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. 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 A. fumigatus on first contact with the epithelium remains to be determined

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. 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 A. fumigatus on first contact with the epithelium remains to be determined

Interactions in vitro entre cellules épithéliales trachéales de porc (CETP) – conidies d'Aspergillus fumigatus et formulation liposomale d'amphotéricine B

National audienc

Therapeutic evaluation of free and nanocapsule-encapsulated atovaquone in the treatment of murine visceral leishmaniasis

International audienceThe activities of free atovaquone (ATV) and of poly(D,L-lactide) nanocapsules loaded with the drug, in the treatment of mice with visceral leishmaniasis caused by Leishmania infantum, were compared. Each mouse was infected intravenously with 2 x 10(7) promastigotes, on day 0. On days 15, 17 and 19, most of the infected mice were treated either with free ATV, in a dimethylsulphoxide/cremophor/water mixture, or with the ATV-loaded nanocapsules (at, respectively, 0.2-1.6 and 0.125-1.0 mg ATV/kg, on each treatment day). The rest of the mice were left untreated, as controls. All the mice were killed on day 21 and dissected so that their livers and spleens could be weighed. The liver parasite burdens, evaluated using the Stauber method, indicated that the ATV-loaded nanocapsules were significantly more effective than the free drug. In nanocapsules, for example, a total dose of 3.0 mg ATV/kg reduced liver burdens by 71.3%, whereas treatment with a higher total dose of the free drug (4.8 mg/kg) only cut the number of liver parasites by 34.4%. The dose-response data indicated that livers would have been cleared of parasites if the nanocapsule preparation had been given as three doses each equivalent to 3 mg ATV/kg, whereas the maximum suppression possible with the free drug would have been about 61%, whatever the dose

Interactions in vitro entre cellules épithéliales trachéales de porc (CETP) – conidies d'Aspergillus fumigatus et formulation liposomale d'amphotéricine B

National audienc

The toxin verruculogen of A? fumigatus is responsable for electrophysiological modifications of human nasal epithelial cells in vitro

International audienc

The toxin verruculogen of A fumigatus is responsable for electrophysiological modifications of human nasal epithelial cells in vitro

International audienc

Phagocytic uptake of Aspergillus fumigatus conidia by human airway epithelial cells

International audienc

The toxin verruculogen of A fumigatus is responsable for electrophysiological modifications of human nasal epithelial cells in vitro

International audienc

The verruculogen toxin of A fumigatus is responsible for electrophysiological modifications of human nasal epithelial celles in vitro

International audienc