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Kang M, Park JH, Kim HJ. Predictive modeling of the potentially hazardous psychrotolerant Bacillus cereus group in fried rice. Food Res Int 2025; 202:115698. [PMID: 39967155 DOI: 10.1016/j.foodres.2025.115698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 12/10/2024] [Accepted: 01/05/2025] [Indexed: 02/20/2025]
Abstract
Bacillus cereus group (BCG) includes closely related bacterial species with different phenotypic characteristics, such as pathogenic potential, enzymatic capacity, and thermotypes. Psychrotolerant BCG (pBCG) strains can grow and produce toxins at low temperatures, creating concerns for the food industry. However, many current routine food diagnosis methods do not consider pBCG, and predictive modeling, which is an essential tool for food safety and public health, has not been developed using pBCG, but rather using mesophilic strains (mBCG). Given the limited information on predictive modeling and accurate strain identification of pBCG, we developed a predictive model for fried rice, a known causative food for BCG foodborne disease, using pBCG food isolates and whole-genome sequencing for accurate taxonomic classification. In predictive modeling, four pBCG food isolates selected through phenotypic screening grew at temperatures above 5 °C, whereas mBCG reference strains did not grow below 13 °C. The primary and secondary models for pBCG (covering 5-37 °C) and mBCG (covering 13-37 °C) fit well, with R2 > 0.98. By validating the dynamic model under three time-varying temperature profiles, we observed root mean square error values < 0.42 log CFU/g and acceptable simulation zone values > 82%. The four pBCG isolates used in the predictive model were identified using whole-genome sequencing as B. cereus sensu stricto, B. toyonensis, and B. mycoides, which carried enterotoxin genes. Psychrotolerant signatures of the 16S rRNA and cspA were detected in the BCG9 isolate. The predictive model and genomic characterization of pBCG strains can be applied to manage and control pBCG, ensuring the food quality and safety of fried rice products in the cold chains.
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Affiliation(s)
- Miseon Kang
- Food Safety and Distribution Research Group, Korea Food Research Institute, Wanju 55365 Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Daejeon 34113 Republic of Korea
| | - Jin Hwa Park
- Food Safety and Distribution Research Group, Korea Food Research Institute, Wanju 55365 Republic of Korea
| | - Hyun Jung Kim
- Food Safety and Distribution Research Group, Korea Food Research Institute, Wanju 55365 Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Daejeon 34113 Republic of Korea.
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Chatelanat O, de Lorenzi-Tognon M, Spahr L, Cherkaoui A, Stephan R, Ongaro M, Kaiser L, Goossens N. Liver failure after Bacillus cereus food poisoning, an under-recognized entity: A case report. World J Hepatol 2024; 16:1339-1347. [PMID: 39606173 PMCID: PMC11586756 DOI: 10.4254/wjh.v16.i11.1339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 07/29/2024] [Accepted: 08/21/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Bacillus cereus (B. cereus) is known to cause 2 types of foodborne diseases; the diarrheal and emetic syndromes. They are largely underreported due to their usually self-limiting course. Rare and sometimes fatal cases of liver failure, pulmonary hemorrhage and cerebral oedema have been reported mainly in children and young adults. We present here a case of liver failure associated with B. cereus food poisoning in a middle-aged patient. CASE SUMMARY A 48-year-old female patient presented to the emergency department for emesis, diarrhea, chills without fever, asthenia and diffuse abdominal cramps that started less than 30 minutes after eating a rice salad. Her past medical history was relevant for cholecystectomy and a cured Hashimoto's disease. She did not take any medication, drugs and declared a consumption of one glass of wine per week. In the emergency department, she was treated with acetaminophen, metoclopramide, ondansetron, and an intravenous normal saline infusion. Blood gas analysis revealed a metabolic acidosis with hyperlactatemia, coagulation revealed a low prothrombin activity [32 %; normal values (N): 70-140] and a low Factor V activity (15%; N: > 70). Transaminases were elevated with hyperbilirubinemia, elevated lipase and rhabdomyolysis. N-acetylcysteine treatment was introduced. Abdominal echography revealed no signs of chronic hepatopathy or hepatomegaly. Day after the admission, psychomotor activity improved, transaminases and lipase started decreasing. Rhabdomyolysis gradually worsened to peak on day 3. Screening tests for liver disease were negative for viral and autoimmune cause of liver failure. Stools cultures were positive for colonies of the B. cereus group which were also identified in the rice salad samples processed whereas blood cultures were negative. The patient's condition improved gradually including her liver function parameters and psychomotor activity which allowed her discharged home on day 9. CONCLUSION We describe a rare case of hepatocellular dysfunction due to a foodborne B. cereus intoxication in an adult patient. Even if it is uncommon, the severity of liver dysfunction reported and mechanism of the cereulide toxin toxicity on liver suggest that acetaminophen should be avoided in case of a foodborne intoxication and n-acetylcysteine could be a potential therapy helping to prevent hepatocytes necrosis due to the oxidative stress induced by mitochondrial dysfunction.
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Affiliation(s)
- Olivier Chatelanat
- Department of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva 1205, Switzerland.
| | | | - Laurent Spahr
- Department of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva 1205, Switzerland
| | - Abdessalam Cherkaoui
- Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva 1205, Switzerland
| | - Roger Stephan
- Institute for Food Safety and Hygiene, University of Zürich, Zurich 8057, Switzerland
| | - Marie Ongaro
- Department of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva 1205, Switzerland
| | - Laurent Kaiser
- Department of Infectious Diseases, Geneva University Hospitals, Geneva 1205, Switzerland
| | - Nicolas Goossens
- Department of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva 1205, Switzerland
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Kranzler M, Walser V, Stark TD, Ehling-Schulz M. A poisonous cocktail: interplay of cereulide toxin and its structural isomers in emetic Bacillus cereus. Front Cell Infect Microbiol 2024; 14:1337952. [PMID: 38596651 PMCID: PMC11002159 DOI: 10.3389/fcimb.2024.1337952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 03/11/2024] [Indexed: 04/11/2024] Open
Abstract
Food intoxications evoked by emetic Bacillus cereus strains constitute a serious threat to public health, leading to emesis and severe organ failure. The emetic peptide toxin cereulide, assembled by the non-ribosomal peptide synthetase CesNRPS, cannot be eradicated from contaminated food by usual hygienic measures due to its molecular size and structural stability. Next to cereulide, diverse chemical variants have been described recently that are produced concurrently with cereulide by CesNRPS. However, the contribution of these isocereulides to the actual toxicity of emetic B. cereus, which produces a cocktail of these toxins in a certain ratio, is still elusive. Since cereulide isoforms have already been detected in food remnants from foodborne outbreaks, we aimed to gain insights into the composition of isocereulides and their impact on the overall toxicity of emetic B. cereus. The amounts and ratios of cereulide and isocereulides were determined in B. cereus grown under standard laboratory conditions and in a contaminated sample of fried rice balls responsible for one of the most severe food outbreaks caused by emetic B. cereus in recent years. The ratios of variants were determined as robust, produced either under laboratory or natural, food-poisoning conditions. Examination of their actual toxicity in human epithelial HEp2-cells revealed that isocereulides A-N, although accounting for only 10% of the total cereulide toxins, were responsible for about 40% of the total cytotoxicity. An this despite the fact that some of the isocereulides were less cytotoxic than cereulide when tested individually for cytotoxicity. To estimate the additive, synergistic or antagonistic effects of the single variants, each cereulide variant was mixed with cereulide in a 1:9 and 1:1 binary blend, respectively, and tested on human cells. The results showed additive and synergistic impacts of single variants, highlighting the importance of including not only cereulide but also the isocereulides in routine food and clinical diagnostics to achieve a realistic toxicity evaluation of emetic B. cereus in contaminated food as well as in patient samples linked to foodborne outbreaks. Since the individual isoforms confer different cell toxicity both alone and in association with cereulide, further investigations are needed to fully understand their cocktail effect.
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Affiliation(s)
- Markus Kranzler
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
| | - Veronika Walser
- Food Chemistry and Molecular and Sensory Science, Technical University of Munich, Freising, Germany
| | - Timo D. Stark
- Food Chemistry and Molecular and Sensory Science, Technical University of Munich, Freising, Germany
| | - Monika Ehling-Schulz
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
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Leong SS, Korel F, King JH. Bacillus cereus: A review of "fried rice syndrome" causative agents. Microb Pathog 2023; 185:106418. [PMID: 37866551 DOI: 10.1016/j.micpath.2023.106418] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 10/19/2023] [Accepted: 10/19/2023] [Indexed: 10/24/2023]
Abstract
"Fried rice syndrome" originated from the first exposure to a fried rice dish contaminated with Bacillus cereus. This review compiles available data on the prevalence of B. cereus outbreak cases that occurred between 1984 and 2019. The outcome of B. cereus illness varies dramatically depending on the pathogenic strain encounter and the host's immune system. B. cereus causes a self-limiting, diarrheal illness caused by heat-resistant enterotoxin proteins, and an emetic illness caused by the deadly toxin named cereulide. The toxins together with their extrinsic factors are discussed. The possibility of more contamination of B. cereus in protein-rich food has also been shown. Therefore, the aim of this review is to summarize the available data, focusing mainly on B. cereus physiology as the causative agent for "fried rice syndrome." This review emphasizes the prevalence of B. cereus in starchy food contamination and outbreak cases reported, the virulence of both enterotoxins and emetic toxins produced, and the possibility of contaminated in protein-rich food. The impact of emetic or enterotoxin-producing B. cereus on public health cannot be neglected. Thus, it is essential to constantly monitor for B. cereus contamination during food handling and hygiene practices for food product preparation.
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Affiliation(s)
- Sui Sien Leong
- Department of Animal Sciences and Fishery, Faculty of Agricultural and Forestry Sciences, Universiti Putra Malaysia, Nyabau Road, Bintulu, 97008, Sarawak, Malaysia; Institute of Ecosystem Science Borneo, Universiti Putra Malaysia Bintulu Sarawak Campus, Nyabau Road, Bintulu, 97008, Sarawak, Malaysia.
| | - Figen Korel
- Food Engineering Department, Faculty of Engineering, Izmir Institute of Technology, Urla, 35430, İzmir, Turkey
| | - Jie Hung King
- Department of Crop Science, Faculty of Agricultural and Forestry Sciences, Universiti Putra Malaysia, Nyabau Road, Bintulu, 97008, Sarawak, Malaysia
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Jenull S, Bauer T, Silbermayr K, Dreer M, Stark TD, Ehling-Schulz M. The toxicological spectrum of the Bacillus cereus toxin cereulide points towards niche-specific specialisation. Environ Microbiol 2023; 25:2231-2249. [PMID: 37354053 DOI: 10.1111/1462-2920.16454] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 06/06/2023] [Indexed: 06/26/2023]
Abstract
Most microbes share their environmental niches with very different forms of life thereby engaging in specialised relationships to enable their persistence. The bacterium Bacillus cereus occurs ubiquitously in the environment with certain strain backgrounds causing foodborne and opportunistic infections in humans. The emetic lineage of B. cereus is capable of producing the toxin cereulide, which evokes emetic illnesses. Although food products favouring the accumulation of cereulide are known, the ecological role of cereulide and the environmental niche of emetic B. cereus remain elusive. To better understand the ecology of cereulide-producing B. cereus, we systematically assayed the toxicological spectrum of cereulide on a variety of organisms belonging to different kingdoms. As cereulide is a potassium ionophore, we further tested the effect of environmental potassium levels on the action of cereulide. We found that adverse effects of cereulide exposure are species-specific, which can be exacerbated with increased environmental potassium. Additionally, we demonstrate that cereulide is produced within an insect cadaver indicating its potential ecological function for a saprophytic lifestyle. Collectively, distinct cereulide susceptibilities of other organisms may reflect its role in enabling competitive niche specialization of emetic B. cereus.
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Affiliation(s)
- Sabrina Jenull
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Tobias Bauer
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Katja Silbermayr
- Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Maximilian Dreer
- Department of Functional and Evolutionary Ecology, Archaea Biology and Ecogenomics Unit, University of Vienna, Vienna, Austria
| | - Timo D Stark
- Food Chemistry and Molecular Sensory Science, Technical University of Munich, Freising, Germany
| | - Monika Ehling-Schulz
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria
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Wang Z, Xia H, Fan F, Zhang J, Liu H, Cao J. Survival of community-acquired Bacillus cereus sepsis with venous sinus thrombosis in an immunocompetent adult man - a case report and literature review. BMC Infect Dis 2023; 23:213. [PMID: 37024789 PMCID: PMC10080751 DOI: 10.1186/s12879-023-08176-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 03/16/2023] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND Bacillus cereus infections in immunocompetent patients are uncommon and mainly observed in fragile patients. It can cause lethal infections with multiple organ dysfunction syndrome (MODS). However, a patient presenting as venous sinus thrombosis and survival without sequela has not been reported. CASE PRESENTATION A 20-year-old previously healthy male developed gastroenteritis after a meal, followed by fever, convulsions, and severe disturbance of consciousness. The patient had significant leukocytosis with a mildly elevated D-dimer, creatinine level, and respiratory failure. The CT(computed tomography) revealed fatal brain edema and subarachnoid hemorrhage. Previous blood culture in a local hospital revealed B. cereus, which was confirmed by mNGS(metagenomic next-generation sequencing) using blood and urine in our hospital. Accordingly, B. cereus sepsis with MODS were considered. Later, cerebral venous sinus thrombosis was proved. After anti-infection (linezolid 0.6 g, Q12h; and meropenem 1.0 g, Q8h), anti-coagulant (enoxaparin 6000U, Q12h), and other symptomatic treatments, the patient recovered completely without sequela at the 6-month follow-up. CONCLUSIONS This case suggests that in immunocompetent adults, there is still a risk of infection with B. cereus, causing severe MODS. Special attention should be paid to venous sinus thrombosis and subarachnoid hemorrhage in such cases, while, anti-coagulant is essential therapy.
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Affiliation(s)
- Zengrong Wang
- Department of Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Han Xia
- Department of Scientific Affairs, Hugo Biotech Co., Ltd., No.1, East Disheng Road, Beijing, 100176, China
| | - Fangfang Fan
- Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Jin Zhang
- Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Hong Liu
- Department of Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Jing Cao
- Department of Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
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Detection of Bacillus cereus as a causative agent of emetic food poisoning by an unconventional culture procedure. J Infect Chemother 2022; 28:1575-1577. [PMID: 35870790 DOI: 10.1016/j.jiac.2022.07.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 07/05/2022] [Accepted: 07/15/2022] [Indexed: 11/21/2022]
Abstract
Bacillus cereus is known to cause two types of food poisoning: emetic and diarrhoeal. Both diseases are usually self-limiting; however, severe cases have been reported, presenting with acute liver failure and encephalopathy, including rarely fatal cases of vomiting. Clinical laboratories do not routinely test for B. cereus in patients with gastrointestinal disease. Therefore, B. cereus causing food poisoning goes undetected. We report a successful isolation of emetic B. cereus from a patient with food poisoning who presented with severe vomiting, fulminant hepatic failure, and acute encephalopathy, by a non-conventional method. Initially, stool specimens from the patients were routinely cultured to identify the causative organisms of food poisoning. No foodborne pathogens were detected in this study. In contrast, additional clinical and epidemiological information strongly suggested food poisoning by emetic B. cereus. Consequently, we allowed Drigalski agar medium smeared with patient stool specimens to stand at room temperature (approximately 25 °C) for 9 days. After 9 days, mixed bacteria grown on the medium were inoculated onto mannitol egg yolk polymyxin (MYP) agar plates, a selective medium for B. cereus. Typical colonies of B. cereus developed on MYP agar plates. The isolated B. cereus had a cereulide-producing genetic locus (ces) gene encoding the emetic toxin cereulide. The method used in this case study was unique. This method is easy to apply after obtaining an additional clinical and epidemiological information, and this method will improve the diagnostic rate of severe B. cereus food poisoning. This will contribute to the advancement of therapeutics in the future.
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Acute Liver Failure after Ingestion of Fried Rice Balls: A Case Series of Bacillus cereus Food Poisonings. Toxins (Basel) 2021; 14:toxins14010012. [PMID: 35050989 PMCID: PMC8779543 DOI: 10.3390/toxins14010012] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 12/19/2021] [Accepted: 12/22/2021] [Indexed: 12/30/2022] Open
Abstract
Bacillus cereus foodborne intoxications and toxicoinfections are on a rise. Usually, symptoms are self-limiting but occasionally hospitalization is necessary. Severe intoxications with the emetic Bacillus cereus toxin cereulide, which is notably resistant heat and acid during cooking, can cause acute liver failure and encephalopathy. We here present a case series of food poisonings in five immunocompetent adults after ingestion of fried rice balls, which were massively contaminated with Bacillus cereus. The patients developed a broad clinical spectrum, ranging from emesis and diarrhoea to life-threatening acute liver failure and acute tubular necrosis of the kidney in the index patient. In the left-over rice ball, we detected 8 × 106Bacillus cereus colony-forming units/g foodstuff, and cereulide in a concentration of 37 μg/g foodstuff, which is one of the highest cereulide toxin contaminations reported so far from foodborne outbreaks. This report emphasizes the potential biological hazard of contaminated rice meals that are not freshly prepared. It exemplifies the necessity of a multidisciplinary approach in cases of Bacillus cereus associated food poisonings to rapidly establish the diagnosis, to closely monitor critically ill patients, and to provide supportive measures for acute liver failure and—whenever necessary—urgent liver transplantation.
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Arora S, Thakkar D, Upasana K, Yadav A, Rastogi N, Yadav SP. Bacillus cereus infection in pediatric oncology patients: A case report and review of literature. IDCases 2021; 26:e01302. [PMID: 34745884 PMCID: PMC8554482 DOI: 10.1016/j.idcr.2021.e01302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/26/2021] [Accepted: 10/04/2021] [Indexed: 11/29/2022] Open
Abstract
Introduction Bacillus Cereus infection can be life-threatening in immunocompromised patients. We report here a case of Bacillus Cereus septicemia in a child with relapsed acute lymphoblastic leukemia (ALL) and present review of literature. Methods We collected clinical, laboratory and outcome data of our patient with relapsed ALL and Bacillus Cereus infection. We reviewed literature for Bacillus Cereus infection in pediatric oncology patients by searching MED-LINE/PubMed/Google/Google Scholar/Cochrane and summarized the data obtained. Various risk factors like presence of gastrointestinal or central nervous system (CNS) symptoms, neutropenia, central venous catheter in-situ, corticosteroids use, intrathecal chemotherapy and outcomes were analyzed using Fisher Exact Chi Square test. Results A 15-years-old boy with relapsed ALL on induction chemotherapy presented with giddiness and difficulty in breathing. He had an episode of hematemesis followed by fainting at home. He had refractory shock which did not respond to fluid boluses, inotropes and hydrocortisone. He had severe metabolic acidosis with high lactate and ammonia and died within 36-hours of onset of symptoms. His blood culture was positive for Bacillus Cereus. We came across 36 published cases of Bacillus Cereus in children with cancer including present case. Of these, 28 had acute leukemia and rest 8 had other cancers. CNS symptoms were present in 13 patients. Overall mortality was 25%. Patients with multisystem involvement had significantly higher mortality compared to those having localized disease (p-value 0.033). Conclusion In pediatric oncology patients on chemotherapy, cultures positive for Bacillus Cereus should be considered significant. Mortality is higher in those with multisystem involvement.
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Affiliation(s)
| | | | | | | | | | - Satya Prakash Yadav
- Correspondence to: Pediatric Hematology Oncology & BMT Unit, Cancer Institute, Medanta -The Medicity, Gurgaon, Haryana 122001, India.
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Cereulide Exposure Caused Cytopathogenic Damages of Liver and Kidney in Mice. Int J Mol Sci 2021; 22:ijms22179148. [PMID: 34502057 PMCID: PMC8431326 DOI: 10.3390/ijms22179148] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 08/20/2021] [Accepted: 08/20/2021] [Indexed: 12/18/2022] Open
Abstract
Cereulide is one of the main food-borne toxins for vomiting synthesized by Bacillus cereus, and it widely contaminates meat, eggs, milk, and starchy foods. However, the toxicological effects and mechanisms of the long-time exposure of cereulide in vivo remain unknown. In this study, oral administration of 50 and 200 μg/kg body weight cereulide in the mice for 28 days caused oxidative stress in liver and kidney tissues and induce abnormal expression of inflammatory factors. In pathogenesis, cereulide exposure activated endoplasmic reticulum stress (ER stress) via the pathways of inositol-requiring enzyme 1α (IRE1α)/Xbox binding protein (XBP1) and PRKR-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α), and consequently led to the apoptosis and tissue damages in mouse liver and kidney. In vitro, we confirmed that the accumulation of reactive oxygen species (ROS) caused by cereulide is the main factor leading to ER stress in HepaRG and HEK293T cells. Supplementation of sodium butyrate (NaB) inhibited the activations of IRE1α/XBP1 and PERK/eIF2α pathways caused by cereulide exposure in mice, and reduced the cell apoptosis in liver and kidney. In conclusion, this study provides a new insight in understanding the toxicological mechanism and prevention of cereulide exposure.
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Walser V, Kranzler M, Dawid C, Ehling-Schulz M, Stark TD, Hofmann TF. Distribution of the Emetic Toxin Cereulide in Cow Milk. Toxins (Basel) 2021; 13:toxins13080528. [PMID: 34437398 PMCID: PMC8402402 DOI: 10.3390/toxins13080528] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 07/22/2021] [Accepted: 07/26/2021] [Indexed: 12/21/2022] Open
Abstract
Bacillus cereus is frequently associated with food-borne intoxications, and its emetic toxin cereulide causes emesis and nausea after consumption of contaminated foods. The major source for contamination is found within contaminated raw materials containing the highly chemically resistant cereulide, independent of vegetative bacteria cells. Up to date, non-existing removal strategies for cereulide evoke the question of how the toxin is distributed within a food sample, especially cow milk. Milk samples with different milk fat contents were incubated with purified cereulide, separated by centrifugation into a lipid and an aqueous phase, and cereulide was quantified in both fractions by SIDA-LC-MS/MS. By artificially increasing the milk fat content from 0.5% to 50%, the amount of cereulide recovered in the lipid phase and could be augmented from 13.3 to 78.6%. Further, the ratio of cereulide increased in the lipid phase of milk with additional plant-based lipid (sunflower oil) to 47.8%. This demonstrated a clear affinity of cereulide towards the hydrophobic, lipid phase, aligning with cereulide's naturally strong hydrophobic properties. Therefore, an intensified cereulide analysis of lipid enriched dairy products to prevent severe cereulide intoxications or cross-contamination in processed foods is suggested.
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Affiliation(s)
- Veronika Walser
- Food Chemistry and Molecular Sensory Science, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, Lise-Meitner-Str. 34, 85354 Freising, Germany; (V.W.); (C.D.); (T.F.H.)
| | - Markus Kranzler
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria; (M.K.); (M.E.-S.)
| | - Corinna Dawid
- Food Chemistry and Molecular Sensory Science, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, Lise-Meitner-Str. 34, 85354 Freising, Germany; (V.W.); (C.D.); (T.F.H.)
| | - Monika Ehling-Schulz
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria; (M.K.); (M.E.-S.)
| | - Timo D. Stark
- Food Chemistry and Molecular Sensory Science, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, Lise-Meitner-Str. 34, 85354 Freising, Germany; (V.W.); (C.D.); (T.F.H.)
- Correspondence: ; Tel.: +49-8161-71-2911
| | - Thomas F. Hofmann
- Food Chemistry and Molecular Sensory Science, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, Lise-Meitner-Str. 34, 85354 Freising, Germany; (V.W.); (C.D.); (T.F.H.)
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Jovanovic J, Ornelis VFM, Madder A, Rajkovic A. Bacillus cereus food intoxication and toxicoinfection. Compr Rev Food Sci Food Saf 2021; 20:3719-3761. [PMID: 34160120 DOI: 10.1111/1541-4337.12785] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 05/13/2021] [Accepted: 05/15/2021] [Indexed: 12/12/2022]
Abstract
Bacillus cereus is one of the leading etiological agents of toxin-induced foodborne diseases. Its omnipresence in different environments, spore formation, and its ability to adapt to varying conditions and produce harmful toxins make this pathogen a health hazard that should not be underestimated. Food poisoning by B. cereus can manifest itself as an emetic or diarrheal syndrome. The former is caused by the release of the potent peptide toxin cereulide, whereas the latter is the result of proteinaceous enterotoxins (e.g., hemolysin BL, nonhemolytic enterotoxin, and cytotoxin K). The final harmful effect is not only toxin and strain dependent, but is also affected by the stress responses, accessory virulence factors, and phenotypic properties under extrinsic, intrinsic, and explicit food conditions and host-related environment. Infamous portrait of B. cereus as a foodborne pathogen, as well as a causative agent of nongastrointestinal infections and even nosocomial complications, has inspired vast volumes of multidisciplinary research in food and clinical domains. As a result, extensive original data became available asking for a new, both broad and deep, multifaceted look into the current state-of-the art regarding the role of B. cereus in food safety. In this review, we first provide an overview of the latest knowledge on B. cereus toxins and accessory virulence factors. Second, we describe the novel taxonomy and some of the most pertinent phenotypic characteristics of B. cereus related to food safety. We link these aspects to toxin production, overall pathogenesis, and interactions with its human host. Then we reflect on the prevalence of different toxinotypes in foods opening the scene for epidemiological aspects of B. cereus foodborne diseases and methods available to prevent food poisoning including overview of the different available methods to detect B. cereus and its toxins.
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Affiliation(s)
- Jelena Jovanovic
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
| | - Vincent F M Ornelis
- Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Ghent, Belgium
| | - Annemieke Madder
- Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Ghent, Belgium
| | - Andreja Rajkovic
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
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13
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The Food Poisoning Toxins of Bacillus cereus. Toxins (Basel) 2021; 13:toxins13020098. [PMID: 33525722 PMCID: PMC7911051 DOI: 10.3390/toxins13020098] [Citation(s) in RCA: 140] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/14/2021] [Accepted: 01/25/2021] [Indexed: 12/13/2022] Open
Abstract
Bacillus cereus is a ubiquitous soil bacterium responsible for two types of food-associated gastrointestinal diseases. While the emetic type, a food intoxication, manifests in nausea and vomiting, food infections with enteropathogenic strains cause diarrhea and abdominal pain. Causative toxins are the cyclic dodecadepsipeptide cereulide, and the proteinaceous enterotoxins hemolysin BL (Hbl), nonhemolytic enterotoxin (Nhe) and cytotoxin K (CytK), respectively. This review covers the current knowledge on distribution and genetic organization of the toxin genes, as well as mechanisms of enterotoxin gene regulation and toxin secretion. In this context, the exceptionally high variability of toxin production between single strains is highlighted. In addition, the mode of action of the pore-forming enterotoxins and their effect on target cells is described in detail. The main focus of this review are the two tripartite enterotoxin complexes Hbl and Nhe, but the latest findings on cereulide and CytK are also presented, as well as methods for toxin detection, and the contribution of further putative virulence factors to the diarrheal disease.
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14
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Colaco CMG, Basile K, Draper J, Ferguson PE. Fulminant Bacillus cereus food poisoning with fatal multi-organ failure. BMJ Case Rep 2021; 14:14/1/e238716. [PMID: 33462030 PMCID: PMC7813301 DOI: 10.1136/bcr-2020-238716] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.
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Affiliation(s)
- Clinton M G Colaco
- Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Westmead, Sydney, Australia,Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Kerri Basile
- Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Westmead, Sydney, Australia,Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, Sydney, Australia
| | - Jenny Draper
- Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Westmead, Sydney, Australia,Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, Sydney, Australia
| | - Patricia E Ferguson
- Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Westmead, Sydney, Australia
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15
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Jessberger N, Dietrich R, Granum PE, Märtlbauer E. The Bacillus cereus Food Infection as Multifactorial Process. Toxins (Basel) 2020; 12:E701. [PMID: 33167492 PMCID: PMC7694497 DOI: 10.3390/toxins12110701] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 10/30/2020] [Accepted: 11/02/2020] [Indexed: 02/06/2023] Open
Abstract
The ubiquitous soil bacterium Bacillus cereus presents major challenges to food safety. It is responsible for two types of food poisoning, the emetic form due to food intoxication and the diarrheal form emerging from food infections with enteropathogenic strains, also known as toxico-infections, which are the subject of this review. The diarrheal type of food poisoning emerges after production of enterotoxins by viable bacteria in the human intestine. Basically, the manifestation of the disease is, however, the result of a multifactorial process, including B. cereus prevalence and survival in different foods, survival of the stomach passage, spore germination, motility, adhesion, and finally enterotoxin production in the intestine. Moreover, all of these processes are influenced by the consumed foodstuffs as well as the intestinal microbiota which have, therefore, to be considered for a reliable prediction of the hazardous potential of contaminated foods. Current knowledge regarding these single aspects is summarized in this review aiming for risk-oriented diagnostics for enteropathogenic B. cereus.
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Affiliation(s)
- Nadja Jessberger
- Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Schönleutnerstr. 8, 85764 Oberschleißheim, Germany; (R.D.); (E.M.)
| | - Richard Dietrich
- Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Schönleutnerstr. 8, 85764 Oberschleißheim, Germany; (R.D.); (E.M.)
| | - Per Einar Granum
- Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003 NMBU, 1432 Ås, Norway;
| | - Erwin Märtlbauer
- Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Schönleutnerstr. 8, 85764 Oberschleißheim, Germany; (R.D.); (E.M.)
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16
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Rasooly R, Do P, Hernlem B. Quantitative bioluminescence assay for measuring Bacillus cereus nonhemolytic enterotoxin complex. PLoS One 2020; 15:e0238153. [PMID: 32998160 PMCID: PMC7527251 DOI: 10.1371/journal.pone.0238153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 08/10/2020] [Indexed: 11/19/2022] Open
Abstract
Bacillus cereus is a foodborne pathogen causing emesis and diarrhea in those affected. It is assumed that the non-hemolytic enterotoxin (Nhe) plays a key role in B. cereus induced diarrhea. The ability to trace Nhe activity is important for food safety. While assays such as PCR and ELISA exist to detect Nhe, those methods cannot differentiate between active and inactive forms of Nhe. The existing rabbit ileal loop bioassay used to detect Nhe activity is ethically disfavored because it uses live experimental animals. Here we present a custom built low-cost CCD based luminometer and applied it in conjunction with a cell-based assay using Vero cells transduced to express the luciferase enzyme. The activity of Nhe was measured as its ability to inhibit synthesis of luciferase as quantified by reduction of light emission by the luciferase reaction. Emitted light intensity was observed to be inversely proportional to Nhe concentration over a range of 7 ng/ml to 125 ng/ml, with a limit of detection of 7 ng/ml Nhe.
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Affiliation(s)
- Reuven Rasooly
- Western Regional Research Center, Foodborne Toxin Detection & Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA, United States of America
| | - Paula Do
- Western Regional Research Center, Foodborne Toxin Detection & Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA, United States of America
| | - Bradley Hernlem
- Western Regional Research Center, Foodborne Toxin Detection & Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA, United States of America
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17
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Leo C, Wang Y, Mold A, Quintana J, Shi H, Abdullah M, Alaie D, Petrillo R. Noncirrhotic hyperammonemia: A factor behind dementia to alter mental status. Clin Case Rep 2019; 7:2118-2122. [PMID: 31788262 PMCID: PMC6878079 DOI: 10.1002/ccr3.2436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 07/02/2019] [Accepted: 07/22/2019] [Indexed: 11/07/2022] Open
Abstract
Healthcare givers were recommended to check serum ammonia level for elderly patients with acute-on-chronic alteration of mental status. Early initiation of antihyperammonemia therapy may benefit improvement of alteration of mental status. Baseline mental status becomes necessary for diagnose the acute alteration of mental status and monitor the therapeutic process.
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Affiliation(s)
- Christopher Leo
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Yun Wang
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Alexander Mold
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Junik Quintana
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Hong Shi
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Mahdi Abdullah
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Dariush Alaie
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
| | - Richard Petrillo
- Department of MedicineMontefiore Mount Vernon HospitalMount VernonNY
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18
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Rouzeau-Szynalski K, Stollewerk K, Messelhäusser U, Ehling-Schulz M. Why be serious about emetic Bacillus cereus: Cereulide production and industrial challenges. Food Microbiol 2019; 85:103279. [PMID: 31500702 DOI: 10.1016/j.fm.2019.103279] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Revised: 07/18/2019] [Accepted: 07/25/2019] [Indexed: 01/06/2023]
Abstract
Cereulide, a potent toxin produced by Bacillus cereus, is a small, highly heat- and acid-resistant depsipeptide toxin, which confronts food industry with several challenges. Due to the ubiquitous presence of B. cereus in the environment, this opportunistic pathogen can enter food production and processing at almost any stage. Although the bacteria itself might be removed during food processing, the cereulide toxin will most likely not be destroyed or inactivated by these processes. Because of the high toxicity of cereulide and the high incidence rates often observed in connection with foodborne outbreaks, the understanding of the mechanisms of toxin production as well as accurate data on contamination sources and factors promoting toxin formation are urgently needed to prevent contamination and toxin production in food production processes. Over the last decade, considerable progress had been made on the understanding of cereulide toxin biosynthesis in emetic B. cereus, but an overview of current knowledge on this toxin with regards to food industry perspective is lacking. Thus, we aim in this work to summarize data available on extrinsic parameters acting on cereulide toxin synthesis in emetic B. cereus and to discuss the food industry specific challenges related to this toxin. Furthermore, we emphasize how identification of the cardinals in food production processes can lead to novel effective strategies for prevention of toxin formation in the food processing chain and could contribute to the improvement of existing HACCP studies.
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Affiliation(s)
| | - Katharina Stollewerk
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Austria
| | - Ute Messelhäusser
- Bavarian Health and Food Safety Authority, Veterinaerstr. 2, 85764, Oberschleissheim, Germany
| | - Monika Ehling-Schulz
- Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Austria.
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19
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Bauer T, Sipos W, Stark TD, Käser T, Knecht C, Brunthaler R, Saalmüller A, Hofmann T, Ehling-Schulz M. First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model. Front Microbiol 2018; 9:2652. [PMID: 30464760 PMCID: PMC6234764 DOI: 10.3389/fmicb.2018.02652] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 10/17/2018] [Indexed: 11/13/2022] Open
Abstract
Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10-150 μg cereulide kg-1 body weight to study acute effects or using daily doses of 10 μg cereulide kg-1 body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood-brain-barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations.
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Affiliation(s)
- Tobias Bauer
- Department of Pathobiology, Functional Microbiology, Institute of Microbiology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Wolfgang Sipos
- University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Timo D Stark
- Chair of Food Chemistry and Molecular Sensory Science, Technische Universität München, Freising, Germany
| | - Tobias Käser
- Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine Vienna, Vienna, Austria.,Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University (NCSU), Raleigh, NC, United States
| | - Christian Knecht
- University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Rene Brunthaler
- Department of Pathobiology, Institute of Pathology and Forensic Veterinary Medicine, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Armin Saalmüller
- Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Thomas Hofmann
- Chair of Food Chemistry and Molecular Sensory Science, Technische Universität München, Freising, Germany
| | - Monika Ehling-Schulz
- Department of Pathobiology, Functional Microbiology, Institute of Microbiology, University of Veterinary Medicine Vienna, Vienna, Austria
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20
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Decleer M, Jovanovic J, Vakula A, Udovicki B, Agoua RSEK, Madder A, De Saeger S, Rajkovic A. Oxygen Consumption Rate Analysis of Mitochondrial Dysfunction Caused by Bacillus cereus Cereulide in Caco-2 and HepG2 Cells. Toxins (Basel) 2018; 10:E266. [PMID: 30004412 PMCID: PMC6070949 DOI: 10.3390/toxins10070266] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 06/20/2018] [Accepted: 06/22/2018] [Indexed: 12/28/2022] Open
Abstract
The emetic syndrome of Bacillus cereus is a food intoxication caused by cereulide (CER) and manifested by emesis, nausea and in most severe cases with liver failure. While acute effects have been studied in the aftermath of food intoxication, an exposure to low doses of cereulide might cause unnoticed damages to the intestines and liver. The toxicity which relies on the mitochondrial dysfunction was assessed on Caco-2 and HepG2 cells after exposure of one, three and ten days to a range of low doses of cereulide. Oxygen consumption rate analyses were used to study the impact of low doses of CER on the bioenergetics functions of undifferentiated Caco-2 and HepG2 cells using Seahorse XF extracellular flux analyzer. Both Caco-2 and HepG2 cells experienced measurable mitochondrial impairment after prolonged exposure of 10 days to 0.25 nM of cereulide. Observed mitochondrial dysfunction was greatly reflected in reduction of maximal cell respiration. At 0.50 nM CER, mitochondrial respiration was almost completely shut down, especially in HepG2 cells. These results corresponded with a severe reduction in the amount of cells and an altered morphology, observed by microscopic examination of the cells. Accurate and robust quantification of basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration allowed better understanding of the effects of cereulide in underlying respiratory malfunctions in low-dose exposure.
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Affiliation(s)
- Marlies Decleer
- Department of Food Technology, Food Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
- Laboratory of Food Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
| | - Jelena Jovanovic
- Department of Food Technology, Food Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
| | - Anita Vakula
- Department of Food Preservation Engineering, Faculty of Technology, University of Novi Sad, Bulevar Cara Lazara 1, 21000 Novi Sad, Serbia.
| | - Bozidar Udovicki
- Department of Food Safety and Food Quality Management, Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11081 Zemun-Belgrade, Serbia.
| | - Rock-Seth E K Agoua
- Department of Food Technology, Food Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
| | - Annemieke Madder
- Department of Organic and Macromolecular Chemistry, Organic and Biomimetic Chemistry Research Group, Faculty of Sciences, Campus Sterre, Krijgslaan 281, Building S4, 9000 Gent, Belgium.
| | - Sarah De Saeger
- Laboratory of Food Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
| | - Andreja Rajkovic
- Department of Food Technology, Food Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
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21
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22
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Kranzler M, Stollewerk K, Rouzeau-Szynalski K, Blayo L, Sulyok M, Ehling-Schulz M. Temperature Exerts Control of Bacillus cereus Emetic Toxin Production on Post-transcriptional Levels. Front Microbiol 2016; 7:1640. [PMID: 27826288 PMCID: PMC5078297 DOI: 10.3389/fmicb.2016.01640] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Accepted: 10/03/2016] [Indexed: 11/20/2022] Open
Abstract
In recent years, the emetic toxin cereulide, produced by Bacillus cereus, has gained high relevance in food production and food safety. Cereulide is synthesized non-ribosomal by the multi-enzyme complex Ces-NRPS, which is encoded on a megaplasmid that shares its backbone with the Bacillus anthracis pX01 toxin plasmid. Due to its resistance against heat, proteolysis and extreme pH conditions, the formation of this highly potent depsipeptide toxin is of serious concern in food processing procedures including slow cooling procedures and/or storage of intermediate products at ambient temperatures. So far, systematic data on the effect of extrinsic factors on cereulide synthesis has been lacking. Thus, we investigated the influence of temperature, a central extrinsic parameter in food processing, on the regulation of cereulide synthesis on transcriptional, translational and post-translational levels over the growth temperature range of emetic B. cereus. Bacteria were grown in 3°C interval steps from 12 to 46°C and cereulide synthesis was followed from ces gene transcription to cereulide toxin production. This systematic study revealed that temperature is a cardinal parameter, which primarily impacts cereulide synthesis on post-transcriptional levels, thereby altering the composition of cereulide isoforms. Our work also highlights that the risk of cereulide production could not be predicted from growth parameters or sole cell numbers. Furthermore, for the first time we could show that the formation of the recently identified cereulide isoforms is highly temperature dependent, which may have great importance in terms of food safety and predictive microbiology. Notably the production of isocereulide A, which is about 10-fold more cytotoxic than cereulide, was specifically supported at low temperatures.
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Affiliation(s)
- Markus Kranzler
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna Vienna, Austria
| | - Katharina Stollewerk
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna Vienna, Austria
| | | | - Laurence Blayo
- Food Safety Microbiology, Nestec Ltd, Nestlé Research Center Lausanne, Switzerland
| | - Michael Sulyok
- Center for Analytical Chemistry, Department of Agrobiotechnology, IFA Tulln, University of Natural Resources and Life Sciences Vienna (BOKU) Vienna, Austria
| | - Monika Ehling-Schulz
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna Vienna, Austria
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23
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Marxen S, Stark TD, Rütschle A, Lücking G, Frenzel E, Scherer S, Ehling-Schulz M, Hofmann T. Multiparametric Quantitation of the Bacillus cereus Toxins Cereulide and Isocereulides A-G in Foods. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2015; 63:8307-8313. [PMID: 26352912 DOI: 10.1021/acs.jafc.5b03705] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Consumption of food products contaminated with cereulide (1), a toxin produced by Bacillus cereus, might cause intoxications with symptoms reported to range from indigestion pain and emesis to death. Recently, a series of structural variants, coined isocereulides A-G (2-8), were identified for the first time to be produced along with cereulide (1). The observation that isocereulide A (2) shows an ∼ 8-fold increased cytotoxicity when compared to 1 urges the development of analytical tools enabling an accurate quantitation of these toxins. Therefore, a rapid, sensitive, and robust stable isotope dilution assay (SIDA) was developed for the combined quantitation of 1-8 by means of UPLC-MS/MS. On average, trueness and precision of the method were 112.5 ± 1.8% RSD, repeatability and reproducibility were 2 and 4% for cereulide and isocereulides A-G, and the LOD and LOQ of 0.1 and 0.5 ng/g, respectively, demonstrated a high sensitivity for the developed SIDA method. Application of this method to food samples revealed elevated levels of 1-8 in two suspicious noodle samples, for example, ranging from 0.59 (7) to 189.08 ng/g (1) in sample 1 and from 5.77 (7) to 6198.17 ng/g (1) in sample 2, whereas the analysis of 25 randomly selected food samples, which have not been the subject to any complaints, did not contain detectable amounts of any of these toxins. As a consequence, this SIDA method could add an important contribution to the knowledge-based risk assessment of B. cereus toxins in foods.
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Affiliation(s)
| | | | | | | | - Elrike Frenzel
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna , 1210 Vienna, Austria
| | - Siegfried Scherer
- Chair of Microbial Ecology, Department of Biosciences, WZW, Technische Universität München , 85350 Freising, Germany
| | - Monika Ehling-Schulz
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna , 1210 Vienna, Austria
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24
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Ehling-Schulz M, Frenzel E, Gohar M. Food-bacteria interplay: pathometabolism of emetic Bacillus cereus. Front Microbiol 2015; 6:704. [PMID: 26236290 PMCID: PMC4500953 DOI: 10.3389/fmicb.2015.00704] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2015] [Accepted: 06/26/2015] [Indexed: 11/25/2022] Open
Abstract
Bacillus cereus is a Gram-positive endospore forming bacterium known for its wide spectrum of phenotypic traits, enabling it to occupy diverse ecological niches. Although the population structure of B. cereus is highly dynamic and rather panmictic, production of the emetic B. cereus toxin cereulide is restricted to strains with specific genotypic traits, associated with distinct environmental habitats. Cereulide is an ionophoric dodecadepsipeptide that is produced non-ribosomally by an enzyme complex with an unusual modular structure, named cereulide synthetase (Ces non-ribosomal peptide synthetase). The ces gene locus is encoded on a mega virulence plasmid related to the B. anthracis toxin plasmid pXO1. Cereulide, a highly thermo- and pH- resistant molecule, is preformed in food, evokes vomiting a few hours after ingestion, and was shown to be the direct cause of gastroenteritis symptoms; occasionally it is implicated in severe clinical manifestations including acute liver failures. Control of toxin gene expression in emetic B. cereus involves central transcriptional regulators, such as CodY and AbrB, thereby inextricably linking toxin gene expression to life cycle phases and specific conditions, such as the nutrient supply encountered in food matrices. While in recent years considerable progress has been made in the molecular and biochemical characterization of cereulide toxin synthesis, far less is known about the embedment of toxin synthesis in the life cycle of B. cereus. Information about signals acting on toxin production in the food environment is lacking. We summarize the data available on the complex regulatory network controlling cereulide toxin synthesis, discuss the role of intrinsic and extrinsic factors acting on toxin biosynthesis in emetic B. cereus and stress how unraveling these processes can lead to the development of novel effective strategies to prevent toxin synthesis in the food production and processing chain.
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Affiliation(s)
- Monika Ehling-Schulz
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine ViennaVienna, Austria
| | - Elrike Frenzel
- Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine ViennaVienna, Austria
| | - Michel Gohar
- INRA, UMR1319 Micalis, AgroParistech – Domaine de Vilvert, Génétique Microbienne et EnvironnementJouy-en-Josas, France
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Yamaguchi M, Kawai T, Kitagawa M, Kumeda Y. A new method for rapid and quantitative detection of the Bacillus cereus emetic toxin cereulide in food products by liquid chromatography-tandem mass spectrometry analysis. Food Microbiol 2013; 34:29-37. [DOI: 10.1016/j.fm.2012.11.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2012] [Revised: 10/22/2012] [Accepted: 11/19/2012] [Indexed: 11/16/2022]
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Scientific Opinion on the risk posed by pathogens in food of non-animal origin. Part 1 (outbreak data analysis and risk ranking of food/pathogen combinations). EFSA J 2013. [DOI: 10.2903/j.efsa.2013.3025] [Citation(s) in RCA: 133] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Saleh M, Al Nakib M, Doloy A, Jacqmin S, Ghiglione S, Verroust N, Poyart C, Ozier Y. Bacillus cereus, an unusual cause of fulminant liver failure: diagnosis may prevent liver transplantation. J Med Microbiol 2012; 61:743-745. [DOI: 10.1099/jmm.0.038547-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Mohamed Saleh
- Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- Service d’Anesthésie-Réanimation Chirurgicale, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Malik Al Nakib
- Service de Bactériologie, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
- Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Alexandra Doloy
- Service de Bactériologie, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Sébastien Jacqmin
- Service d’Anesthésie-Réanimation Chirurgicale, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Sébastien Ghiglione
- Service d’Anesthésie-Réanimation Chirurgicale, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Nicolas Verroust
- Service d’Anesthésie-Réanimation Chirurgicale, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Claire Poyart
- Service de Bactériologie, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
- Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Yves Ozier
- Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- Service d’Anesthésie-Réanimation Chirurgicale, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique – Hôpitaux de Paris, Paris, France
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Psychrotolerant Paenibacillus tundrae isolates from barley grains produce new cereulide-like depsipeptides (paenilide and homopaenilide) that are highly toxic to mammalian cells. Appl Environ Microbiol 2012; 78:3732-43. [PMID: 22407690 DOI: 10.1128/aem.00049-12] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Paenilide is a novel, heat-stable peptide toxin from Paenibacillus tundrae, which colonizes barley. P. tundrae produced 20 to 50 ng of the toxin mg(-1) of cells (wet weight) throughout a range of growth temperatures from +5°C to +28°C. Paenilide consisted of two substances of 1,152 Da and 1,166 Da, with masses and tandem mass spectra identical to those of cereulide and a cereulide homolog, respectively, produced by Bacillus cereus NS-58. The two components of paenilide were separated from those of cereulide by high-performance liquid chromatography (HPLC), showing a structural difference suggesting the replacement of O-Leu (cereulide) by O-Ile (paenilide). The exposure of porcine spermatozoa and kidney tubular epithelial (PK-15) cells to subnanomolar concentrations of paenilide resulted in inhibited motility, the depolarization of mitochondria, excessive glucose consumption, and metabolic acidosis. Paenilide was similar to cereulide in eight different toxicity endpoints with porcine and murine cells. In isolated rat liver mitochondria, nanomolar concentrations of paenilide collapsed respiratory control, zeroed the mitochondrial membrane potential, and induced swelling. The toxic effect of paenilide depended on its high lipophilicity and activity as a high-affinity potassium ion carrier. Similar to cereulide, paenilide formed lipocations, i.e., lipophilic cationic compounds, with K(+) ions already at 4 mM [K(+)], rendering lipid membranes electroconductive. Paenilide-producing P. tundrae was negative in a PCR assay with primers specific for the cesB gene, indicating that paenilide was not a product of plasmid pCER270, encoding the biosynthesis of cereulide in B. cereus. Paenilide represents the first potassium ionophoric compound described for Paenibacillus. The findings in this paper indicate that paenilide from P. tundrae is a potential food-poisoning agent.
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Hyperammonemia in review: pathophysiology, diagnosis, and treatment. Pediatr Nephrol 2012; 27:207-22. [PMID: 21431427 DOI: 10.1007/s00467-011-1838-5] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2010] [Revised: 01/09/2011] [Accepted: 01/12/2011] [Indexed: 12/31/2022]
Abstract
Ammonia is an important source of nitrogen and is required for amino acid synthesis. It is also necessary for normal acid-base balance. When present in high concentrations, ammonia is toxic. Endogenous ammonia intoxication can occur when there is impaired capacity of the body to excrete nitrogenous waste, as seen with congenital enzymatic deficiencies. A variety of environmental causes and medications may also lead to ammonia toxicity. Hyperammonemia refers to a clinical condition associated with elevated ammonia levels manifested by a variety of symptoms and signs, including significant central nervous system (CNS) abnormalities. Appropriate and timely management requires a solid understanding of the fundamental pathophysiology, differential diagnosis, and treatment approaches available. The following review discusses the etiology, pathogenesis, differential diagnosis, and treatment of hyperammonemia.
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Ekman JV, Kruglov A, Andersson MA, Mikkola R, Raulio M, Salkinoja-Salonen M. Cereulide produced by Bacillus cereus increases the fitness of the producer organism in low-potassium environments. MICROBIOLOGY-SGM 2012; 158:1106-1116. [PMID: 22241046 DOI: 10.1099/mic.0.053520-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Cereulide, produced by certain Bacillus cereus strains, is a lipophilic cyclic peptide of 1152 Da that binds K(+) ions with high specificity and affinity. It is toxic to humans, but its role for the producer organism is not known. We report here that cereulide operates for B. cereus to scavenge potassium when the environment is growth limiting for this ion. Cereulide-producing B. cereus showed higher maximal growth rates (µ(max)) than cereulide non-producing B. cereus in K(+)-deficient medium (K(+) concentration ~1 mM). The cereulide-producing strains grew faster in K(+)-deficient than in K(+)-rich medium with or without added cereulide. Cereulide non-producing B. cereus neither increased µ(max) in K(+)-deficient medium compared with K(+)-rich medium, nor benefited from added cereulide. Cereulide-producing strains outcompeted GFP-labelled Bacillus thuringiensis in potassium-deficient (K(+) concentration ~1 mM) but not in potassium-rich (K(+) concentration ~30 mM) medium. Exposure to 2 µM cereulide in potassium-free medium lacking an energy source caused, within seconds, a major efflux of cellular K(+) from B. cereus not producing cereulide as well as from Bacillus subtilis. Cereulide depleted the cereulide non-producing B. cereus and B. subtilis cells of a major part of their K(+) stores, but did not affect cereulide-producing B. cereus strains. Externally added 6-10 µM cereulide triggered the generation of biofilms and pellicles by B. cereus. The results indicate that both endogenous and externally accessible cereulide supports the fitness of cereulide-producing B. cereus in environments where the potassium concentration is low.
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Affiliation(s)
- Jaakko V Ekman
- Department of Food and Environmental Science, PO Box 56, 00014 University of Helsinki, Helsinki, Finland
| | - Alexey Kruglov
- Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, Moscow Region, 142290 Russia
| | - Maria A Andersson
- Department of Food and Environmental Science, PO Box 56, 00014 University of Helsinki, Helsinki, Finland
| | - Raimo Mikkola
- Department of Food and Environmental Science, PO Box 56, 00014 University of Helsinki, Helsinki, Finland
| | - Mari Raulio
- Department of Food and Environmental Science, PO Box 56, 00014 University of Helsinki, Helsinki, Finland
| | - Mirja Salkinoja-Salonen
- Department of Food and Environmental Science, PO Box 56, 00014 University of Helsinki, Helsinki, Finland
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Abstract
Species of Bacillus and related genera have long been troublesome to food producers on account of their resistant endospores. These organisms have undergone huge taxonomic changes in the last 30 years, with numbers of genera and species now standing at 56 and over 545, respectively. Despite this expansion, relatively few new species have been isolated from infections, few are associated with food and no important new agents of foodborne illness have been reported. What has changed is our knowledge of the established agents. Bacillus cereus is well known as a cause of food poisoning, and much more is now understood about its toxins and their involvement in infections and intoxications. Also, although B. licheniformis, B. subtilis and B. pumilus have occasionally been isolated from cases of food-associated illness, their roles were usually uncertain. Much more is now known about the toxins that strains of these species may produce, so that their significances in such episodes are clearer; however, it is still unclear why such cases are so rarely reported. Another important development is the use of aerobic endosporeformers as probiotics, as the potentials of such organisms to cause illness or to be sources of antibiotic resistance need to be borne in mind.
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Affiliation(s)
- N A Logan
- Department of Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, UK.
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Frenzel E, Letzel T, Scherer S, Ehling-Schulz M. Inhibition of cereulide toxin synthesis by emetic Bacillus cereus via long-chain polyphosphates. Appl Environ Microbiol 2011; 77:1475-82. [PMID: 21169440 PMCID: PMC3067231 DOI: 10.1128/aem.02259-10] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2010] [Accepted: 12/07/2010] [Indexed: 01/15/2023] Open
Abstract
Severe intoxications caused by the Bacillus cereus emetic toxin cereulide can hardly be prevented due to the ubiquitous distribution and heat resistance of spores and the extreme thermal and chemical stability of cereulide. It would therefore be desirable to inhibit cereulide synthesis during food manufacturing processes or in prepared foods, which are stored under time-temperature abuse conditions. Toward this end, the impacts of three long-chain polyphosphate (polyP) formulations on growth and cereulide production were examined. The inhibition was dependent on the concentration and the type of the polyP blend, indicating that polyPs and not the orthophosphates were effective. Quantitative PCR (qPCR) monitoring at sublethal concentrations revealed that polyPs reduced the transcription of ces nonribosomal peptide synthetase (NRPS) genes by 3- to 4-fold along with a significantly reduced toxin production level. At lower concentrations, toxin synthesis was decreased, although the growth rate was not affected. These data indicate a differential effect on toxin synthesis independent of growth inhibition. The inhibition of toxin synthesis in food was also observed. Despite the growth of B. cereus, toxin synthesis was reduced by 70 to 100% in two model food systems (reconstituted infant food and oat milk), which were analyzed with HEp-2 cell culture assays and high-performance liquid chromatography (HPLC)/electrospray ionization-time of flight mass spectrometry (ESI-TOF-MS). Accordingly, ces promoter activity was strongly downregulated, as visualized by using a lux-based reporter strain. These data illustrate the potential of polyphosphate formulations to reduce the risk of cereulide synthesis in food and may contribute to targeted hurdle concepts.
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Affiliation(s)
- Elrike Frenzel
- Microbial Ecology Group, Department of Biosciences, Technische Universität München, D-85350 Freising, Germany, Competence Pool Weihenstephan, Technische Universität München, D-85354 Freising, Germany, Microbiology Unit, Nutrition and Food Research Center ZIEL, Technische Universität München, D-85350 Freising, Germany, Food Microbiology Unit, Clinic for Ruminants, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
| | - Thomas Letzel
- Microbial Ecology Group, Department of Biosciences, Technische Universität München, D-85350 Freising, Germany, Competence Pool Weihenstephan, Technische Universität München, D-85354 Freising, Germany, Microbiology Unit, Nutrition and Food Research Center ZIEL, Technische Universität München, D-85350 Freising, Germany, Food Microbiology Unit, Clinic for Ruminants, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
| | - Siegfried Scherer
- Microbial Ecology Group, Department of Biosciences, Technische Universität München, D-85350 Freising, Germany, Competence Pool Weihenstephan, Technische Universität München, D-85354 Freising, Germany, Microbiology Unit, Nutrition and Food Research Center ZIEL, Technische Universität München, D-85350 Freising, Germany, Food Microbiology Unit, Clinic for Ruminants, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
| | - Monika Ehling-Schulz
- Microbial Ecology Group, Department of Biosciences, Technische Universität München, D-85350 Freising, Germany, Competence Pool Weihenstephan, Technische Universität München, D-85354 Freising, Germany, Microbiology Unit, Nutrition and Food Research Center ZIEL, Technische Universität München, D-85350 Freising, Germany, Food Microbiology Unit, Clinic for Ruminants, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
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Abstract
Hepatic encephalopathy is a serious complication of acute and chronic liver diseases and has a high mortality rate. The pathogenesis of hepatic encephalopathy remains unclear, and there is no means of prevention or effective cure for the disease. Therefore, there is an urgent need for the basic and clinical research of hepatic encephalopathy to elucidate its pathogenesis. The development of animal models is important for elucidating the pathogenesis of hepatic encephalopathy and providing new avenues for diagnosis and therapy of the disease. Among a variety of animal models, rat model is applied most widely for similarity to humans, repeatability, reliability, applicability, controllability, simplicity and economy. In this paper, we briefly review various rat models of hepatic encephalopathy that have different origins.
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