In vitro toxicity of cereulide on porcine pancreatic Langerhans islets.
Cereulide is a K(+) ionophore cytotoxic and mitochondriotoxic to primary cells and cell lines of human and other mammalian origins. It is a heat-stable, highly lipophilic (logK(ow) 5.96) peptide (1152 g mol(-1)) produced by certain strains of Bacillus cereus, a bacterium connected to emetic food poisonings. In this study the pancreatic toxicity of purified cereulide, and cereulide-containing bacterial extracts, was studied using fetal porcine Langerhans islets in culture. Exposure to 1ngml(-1) of purified cereulide caused necrotic cell death of the islet cells impairing their insulin content within 2 days. Cell extracts of cereulide-positive B. cereus strains connected to food poisoning or isolated from foodstuffs were toxic, corresponding to their measured cereulide content. Extracts of B. cereus strains producing or not producing the B. cereus diarrheal toxin, but no cereulide, were tolerated by the porcine islet cultures up to concentrations 1000-fold higher compared to extracts from strains containing cereulide, and up to exposure times of 7d. Cereulide thus was identified as the B. cereus-produced substance toxic towards porcine fetal Langerhans islets and beta cells.
Virtanen
Suvi M
SM
Tampere School of Public Health, FI-33014, Finland and Research Unit, Tampere University Hospital, FI-33000 Tampere, Finland.
Roivainen
Merja
M
Andersson
Maria A
MA
Ylipaasto
Petri
P
Hoornstra
Douwe
D
Mikkola
Raimo
R
Salkinoja-Salonen
Mirja S
MS
D000818:Animals; D001409:Bacillus cereus; D001427:Bacterial Toxins / Q000032:analysis / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D047630:Depsipeptides / Q000032:analysis / Q000633:toxicity; D003967:Diarrhea / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005517:Foodborne Diseases; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D018675:Toxicity Tests
D001427:Bacterial Toxins; D047630:Depsipeptides; D007328:Insulin; C089294:cereulide