Culture supernatants of patient-derived Aspergillus isolates have toxic and lytic activity towards neurons and glial cells

Infection of the central nervous system by the ubiquitous fungi Aspergillus spp. is a life-threatening disease. Therefore we investigated the mechanis m of brain damage by fungal infection. To examine whether secretory factors of Aspergillus isolates derived from patients can induce death of differen t brain cells, culture supernatants of Aspergillus fumigatus, Aspergillus t erreus, Aspergillus terreus and Aspergillus niger were added to different a strocytes as well as to the neuroblastoma cell line SK-N-SH, and to the mic roglial cell line CHME. All four fungal species were shown to secrete toxic factors with neurons being most sensitive against these factors. Very low amounts and short incubation times are sufficient to induce irreversible ce ll damage, indicating that secreted factors might also affect distant brain regions. Further characterization of the toxic factors revealed that A. fu migatus and A. terreus produced small, heat-stable components whereas the t oxic activity of A. niger filtrates was triggered by a high molecular mass factor which could be inactivated by heat. The active component of A. flavu s had a molecular mass similar to that of A. niger but was heat-stable and had a significantly lower activity. Taken together these results indicate t hat secretion of different necrotizing factors might contribute to brain le sions in patients with cerebral aspergillosis. (C) 2000 Federation of Europ ean Microbiological Societies. Published by Elsevier Science B.V. All right s reserved.