title: The peptide toxin amylosin of Bacillus amyloliquefaciens from moisture-damaged buildings is immunotoxic, induces potassium efflux from mammalian cells, and has antimicrobial activity.
abstract: Amylosin, a heat-stable channel-forming non-ribosomally synthesized peptide toxin produced by strains of Bacillus amyloliquefaciens isolated from moisture-damaged buildings, is shown in this paper to have immunotoxic and cytotoxic effects on human cells as well as antagonistic effects on microbes. Human macrophages exposed to 50 ng of amylosin ml(-1) secreted high levels of cytokines interleukin-1β (IL-1β) and IL-18 within 2 h, indicating activation of the NLRP3 inflammasome, an integral part of the innate immune system. At the same exposure level, expression of IL-1β and IL-18 mRNA increased. Amylosin caused dose-dependent potassium ion efflux from all tested mammalian cells (human monocytes and keratinocytes and porcine sperm cells) at 1 to 2 μM exposure. Amylosin also inhibited the motility of porcine sperm cells and depolarized the mitochondria of human keratinocytes. Amylosin may thus trigger the activation of the NLRP3 inflammasome and subsequently cytokine release by causing potassium efflux from exposed cells. The results of this study indicate that exposure to amylosin activates the innate immune system, which could offer an explanation for the inflammatory symptoms experienced by occupants of moisture-damaged buildings. In addition, the amylosin-producing B. amyloliquefaciens inhibited the growth of both prokaryotic and eukaryotic indoor microbes, and purified amylosin also had an antimicrobial effect. These antimicrobial effects could make amylosin producers dominant and therefore significant causal agents of health problems in some moisture-damaged sites.
authors: Department of Food and Environmental Sciences (Microbiology), University of Helsinki, Helsinki, Finland stiina.rasimus@helsinki.fi.
authors: Stiina
authors: S
authors: Rasimus-Sahari
authors: Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow, Russia.
authors: Vera V
authors: VV
authors: Teplova
authors: Department of Food and Environmental Sciences (Microbiology), University of Helsinki, Helsinki, Finland.
authors: Maria A
authors: MA
authors: Andersson
authors: Department of Food and Environmental Sciences (Microbiology), University of Helsinki, Helsinki, Finland.
authors: Raimo
authors: R
authors: Mikkola
authors: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Päivi
authors: P
authors: Kankkunen
authors: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors: Sampsa
authors: S
authors: Matikainen
authors: Department of Biosciences (Biochemistry and Biotechnology), University of Helsinki, Helsinki, Finland.
authors: Carl G
authors: CG
authors: Gahmberg
authors: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Leif C
authors: LC
authors: Andersson
authors: Department of Food and Environmental Sciences (Microbiology), University of Helsinki, Helsinki, Finland.
authors: Mirja
authors: M
authors: Salkinoja-Salonen
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001407:Bacillus / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects*; D001427:Bacterial Toxins / Q000276:immunology / Q000633:toxicity*; D002597:Chaetomium / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D015603:Keratinocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D011188:Potassium / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects; D013552:Swine
chemical_list: D000890:Anti-Infective Agents; D001427:Bacterial Toxins; C545909:amylosin, Bacillus; D011188:Potassium