine
C
Escudier
Estelle
E
Botterel
Françoise
F
Bretagne
Stéphane
S
D001232:Aspergillus fumigatus / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D017097:Electric Impedance; D006801:Humans; D025301:Hyphae / Q000378:metabolism; D007211:Indoles / Q000032:analysis / Q000494:pharmacology*; D009183:Mycotoxins / Q000032:analysis / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology; D013172:Spores, Fungal / Q000378:metabolism
D007211:Indoles; D009183:Mycotoxins; C009658:verruculogen