title: Toxic indole alkaloids avrainvillamide and stephacidin B produced by a biocide tolerant indoor mold Aspergillus westerdijkiae.
abstract: Toxic Aspergillus westerdijkiae were present in house dust and indoor air fall-out from a residence and a kindergarten where the occupants suffered from building related ill health. The A. westerdijkiae isolates produced indole alkaloids avrainvillamide (445 Da) and its dimer stephacidin B (890 Da). It grew and sporulated in presence of high concentrations of boron or polyguanidine (PHMB, PHMG) based antimicrobial biocides used to remediate mold infested buildings. The boar sperm cells were used as sensor cells to purify toxins from HPLC fractions of the fungal biomass. Submicromolar concentrations (EC50 0.3-0.4 μM) blocked boar spermatozoan motility and killed porcine kidney tubular epithelial cells (PK-15). Plate grown hyphal mass of the A. westerdijkiae isolates contained 300-750 ng of avrainvillamide and 30-300 ng of stephacidin B per mg (wet weight). The toxins induced rapid (30 min) loss of boar sperm motility, followed (24 h) by loss of mitochondrial membrane potential (ΔΨm). Apoptotic cell death was observed in PK-15 cell monolayers, prior to cessation of glucose uptake or loss of ΔΨm. Avrainvillamide and stephacidin B were 100-fold more potent towards the porcine cells than the mycotoxins stephacidin A, ochratoxin A, sterigmatocystin and citrinin. The high toxicity of stephacidin B indicates a role of nitrone group in the mechanism of toxicity. Avrainvillamide and stephacidin B represent a new class of toxins with possible a threat to human health in buildings. Furthermore, the use of biocides highly enhanced the growth of toxigenic A. westerdijkiae.
authors: Dept of Food and Environmental Science, POB56, University of Helsinki, FI-00014 Finland. Electronic address: Raimo.mikkola@aalto.fi.
authors: Raimo
authors: R
authors: Mikkola
authors: Dept of Food and Environmental Science, POB56, University of Helsinki, FI-00014 Finland.
authors: Maria A
authors: MA
authors: Andersson
authors: Finnish Food Safety Authority (EVIRA), Mustialankatu 3, FI000790 Helsinki, Finland.
authors: Maria
authors: M
authors: Hautaniemi
authors: Dept of Food and Environmental Science, POB56, University of Helsinki, FI-00014 Finland.
authors: Mirja S
authors: MS
authors: Salkinoja-Salonen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001230:Aspergillus / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D001645:Biguanides / Q000494:pharmacology; D002460:Cell Line; D026141:Drug Resistance, Multiple, Fungal; D018876:Environmental Illness / Q000382:microbiology; D005659:Fungicides, Industrial / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008970:Molecular Weight; D009183:Mycotoxins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D013081:Sperm Motility / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D001645:Biguanides; D005659:Fungicides, Industrial; D006146:Guanidines; D026121:Indole Alkaloids; D007211:Indoles; D009183:Mycotoxins; C480558:avrainvillamide; C470894:stephacidin B; C060540:polyhexamethyleneguanidine; C031233:polihexanide
keywords: Aspergillus; Biocide tolerance; Indole alkaloid; Indoor mold; Mitochondriotoxin; Nitrone