Acrebol, a novel toxic peptaibol produced by an Acremonium exuviarum indoor isolate |
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Authors: | MA Andersson R Mikkola M Raulio L Kredics P Maijala MS Salkinoja-Salonen |
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Institution: | Department of Applied Chemistry and Microbiology, University of Helsinki, POB56, FI 00014 Helsinki University, Finland; Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary |
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Abstract: | Aims: To identify a toxin and its producer isolated from woody material in a building where the occupants experienced serious ill health symptoms. Methods and Results: Hyphal extracts of an indoor fungus, identified as the cycloheximide-tolerant species Acremonium exuviarum , inhibited motility of boar spermatozoa (EC50 5 ± 2 μg of crude solids ml?1) and caused cytolysis of murine neuroblastoma cells (MNA) and feline fetal lung cells (FL). The responsible substances were purified and identified as two structurally similar, heat-stable, novel, toxic peptaibols, 1726 Da and 1740 Da, respectively, with amino acid sequences of Acetyl-Phe-Iva/Val-Gln-Aib-Ile-Thr-Leu-Aib-Pro-Aib-Gln-Pro-Aib-(X-X-X)-SerOH and Acetyl-Phe-Iva/Val-Gln-Aib-Ile-Thr-Leu-Val-Pro-Aib-Gln-Pro-Aib-(X-X-X)-SerOH. Purified acrebol inhibited motility of boar sperm, depleted ATP half-content in 1 day (EC50 of 0·1 μg ml?1, 60 nmol l?1) depolarised the mitochondria after 2 days, but did not affect the cellular content in NADH. This indicates mitochondrial toxicity. Plate-grown biomass of A. exuviarum BMB4 contained 0·1–1% (w/w) of acrebol, depending on the culture medium. Conclusions: Acrebol paralysed the energy generation of mammalian cells suggesting that mitochondria were its target of action. Significance and Impact of the Study: Acremonium exuviarum, as an indoor fungus, is potentially hazardous to health because of the toxic peptaibols that it produces. |
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Keywords: | acrebol antimycin mitochondrial toxicity moldy building myxothiazol sperm toxic |
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