Emetic Toxin Research Articles

Production of an emetic toxin, cereulide, is associated with a specific class of Bacillus cereus.

The emetic toxin (cereulide) of Bacillus cereus was quantified in several isolates of B. cereus and in various food sources. When the emetic toxin was produced, vomiting-type food poisoning was observed in humans. We also found that the H-1 serovar phenotype was strongly associated with the production of cereulide and that none of the isolates that hydrolyzed starch or expressed diarrheal enterotoxin activity produced cereulide.

ChemInform Abstract: Synthesis and Activity of Cereulide, a Cyclic Dodecadepsipeptide Ionophore as Emetic Toxin from Bacillus cereus.

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Synthesis and activity of cereulide, a cyclic dodecadepsipeptide ionophore as emetic toxin from Bacillus cereus

Cereulide, a 36 membered cyclic dodecadepsipeptide ionophore, was chemically synthesized to reveal that cereulide is in fact the emetic toxin from Bacillus cereus.

Emesis of rhesus monkeys induced by intragastric administration with the HEp-2 vacuolation factor (cereulide) produced by Bacillus cereus

To study the correlation between emetic toxin and HEp-2 vacuole activity produced by Bacillus cereus isolated from an outbreak of vomiting-type food poisoning, some properties and emetic activities of both purified HEp-2 factor (cereulide) and partially purified factor to rhesus monkeys were determined. The results indicate that both cereulide and partially purified factor were very stable to digestion with proteolytic enzymes, different pH, and heating. Vomiting was induced in the rhesus monkeys orally administered with both substances. From these findings, cereulide (or HEp-2 vacuole factor) is strongly suggested to be an emetic toxin itself.

Emesis of rhesus monkeys induced by intragastric administration with the HEp-2 vacuolation factor (cereulide) produced byBacillus cereus

To study the correlation between emetic toxin and HEp-2 vacuole activity produced by Bacillus cereus isolated from an outbreak of vomiting-type food poisoning, some properties and emetic activities of both purified HEp-2 factor (cereulide) and partially purified factor to rhesus monkeys were determined. The results indicate that both cereulide and partially purified factor were very stable to digestion with proteolytic enzymes, different pH, and heating. Vomiting was induced in the rhesus monkeys orally administered with both substances. From these findings, cereulide (or HEp-2 vacuole factor) is strongly suggested to be an emetic toxin itself.

A novel dodecadepsipeptide, cereulide, is an emetic toxin of Bacillus cereus

A vacuole-formation substance, cereulide of Bacillus cereus, is an emetic toxin in animals. Both oral administration and intraperitoneal injection of cereulide caused dose-dependent emesis in Suncus murinus, a new animal model of emesis. Vagotomy or a 5-HT3 receptor antagonist completely abolished this emetic effect. Therefore, cereulide causes emesis through the 5-HT3 receptor and stimulation of the vagus afferent. We also found that our purified cereulide caused swelling of mitochondria of HEp-2 cells.

A novel dodecadepsipeptide, cereulide, is an emetic toxin ofBacillus cereus

A novel dodecadepsipeptide, cereulide, is an emetic toxin of<i>Bacillus cereus</i>

Examination of toxin production from environmental Bacillus cereus and Bacillus thuringiensis

Emetic toxin- and entero toxin-producing activities were examined for 524 strains of Bacillus cereus and 90 strains of Bacillus thuringiensis to determine the distribution and contamination in natural environment, including foods, vegetable, soil and etc. Emetic toxin was assayed by the production of acid from HEp-2 cells induced by the culture supernatants of Bacillus, which was developed as an improved method for the detection of B. cereus heat-stable emetic-toxin by us. In the 524 strains of B. cereus tested, 11 out of 60 strains obtained from bean paste and 5 out of 20 strains obtained from peach produced emetic toxin which was detected by the HEp-2 cell method. All these emetic toxin-producing isolate strains were classified into H1 serotype. The 90 strains of B. thuringiensis did not produce emetic toxin, but the 47 strains produced entero toxin.

Structure of cereulide, a cyclic dodecadepsipeptide toxin from Bacillus cereus and studies on NMR characteristics of its alkali metal complexes including a conformational structure of the K+ complex

The structure and stereochemistry of cereulide 1 or 1a, an emetic toxin produced by Bacillus cereus, have been determined through spectral analysis and chemical methods. It is a 36-membered cyclic depsipeptide with the sequence of cyclo(D-O-Leu-D-Ala-L-O-Val-L-Val)3. The outstanding property of cereulide is a Rb+-and K+-ion-selective ionophore, the same as in valinomycin 2. Cereulide forms a 1:1 complex with alkali metal ions. Owing to its structural similarity to valinomycin 2 and our well established conformational knowledge about compound 2, the NMR data of cereulide–alkali metal complexes in chloroform gave us a partial view of the conformational structure in solution and a calculated modelling of the complex with K+ is proposed. The main chain shows a hexagonal cyclinder-like framework which is similar to the known bracelet-like structure of the valinomycin–K+ complex. All amide carbonyls arrange along the cylindrical side-wall planes so that they can form β-turn hydrogen bonds with NH protons. Every alpha carbon is located at a corner in both the top and the bottom planes, enabling alpha protons of oxy acids to turn inwards towards the cavity and those of the amino acids turn outwards. The K+ is centrally situated in the cavity of the host cereulide by the ion–dipole interactions with three carbonyl oxygens of L-Val in the top plane and the three carbonyls of D-Ala in the bottom plane. The experimental coupling constant and NOE data of the K+ complex had conformity with the calculated dihedral angle and distance measured from the proposed conformational structure. Partial views of the conformations of cereulide complexed with Li+ and Na+ are analysed as follows: The frameworks of the Li+ complex main chain lose their compactness, becoming more linearly extended, which results in a bigger cavity diameter, have fewer hydrogen bonds, and all the residual side-chains can freely rotate whereas the conformation(s) of the Na+ complex takes the intermediate conformation(s) between those of the highly stable (the K+ and Rb+) and that of the less stable (the Li+) complexes.

The Area Postrema and Vomiting

The area postrema (AP) has been implicated as a chemoreceptor trigger zone for vomiting (emesis) for over 40 years. The AP is located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle. It is one of the so-called circumventricular organs that serve as an interface between the brain parenchyma and the cerebrospinal fluid (CSF)-containing ventricles. The AP lacks a specific blood-brain diffusion barrier to large polar molecules (i.e., a "blood-brain barrier") and is thus anatomically positioned to detect emetic toxins in the blood as well as in the CSF. The AP along with the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus makes up the so-called dorsal vagal complex, which is the major termination site of vagal afferent nerve fibers. Lesions of the AP prevent vomiting in response to most, but not all, emetic drugs. However, the AP is not essential for vomiting induced by motion or by activation of vagal nerve afferents. The role of the AP in radiation-induced vomiting remains controversial. Electrophysiological studies have reported that neurons in the AP increase their firing in response to emetic drugs. Similarly, studies using the 2-deoxyglucose uptake and c- fos expression techniques have shown that the AP is excited by systemic administration of emetic drugs. Activation of the AP probably leads to nausea and vomiting through its projection to the neighboring NTS. The NTS may serve as the beginning of a final common pathway by which different emetic inputs trigger vomiting.

An improved method for detecting cytostatic toxin (emetic toxin) of Bacillus cereus and its application to food samples.

We developed an improved HEp-2 cell assay method for the detection of Bacillus cereus toxin, which affects the proliferation of HEp-2 cells. The cytostatic toxin was stable upon exposure to heat, pH 2, pH 11 and trypsin, which suggests it is an emetic. Using the HEp-2 cell assay, we examined the distribution and contamination of B. cereus strains that produced an emetic toxin in various foods. Although there were 228 enterotoxin producers among 310 B. cereus strains obtained from foods, 16 of them produced the cytostatic type (emetic toxin). All of the strains that produced the cytostatic toxin were of the H.1 serotype.

An improved method for detecting cytostatic toxin (emetic toxin) of Bacillus cereus and its application to food samples

An improved method for detecting cytostatic toxin (emetic toxin) of Bacillus cereus and its application to food samples

The rice culture filtrate of Bacillus cereus isolated from emetic-type food poisoning causes mitochondrial swelling in a HEp-2 cell.

Rice culture filtrates of Bacillus cereus SA-50, an emetic-type strain, produced a toxin which caused cytoplasmic vacuole formation in HEp-2 and HeLa cells. Electron microscopic observation revealed that the apparent vacuoles in HEp-2 seen under a light microscope were actually swollen mitochondria. The oxygen consumption of HEp-2 cells was accelerated by the addition of the rice culture filtrate as was measured with a polarographic oxymeter; a respiratory control ratio was 1.0 for control cells, while 1.4 for ones with the filtrates. The culture filtrates showed a similar effect on the isolated mouse liver mitochondria; respiratory control ratios for the mitochondria with and without the filtrates were 3.6 and 1.0, respectively. The affecting manner of the culture filtrates on the oxygen consumption of mitochondria was similar to that of 2,4-dinitrophenol, suggesting that the culture filtrate contains a toxin acting as an uncoupler of oxidative phosphorylation in mitochondria. It is likely that the culture filtrates containing the emetic toxin of B. cereus causes mitochondrial swelling with a close relationship to the uncoupling of the oxidative phosphorylation of mitochondria.

Bacillus cereus and related species.

Bacillus cereus is a gram-positive aerobic or facultatively anaerobic spore-forming rod. It is a cause of food poisoning, which is frequently associated with the consumption of rice-based dishes. The organism produces an emetic or diarrheal syndrome induced by an emetic toxin and enterotoxin, respectively. Other toxins are produced during growth, including phospholipases, proteases, and hemolysins, one of which, cereolysin, is a thiol-activated hemolysin. These toxins may contribute to the pathogenicity of B. cereus in nongastrointestinal disease. B. cereus isolated from clinical material other than feces or vomitus was commonly dismissed as a contaminant, but increasingly it is being recognized as a species with pathogenic potential. It is now recognized as an infrequent cause of serious nongastrointestinal infection, particularly in drug addicts, the immunosuppressed, neonates, and postsurgical patients, especially when prosthetic implants such as ventricular shunts are inserted. Ocular infections are the commonest types of severe infection, including endophthalmitis, panophthalmitis, and keratitis, usually with the characteristic formation of corneal ring abscesses. Even with prompt surgical and antimicrobial agent treatment, enucleation of the eye and blindness are common sequelae. Septicemia, meningitis, endocarditis, osteomyelitis, and surgical and traumatic wound infections are other manifestations of severe disease. B. cereus produces beta-lactamases, unlike Bacillus anthracis, and so is resistant to beta-lactam antibiotics; it is usually susceptible to treatment with clindamycin, vancomycin, gentamicin, chloramphenicol, and erythromycin. Simultaneous therapy via multiple routes may be required.

Bacillus cereus

Abstract Bacillus cereus is an environmentally ubiquitous, Grampositive, spore-forming bacillus responsible for 2 distinct foodborne disease syndromes as well as other manifestations of pathogenicity. The rapid-onset, "emetic," foodborne-disease syndrome is associated with an emetic toxin; the delayed-onset, "diarrheal" syndrome is associated with elaboration of enterotoxin. The majority of methods for detection of these toxins have relied on In vivo testing. More recent work on purification of enterotoxin facilitated the development of a rapid, specific, fluorescent Immunodot assay and a tissue culture screening assay for enterotoxin. Work on characterization and detection of emetic toxin is ongoing

Analytical methods for Bacillus cereus and other Bacillus species

Bacillus cereus can give rise to two distinct forms of foodborne disease, the emetic and the diarrhoeal syndromes. The emetic syndrome is believed to be associated with an emetic toxin pre-formed in food. Cooked rice is the most common vehicle, and the symptoms are similar to those of Staphylococcus aureus intoxication. The diarrhoeal type is caused by an enterotoxin and the symptoms generally parallel those of the Clostridium perfringens food poisoning. The heat resistance of B. cereus spores and the non-fastidious nature of the organism facilitates its survival and/or growth in a wide variety of foods. This review describes analytical methods available for the isolation, identification, and enumeration of the organism, in addition to details about biological and immunological methods for toxin assay. Data are also presented concerning the incidence and epidemiology of B. cereus food poisoning around the world, and especially in Japan.

Properties and production characteristics of vomiting, diarrheal, and necrotizing toxins of Bacillus cereus

Evidence is provided that the enterotoxin of Bacillus cereus variously described in the literature as diarrheagenic toxin, diarrheal agent, fluid accumulation factor, vascular permeability factor, dermonecrotic toxin, and intestinonecrotic toxin is a single relatively unstable protein of molecular weight approximately 50,000 and isoelectric point of the order of 4.9. It is presumed to be the enterotoxin responsible for the diarrheal-type B. cereus food poisoning syndrome and it may also be the pyogenic and pyrogenic factor in nongastrointestinal B. cereus infections of man and animals. The enterotoxin is a vegetative growth metabolite produced to one degree or another by almost all B. cereus strains and is readily separated from phospholipase and heat-labile cereolysin but less readily differentiated from a heat-stable hemolysin. It is lethal to mice but may also be separable from another mouse lethal factor by electrofocusing. The emetic toxin responsible for the vomiting-type B. cereus food poisoning syndrome is clearly distinguishable from the diarrheal and other toxic factors and appears to be a highly stable compound of molecular size <5000.

Studies on the irradiation of microorganisms in relation to food preservation. I. The comparative sensitivities of specific bacteria of public health significance.

The limits of tolerance to gamma irradiation have been determined for 21 cultures representative of the following bacterial species of public health significance in foods: Staphylococcus aureus, Escherichia coli (types I and II), Aerobacler aerogenes, A. cloacae, Streptococcus faecalis, Salmonella gallinarum, S. tennessee, Mycobacterium tuberculosis, Clostridium botulinum (types A and E). A several-fold difference in radiation sensitivity has been demonstrated, specific sensitivity being influenced by the nature of the suspending medium during irradiation.Spores of C. botulinum, type A, were more resistant than those of type E, while six strains of staphylococci of differing phage pattern showed closely similar tolerances. The most sensitive species among those tested was M. tuberculosis. The coliform organisms were more sensitive than the salmonellae, which, in turn, were more sensitive than the staphylococci and S. faecalis. Destruction of coliform bacteria in irradiated foods cannot, therefore, be used as an index of adequate pasteurization.Staphylococcal emetic toxin present in pork sausage and suspended in culture filtrates was destroyed by irradiation at comparatively low levels in contradistinction to the findings for the toxin of C. botulinum.