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 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.
Andersson
Maria A
MA
Department of Applied Chemistry and Microbiology, University of Helsinki, Biocenter, P.O. Box 56, Fi 00014 Helsinki University, Finland.
Hakulinen
Pasi
P
Honkalampi-Hämäläinen
Ulla
U
Hoornstra
Douwe
D
Lhuguenot
Jean-Claude
JC
Mäki-Paakkanen
Jorma
J
Savolainen
Martti
M
Severin
Isabelle
I
Stammati
Anna-Laura
AL
Turco
Laura
L
Weber
Assi
A
von Wright
Atte
A
Zucco
Flavia
F
Salkinoja-Salonen
Mirja
M
D048908:Aliivibrio fischeri / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001409:Bacillus cereus / Q000378:metabolism*; D001427:Bacterial Toxins / Q000633:toxicity*; D001681:Biological Assay; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D049449:Luminescence; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013552:Swine
D001427:Bacterial Toxins; D047630:Depsipeptides; D012334:RNA, Neoplasm; C089294:cereulide