Toxicological profile of cereulide, the Bacillus cereus emetic toxin, in functional assays with human, animal and bacterial cells

Some strains of the endospore-forming bacterium Bacillus cereus produce a heat-stable ionophoric peptide, cereulide, of high human toxicity. We assessed cell toxicity of cereulide by measuring the toxicities of crude extracts of cereulide producing and non-producing strains of B. cereus, and of pure...

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Published in:	Toxicon (Oxford) Vol. 49; no. 3; pp. 351 - 367
Main Authors:	Andersson, Maria A., Hakulinen, Pasi, Honkalampi-Hämäläinen, Ulla, Hoornstra, Douwe, Lhuguenot, Jean-Claude, Mäki-Paakkanen, Jorma, Savolainen, Martti, Severin, Isabelle, Stammati, Anna-Laura, Turco, Laura, Weber, Assi, von Wright, Atte, Zucco, Flavia, Salkinoja-Salonen, Mirja
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-03-2007 Elsevier Science Elsevier
Subjects:	Aliivibrio fischeri - drug effects Aliivibrio fischeri - metabolism Ames test Animals Bacillus cereus Bacillus cereus - metabolism Bacterial Toxins - toxicity Bacteriology Biological and medical sciences Biological Assay Bioluminescence Boar sperm Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Cereulide Comet test (SCG) CYP1A1 Cytotoxicity Depsipeptides - toxicity Dose-Response Relationship, Drug EROD Fundamental and applied biological sciences. Psychology Genotoxicity HEp-2 Hepa-1 Hepatocytes - drug effects Hepatocytes - enzymology Hepatocytes - pathology HepG2 Humans Ionophore Life Sciences Luminescence Male Mice Microbiology Micronucleus assay Motility Mutagenicity Tests Neutral red uptake (NRU) Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains Potassium carrier RNA synthesis RNA, Neoplasm - biosynthesis RNA, Neoplasm - drug effects Salmonella typhimurium Sperm Motility - drug effects Spermatozoa - drug effects Swine Toxicology Vibrio fischeri Comet test (SCG) EROD Bioluminescence Motility Genotoxicity Potassium carrier Cytotoxicity Neutral red uptake (NRU) HEp-2 Vibrio fischeri Hepa-1 Bacillus cereus Ames test RNA synthesis Micronucleus assay Boar sperm CYP1A1 HepG2 Ionophore Cereulide Toxicity Potassium ion Bacillaceae Comet assay Bacillales lonophore Bacteria Human Micronucleus test Cytochrome P450 Uptake Infection Toxin Animal Bacteriosis Emetic comet test (SCG)
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Summary:	Some strains of the endospore-forming bacterium Bacillus cereus produce a heat-stable ionophoric peptide, cereulide, of high human toxicity. We assessed cell toxicity of cereulide by measuring the toxicities of crude extracts of cereulide producing and non-producing strains of B. cereus, and of pure cereulide, using cells of human, animal and bacterial origins. Hepatic cell lines and boar sperm, with cytotoxicity and sperm motility, respectively, as the end points, were inhibited by ⩽1 nM of cereulide present as B. cereus extract. RNA synthesis and cell proliferation in HepG2 cells was inhibited by 2 nM of cereulide. These toxic effects were explainable by the action of cereulide as a high-affinity mobile K + carrier. Exposure to cereulide containing extracts of B. cereus caused neither activation of CYP1A1 nor genotoxicity (comet assay, micronucleus test) at concentrations below those that were cytotoxic (0.6 nM cereulide). Salmonella typhimurium reverse mutation (Ames) test was negative. Exposure of Vibrio fischeri to extracts of B. cereus caused stimulated luminescence up to 600%, independent on the presence of cereulide, but purified cereulide inhibited the luminescence with an IC 50% (30 min) of 170 nM. Thus the luminescence-stimulating B. cereus substance(s) masked the toxicity of cereulide in B. cereus extracts to V. fischeri.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-0101 1879-3150 0041-0101
DOI:	10.1016/j.toxicon.2006.10.006