Toxins

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Open AccessArticle

Short Toxin-like Proteins Attack the Defense Line of Innate Immunity

by Yitshak Tirosh, Dan Ofer, Tsiona Eliyahu and Michal Linial

Toxins 2013, 5(7), 1314-1331; https://doi.org/10.3390/toxins5071314 - 23 Jul 2013

Cited by 13 | Viewed by 9399

ClanTox (classifier of animal toxins) was developed for identifying toxin-like candidates from complete proteomes. Searching mammalian proteomes for short toxin-like proteins (coined TOLIPs) revealed a number of overlooked secreted short proteins with an abundance of cysteines throughout their sequences. We applied bioinformatics and [...] Read more.

ClanTox (classifier of animal toxins) was developed for identifying toxin-like candidates from complete proteomes. Searching mammalian proteomes for short toxin-like proteins (coined TOLIPs) revealed a number of overlooked secreted short proteins with an abundance of cysteines throughout their sequences. We applied bioinformatics and data-mining methods to infer the function of several top predicted candidates. We focused on cysteine-rich peptides that adopt the fold of the three-finger proteins (TFPs). We identified a cluster of duplicated genes that share a structural similarity with elapid neurotoxins, such as α-bungarotoxin. In the murine proteome, there are about 60 such proteins that belong to the Ly6/uPAR family. These proteins are secreted or anchored to the cell membrane. Ly6/uPAR proteins are associated with a rich repertoire of functions, including binding to receptors and adhesion. Ly6/uPAR proteins modulate cell signaling in the context of brain functions and cells of the innate immune system. We postulate that TOLIPs, as modulators of cell signaling, may be associated with pathologies and cellular imbalance. We show that proteins of the Ly6/uPAR family are associated with cancer diagnosis and malfunction of the immune system. Full article

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

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Open AccessArticle

Development and Evaluation of Monoclonal Antibodies for the Glucoside of T-2 Toxin (T2-Glc)

by Chris M. Maragos, Cletus Kurtzman, Mark Busman, Neil Price and Susan McCormick

Toxins 2013, 5(7), 1299-1313; https://doi.org/10.3390/toxins5071299 - 19 Jul 2013

Cited by 19 | Viewed by 7858

Abstract

The interactions between fungi and plants can yield metabolites that are toxic in animal systems. Certain fungi are known to produce sesquiterpenoid trichothecenes, such as T-2 toxin, that are biotransformed by several mechanisms including glucosylation. The glucosylated forms have been found in grain [...] Read more.

The interactions between fungi and plants can yield metabolites that are toxic in animal systems. Certain fungi are known to produce sesquiterpenoid trichothecenes, such as T-2 toxin, that are biotransformed by several mechanisms including glucosylation. The glucosylated forms have been found in grain and are of interest as potential reservoirs of T-2 toxin that are not detected by many analytical methods. Hence the glucosides of trichothecenes are often termed “masked” mycotoxins. The glucoside of T-2 toxin (T2-Glc) was linked to keyhole limpet hemocyanin and used to produce antibodies in mice. Ten monoclonal antibody (Mab)-producing hybridoma cell lines were developed. The Mabs were used in immunoassays to detect T2-Glc and T-2 toxin, with midpoints of inhibition curves (IC₅₀s) in the low ng/mL range. Most of the Mabs demonstrated good cross-reactivity to T-2 toxin, with lower recognition of HT-2 toxin. One of the clones (2-13) was further characterized with in-depth cross-reactivity and solvent tolerance studies. Results suggest Mab 2-13 will be useful for the simultaneous detection of T-2 toxin and T2-Glc. Full article

(This article belongs to the Special Issue Advances in Toxin Detection)

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Open AccessArticle

Differences in the Regulation of Ochratoxin A by the HOG Pathway in Penicillium and Aspergillus in Response to High Osmolar Environments

by Dominic Stoll, Markus Schmidt-Heydt and Rolf Geisen

Toxins 2013, 5(7), 1282-1298; https://doi.org/10.3390/toxins5071282 - 19 Jul 2013

Cited by 42 | Viewed by 6876

Abstract

Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three important ochratoxin A producing species. P. verrucosum is in addition able to produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl rich environments like salt rich dry cured [...] Read more.

Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three important ochratoxin A producing species. P. verrucosum is in addition able to produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl rich environments like salt rich dry cured foods or even salines. In this organism, the biosynthesis of ochratoxin A plays an adaptive role in this habitat. P. verrucosum generally can be found on cereals, but occasionally also on salt rich dry cured foods. In contrast A. carbonarius usually cannot be found in NaCl rich environments, but it occurs in another environment with high concentration of solutes, e.g., in sugar rich substrates like grapes and grape juices. Usually osmotic challenging conditions activate the HOG MAP kinase signal cascade, which in turn activates various osmo-regulated genes. In the current analysis, it could be demonstrated that in case of P. nordicum and P. verrucosum the NaCl induced production of ochratoxin A is correlated to the phosphorylation status of the HOG MAP kinase. Just the opposite was true for A. carbonarius. In this case, also higher amounts of NaCl in the medium lead to an increased phosphorylation status of HOG, but no increase in ochratoxin biosynthesis was observed. In contrast to the Penicillia, higher NaCl concentrations lead to a rapid cessation of growth by A. carbonarius. High glucose concentrations have much less impact on growth and the phosphorylation of HOG. Full article

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

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Open AccessArticle

The Use of Feed Additives to Reduce the Effects of Aflatoxin and Deoxynivalenol on Pig Growth, Organ Health and Immune Status during Chronic Exposure

by Alexandra C. Weaver, M. Todd See, Jeff A. Hansen, Yong B. Kim, Anna L. P. De Souza, Teena F. Middleton and Sung Woo Kim

Toxins 2013, 5(7), 1261-1281; https://doi.org/10.3390/toxins5071261 - 17 Jul 2013

Cited by 89 | Viewed by 10133

Abstract

Three feed additives were tested to improve the growth and health of pigs chronically challenged with aflatoxin (AF) and deoxynivalenol (DON). Gilts (n = 225, 8.8 ± 0.4 kg) were allotted to five treatments: CON (uncontaminated control); MT (contaminated with 150 µg/kg [...] Read more.

Three feed additives were tested to improve the growth and health of pigs chronically challenged with aflatoxin (AF) and deoxynivalenol (DON). Gilts (n = 225, 8.8 ± 0.4 kg) were allotted to five treatments: CON (uncontaminated control); MT (contaminated with 150 µg/kg AF and 1100 µg/kg DON); A (MT + a clay additive); B (MT + a clay and dried yeast additive); and C (MT + a clay and yeast culture additive). Average daily gain (ADG) and feed intake (ADFI) were recorded for 42 days, blood collected for immune analysis and tissue samples to measure damage. Feeding mycotoxins tended to decrease ADG and altered the immune system through a tendency to increase monocytes and immunoglobulins. Mycotoxins caused tissue damage in the form of liver bile ductule hyperplasia and karyomegaly. The additives in diets A and B reduced mycotoxin effects on the immune system and the liver and showed some ability to improve growth. The diet C additive played a role in reducing liver damage. Collectively, we conclude that AF and DON can be harmful to the growth and health of pigs consuming mycotoxins chronically. The selected feed additives improved pig health and may play a role in pig growth. Full article

(This article belongs to the Special Issue Mycotoxins in Food and Feed)

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Mini-Review: Novel Therapeutic Strategies to Blunt Actions of Pneumolysin in the Lungs

by Rudolf Lucas, Istvan Czikora, Supriya Sridhar, Evgeny Zemskov, Boris Gorshkov, Umapathy Siddaramappa, Aluya Oseghale, Jonathan Lawson, Alexander Verin, Ferenc G. Rick, Norman L. Block, Helena Pillich, Maritza Romero, Martin Leustik, Andrew V. Schally and Trinad Chakraborty

Toxins 2013, 5(7), 1244-1260; https://doi.org/10.3390/toxins5071244 - 15 Jul 2013

Cited by 27 | Viewed by 8838

Abstract

Severe pneumonia is the main single cause of death worldwide in children under five years of age. The main etiological agent of pneumonia is the G⁺ bacterium Streptococcus pneumoniae, which accounts for up to 45% of all cases. Intriguingly, patients can [...] Read more.

Severe pneumonia is the main single cause of death worldwide in children under five years of age. The main etiological agent of pneumonia is the G⁺ bacterium Streptococcus pneumoniae, which accounts for up to 45% of all cases. Intriguingly, patients can still die days after commencing antibiotic treatment due to the development of permeability edema, although the pathogen was successfully cleared from their lungs. This condition is characterized by a dramatically impaired alveolar epithelial-capillary barrier function and a dysfunction of the sodium transporters required for edema reabsorption, including the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed sodium potassium pump (Na⁺-K⁺-ATPase). The main agent inducing this edema formation is the virulence factor pneumolysin, a cholesterol-binding pore-forming toxin, released in the alveolar compartment of the lungs when pneumococci are being lysed by antibiotic treatment or upon autolysis. Sub-lytic concentrations of pneumolysin can cause endothelial barrier dysfunction and can impair ENaC-mediated sodium uptake in type II alveolar epithelial cells. These events significantly contribute to the formation of permeability edema, for which currently no standard therapy is available. This review focuses on discussing some recent developments in the search for the novel therapeutic agents able to improve lung function despite the presence of pore-forming toxins. Such treatments could reduce the potentially lethal complications occurring after antibiotic treatment of patients with severe pneumonia. Full article

(This article belongs to the Special Issue Pore-Forming Toxins)

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Open AccessArticle

Fluoxetine Induced Suicidal Erythrocyte Death

by Kashif Jilani, Sigrid Enkel, Rosi Bissinger, Ahmad Almilaji, Majed Abed and Florian Lang

Toxins 2013, 5(7), 1230-1243; https://doi.org/10.3390/toxins5071230 - 15 Jul 2013

Cited by 57 | Viewed by 7534

Abstract

The antidepressant fluoxetine inhibits ceramide producing acid sphingomyelinase. Ceramide is in turn known to trigger eryptosis the suicidal death of erythrocytes characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Ceramide is effective through sensitizing the erythrocytes to the pro-eryptotic [...] Read more.

The antidepressant fluoxetine inhibits ceramide producing acid sphingomyelinase. Ceramide is in turn known to trigger eryptosis the suicidal death of erythrocytes characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Ceramide is effective through sensitizing the erythrocytes to the pro-eryptotic effect of increased cytosolic Ca²⁺ activity ([Ca²⁺]_i). In nucleated cells, fluoxetine could either inhibit or stimulate suicidal death or apoptosis. The present study tested whether fluoxetine influences eryptosis. To this end cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, hemolysis from hemoglobin release and [Ca²⁺]_i from Fluo-3 fluorescence intensity. As a result, a 48 h exposure of erythrocytes to fluoxetine (≥25 µM) significantly decreased forward scatter, increased annexin V binding and enhanced [Ca²⁺]_i. The effect on annexin V binding was significantly blunted, but not abolished, in the absence of extracellular Ca²⁺. In conclusion, fluoxetine stimulates eryptosis, an effect at least in part due to increase of cytosolic Ca²⁺ activity. Full article

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580 KiB

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Degradation of Aflatoxin B₁ during the Fermentation of Alcoholic Beverages

by Tomonori Inoue, Yasushi Nagatomi, Atsuo Uyama and Naoki Mochizuki

Toxins 2013, 5(7), 1219-1229; https://doi.org/10.3390/toxins5071219 - 28 Jun 2013

Cited by 34 | Viewed by 8729

Abstract

Aflatoxin B₁ (AFB₁) is a contaminant of grain and fruit and has one of the highest levels of carcinogenicity of any natural toxin. AFB₁ and the fungi that produce it can also contaminate the raw materials used for beer [...] Read more.

Aflatoxin B₁ (AFB₁) is a contaminant of grain and fruit and has one of the highest levels of carcinogenicity of any natural toxin. AFB₁ and the fungi that produce it can also contaminate the raw materials used for beer and wine manufacture, such as corn and grapes. Therefore, brewers must ensure strict monitoring to reduce the risk of contamination. In this study, the fate of AFB₁ during the fermentation process was investigated using laboratory-scale bottom and top beer fermentation and wine fermentation. During fermentation, cool wort beer samples and wine must samples were artificially spiked with AFB₁ and the levels of AFB₁ remaining after fermentation were analyzed. AFB₁ levels were unchanged during both types of fermentation used for beer but were reduced to 30% of their initial concentration in wine. Differential analysis of the spiked and unspiked wine samples showed that the degradation compound was AFB_2a, a hydrated derivative of AFB₁. Thus, the results showed that the risk of AFB₁ carryover was still present for both types of beer fermentation but was reduced in the case of wine fermentation because of hydration. Full article

(This article belongs to the Special Issue Mycotoxins in Food and Feed)

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Toxins, Volume 5, Issue 7 (July 2013) – 7 articles , Pages 1219-1331

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