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Toxins, Volume 5, Issue 5 (May 2013), Pages 865-1050

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Research

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Open AccessArticle An Ultrasensitive Electrochemiluminescent Immunoassay for Aflatoxin M1 in Milk, Based on Extraction by Magnetic Graphene and Detection by Antibody-Labeled CdTe Quantumn Dots-Carbon Nanotubes Nanocomposite
Toxins 2013, 5(5), 865-883; doi:10.3390/toxins5050865
Received: 20 February 2013 / Revised: 15 April 2013 / Accepted: 16 April 2013 / Published: 29 April 2013
Cited by 15 | PDF Full-text (2031 KB) | HTML Full-text | XML Full-text
Abstract
An ultrasensitive electrochemiluminescent immunoassay (ECLIA) for aflatoxins M1 (ATM1) in milk using magnetic Fe3O4-graphene oxides (Fe-GO) as the absorbent and antibody-labeled cadmium telluride quantum dots (CdTe QDs) as the signal tag is presented. Firstly, Fe3O4 [...] Read more.
An ultrasensitive electrochemiluminescent immunoassay (ECLIA) for aflatoxins M1 (ATM1) in milk using magnetic Fe3O4-graphene oxides (Fe-GO) as the absorbent and antibody-labeled cadmium telluride quantum dots (CdTe QDs) as the signal tag is presented. Firstly, Fe3O4 nanoparticles were immobilized on GO to fabricate the magnetic nanocomposites, which were used as absorbent to ATM1. Secondly, aflatoxin M1 antibody (primary antibody, ATM1 Ab1), was attached to the surface of the CdTe QDs-carbon nanotubes nanocomposite to form the signal tag (ATM1 Ab1/CdTe-CNT). The above materials were characterized. The optimal experimental conditions were obtained. Thirdly, Fe-GO was employed for extraction of ATM1 in milk. Results indicated that it can adsorb ATM1 efficiently and selectively within a large extent of pH from 3.0 to 8.0. Adsorption processes reached 95% of the equilibrium within 10 min. Lastly, the ATM1 with a serial of concentrations absorbed on Fe-GO was conjugated with ATM1 Ab1/CdTe-CNT signal tag based on sandwich immunoassay. The immunocomplex can emit a strong ECL signal whose intensity depended linearly on the logarithm of ATM1 concentration from 1.0 to 1.0 × 105 pg/mL, with the detection limit (LOD) of 0.3 pg/mL (S/N = 3). The method was more sensitive for ATM1 detection compared to the ELISA method. Finally, ten samples of milk were tested based on the immunoassay. The method is fast and requires very little sample preparation, which was suitable for high-throughput screening of mycotoxins in food. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
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Open AccessArticle Assessment of Aflatoxin Contamination of Maize, Peanut Meal and Poultry Feed Mixtures from Different Agroecological Zones in Cameroon
Toxins 2013, 5(5), 884-894; doi:10.3390/toxins5050884
Received: 4 March 2013 / Revised: 11 April 2013 / Accepted: 12 April 2013 / Published: 29 April 2013
Cited by 10 | PDF Full-text (332 KB) | HTML Full-text | XML Full-text
Abstract
Mycotoxins affect poultry production by being present in the feed and directly causing a negative impact on bird performance. Carry-over rates of mycotoxins in animal products are, in general, small (except for aflatoxins in milk and eggs) therefore representing a small source [...] Read more.
Mycotoxins affect poultry production by being present in the feed and directly causing a negative impact on bird performance. Carry-over rates of mycotoxins in animal products are, in general, small (except for aflatoxins in milk and eggs) therefore representing a small source of mycotoxins for humans. Mycotoxins present directly in human food represent a much higher risk. The contamination of poultry feed by aflatoxins was determined as a first assessment of this risk in Cameroon. A total of 201 samples of maize, peanut meal, broiler and layer feeds were collected directly at poultry farms, poultry production sites and poultry feed dealers in three agroecological zones (AEZs) of Cameroon and analyzed for moisture content and aflatoxin levels. The results indicate that the mean of the moisture content of maize (14.1%) was significantly (P < 0.05) higher than all other commodities (10.0%–12.7%). Approximately 9% of maize samples were positive for aflatoxin, with concentrations overall ranging from <2 to 42 µg/kg. Most of the samples of peanut meal (100%), broiler (93.3%) and layer feeds (83.0%) were positive with concentrations of positive samples ranging from 39 to 950 µg/kg for peanut meal, 2 to 52 µg/kg for broiler feed and 2 to 23 µg/kg for layer feed. The aflatoxin content of layer feed did not vary by AEZ, while the highest (16.8 µg/kg) and the lowest (8.2 µg/kg) aflatoxin content of broiler feed were respectively recorded in Western High Plateau and in Rainforest agroecological zones. These results suggest that peanut meal is likely to be a high risk feed, and further investigation is needed to guide promotion of safe feeds for poultry in Cameroon. Full article
Open AccessArticle Effects of Clostridium difficile Toxin A and B on Human T Lymphocyte Migration
Toxins 2013, 5(5), 926-938; doi:10.3390/toxins5050926
Received: 12 January 2013 / Revised: 27 March 2013 / Accepted: 23 April 2013 / Published: 3 May 2013
Cited by 4 | PDF Full-text (1621 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial products such as toxins can interfere with a variety of cellular processes, leading to severe human diseases. Clostridium difficile toxins, TcdA and TcdB are the primary contributing factors to the pathogenesis of C. difficile-associated diseases (CDAD). While the mechanisms for [...] Read more.
Bacterial products such as toxins can interfere with a variety of cellular processes, leading to severe human diseases. Clostridium difficile toxins, TcdA and TcdB are the primary contributing factors to the pathogenesis of C. difficile-associated diseases (CDAD). While the mechanisms for TcdA and TcdB mediated cellular responses are complex, it has been shown that these toxins can alter chemotactic responses of neutrophils and intestinal epithelial cells leading to innate immune responses and tissue damages. The effects of C. difficile toxins on the migration and trafficking of other leukocyte subsets, such as T lymphocytes, are not clear and may have potential implications for adaptive immunity. We investigated here the direct and indirect effects of TcdA and TcdB on the migration of human blood T cells using conventional cell migration assays and microfluidic devices. It has been found that, although both toxins decrease T cell motility, only TcdA but not TcdB decreases T cell chemotaxis. Similar effects are observed in T cell migration toward the TcdA- or TcdB-treated human epithelial cells. Our study demonstrated the primary role of TcdA (compared to TcdB) in altering T cell migration and chemotaxis, suggesting possible implications for C. difficile toxin mediated adaptive immune responses in CDAD. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
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Open AccessArticle Sedimentation Patterns of Toxin-Producing Microcystis Morphospecies in Freshwater Reservoirs
Toxins 2013, 5(5), 939-957; doi:10.3390/toxins5050939
Received: 21 February 2013 / Revised: 16 April 2013 / Accepted: 22 April 2013 / Published: 3 May 2013
Cited by 5 | PDF Full-text (439 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Understanding the annual cycle of Microcystis is essential for managing the blooms of this toxic cyanobacterium. The current work investigated the sedimentation of microcystin-producing Microcystis spp. in three reservoirs from Central Spain during the summer and autumn of 2006 and 2007. We [...] Read more.
Understanding the annual cycle of Microcystis is essential for managing the blooms of this toxic cyanobacterium. The current work investigated the sedimentation of microcystin-producing Microcystis spp. in three reservoirs from Central Spain during the summer and autumn of 2006 and 2007. We confirmed remarkable settling fluxes during and after blooms ranging 106–109 cells m−2 d−1, which might represent 0.1%–7.6% of the organic matter settled. A comprehensive analysis of the Valmayor reservoir showed average Microcystis settling rates (0.04 d−1) and velocities (0.7 m d−1) that resembled toxin settling in the same reservoir and were above most reported elsewhere. M. aeruginosa settling rate was significantly higher than that of M. novacekii and M. flos-aquae. Despite the fact that colony sizes did not differ significantly in their average settling rates, we observed extremely high and low rates in large colonies (>5000 cells) and a greater influence of a drop in temperature on small colonies (<1000 cells). We found a 4–14 fold decrease in microcystin cell quota in settling Microcystis of the Cogotas and Valmayor reservoirs compared with pelagic populations, and the hypothetical causes of this are discussed. Our study provides novel data on Microcystis settling patterns in Mediterranean Europe and highlights the need for including morphological, chemotypical and physiological criteria to address the sedimentation of complex Microcystis populations. Full article
(This article belongs to the Special Issue Cyanotoxins)
Open AccessArticle BiP Negatively Affects Ricin Transport
Toxins 2013, 5(5), 969-982; doi:10.3390/toxins5050969
Received: 22 March 2013 / Revised: 2 May 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
Cited by 6 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text
Abstract
The AB plant toxin ricin binds both glycoproteins and glycolipids at the cell surface via its B subunit. After binding, ricin is endocytosed and then transported retrogradely through the Golgi to the endoplasmic reticulum (ER). In the ER, the A subunit is [...] Read more.
The AB plant toxin ricin binds both glycoproteins and glycolipids at the cell surface via its B subunit. After binding, ricin is endocytosed and then transported retrogradely through the Golgi to the endoplasmic reticulum (ER). In the ER, the A subunit is retrotranslocated to the cytosol in a chaperone-dependent process, which is not fully explored. Recently two separate siRNA screens have demonstrated that ER chaperones have implications for ricin toxicity. ER associated degradation (ERAD) involves translocation of misfolded proteins from ER to cytosol and it is conceivable that protein toxins exploit this pathway. The ER chaperone BiP is an important ER regulator and has been implicated in toxicity mediated by cholera and Shiga toxin. In this study, we have investigated the role of BiP in ricin translocation to the cytosol. We first show that overexpression of BiP inhibited ricin translocation and protected cells against the toxin. Furthermore, shRNA-mediated depletion of BiP enhanced toxin translocation resulting in increased cytotoxicity. BiP-dependent inhibition of ricin toxicity was independent of ER stress. Our findings suggest that in contrast to what was shown with the Shiga toxin, the presence of BiP does not facilitate, but rather inhibits the entry of ricin into the cytosol. Full article
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Open AccessArticle Feasibility of Video Clip Analysis on Effect of Botulinum Toxin-A Injection for Post-Stroke Upper Limb Spasticity
Toxins 2013, 5(5), 983-991; doi:10.3390/toxins5050983
Received: 6 January 2013 / Revised: 25 March 2013 / Accepted: 24 April 2013 / Published: 10 May 2013
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Abstract
Existing functional evaluation tools do not accurately reveal the improved function following botulinum toxin A (BTX-A) injection for post-stroke upper limb spasticity. With the aim of developing an alternate method of measuring functional improvement following BTX-A injection, this study tested the feasibility, [...] Read more.
Existing functional evaluation tools do not accurately reveal the improved function following botulinum toxin A (BTX-A) injection for post-stroke upper limb spasticity. With the aim of developing an alternate method of measuring functional improvement following BTX-A injection, this study tested the feasibility, validity and reliability of video clip analysis performed by the clinicians. Seventy-nine patients administered BTX-A due to post-stroke upper limb spasticity, were retrospectively evaluated using video clip analysis. Pre- and post-injection video clips recorded at 1-month intervals were randomly allocated and sent to three blinded physician evaluators who were asked to choose the one that seemed more improved in terms of hand motion and associated upper limb reaction during gait. The three physicians chose the post-injection video clip as depicting improved hand motion (82.3%, 79.7%, and 72.2%) and associated upper limb reaction during gait (73.4%, 70.9%, and 70.9%). Kappa and intraclass correlation coefficient as a measure of interrater reliability among the three physicians was 0.86 and 0.79 for the hand, and 0.92 and 0.92 for associated upper limb reaction during gait, respectively. The percent overall agreement of the physicians was 78.1% and 71.7% for hand function and associated upper limb reaction, respectively. Retrospective pre- and post-BTX-A injection video clip analyses is a clinically feasible alternative method to evaluate the improvement following BTX-A injection for post-stroke upper limb spasticity, especially in busy clinical practice setting. Full article
Open AccessArticle Variations in the Microcystin Content of Different Fish Species Collected from a Eutrophic Lake
Toxins 2013, 5(5), 992-1009; doi:10.3390/toxins5050992
Received: 2 April 2013 / Revised: 30 April 2013 / Accepted: 14 May 2013 / Published: 15 May 2013
Cited by 12 | PDF Full-text (375 KB) | HTML Full-text | XML Full-text
Abstract
Microcystins produced from cyanobacteria can accumulate in fish tissues. Liquid chromatography coupled with tandem quadrupole mass spectrometry (LC-MS/MS) is an attractive alternative to immunoassays for the determination of low concentrations of microcystins in tissues. Fish taken from Grand Lake St. Marys, a [...] Read more.
Microcystins produced from cyanobacteria can accumulate in fish tissues. Liquid chromatography coupled with tandem quadrupole mass spectrometry (LC-MS/MS) is an attractive alternative to immunoassays for the determination of low concentrations of microcystins in tissues. Fish taken from Grand Lake St. Marys, a eutrophic lake in Ohio, USA, were analyzed for microcystin-LR in their fillets using LC-MS/MS. Of 129 fish tested for microcystins, only black crappie (Pomoxis nigromaculatus) and common carp (Cyprinus carpio) tested positive for microcystin-LR. Less than 10% of Pomoxis and 7% of Cyprinus samples contained measurable levels of microcystin-LR. Statistical analysis yielded a p-value of 0.07 between Pomoxis and the pooled results of the other four fish species. However, this comparison was complicated by the large difference in sample size between species. Further sampling in Grand Lake St. Marys for microcystin-LR would help determine if microcystin-LR exposure occurs through foodweb transfer. Full article
(This article belongs to the Special Issue Cyanotoxins)
Open AccessCommunication Estimated Dietary Exposure to Mycotoxins after Taking into Account the Cooking of Staple Foods in Japan
Toxins 2013, 5(5), 1032-1042; doi:10.3390/toxins5051032
Received: 19 February 2013 / Revised: 25 March 2013 / Accepted: 2 May 2013 / Published: 21 May 2013
Cited by 5 | PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
Mycotoxins are commonly present in cereal grains and are not completely destroyed during their cooking and processing. When mycotoxins contaminate staple foods, the risk for exposure becomes serious. In East Asia, including Japan, rice is consumed as a staple food, and with [...] Read more.
Mycotoxins are commonly present in cereal grains and are not completely destroyed during their cooking and processing. When mycotoxins contaminate staple foods, the risk for exposure becomes serious. In East Asia, including Japan, rice is consumed as a staple food, and with the increasingly Westernized lifestyle, the consumption of wheat has increased. The mycotoxins commonly associated with rice and wheat are total aflatoxin (AFL) and ochratoxin A (OTA), respectively. This study examined the retention of AFL and OTA during the cooking of rice and pasta. AFL was retained at 83%–89% the initial level after the cooking of steamed rice. In pasta noodles, more than 60% of the OTA was retained. These results show that AFL and OTA are relatively stable during the cooking process, suggesting that a major reduction in the exposure to these mycotoxins cannot be expected to occur by cooking rice and pasta. The estimated exposure assessment at the high consumer level (95th percentile) and the mycotoxin contamination level determined by taking into account these reductions in the present study should be useful for the establishment of practical regulations for mycotoxins in staple foods. Full article
Open AccessArticle Venomous Secretions from Marine Snails of the Terebridae Family Target Acetylcholine Receptors
Toxins 2013, 5(5), 1043-1050; doi:10.3390/toxins5051043
Received: 5 December 2012 / Revised: 13 May 2013 / Accepted: 13 May 2013 / Published: 21 May 2013
Cited by 5 | PDF Full-text (625 KB) | HTML Full-text | XML Full-text
Abstract
Venoms from cone snails (Conidae) have been extensively studied during the last decades, but those from other members of the suborder Toxoglossa, such as of Terebridae and Turridae superfamilies attracted less interest so far. Here, we report the effects of venom and [...] Read more.
Venoms from cone snails (Conidae) have been extensively studied during the last decades, but those from other members of the suborder Toxoglossa, such as of Terebridae and Turridae superfamilies attracted less interest so far. Here, we report the effects of venom and gland extracts from three species of the superfamily Terebridae. By 2-electrode voltage-clamp technique the gland extracts were tested on Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) of rat neuronal (α3β2, α3β4, α4β2, α4β4, α7) and muscle subtypes (α1β1γδ), and expressing potassium (Kv1.2 and Kv1.3) and sodium channels (Nav1.2, 1.3, 1.4, 1.6). The extracts were shown to exhibit remarkably high inhibitory activities on almost all nAChRs tested, in particular on the α7 subtype suggesting the presence of peptides of the A-superfamily from the venom of Conus species. In contrast, no effects on the potassium and sodium channels tested were observed. The venoms of terebrid snails may offer an additional source of novel biologically active peptides. Full article
(This article belongs to the Special Issue Toxins from Aquatic Organisms)
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Review

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Open AccessReview Structure, Function, and Biology of the Enterococcus faecalis Cytolysin
Toxins 2013, 5(5), 895-911; doi:10.3390/toxins5050895
Received: 25 March 2013 / Revised: 22 April 2013 / Accepted: 23 April 2013 / Published: 29 April 2013
Cited by 19 | PDF Full-text (566 KB) | HTML Full-text | XML Full-text
Abstract
Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, [...] Read more.
Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, called cytolysin, which lyses both bacterial and eukaryotic cells in response to quorum signals. Originally described in the 1930s, the cytolysin is a member of a large class of lanthionine-containing bacteriocins produced by Gram-positive bacteria. While the cytolysin shares some core features with other lantibiotics, it possesses unique characteristics as well. The current understanding of cytolysin biosynthesis, structure/function relationships, and contribution to the biology of E. faecalis are reviewed, and opportunities for using emerging technologies to advance this understanding are discussed. Full article
(This article belongs to the Special Issue Pore-Forming Toxins)
Open AccessReview The Toxicological Impacts of the Fusarium Mycotoxin, Deoxynivalenol, in Poultry Flocks with Special Reference to Immunotoxicity
Toxins 2013, 5(5), 912-925; doi:10.3390/toxins5050912
Received: 18 February 2013 / Revised: 19 April 2013 / Accepted: 19 April 2013 / Published: 29 April 2013
Cited by 14 | PDF Full-text (216 KB) | HTML Full-text | XML Full-text
Abstract
Deoxynivalenol (DON) is a common Fusarium toxin in poultry feed. Chickens are more resistant to the adverse impacts of deoxynivalenol (DON) compared to other species. In general, the acute form of DON mycotoxicosis rarely occurs in poultry flocks under normal conditions. However, [...] Read more.
Deoxynivalenol (DON) is a common Fusarium toxin in poultry feed. Chickens are more resistant to the adverse impacts of deoxynivalenol (DON) compared to other species. In general, the acute form of DON mycotoxicosis rarely occurs in poultry flocks under normal conditions. However, if diets contain low levels of DON (less than 5 mg DON/kg diet), lower productivity, impaired immunity and higher susceptibility to infectious diseases can occur. The molecular mechanism of action of DON has not been completely understood. A significant influence of DON in chickens is the impairment of immunological functions. It was known that low doses of DON elevated the serum IgA levels and affected both cell-mediated and humoral immunity in animals. DON is shown to suppress the antibody response to infectious bronchitis vaccine (IBV) and to Newcastle disease virus (NDV) in broilers (10 mg DON/kg feed) and laying hens (3.5 to 14 mg of DON/kg feed), respectively. Moreover, DON (10 mg DON/kg feed) decreased tumor necrosis factor alpha (TNF-α) in the plasma of broilers. DON can severely affect the immune system and, due to its negative impact on performance and productivity, can eventually result in high economic losses to poultry producers. The present review highlights the impacts of DON intoxication on cell mediated immunity, humoral immunity, gut immunity, immune organs and pro-inflammatory cytokines in chickens. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview Sialorrhea: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins
Toxins 2013, 5(5), 1010-1031; doi:10.3390/toxins5051010
Received: 1 March 2013 / Revised: 9 April 2013 / Accepted: 24 April 2013 / Published: 21 May 2013
Cited by 17 | PDF Full-text (774 KB) | HTML Full-text | XML Full-text
Abstract
Sialorrhea or excessive drooling is a major issue in children with cerebral palsy and adults with neurodegenerative disorders. In this review, we describe the clinical features, anatomy and physiology of sialorrhea, as well as a review of the world literature on medical [...] Read more.
Sialorrhea or excessive drooling is a major issue in children with cerebral palsy and adults with neurodegenerative disorders. In this review, we describe the clinical features, anatomy and physiology of sialorrhea, as well as a review of the world literature on medical treatment using Yale University’s search engine; including but not limited to Medline and Erasmus. Level of drug efficacy is defined according to the guidelines of American Academy of Neurology. Current medical management is unsatisfactory. Topical agents (scopolamine and tropicamide) and oral agents (glyccopyrolate) combined render a level B evidence (probably effective); however, this treatment is associated with troublesome side effects. Double-blind and placebo-controlled studies of botulinum toxin (BoNT) provide a level A evidence for type B (two class I studies; effective and established) and both overall and individual B level of evidence for OnabotulinumtoxinA (A/Ona) and AbobotulinumtoxinA (A/Abo); these are probably effective. For IncobotulinumtoxinA (A/Inco), the level of evidence is U (insufficient) due to lack of blinded studies. Side effects are uncommon; transient and comparable between the two types of toxin. A clinical note at the end of this review comments on fine clinical points. Administration of BoNTs into salivary glands is currently the most effective way of treating sialorrhea. Full article
(This article belongs to the Special Issue Neurotoxins: Health Threats and Biological Tools)

Other

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Open AccessBrief Report Insights into Diphthamide, Key Diphtheria Toxin Effector
Toxins 2013, 5(5), 958-968; doi:10.3390/toxins5050958
Received: 14 March 2013 / Revised: 17 April 2013 / Accepted: 26 April 2013 / Published: 3 May 2013
Cited by 7 | PDF Full-text (1001 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Diphtheria toxin (DT) inhibits eukaryotic translation elongation factor 2 (eEF2) by ADP-ribosylation in a fashion that requires diphthamide, a modified histidine residue on eEF2. In budding yeast, diphthamide formation involves seven genes, DPH1-DPH7. In an effort to further study diphthamide synthesis [...] Read more.
Diphtheria toxin (DT) inhibits eukaryotic translation elongation factor 2 (eEF2) by ADP-ribosylation in a fashion that requires diphthamide, a modified histidine residue on eEF2. In budding yeast, diphthamide formation involves seven genes, DPH1-DPH7. In an effort to further study diphthamide synthesis and interrelation among the Dph proteins, we found, by expression in E. coli and co-immune precipitation in yeast, that Dph1 and Dph2 interact and that they form a complex with Dph3. Protein-protein interaction mapping shows that Dph1-Dph3 complex formation can be dissected by progressive DPH1 gene truncations. This identifies N- and C-terminal domains on Dph1 that are crucial for diphthamide synthesis, DT action and cytotoxicity of sordarin, another microbial eEF2 inhibitor. Intriguingly, dph1 truncation mutants are sensitive to overexpression of DPH5, the gene necessary to synthesize diphthine from the first diphthamide pathway intermediate produced by Dph1-Dph3. This is in stark contrast to dph6 mutants, which also lack the ability to form diphthamide but are resistant to growth inhibition by excess Dph5 levels. As judged from site-specific mutagenesis, the amidation reaction itself relies on a conserved ATP binding domain in Dph6 that, when altered, blocks diphthamide formation and confers resistance to eEF2 inhibition by sordarin. Full article
(This article belongs to the Special Issue Diphtheria Toxin)
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