PMID- 19191958 OWN - NLM STAT- MEDLINE DCOM- 20100416 LR - 20090323 IS - 1365-2672 (Electronic) IS - 1364-5072 (Linking) VI - 106 IP - 3 DP - 2009 Mar TI - Acrebol, a novel toxic peptaibol produced by an Acremonium exuviarum indoor isolate. PG - 909-23 LID - 10.1111/j.1365-2672.2008.04062.x [doi] AB - 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 (EC(50) 5 +/- 2 microg 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 (EC(50) of 0.1 microg 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. FAU - Andersson, M A AU - Andersson MA AD - Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki, Finland. FAU - Mikkola, R AU - Mikkola R FAU - Raulio, M AU - Raulio M FAU - Kredics, L AU - Kredics L FAU - Maijala, P AU - Maijala P FAU - Salkinoja-Salonen, M S AU - Salkinoja-Salonen MS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090121 PL - England TA - J Appl Microbiol JT - Journal of applied microbiology JID - 9706280 RN - 0 (Bacterial Toxins) RN - 0 (Peptaibols) SB - IM MH - Acremonium/*chemistry/metabolism MH - Amino Acid Sequence MH - Animals MH - Apoptosis/drug effects MH - Bacterial Toxins/toxicity MH - Cats MH - Chromatography, High Pressure Liquid MH - Housing MH - Lung/drug effects/pathology MH - Male MH - Mass Spectrometry MH - Molecular Weight MH - Neuroblastoma/pathology MH - Peptaibols/*chemistry/pharmacology MH - Rats MH - Spermatozoa/drug effects MH - Wood/microbiology EDAT- 2009/02/05 09:00 MHDA- 2010/04/17 06:00 CRDT- 2009/02/05 09:00 PHST- 2009/02/05 09:00 [entrez] PHST- 2009/02/05 09:00 [pubmed] PHST- 2010/04/17 06:00 [medline] AID - JAM4062 [pii] AID - 10.1111/j.1365-2672.2008.04062.x [doi] PST - ppublish SO - J Appl Microbiol. 2009 Mar;106(3):909-23. doi: 10.1111/j.1365-2672.2008.04062.x. Epub 2009 Jan 21.