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Toxins, Volume 2, Issue 7 (July 2010), Pages 1595-1927

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Research

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Open AccessArticle Plant Natural Compounds with Antibacterial Activity towards Common Pathogens of Pond-Cultured Channel Catfish (Ictalurus punctatus)
Toxins 2010, 2(7), 1676-1689; doi:10.3390/toxins2071676
Received: 28 April 2010 / Revised: 23 June 2010 / Accepted: 25 June 2010 / Published: 28 June 2010
Cited by 5 | PDF Full-text (153 KB) | HTML Full-text | XML Full-text
Abstract
The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds
[...] Read more.
The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds as potential therapeutants. Chelerythrine chloride and ellagic acid were the most toxic toward E. ictaluri, with 24-h IC50 of 7.3 mg/L and 15.1 mg/L, respectively, and MIC of 2.1 mg/L and 6.5 mg/L, respectively. Chelerythrine chloride, ellagic acid, β-glycyrrhetinic acid, sorgoleone, and wogonin were the most toxic towards two genomovars of F. columnare, and wogonin had the strongest antibacterial activity (MIC = 0.3 mg/L). Full article
(This article belongs to the Special Issue The Toxicity of Natural Products)
Open AccessArticle Uncoupling of T Cell Receptor Zeta Chain Function during the Induction of Anergy by the Superantigen, Staphylococcal Enterotoxin A
Toxins 2010, 2(7), 1704-1717; doi:10.3390/toxins2071704
Received: 5 May 2010 / Revised: 17 June 2010 / Accepted: 28 June 2010 / Published: 30 June 2010
PDF Full-text (267 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcus aureus enterotoxins have immunomodulatory properties. In this study, we show that Staphylococcal enterotoxin A (SEA) induces a strong proliferative response in a murine T cell clone independent of MHC class II bearing cells. SEA stimulation also induces a state of hypo-responsiveness (anergy).
[...] Read more.
Staphylococcus aureus enterotoxins have immunomodulatory properties. In this study, we show that Staphylococcal enterotoxin A (SEA) induces a strong proliferative response in a murine T cell clone independent of MHC class II bearing cells. SEA stimulation also induces a state of hypo-responsiveness (anergy). We characterized the components of the T cell receptor (TCR) during induction of anergy by SEA. Most interestingly, TCR zeta chain phosphorylation was absent under SEA anergizing conditions, which suggests an uncoupling of zeta chain function. We characterize here a model system for studying anergy in the absence of confounding costimulatory signals. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessArticle Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen
Toxins 2010, 2(7), 1825-1847; doi:10.3390/toxins2071825
Received: 14 May 2010 / Revised: 23 June 2010 / Accepted: 6 July 2010 / Published: 9 July 2010
Cited by 11 | PDF Full-text (555 KB) | HTML Full-text | XML Full-text
Abstract
The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for
[...] Read more.
The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for countering the cytotoxic activity of the toxin in exposed individuals. Using a robust cell-based high-throughput screening (HTS) assay, we screened a 151,616-compound library for the ability to inhibit e-toxin-induced cytotoxicity. Survival of MDCK cells exposed to the toxin was assessed by addition of resazurin to detect metabolic activity in surviving cells. The hit rate for this screen was 0.6%. Following a secondary screen of each hit in triplicate and assays to eliminate false positives, we focused on three structurally-distinct compounds: an N-cycloalkylbenzamide, a furo[2,3-b]quinoline, and a 6H-anthra[1,9-cd]isoxazol. None of the three compounds appeared to inhibit toxin binding to cells or the ability of the toxin to form oligomeric complexes. Additional assays demonstrated that two of the inhibitory compounds inhibited ε-toxin-induced permeabilization of MDCK cells to propidium iodide. Furthermore, the two compounds exhibited inhibitory effects on cells pre-treated with toxin. Structural analogs of one of the inhibitors identified through the high-throughput screen were analyzed and provided initial structure-activity data. These compounds should serve as the basis for further structure-activity refinement that may lead to the development of effective anti-ε-toxin therapeutics. Full article
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Review

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Open AccessReview Specificity of Interaction between Clostridium perfringens Enterotoxin and Claudin-Family Tight Junction Proteins
Toxins 2010, 2(7), 1595-1611; doi:10.3390/toxins2071595
Received: 18 May 2010 / Revised: 7 June 2010 / Accepted: 23 June 2010 / Published: 24 June 2010
Cited by 16 | PDF Full-text (568 KB) | HTML Full-text | XML Full-text
Abstract
Clostridium perfringens enterotoxin (CPE), a major cause of food poisoning, forms physical pores in the plasma membrane of intestinal epithelial cells. The ability of CPE to recognize the epithelium is due to the C-terminal binding domain, which binds to a specific motif
[...] Read more.
Clostridium perfringens enterotoxin (CPE), a major cause of food poisoning, forms physical pores in the plasma membrane of intestinal epithelial cells. The ability of CPE to recognize the epithelium is due to the C-terminal binding domain, which binds to a specific motif on the second extracellular loop of tight junction proteins known as claudins. The interaction between claudins and CPE plays a key role in mediating CPE toxicity by facilitating pore formation and by promoting tight junction disassembly. Recently, the ability of CPE to distinguish between specific claudins has been used to develop tools for studying roles for claudins in epithelial barrier function. Moreover, the high affinity of CPE to selected claudins makes CPE a useful platform for targeted drug delivery to tumors expressing these claudins. Full article
(This article belongs to the Special Issue Enterotoxins)
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Open AccessReview AB Toxins: A Paradigm Switch from Deadly to Desirable
Toxins 2010, 2(7), 1612-1645; doi:10.3390/toxins2071612
Received: 26 May 2010 / Revised: 8 June 2010 / Accepted: 23 June 2010 / Published: 25 June 2010
Cited by 22 | PDF Full-text (894 KB) | HTML Full-text | XML Full-text
Abstract
To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually.
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To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessReview Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life
Toxins 2010, 2(7), 1646-1675; doi:10.3390/toxins2071646
Received: 29 April 2010 / Revised: 28 May 2010 / Accepted: 11 June 2010 / Published: 28 June 2010
Cited by 12 | PDF Full-text (1071 KB) | HTML Full-text | XML Full-text
Abstract
Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died;
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Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages. Full article
(This article belongs to the Special Issue Marine Biotoxins: Novel Issues about Old Compounds)
Open AccessReview Production, Secretion and Biological Activity of Bacillus cereus Enterotoxins
Toxins 2010, 2(7), 1690-1703; doi:10.3390/toxins2071690
Received: 4 May 2010 / Revised: 14 June 2010 / Accepted: 28 June 2010 / Published: 29 June 2010
Cited by 24 | PDF Full-text (131 KB) | HTML Full-text | XML Full-text
Abstract
Bacillus cereus behaves as an opportunistic pathogen frequently causing gastrointestinal diseases, and it is increasingly recognized to be responsible for severe local or systemic infections. Pathogenicity of B. cereus mainly relies on the secretion of a wide array of toxins and enzymes and
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Bacillus cereus behaves as an opportunistic pathogen frequently causing gastrointestinal diseases, and it is increasingly recognized to be responsible for severe local or systemic infections. Pathogenicity of B. cereus mainly relies on the secretion of a wide array of toxins and enzymes and also on the ability to undergo swarming differentiation in response to surface-sensing. In this report, the pathogenicity exerted by B. cereus toxins is described with particular attention to the regulatory mechanisms of production and secretion of HBL, Nhe and CytK enterotoxins. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessReview Chemical, Physical and Biological Approaches to Prevent Ochratoxin Induced Toxicoses in Humans and Animals
Toxins 2010, 2(7), 1718-1750; doi:10.3390/toxins2071718
Received: 6 May 2010 / Revised: 25 June 2010 / Accepted: 29 June 2010 / Published: 1 July 2010
Cited by 26 | PDF Full-text (418 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard
[...] Read more.
Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard to animals and humans. Several strategies have been investigated for lowering the ochratoxin content in agricultural products. These strategies can be classified into three main categories: prevention of ochratoxin contamination, decontamination or detoxification of foods contaminated with ochratoxins, and inhibition of the absorption of consumed ochratoxins in the gastrointestinal tract. This paper gives an overview of the strategies that are promising with regard to lowering the ochratoxin burden of animals and humans. Full article
(This article belongs to the Special Issue Ochratoxins)
Open AccessReview Food Poisoning and Staphylococcus aureus Enterotoxins
Toxins 2010, 2(7), 1751-1773; doi:10.3390/toxins2071751
Received: 3 May 2010 / Revised: 24 June 2010 / Accepted: 30 June 2010 / Published: 5 July 2010
Cited by 183 | PDF Full-text (476 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcus aureus produces a wide variety of toxins including staphylococcal enterotoxins (SEs; SEA to SEE, SEG to SEI, SER to SET) with demonstrated emetic activity, and staphylococcal-like (SEl) proteins, which are not emetic in a primate model (SElL and
[...] Read more.
Staphylococcus aureus produces a wide variety of toxins including staphylococcal enterotoxins (SEs; SEA to SEE, SEG to SEI, SER to SET) with demonstrated emetic activity, and staphylococcal-like (SEl) proteins, which are not emetic in a primate model (SElL and SElQ) or have yet to be tested (SElJ, SElK, SElM to SElP, SElU, SElU2 and SElV). SEs and SEl s have been traditionally subdivided into classical (SEA to SEE) and new (SEG to SElU2) types. All possess superantigenic activity and are encoded by accessory genetic elements, including plasmids, prophages, pathogenicity islands, νSa genomic islands, or by genes located next to the staphylococcal cassette chromosome (SCC) implicated in methicillin resistance. SEs are a major cause of food poisoning, which typically occurs after ingestion of different foods, particularly processed meat and dairy products, contaminated with S. aureus by improper handling and subsequent storage at elevated temperatures. Symptoms are of rapid onset and include nausea and violent vomiting, with or without diarrhea. The illness is usually self-limiting and only occasionally it is severe enough to warrant hospitalization. SEA is the most common cause of staphylococcal food poisoning worldwide, but the involvement of other classical SEs has been also demonstrated. Of the new SE/SEls, only SEH have clearly been associated with food poisoning. However, genes encoding novel SEs as well as SEls with untested emetic activity are widely represented in S. aureus, and their role in pathogenesis may be underestimated. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessReview Cholera-Like Enterotoxins and Regulatory T cells
Toxins 2010, 2(7), 1774-1795; doi:10.3390/toxins2071774
Received: 4 May 2010 / Revised: 23 June 2010 / Accepted: 28 June 2010 / Published: 6 July 2010
Cited by 7 | PDF Full-text (375 KB) | HTML Full-text | XML Full-text
Abstract
Cholera toxin (CT) and the heat-labile enterotoxin of E. coli (LT), as well as their non toxic mutants, are potent mucosal adjuvants of immunization eliciting mucosal and systemic responses against unrelated co-administered antigens in experimental models and in humans (non toxic mutants). These
[...] Read more.
Cholera toxin (CT) and the heat-labile enterotoxin of E. coli (LT), as well as their non toxic mutants, are potent mucosal adjuvants of immunization eliciting mucosal and systemic responses against unrelated co-administered antigens in experimental models and in humans (non toxic mutants). These enterotoxins are composed of two subunits, the A subunit, responsible for an ADP-ribosyl transferase activity and the B subunit, responsible for cell binding. Paradoxically, whereas the whole toxins have adjuvant properties, the B subunits of CT (CTB) and of LT (LTB) have been shown to induce antigen specific tolerance when administered mucosally with antigens in experimental models as well as, recently, in humans, making them an attractive strategy to prevent or treat autoimmune or allergic disorders. Immunomodulation is a complex process involving many cell types notably antigen presenting cells and regulatory T cells (Tregs). In this review, we focus on Treg cells and cholera-like enterotoxins and their non toxic derivates, with regard to subtype, in vivo/in vitro effects and possible role in the modulation of immune responses to coadministered antigens. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessReview Effects of Ochratoxin A on Livestock Production
Toxins 2010, 2(7), 1796-1824; doi:10.3390/toxins2071796
Received: 4 June 2010 / Revised: 24 June 2010 / Accepted: 6 July 2010 / Published: 8 July 2010
Cited by 17 | PDF Full-text (429 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain
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Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain to humans. The aim of this paper is to review the available literature on: (1) the frequency and degree of occurrence of OTA in different feedstuffs; (2) the toxicological effects of OTA intake on the performance of the main livestock (i.e., poultry, swine, cattle, goats and sheep); and (3) the transfer of OTA, or its metabolites, from animal feed into animal products such as milk, meat and eggs. Full article
(This article belongs to the Special Issue Ochratoxins)
Open AccessReview The Enterotoxicity of Clostridium difficile Toxins
Toxins 2010, 2(7), 1848-1880; doi:10.3390/toxins2071848
Received: 18 June 2010 / Revised: 23 June 2010 / Accepted: 9 July 2010 / Published: 14 July 2010
Cited by 31 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and
[...] Read more.
The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and proinflammatory in the human intestine. Both purified TcdA and TcdB are capable of inducing the pathophysiology of CDI, although most studies have focused on TcdA. C. difficile toxins exert a wide array of biological activities by acting directly on intestinal epithelial cells. Alternatively, the toxins may target immune cells and neurons once the intestinal epithelial barrier is disrupted. The toxins may also act indirectly by stimulating cells to produce chemokines, proinflammatory cytokines, neuropeptides and other neuroimmune signals. This review considers the mechanisms of TcdA- and TcdB-induced enterotoxicity, and recent developments in this field. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessReview Emergence of Anthrax Edema Toxin as a Master Manipulator of Macrophage and B Cell Functions
Toxins 2010, 2(7), 1881-1897; doi:10.3390/toxins2071881
Received: 18 June 2010 / Revised: 6 July 2010 / Accepted: 12 July 2010 / Published: 19 July 2010
Cited by 5 | PDF Full-text (599 KB) | HTML Full-text | XML Full-text
Abstract
Anthrax edema toxin (ET), a powerful adenylyl cyclase, is an important virulence factor of Bacillus anthracis. Until recently, only a modest amount of research was performed to understand the role this toxin plays in the organism’s immune evasion strategy. A new wave
[...] Read more.
Anthrax edema toxin (ET), a powerful adenylyl cyclase, is an important virulence factor of Bacillus anthracis. Until recently, only a modest amount of research was performed to understand the role this toxin plays in the organism’s immune evasion strategy. A new wave of studies have begun to elucidate the effects this toxin has on a variety of host cells. While efforts have been made to illuminate the effect ET has on cells of the adaptive immune system, such as T cells, the greatest focus has been on cells of the innate immune system, particularly the macrophage. Here we discuss the immunoevasive activities that ET exerts on macrophages, as well as new research on the effects of this toxin on B cells. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview The Systemic and Pulmonary Immune Response to Staphylococcal Enterotoxins
Toxins 2010, 2(7), 1898-1912; doi:10.3390/toxins2071898
Received: 21 June 2010 / Accepted: 12 July 2010 / Published: 21 July 2010
Cited by 2 | PDF Full-text (133 KB) | HTML Full-text | XML Full-text
Abstract
In response to environmental cues the human pathogen Staphylococcus aureus synthesizes and releases proteinaceous enterotoxins. These enterotoxins are natural etiologic entities of severe food poisoning, toxic shock syndrome, and acute diseases. Staphylococcal enterotoxins are currently listed as Category B Bioterrorism Agents by the
[...] Read more.
In response to environmental cues the human pathogen Staphylococcus aureus synthesizes and releases proteinaceous enterotoxins. These enterotoxins are natural etiologic entities of severe food poisoning, toxic shock syndrome, and acute diseases. Staphylococcal enterotoxins are currently listed as Category B Bioterrorism Agents by the Center for Disease Control and Prevention. They are associated with respiratory illnesses, and may contribute to exacerbation of pulmonary disease. This likely stems from the ability of Staphylococcal enterotoxins to elicit powerful episodes of T cell stimulation resulting in release of pro-inflammatory cytokines. Here, we discuss the role of the immune system and potential mechanisms of disease initiation and progression. Full article
(This article belongs to the Special Issue Enterotoxins)
Open AccessReview NetB, a Pore-Forming Toxin from Necrotic Enteritis Strains of Clostridium perfringens
Toxins 2010, 2(7), 1913-1927; doi:10.3390/toxins2071913
Received: 22 June 2010 / Revised: 9 July 2010 / Accepted: 22 July 2010 / Published: 23 July 2010
Cited by 31 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text
Abstract
The Clostridium perfringens necrotic enteritis B-like toxin (NetB) is a recently discovered member of the β-barrel pore-forming toxin family and is produced by a subset of avian C. perfringens type A strains. NetB is cytotoxic for avian cells and is associated with avian
[...] Read more.
The Clostridium perfringens necrotic enteritis B-like toxin (NetB) is a recently discovered member of the β-barrel pore-forming toxin family and is produced by a subset of avian C. perfringens type A strains. NetB is cytotoxic for avian cells and is associated with avian necrotic enteritis. This review examines the current state of knowledge of NetB: its role in pathogenesis, its distribution and expression in C. perfringens and its vaccine potential. Full article
(This article belongs to the Special Issue Enterotoxins)

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