The open toxinology journal最新文献

{"title":"Iota Toxin, S Toxin and CDT: Members of the Same Class of Clostridial Binary Toxins in Feces of Humans and Other Animals","authors":"R. Carman, A. Stevens, C. Genheimer, T. Wilkins","doi":"10.2174/1875414701003010043","DOIUrl":"https://doi.org/10.2174/1875414701003010043","url":null,"abstract":"Some strains of Clostridium perfringens, Clostridium spiroforme and Clostridium difficile produce binary toxins known respectively as iota toxin, S toxin and CDT. Each toxin consists of two unlinked polypeptides (e.g. CDTa and CDTb) that only together have biological activity. Taking an historical perspective, we review the development and early use of assays employing the specific neutralization of a biological activity for the detection and quantification of binary toxin. The survey moves on to more recent immunological assays and culminates with a discussion of the relevance of binary toxin, especially CDT, in feces.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"43-47"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68118459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Host Cell Chaperones in Cellular Uptake of Clostridium Botulinum C2 Toxin","authors":"E. Kaiser, H. Barth","doi":"10.2174/1875414701003010048","DOIUrl":"https://doi.org/10.2174/1875414701003010048","url":null,"abstract":"The binary C2 toxin from Clostridium botulinum consists of two separate proteins: the transport component C2IIa delivers the enzyme component C2I into the cytosol of eukaryotic host cells. In the cytosol, C2I mono-ADP- ribosylates actin, thereby inducing depolymerization of actin filaments resulting in delayed caspase-dependent cell death. The sophisticated cellular uptake mechanism of C2 toxin, in particular our new results regarding the role of host cell chaperones and protein-folding helper enzymes during intracellular membrane translocation of C2I, are focused upon in this minireview. We discovered earlier that translocation of C2I across endosomal membranes in mammalian cells depends on the chaperone activity of the heat shock protein Hsp90. Recently we have demonstrated that cyclosporin A (CsA), an inhibitor of peptidyl-prolyl cis/trans isomerase (PPIase) activity of cyclophilins, inhibited intoxication of various mammalian cell lines with C2 toxin. The underlying reason for this effect was the prevented uptake of C2I into the host cell cytosol. CsA, as well as a specific antibody against cyclophilin A, blocked the pH-dependent translocation of C2I-ADP- ribosyltransferase activity across membranes of intact cells and of partially-purified early endosomes in vitro. In conclusion, our results imply that the activities of Hsp90 and cyclophilin A are crucial for translocation of the C2I ADP- ribosyltransferase from early endosomes into the cytosol of mammalian cells. This is the first observation that a host cell PPIase, in concert with a heat shock protein, facilitates intracellular membrane translocation of a bacterial protein toxin.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"48-52"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68118476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fate and Effects in Soil of Cry Proteins from Bacillus thuringiensis: Influence of Physicochemical and Biological Characteristics of Soil","authors":"D. Saxena, S. Pushalkar, G. Stotzky","doi":"10.2174/1875414701003010151","DOIUrl":"https://doi.org/10.2174/1875414701003010151","url":null,"abstract":"Bacillus thuringiensis (Bt) is a useful alternative or supplement to synthetic chemical pesticides in agriculture, forest management, and control of mosquitoes and some other biting insects. When modified Bt cry genes are inserted into a plant species (e.g., corn, cotton, potato, canola, rice), the plant expresses active larvicidal proteins in its tissues. The toxins continue to be synthesized during growth of the plants, making the plant toxic to various insect pests throughout their life or as biomass incorporated into soil. If production exceeds consumption, inactivation, and degradation, the toxins could accumulate to concentrations that may enhance the control of target pests or constitute a hazard to nontarget organisms, such as the soil microbiota, beneficial insects (e.g., pollinators, predators and parasites of insect pests), and other animal classes. The accumulation and persistence of the toxins could also result in the selection and enrichment of toxin-resistant target insects. Persistence is enhanced when the toxins are bound on surface-active particles in the environment (e.g., clays and humic substances) and, thereby, rendered more resistant to biodegradation while retaining toxic activity. Moreover, major problem we face today is of \"Molecular pharming\" that utilizes transgenic plants and animals for production of pharmaceuticals and chemicals for their use in human beings and industries respectively. Their release to the environment, especially to soil and potentially to waters of the pharmaceutical and industrial products of transgenic plant and animal \"pharms\" could pose a hazard to the environment. In contrast to the products of most transgenic plants currently available commercially (e.g., the insecticidal proteins from subspecies of Bt) that primarily target insects and other pests. These \"pharms\" are being genetically engineered to express products for use primarily in human beings. Consequently, these products constitute a class of compounds that is seldom found in natural habitats and that primarily target \"higher level\" eukaryotes. Hence, they are xenobiotics with respect to the environment, and their persistence in and effects on the environment have not been adequately studied and sober risk assessments on a case-by- case basis must be made before major releases of such transgenic organisms.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"151-171"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Intracellular Journey of Shiga Toxins","authors":"M. Torgersen, N. Engedal, J. Bergan, K. Sandvig","doi":"10.2174/1875414701003010003","DOIUrl":"https://doi.org/10.2174/1875414701003010003","url":null,"abstract":"The Shiga toxin family consists of Shiga toxin (Stx) that is produced as a virulence factor by Shigella dysenteriae, and the Shiga-like toxins produced by certain strains of enterohemorrhagic E. coli as well as by some other types of bacteria. Infection with bacteria producing these toxins is a threat to human health even in industrialized countries, as the initial diarrhea caused by the infection might be followed by a complication named hemolytic uremic syndrome. The Shiga toxins consist of a binding moiety that in most cases binds to the glycosphingolipid Gb3 on the surface of susceptible cells, and an A-moiety responsible for the toxic effect in the cytosol. In order to reach its cytosolic target, the toxin must be internalized and then transported via the retrograde pathway to the Golgi complex and further to the endoplasmic reticulum. From the endoplasmic reticulum the enzymatically active part of the A-moiety is translocated to the cytosol, and cellular protein synthesis is inhibited. Although the Shiga toxins are involved in disease, they may also be exploited for medical diagnosis and treatment. Interestingly, the toxin receptor, Gb3, has a limited expression in normal tissues, but is overexpressed in several types of cancer. Thus, the use of Shiga toxin, or the binding part of the toxin, has great potential in cancer diagnostics and treatment. Furthermore, studies of the various uptake mechanisms and intracellular transport pathways exploited by the toxins, provide important insight in basic cell biology processes.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"3-12"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68118344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergy Between Aedes aegypti Trypsin Modulating Oostatic Factor and δ-Endotoxins","authors":"D. Borovsky, V. Khasdan, S. Nauwelaers, Clara Theunis, Lien Bertie r, E. Ben‐Dov, A. Zaritsky","doi":"10.2174/1875414701003010141","DOIUrl":"https://doi.org/10.2174/1875414701003010141","url":null,"abstract":"Starved first instar Aedes aegypti larvae were 35-fold more sensitive to Bacillus thuringiensis subsp. israelensis (Bti) toxins than fed larvae. Feeding larvae Pichia pastoris yeast cells expressing tmfA (synthetic gene coding for the Trypsin Modulating Oostatic Factor of Ae. aegypti) together with Escherichia coli cells expressing Bti toxin genes (cry4Aa, cry11Aa, cyt1Aa and p20) indicate that TMOF and Cry toxins are synergisitic. tmfA was cloned and expressed in the cyanobacterium Anabaena PCC 7120 and the hormone was purified by HPLC and identified by ELISA. The amount of TMOF synthesized by Anabaena was low (0.5 - 1 μg in 10 8 cells). P. pastoris, which synthesizes high amounts of heterologous proteins in the presence of methanol and is readily consumed by mosquito larvae, was genetically engineered to produce more TMOF. Codon-optimized synthetic genes, cry11Aa- tmfA and gst-cry11Aa- tmfA, that were cloned into P. pastoris and fed to Ae. aegypti larvae caused 87.5% mortality in 5 days. GST (glutathione-S-transferase) enhanced the activity of Cry11A-TMOF and protected it from heat denaturation. Cell free extracts of recombinant P. pastoris cells killed 40% of tested 4 th instar larvae within 24 h, and mass spectra analysis confirmed that the recombinants synthesize Cry11Aa. This report shows for the first time that Cry toxins and TMOF are synergists to Ae. aegypti larvae when jointly fed or expressed in recombinant P. pastoris.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"39 1","pages":"141-150"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of the Basic Biology of Bacillus thuringiensis with Emphasis on Genetic Engineering of Bacterial Larvicides for Mosquito Control","authors":"B. Federici","doi":"10.2174/1875414701003010083","DOIUrl":"https://doi.org/10.2174/1875414701003010083","url":null,"abstract":"The insecticidal bacterium, Bacillus thuringiensis, consists of a wide variety of subspecies, most of which are insecticidal for either lepidopteran, coleopteran, or dipteran insect larvae. Subspecies such as B. thuringiensis subsp. kurstaki have been used with remarkable safety for more than forty years to control lepidopteran pests in agriculture and forestry, and over the past thirty years, B. thruingeinsis subsp. israelensis, has proven to be a safe and effective larvicide for controlling mosquito and black fly larvae. Studies of the basic biology of B. thuringiensis have shown that it produces a variety of insecticidal proteins produced during vegetative growth and sporulation that determines its activity for insect species belonging to different orders, with the most important of these being the Cry proteins active against lepidopteran and coleopteran pests, and a combination of Cry and Cyt proteins for mosquitoes and blackflies. After intoxication by these proteins, spores typically germinate and invade larvae, contributing to insect mortality. Whereas strains of many wild type isolates have been commercialized and are now used worldwide, the use of recombinant DNA techniques, i.e., genetic engineering, has been used over the past decade to recombine the proteins of different B. thuringiensis strains with those of B. sphaericus to generate recombinant larvicides as much as ten-fold more toxic than the parental strains. In this chapter, we begin with a general overview of the basic biology of B. thuringiensis and B. sphaericus, then show how studies of its molecular genetics combined with recombinant DNA techniques have been used to generate highly improved bacterial larvicides for control of nuisance and vector mosquitoes.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"83-100"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insecticidal Properties and Chemical Composition of Conyza Aegyptiaca (L.) Oil: Studies on Two Dipterous Insect Pests","authors":"S. A. Mansour, R. I. Mohamed","doi":"10.2174/1875414701305010001","DOIUrl":"https://doi.org/10.2174/1875414701305010001","url":null,"abstract":"The herb, Conyza aegyptiaca L., was subjected to hydrodistillation process to extract the essential oil from the whole dry plant material. Larvae and adult stages of the mosquito, Anopheles pharoensis, and the housefly, Musca domes- tica, were used as test model organisms representing two dipterous insect pests of medical importance. Under standard bioassay test methods, the LC50 of the oil accounted to 37.8 ppm and 0.087 mg/cm 2 against larvae and adults of An. pharoensis, respectively. These toxicity parameters were found to be 71.8 ppm as LC50 and 0.125 µg/insect as LD50 against larvae and adults of M. domestica, respectively. Using GC/MS analysis, we identified 19 compounds constituting ca. 97% of phytochemicals present in the oil, such as monoterpenes, sesquiterpenes and esters. Limonene constituted about 50% of the plant oil (48.79%), followed by (E) - β-Ocimene (8.66%), Germacrene D (7.54%) and β-pinene (6.91%). The occurrence of the other constituents ranged between 0.27% and 5.29%. It was concluded that the potency of C. aegyptiaca oil refers mainly to the presence of limonene. The findings of this study may encourage more research aiming at investi- gation of eco-friendly biopesticides based on botanical resources.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"44 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2013-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Larvicidal Activity of Some Botanical Extracts, Commercial Insecticides and their Binary Mixtures Against the Housefly, Musca Domestica L.","authors":"S. Mansour","doi":"10.2174/1875414701104010001","DOIUrl":"https://doi.org/10.2174/1875414701104010001","url":null,"abstract":"Following preliminary screening of 13 ethanolic plant extracts, belonging to 10 different families, a total of 11 extracts were subjected to detailed toxicity evaluation against the larval stage of the housefly, Musca domestica L. The larvicidal LC50 values were < 100 ppm for Piper nigrum (50.1 ppm), Azadirachta indica (76.9 ppm), Conyza aegyptiaca (77.0 ppm) and Cichorium intybus (96.8 ppm); representing the highest potent extracts among the bioassayed candidates. Punica granatum extract exhibited the lowest toxicity (213.9 ppm). In comparison, commercial insecticides showed superior larvicidal toxicity; accounting to the following LC50 values: 0.029, 0.03, 0.61 and 0.64 ppm for deltamethrin, methomyl, chlorpyrifos and flufenoxuron, respectively. Combining botanical extracts with insecticides, at equitoxic dosages (e.g., LC25 values), induced potentiating effects for a 44 bioassayed mixtures against the housefly larvae. Moreover, mixing the insecticides at LC0 (a concentration level causing no observed mortality) with the LC50 of each of the plant extracts have resulted in 44 paired combinations. Mostly, the \"synergistic factor; S.F.\" ranged between 1.6 1.9; giving rise to high synergistic effects. Specifically, the synergistic effect was much pronounced for mixtures of the insecticide deltamethrin with different botanical extracts. Most of the tested toxicants induced different forms of developmental effects after exposure of 3 larval instars to sublethal concentrations (LC25 ppm). Larvae treated with A. indica, Citrus aurantifolia, Eucalyptus globulus (leaves or fruits), P. granatum, Salix safsaf, Sonchus oleraceus, Zea mays, as well as the insecticides chlorpyrifos, deltamethrin and methomyl failed to develop into adult stages. Morphologically, there were different forms of pupal and adult abnormalities, where the treatments of P. granatum and S. oleraceus caused abnormal pupal size in addition to pupal-adult intermediate. In the resulted Musca domestica adults, the effects were seen as one-winged insects, small size, compressed body and abdomen elongation. Such deformations were attributed to treatments of C. intybus, C. aegyptiaca, Piper nigrum and the IGR flufenoxuron. The overall results of the present investigation reveal the broad-spectrum toxic properties of the tested plant extracts against Musca domestica larvae; which may encourage further research on housefly control in tropics using indigenous plants.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"4 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2011-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Staphylococcal and Streptococcal Superantigens: Basic Biology of Conserved Protein Toxins~!2009-07-13~!2009-09-18~!2010-03-09~!","authors":"Eileen A. Larkin, T. Krakauer, R. Ulrich, B. Stiles","doi":"10.2174/1875414701003020069","DOIUrl":"https://doi.org/10.2174/1875414701003020069","url":null,"abstract":"Staphylococcus aureus and Streptococcus pyogenes are gram-positive bacteria that possess great pathogenic potential in humans, causing numerous maladies such as arthritis, cutaneous infections, endocarditis, enterocolitis, food poisoning, pharyngitis, pneumonia, rheumatic fever, surgical site infections, and toxic shock. These prevalent pathogens produce various virulence factors that include the staphylococcal enterotoxins (SEs), toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxins (SPEs). Minute (picomolar) amounts of these structurally-similar “superantigens” (SAgs) elicit high levels of proinflammatory cytokines and chemokines that can induce fever, hypotension, and lethal shock. In vitro and in vivo models have provided important tools for studying the biological effects of, and potential vaccines plus therapeutics against, these related protein toxins. This review will delve into the known physical and biological properties of the SEs, TSST-1, and SPEs. The reader will hopefully derive a general appreciation of these wonderfully-complex, structurally-similar toxins produced by S. aureus and S. pyogenes.","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"69-81"},"PeriodicalIF":0.0,"publicationDate":"2010-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Host Cell Chaperones in Cellular Uptake of Clostridium Botulinum C2 Toxin~!2009-08-23~!2009-09-18~!2010-03-09~!","authors":"E. Kaiser, H. Barth","doi":"10.2174/1875414701003020048","DOIUrl":"https://doi.org/10.2174/1875414701003020048","url":null,"abstract":"","PeriodicalId":90367,"journal":{"name":"The open toxinology journal","volume":"3 1","pages":"48-52"},"PeriodicalIF":0.0,"publicationDate":"2010-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68119376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}