Toxins

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Open AccessReview

Signaling Cascades of Pasteurella multocida Toxin in Immune Evasion

by Katharina F. Kubatzky, Bianca Kloos and Dagmar Hildebrand

Toxins 2013, 5(9), 1664-1681; https://doi.org/10.3390/toxins5091664 - 24 Sep 2013

Cited by 19 | Viewed by 9568

Pasteurella multocida toxin (PMT) is a protein toxin found in toxigenic strains of Pasteurella multocida. PMT is the causative agent for atrophic rhinitis in pigs, a disease characterized by loss of nasal turbinate bones due to an inhibition of osteoblast function and [...] Read more.

Pasteurella multocida toxin (PMT) is a protein toxin found in toxigenic strains of Pasteurella multocida. PMT is the causative agent for atrophic rhinitis in pigs, a disease characterized by loss of nasal turbinate bones due to an inhibition of osteoblast function and an increase in osteoclast activity and numbers. Apart from this, PMT acts as a strong mitogen, protects from apoptosis and has an impact on the differentiation and function of immune cells. Many signaling pathways have been elucidated, however, the effect of these signaling cascades as a means to subvert the host’s immune system are just beginning to unravel. Full article

(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)

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Open AccessCommunication

Influence of Carbohydrates on Secondary Metabolism in Fusarium avenaceum

by Jens Laurids Sørensen and Henriette Giese

Toxins 2013, 5(9), 1655-1663; https://doi.org/10.3390/toxins5091655 - 24 Sep 2013

Cited by 29 | Viewed by 7296

Abstract

Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in [...] Read more.

Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in response to cultivation on different carbon sources in order to gain insight into the regulation and production of secondary metabolites in F. avenaceum. Seven monosaccharides (arabinose, xylose, fructose, sorbose, galactose, mannose, glucose), five disaccharides (cellobiose, lactose, maltose, sucrose and trehalose) and three polysaccharides (dextrin, inulin and xylan) were used as substrates. Three F. avenaceum strains were used in the experiments. These were all able to grow and produce aurofusarin on the tested carbon sources. Moniliformin and enniatins were produced on all carbon types, except on lactose, which suggest a common conserved regulation mechanism. Differences in the strains was observed for production of fusarin C, 2-AOD-3-ol, chlamydosporol and antibiotic Y, which suggests that carbon source plays a role in the regulation of their biosynthesis. Full article

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Open AccessReview

Update on Staphylococcal Superantigen-Induced Signaling Pathways and Therapeutic Interventions

by Teresa Krakauer

Toxins 2013, 5(9), 1629-1654; https://doi.org/10.3390/toxins5091629 - 24 Sep 2013

Cited by 49 | Viewed by 9013

Abstract

Staphylococcal enterotoxin B (SEB) and related bacterial toxins cause diseases in humans and laboratory animals ranging from food poisoning, acute lung injury to toxic shock. These superantigens bind directly to the major histocompatibility complex class II molecules on antigen-presenting cells and specific Vβ [...] Read more.

Staphylococcal enterotoxin B (SEB) and related bacterial toxins cause diseases in humans and laboratory animals ranging from food poisoning, acute lung injury to toxic shock. These superantigens bind directly to the major histocompatibility complex class II molecules on antigen-presenting cells and specific Vβ regions of T-cell receptors (TCR), resulting in rapid hyper-activation of the host immune system. In addition to TCR and co-stimulatory signals, proinflammatory mediators activate signaling pathways culminating in cell-stress response, activation of NFκB and mammalian target of rapamycin (mTOR). This article presents a concise review of superantigen-activated signaling pathways and focuses on the therapeutic challenges against bacterial superantigens. Full article

(This article belongs to the Special Issue Enterotoxins: Microbial Proteins and Host Cell Dysregulation)

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Open AccessArticle

Canine Cyanotoxin Poisonings in the United States (1920s–2012): Review of Suspected and Confirmed Cases from Three Data Sources

by Lorraine C. Backer, Jan H. Landsberg, Melissa Miller, Kevin Keel and Tegwin K. Taylor

Toxins 2013, 5(9), 1597-1628; https://doi.org/10.3390/toxins5091597 - 24 Sep 2013

Cited by 103 | Viewed by 13292

Abstract

Cyanobacteria (also called blue-green algae) are ubiquitous in aquatic environments. Some species produce potent toxins that can sicken or kill people, domestic animals, and wildlife. Dogs are particularly vulnerable to cyanotoxin poisoning because of their tendency to swim in and drink contaminated water [...] Read more.

Cyanobacteria (also called blue-green algae) are ubiquitous in aquatic environments. Some species produce potent toxins that can sicken or kill people, domestic animals, and wildlife. Dogs are particularly vulnerable to cyanotoxin poisoning because of their tendency to swim in and drink contaminated water during algal blooms or to ingestalgal mats.. Here, we summarize reports of suspected or confirmed canine cyanotoxin poisonings in the U.S. from three sources: (1) The Harmful Algal Bloom-related Illness Surveillance System (HABISS) of the National Center for Environmental Health (NCEH), Centers for Disease Control and Prevention (CDC); (2) Retrospective case files from a large, regional veterinary hospital in California; and (3) Publicly available scientific and medical manuscripts; written media; and web-based reports from pet owners, veterinarians, and other individuals. We identified 231 discreet cyanobacteria harmful algal bloom (cyanoHAB) events and 368 cases of cyanotoxin poisoning associated with dogs throughout the U.S. between the late 1920s and 2012. The canine cyanotoxin poisoning events reviewed here likely represent a small fraction of cases that occur throughout the U.S. each year. Full article

(This article belongs to the Special Issue Cyanotoxins)

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Open AccessArticle

Quantitative Mass Spectrometric Analysis and Post-Extraction Stability Assessment of the Euglenoid Toxin Euglenophycin

by Danielle B. Gutierrez, Alexandra Rafalski, Kevin Beauchesne, Peter D. Moeller, Richard E. Triemer and Paul V. Zimba

Toxins 2013, 5(9), 1587-1596; https://doi.org/10.3390/toxins5091587 - 18 Sep 2013

Cited by 6 | Viewed by 7062

Abstract

Euglenophycin is a recently discovered toxin produced by at least one species of euglenoid algae. The toxin has been responsible for several fish mortality events. To facilitate the identification and monitoring of euglenophycin in freshwater ponds, we have developed a specific mass spectrometric [...] Read more.

Euglenophycin is a recently discovered toxin produced by at least one species of euglenoid algae. The toxin has been responsible for several fish mortality events. To facilitate the identification and monitoring of euglenophycin in freshwater ponds, we have developed a specific mass spectrometric method for the identification and quantitation of euglenophycin. The post-extraction stability of the toxin was assessed under various conditions. Euglenophycin was most stable at room temperature. At 8 °C there was a small, but statistically significant, loss in toxin after one day. These methods and knowledge of the toxin’s stability will facilitate identification of the toxin as a causative agent in fish kills and determination of the toxin’s distribution in the organs of exposed fish. Full article

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Open AccessReview

Producers and Important Dietary Sources of Ochratoxin A and Citrinin

by Vladimir Ostry, Frantisek Malir and Jiri Ruprich

Toxins 2013, 5(9), 1574-1586; https://doi.org/10.3390/toxins5091574 - 17 Sep 2013

Cited by 175 | Viewed by 11860

Abstract

Ochratoxin A (OTA) is a very important mycotoxin, and its research is focused right now on the new findings of OTA, like being a complete carcinogen, information about OTA producers and new exposure sources of OTA. Citrinin (CIT) is another important mycotoxin, too, [...] Read more.

Ochratoxin A (OTA) is a very important mycotoxin, and its research is focused right now on the new findings of OTA, like being a complete carcinogen, information about OTA producers and new exposure sources of OTA. Citrinin (CIT) is another important mycotoxin, too, and its research turns towards nephrotoxicity. Both additive and synergistic effects have been described in combination with OTA. OTA is produced in foodstuffs by Aspergillus Section Circumdati (Aspergillus ochraceus, A. westerdijkiae, A. steynii) and Aspergillus Section Nigri (Aspergillus carbonarius, A. foetidus, A. lacticoffeatus, A. niger, A. sclerotioniger, A. tubingensis), mostly in subtropical and tropical areas. OTA is produced in foodstuffs by Penicillium verrucosum and P. nordicum, notably in temperate and colder zones. CIT is produced in foodstuffs by Monascus species (Monascus purpureus, M. ruber) and Penicillium species (Penicillium citrinum, P. expansum, P. radicicola, P. verrucosum). OTA was frequently found in foodstuffs of both plant origin (e.g., cereal products, coffee, vegetable, liquorice, raisins, wine) and animal origin (e.g., pork/poultry). CIT was also found in foodstuffs of vegetable origin (e.g., cereals, pomaceous fruits, black olive, roasted nuts, spices), food supplements based on rice fermented with red microfungi Monascus purpureus and in foodstuffs of animal origin (e.g., cheese). Full article

15903 KiB

Open AccessArticle

The Effect of Aflatoxin-B₁ on Red Drum (Sciaenops ocellatus) and Assessment of Dietary Supplementation of NovaSil for the Prevention of Aflatoxicosis

by Katherine E. Zychowski, Aline Rodrigues Hoffmann, Hoai J. Ly, Camilo Pohlenz, Alejandro Buentello, Amelia Romoser, Delbert M. Gatlin and Timothy D. Phillips

Toxins 2013, 5(9), 1555-1573; https://doi.org/10.3390/toxins5091555 - 16 Sep 2013

Cited by 48 | Viewed by 7898

Abstract

Aflatoxin B₁ (AFB₁) is a potent carcinogen that causes growth stunting, immunosuppression and liver cancer in multiple species. The recent trend of replacing fishmeal with plant-based proteins in fish feed has amplified the AFB₁ exposure risk in farm-raised fish. [...] Read more.

Aflatoxin B₁ (AFB₁) is a potent carcinogen that causes growth stunting, immunosuppression and liver cancer in multiple species. The recent trend of replacing fishmeal with plant-based proteins in fish feed has amplified the AFB₁ exposure risk in farm-raised fish. NovaSil (NS), a calcium montmorillonite clay, has previously been shown to reduce AFB₁ bioavailability safely and efficaciously in several mammalian species. This study was designed to: (1) evaluate AFB₁ impact on cultured red drum, Sciaenops ocellatus, over the course of seven weeks; and (2) assess NS supplementation as a strategy to prevent aflatoxicosis. Fish were fed diets containing 0, 0.1, 0.25, 0.5, 1, 2, 3, or 5 ppm AFB₁. Two additional treatment groups were fed either 5 ppm AFB₁ + 1% NS or 5 ppm AFB₁ + 2% NS. Aflatoxin B₁ negatively impacted red drum weight gain, survival, feed efficiency, serum lysozyme concentration, hepatosomatic index (HSI), whole-body lipid levels, liver histopathological scoring, as well as trypsin inhibition. NovaSil inclusion in AFB₁-contaminated diets improved weight gain, feed efficiency, serum lysozyme concentration, muscle somatic index, and intraperitoneal fat ratios compared to AFB₁-treated fish. Although not significant, NS reduced AFB₁-induced histopathological changes in the liver and decreased Proliferating Cell Nuclear Antigen (PCNA) staining. Importantly, NS supplementation improved overall health of AFB₁-exposed red drum. Full article

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Open AccessArticle

Triggering of Suicidal Erythrocyte Death by Celecoxib

by Adrian Lupescu, Rosi Bissinger, Kashif Jilani and Florian Lang

Toxins 2013, 5(9), 1543-1554; https://doi.org/10.3390/toxins5091543 - 10 Sep 2013

Cited by 55 | Viewed by 6247

Abstract

The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib triggers apoptosis of tumor cells and is thus effective against malignancy. The substance is at least partially effective through mitochondrial depolarization. Even though lacking mitochondria, erythrocytes may enter apoptosis-like suicidal death or eryptosis, which is characterized by [...] Read more.

The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib triggers apoptosis of tumor cells and is thus effective against malignancy. The substance is at least partially effective through mitochondrial depolarization. Even though lacking mitochondria, erythrocytes may enter apoptosis-like suicidal death or eryptosis, which is characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). The present study explored whether celecoxib stimulates eryptosis. Forward scatter was determined to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to depict hemolysis, and Fluo3-fluorescence to quantify [Ca²⁺]_i. A 48 h exposure of human erythrocytes to celecoxib was followed by significant increase of [Ca²⁺]_i (15 µM), significant decrease of forward scatter (15 µM) and significant increase of annexin-V-binding (10 µM). Celecoxib (15 µM) induced annexin-V-binding was blunted but not abrogated by removal of extracellular Ca²⁺. In conclusion, celecoxib stimulates suicidal erythrocyte death or eryptosis, an effect partially due to stimulation of Ca²⁺ entry. Full article

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Open AccessReview

CD28: Direct and Critical Receptor for Superantigen Toxins

by Raymond Kaempfer, Gila Arad, Revital Levy, Dalia Hillman, Iris Nasie and Ziv Rotfogel

Toxins 2013, 5(9), 1531-1542; https://doi.org/10.3390/toxins5091531 - 9 Sep 2013

Cited by 30 | Viewed by 10408

Abstract

Every adaptive immune response requires costimulation through the B7/CD28 axis, with CD28 on T-cells functioning as principal costimulatory receptor. Staphylococcal and streptococcal superantigen toxins hyperstimulate the T-cell-mediated immune response by orders of magnitude, inducing a lethal cytokine storm. We show that to elicit [...] Read more.

Every adaptive immune response requires costimulation through the B7/CD28 axis, with CD28 on T-cells functioning as principal costimulatory receptor. Staphylococcal and streptococcal superantigen toxins hyperstimulate the T-cell-mediated immune response by orders of magnitude, inducing a lethal cytokine storm. We show that to elicit an inflammatory cytokine storm and lethality, superantigens must bind directly to CD28. Blocking access of the superantigen to its CD28 receptor with peptides mimicking the contact domains in either toxin or CD28 suffices to protect mice effectively from lethal shock. Our finding that CD28 is a direct receptor of superantigen toxins broadens the scope of microbial pathogen recognition mechanisms. Full article

(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)

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Open AccessReview

Porcine/Chicken or Human Nephropathy as the Result of Joint Mycotoxins Interaction

by Stoycho D. Stoev and Stefan A. Denev

Toxins 2013, 5(9), 1503-1530; https://doi.org/10.3390/toxins5091503 - 4 Sep 2013

Cited by 20 | Viewed by 8727

Abstract

A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific [...] Read more.

A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific conditions for their growth and toxins production were briefly described. A survey was made about the most frequent nephrotoxic fungal contaminants in various feedstuffs from plant origin. In addition, their natural quantities and importance for development of mycotoxic porcine/chick nephropathy (MPN/MCN) are also explored. In addition, a survey was made of the feedstuffs representing the most favorable environment for nephrotoxic fungal growth as well as the most favorable storehouse conditions for this fungal growth were shortly described. The significance of some underestimated fungal species, which can provoke kidney damage, was studied. The importance of joint mycotoxin interaction and newly identified fungal metabolites in the complex etiology of mycotoxic nephropathy ranged in some countries is deeply investigated. The toxicity of the low contamination levels of some combinations of mycotoxins often administered by pigs and chicks in the practice was carefully studied. Full article

(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)

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Toxins, Volume 5, Issue 9 (September 2013) – 10 articles , Pages 1503-1681

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