Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Toxins, Volume 5, Issue 6 (June 2013), Pages 1051-1218

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-9
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle Currencies of Mutualisms: Sources of Alkaloid Genes in Vertically Transmitted Epichloae
Toxins 2013, 5(6), 1064-1088; doi:10.3390/toxins5061064
Received: 1 April 2013 / Revised: 17 May 2013 / Accepted: 29 May 2013 / Published: 6 June 2013
Cited by 28 | PDF Full-text (384 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of [...] Read more.
The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens), which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS), indole-diterpenes (IDT), and lolines (LOL) in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed. Full article
Figures

Open AccessArticle Limited Stability of Microcystins in Oligopeptide Compositions of Microcystis aeruginosa (Cyanobacteria): Implications in the Definition of Chemotypes
Toxins 2013, 5(6), 1089-1104; doi:10.3390/toxins5061089
Received: 30 January 2013 / Revised: 15 May 2013 / Accepted: 28 May 2013 / Published: 6 June 2013
Cited by 5 | PDF Full-text (1065 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The occurrence of diverse oligopeptides in cyanobacteria, including the cyanotoxins microcystins, has been recently used to classify individual clones into sub-specific oligopeptide chemotypes, whose composition and dynamics modulate microcystin concentrations in cyanobacterial blooms. Cyanobacterial chemotyping allows the study of the ecology of [...] Read more.
The occurrence of diverse oligopeptides in cyanobacteria, including the cyanotoxins microcystins, has been recently used to classify individual clones into sub-specific oligopeptide chemotypes, whose composition and dynamics modulate microcystin concentrations in cyanobacterial blooms. Cyanobacterial chemotyping allows the study of the ecology of chemotypical subpopulations, which have been shown to possess dissimilar ecological traits. However, the stability of chemotypes under changing abiotic conditions is usually assumed and has not been assessed in detail. We monitored oligopeptide patterns of three strains of Microcystis aeruginosa under different nutrient and light conditions. MALDI-TOF MS revealed alterations in the microcystins signatures under N and P poor conditions and high light intensities (150 and 400 μmol photons m−2s−1). Variations in the general oligopeptide composition were caused by a gradual disappearance of microcystins with low relative intensity signals from the fingerprint. The extent of such variations seems to be closely related to physiological stress caused by treatments. Under identical clonal compositions, alterations in the oligopeptide fingerprint may be misinterpreted as apparent shifts in chemotype succession. We discuss the nature of such variations, as well as the consequent implications in the use of cyanobacterial chemotyping in studies at the subpopulation level and propose new guidance for the definition of chemotypes as a consistent subpopulation marker. Full article
(This article belongs to the Special Issue Cyanotoxins)
Open AccessArticle Reduction of Streptolysin O (SLO) Pore-Forming Activity Enhances Inflammasome Activation
Toxins 2013, 5(6), 1105-1118; doi:10.3390/toxins5061105
Received: 1 March 2013 / Revised: 29 May 2013 / Accepted: 3 June 2013 / Published: 6 June 2013
Cited by 7 | PDF Full-text (894 KB) | HTML Full-text | XML Full-text
Abstract
Pore-forming toxins are utilized by bacterial and mammalian cells to exert pathogenic effects and induce cell lysis. In addition to rapid plasma membrane repair, macrophages respond to pore-forming toxins through activation of the NLRP3 inflammasome, leading to IL-1β secretion and pyroptosis. The [...] Read more.
Pore-forming toxins are utilized by bacterial and mammalian cells to exert pathogenic effects and induce cell lysis. In addition to rapid plasma membrane repair, macrophages respond to pore-forming toxins through activation of the NLRP3 inflammasome, leading to IL-1β secretion and pyroptosis. The structural determinants of pore-forming toxins required for NLRP3 activation remain unknown. Here, we demonstrate using streptolysin O (SLO) that pore-formation controls IL-1β secretion and direct toxicity. An SLO mutant incapable of pore-formation did not promote direct killing, pyroptosis or IL-1β production. This indicated that pore formation is necessary for inflammasome activation. However, a partially active mutant (SLO N402C) that was less toxic to macrophages than wild-type SLO, even at concentrations that directly lysed an equivalent number of red blood cells, enhanced IL-1β production but did not alter pyroptosis. This suggests that direct lysis may attenuate immune responses by preventing macrophages from successfully repairing their plasma membrane and elaborating more robust cytokine production. We suggest that mutagenesis of pore-forming toxins represents a strategy to enhance adjuvant activity. Full article
(This article belongs to the Special Issue Pore-Forming Toxins)
Open AccessArticle Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
Toxins 2013, 5(6), 1167-1179; doi:10.3390/toxins5061167
Received: 17 May 2013 / Revised: 28 May 2013 / Accepted: 4 June 2013 / Published: 14 June 2013
PDF Full-text (647 KB) | HTML Full-text | XML Full-text
Abstract
Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic [...] Read more.
Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic cargo domains into the host cytosol. Subtle variations in the N-terminal ~500 amino acids of CNFs and PMT could allow for selective recognition of cellular receptors and thus, selective target cell specificity. Through studies with cellular inhibitors, we have identified an additional novel function for this region in modulating responses of these toxin proteins to changes in pH during intoxication and delivery of the catalytic cargo domain into the cytosol. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessArticle Computational Design of Peptide Ligands for Ochratoxin A
Toxins 2013, 5(6), 1202-1218; doi:10.3390/toxins5061202
Received: 2 May 2013 / Revised: 13 June 2013 / Accepted: 13 June 2013 / Published: 21 June 2013
Cited by 8 | PDF Full-text (782 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA). A virtual library of 20 natural amino acids was used as building blocks to design [...] Read more.
In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA). A virtual library of 20 natural amino acids was used as building blocks to design a short peptide library against ochratoxin A template using the de novo design program, LeapFrog, and the dynamic modelling software, FlexiDock. Peptide sequences were ranked according to calculated binding scores in their capacity to bind to ochratoxin A. Two high scoring peptides with the sequences N'-Cys-Ser-Ile-Val-Glu-Asp-Gly-Lys-C' (octapeptide) and N'-Gly-Pro-Ala-Gly-Ile-Asp-Gly-Pro-Ala-Gly-Ile-Arg-Cys-C' (13-mer) were selected for synthesis from the resulting database. These synthesized peptides were characterized using a microtitre plate-based binding assay and a surface plasmon resonance biosensor (Biacore 3000). The binding assay confirmed that both de novo designed peptides did bind to ochratoxin A in vitro. SPR analysis confirmed that the peptides bind to ochratoxin A, with calculated KD values of ~15.7 μM (13-mer) and ~11.8 μM (octamer). The affinity of the peptides corresponds well with the molecular modelling results, as the 13-mer peptide affinity is about 1.3-times weaker than the octapeptide; this is in accordance with the binding energy values modelled by FlexiDock. This work illustrates the potential of using computational modelling to design a peptide sequence that exhibits in vitro binding affinity for a small molecular weight toxin. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)

Review

Jump to: Research, Other

Open AccessReview The Pore-Forming Haemolysins of Bacillus Cereus: A Review
Toxins 2013, 5(6), 1119-1139; doi:10.3390/toxins5061119
Received: 28 February 2013 / Revised: 22 May 2013 / Accepted: 24 May 2013 / Published: 7 June 2013
Cited by 18 | PDF Full-text (855 KB) | HTML Full-text | XML Full-text
Abstract
The Bacillus cereus sensu lato group contains diverse Gram-positive spore-forming bacteria that can cause gastrointestinal diseases and severe eye infections in humans. They have also been incriminated in a multitude of other severe, and frequently fatal, clinical infections, such as osteomyelitis, septicaemia, [...] Read more.
The Bacillus cereus sensu lato group contains diverse Gram-positive spore-forming bacteria that can cause gastrointestinal diseases and severe eye infections in humans. They have also been incriminated in a multitude of other severe, and frequently fatal, clinical infections, such as osteomyelitis, septicaemia, pneumonia, liver abscess and meningitis, particularly in immuno-compromised patients and preterm neonates. The pathogenic properties of this organism are mediated by the synergistic effects of a number of virulence products that promote intestinal cell destruction and/or resistance to the host immune system. This review focuses on the pore-forming haemolysins produced by B. cereus: haemolysin I (cereolysin O), haemolysin II, haemolysin III and haemolysin IV (CytK). Haemolysin I belongs to the cholesterol-dependent cytolysin (CDC) family whose best known members are listeriolysin O and perfringolysin O, produced by L. monocytogenes and C. perfringens respectively. HlyII and CytK are oligomeric ß-barrel pore-forming toxins related to the α-toxin of S. aureus or the ß-toxin of C. perfringens. The structure of haemolysin III, the least characterized haemolytic toxin from the B. cereus, group has not yet been determined. Full article
(This article belongs to the Special Issue Pore-Forming Toxins)
Open AccessReview Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue
Toxins 2013, 5(6), 1140-1166; doi:10.3390/toxins5061140
Received: 27 April 2013 / Revised: 28 May 2013 / Accepted: 3 June 2013 / Published: 13 June 2013
Cited by 95 | PDF Full-text (645 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small β-barrel pore-forming toxin α-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of [...] Read more.
Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small β-barrel pore-forming toxin α-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of α-hemolysin action as nucleated cells also exhibited distinct responses to intoxication. The hemolysin, most aptly referred to as α-toxin based on its broad range of cellular specificity, has long been recognized as an important cause of injury in the context of both skin necrosis and lethal infection. The recent identification of ADAM10 as a cellular receptor for α-toxin has provided keen insight on the biology of toxin action during disease pathogenesis, demonstrating the molecular mechanisms by which the toxin causes tissue barrier disruption at host interfaces lined by epithelial or endothelial cells. This review highlights both the historical studies that laid the groundwork for nearly a century of research on α-toxin and key findings on the structural and functional biology of the toxin, in addition to discussing emerging observations that have significantly expanded our understanding of this toxin in S. aureus disease. The identification of ADAM10 as a proteinaceous receptor for the toxin not only provides a greater appreciation of truths uncovered by many historic studies, but now affords the opportunity to more extensively probe and understand the role of α-toxin in modulation of the complex interaction of S. aureus with its human host. Full article
(This article belongs to the Special Issue Pore-Forming Toxins)
Open AccessReview Heparin-Binding Epidermal Growth Factor-like Growth Factor/Diphtheria Toxin Receptor in Normal and Neoplastic Hematopoiesis
Toxins 2013, 5(6), 1180-1201; doi:10.3390/toxins5061180
Received: 9 May 2013 / Revised: 5 June 2013 / Accepted: 13 June 2013 / Published: 18 June 2013
Cited by 4 | PDF Full-text (927 KB) | HTML Full-text | XML Full-text
Abstract
Heparin-binding EGF-like growth factor (HB-EGF) belongs to the EGF family of growth factors. It is biologically active either as a molecule anchored to the membrane or as a soluble form released by proteolytic cleavage of the extracellular domain. HB-EGF is involved in [...] Read more.
Heparin-binding EGF-like growth factor (HB-EGF) belongs to the EGF family of growth factors. It is biologically active either as a molecule anchored to the membrane or as a soluble form released by proteolytic cleavage of the extracellular domain. HB-EGF is involved in relevant physiological and pathological processes spanning from proliferation and apoptosis to morphogenesis. We outline here the main activities of HB-EGF in connection with normal or neoplastic differentiative or proliferative events taking place primitively in the hematopoietic microenvironment. Full article
(This article belongs to the Special Issue Diphtheria Toxin)

Other

Jump to: Research, Review

Open AccessCase Report Treatment of Cyanobacterial (Microcystin) Toxicosis Using Oral Cholestyramine: Case Report of a Dog from Montana
Toxins 2013, 5(6), 1051-1063; doi:10.3390/toxins5061051
Received: 16 April 2013 / Revised: 6 May 2013 / Accepted: 15 May 2013 / Published: 29 May 2013
Cited by 9 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
A two and a half year old spayed female Miniature Australian Shepherd presented to a Montana veterinary clinic with acute onset of anorexia, vomiting and depression. Two days prior, the dog was exposed to an algal bloom in a community lake. Within [...] Read more.
A two and a half year old spayed female Miniature Australian Shepherd presented to a Montana veterinary clinic with acute onset of anorexia, vomiting and depression. Two days prior, the dog was exposed to an algal bloom in a community lake. Within h, the animal became lethargic and anorexic, and progressed to severe depression and vomiting. A complete blood count and serum chemistry panel suggested acute hepatitis, and a severe coagulopathy was noted clinically. Feces from the affected dog were positive for the cyanobacterial biotoxin, microcystin-LA (217 ppb). The dog was hospitalized for eight days. Supportive therapy consisted of fluids, mucosal protectants, vitamins, antibiotics, and nutritional supplements. On day five of hospitalization, a bile acid sequestrant, cholestyramine, was administered orally. Rapid clinical improvement was noted within 48 h of initiating oral cholestyramine therapy. At 17 days post-exposure the dog was clinically normal, and remained clinically normal at re-check, one year post-exposure. To our knowledge, this is the first report of successful treatment of canine cyanobacterial (microcystin) toxicosis. Untreated microcystin intoxication is commonly fatal, and can result in significant liver damage in surviving animals. The clinical success of this case suggests that oral administration of cholestyramine, in combination with supportive therapy, could significantly reduce hospitalization time, cost-of-care and mortality for microcystin-poisoned animals Full article
(This article belongs to the Special Issue Cyanotoxins)

Journal Contact

MDPI AG
Toxins Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
toxins@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Toxins
Back to Top