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https://www.readbyqxmd.com/read/28210460/cloning-and-expression-of-clostridium-perfringens-type-d-vaccine-strain-epsilon-toxin-gene-in-e-coli-as-a-recombinant-vaccine-candidate
#1
Parastoo Aziminia, Reza Pilehchian-Langroudi, Kasra Esmaeilnia
BACKGROUND AND OBJECTIVES: Clostridium perfringens, a Gram-positive obligate anaerobic bacterium, is able to form resistant spores which are widely distributed in the environment. C. perfringens is subdivided into five types A to E based on its four major alpha, beta, epsilon and iota toxins. The aim of the present study was cloning and expression of C. perfringens type D vaccine strain epsilon toxin gene. MATERIALS AND METHODS: Genomic DNA was extracted and the epsilon toxin gene was amplified using Pfu DNA polymerase...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28209480/thermal-stabilization-of-anti-%C3%AE-cobratoxin-single-domain-antibodies
#2
George P Anderson, Jessica H Liu, Dan Zabetakis, Jinny L Liu, Ellen R Goldman
There is an unmet need for snake antivenoms that can be stored ready to use near the point of care. To address that need we have taken two anti-α-cobratoxin single domain antibodies and increased their thermal stability to improve their ambient temperature shelf-life. The anti-α-cobratoxin single domain antibodies C2 and C20 were first isolated, and demonstrated to be toxin neutralizing by Richard et al., 2013 (Richard, G., Meyers, A.J., McLean, M.D., Arbabi-Ghahroudi, M., MacKenzie, R., Hall, J.C., 2013...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28209477/characterizing-the-biological-and-biochemical-profile-of-six-different-scorpion-venoms-from-the-buthidae-and-scorpionidae-family
#3
Sebastian Estrada-Gómez, Lyz Gomez-Rave, Leidy Vargas-Muñoz, Arie van der Meijden
The objective of this study was to characterize a selection of six different scorpion venoms using biological and biochemical methods, including a preliminary MS/MS and a post-translational modifications analysis. Despite the diversity of scorpion species of medical importance in Africa and Colombia, the venoms of these arachnids have been poorly studied in these two regions. We report the biochemical, electrophoretic, chromatographic profile, internal peptide sequences with a post-translational modification report, and a preliminary antitumor activity of five different scorpions of the Buthidae family, Androctonus amoreuxi, Babycurus jacksoni, Grosphus grandidieri, Hottentotta gentili and Tityus fuhrmanni, and one of the Scorpionidae family Pandinus imperator...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28209206/rethinking-the-role-of-alpha-toxin-in-clostridium-perfringens-associated-enteric-diseases-a-review-on-bovine-necro-haemorrhagic-enteritis
#4
REVIEW
Evy Goossens, Bonnie R Valgaeren, Bart Pardon, Freddy Haesebrouck, Richard Ducatelle, Piet R Deprez, Filip Van Immerseel
Bovine necro-haemorrhagic enteritis is an economically important disease caused by Clostridium perfringens type A strains. The disease mainly affects calves under intensive rearing conditions and is characterized by sudden death associated with small intestinal haemorrhage, necrosis and mucosal neutrophil infiltration. The common assumption that, when causing intestinal disease, C. perfringens relies upon specific, plasmid-encoded toxins, was recently challenged by the finding that alpha toxin, which is produced by all C...
February 16, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28196960/repair-of-a-bacterial-small-%C3%AE-barrel-toxin-pore-depends-on-channel-width
#5
Gisela von Hoven, Amable J Rivas, Claudia Neukirch, Martina Meyenburg, Qianqian Qin, Sapun Parekh, Nadja Hellmann, Matthias Husmann
Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca(2+)-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca(2+) influx, lysosomal exocytosis, and membrane repair...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28186774/quantitative-map-of-%C3%AE-lactone-induced-virulence-regulation
#6
Joanna Krysiak, Matthias Stahl, Jan Vomacka, Christian Fetzer, Markus Lakemeyer, Anja Fux, Stephan A Sieber
β-Lactones have recently been introduced as the first selective ClpP inhibitors that attenuate virulence of both sensitive Staphylococcus aureus and multiresistant strains (MRSA). Although previous knockout studies showed that ClpP is essential for S. aureus alpha-toxin production, a link between β-lactone inhibition and molecular virulence mechanisms has been lacking so far. We here perform a chemical-proteomic approach to elucidate antivirulence pathways. First, we demonstrate by gel-free activity-based protein profiling that ClpP is the predominant target of β-lactones...
February 10, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28137816/effects-of-tedizolid-phosphate-on-survival-outcomes-and-suppression-of-production-of-staphylococcal-toxins-in-a-rabbit-model-of-mrsa-necrotizing-pneumonia
#7
Vien T M Le, Hoan N Le, Marcos Gabriel Pinheiro, Kenneth J Hahn, Mary L Dinh, Kajal B Larson, Shawn D Flanagan, Cedric Badiou, Gerard Lina, Christine Tkaczyk, Bret R Sellman, Binh An Diep
The protective efficacy of tedizolid phosphate, a second-generation oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, or saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. A rabbit dosing regimen of 6 mg/kg tedizolid phosphate IV twice daily, which yielded AUC0-24h values approximating those in humans, was used. Overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P=0...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28115346/targeting-alpha-toxin-to-mitigate-its-lethal-toxicity-in-ferret-and-rabbit-models-of-staphylococcus-aureus-necrotizing-pneumonia
#8
Binh An Diep, Jamese J Hillard, Vien T M Le, Christine Tkaczyk, Hoan N Le, Vuvi G Tran, Renee L Rao, Etyene Castro Dip, Eliane P Pereira-Franchi, Paulyn Cha, Scott Jacobson, Rosemary Broome, Lily I Cheng, William Weiss, Laszlo Prokai, Vien Nguyen, C Ken Stover, Bret R Sellman
The role broad spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on the healthy microbiome have led to advances in pathogen specific approaches for the prevention or treatment of serious bacterial infections. One approach in clinical testing is passive immunization with a monoclonal antibody (mAb) targeting alpha toxin for the prevention or treatment of Staphylococcus aureus pneumonia. Passive immunization with the human anti-alpha toxin mAb, MEDI4893* has been shown to improve disease outcome in murine S...
January 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28104376/lipidomic-profile-of-gm95-cell-death-induced-by-clostridium-perfringens-alpha-toxin
#9
Marco M Manni, Juan G Valero, Miriam Pérez-Cormenzana, Ainara Cano, Cristina Alonso, Félix M Goñi
Clostridium perfringens alpha-toxin (ATX) is considered as a prototype of cytotoxic bacterial phospholipases C, and is the major virulence factor in C. perfringens-induced gas gangrene. It is known that, depending on the dose, ATX causes membrane disruption and cytolysis or only limited hydrolysis of its substrates. In the latter case, toxin activity leads to the unregulated generation of bioactive lipids that can ultimately induce cell death. We have characterized apoptosis and necrosis in highly ATX-sensitive, ganglioside-deficient cells exposed to different concentrations of ATX and we have studied the lipidomic profile of cells treated with ATX as compared to native cells to detect the main changes in the lipidomic profile and the possible involvement of lipid signals in cell death...
January 16, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28088477/selected-scorpion-toxin-exposures-induce-cytokine-release-in-human-peripheral-blood-mononuclear-cells
#10
Gerardo Corzo, Gerardo Pavel Espino-Solis
A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx's) was performed in order to evaluate their effect on human immune cells. The ScTx's chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin)...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28087840/vibrio-cholerae-cholix-toxin-induced-hepg2-cell-death-is-enhanced-by-tumor-necrosis-factor-alpha-through-ros-and-intracellular-signal-regulated-kinases
#11
Kohei Ogura, Yasuhiro Terasaki, Tohru Miyoshi-Akiyama, Mika Terasaki, Joel Moss, Masatoshi Noda, Kinnosuke Yahiro
Cholix toxin (Cholix) from Vibrio cholerae is a potent virulence factor exhibiting ADP-ribosyltransferase activity on eukaryotic elongation factor 2 (eEF2) of host cells, resulting in inhibition of protein synthesis. Administration of Cholix or its homologue Pseudomonas exotoxin A (PEA) to mice causes lethal hepatocyte damage. In this study, we demonstrate cytotoxicity of Cholix on immortalized human hepatocytes in the presence of tumor necrosis factor α (TNF-α), which has been reported to play a fatal role in PEA administered to mice...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28017248/treatment-of-blepharospasm-with-apraclonidine
#12
Dhanya Vijayakumar, Subhashie Wijemanne, Joseph Jankovic
OBJECTIVE: To describe improvement in blepharospasm with apraclonidine. BACKGROUND: Blepharospasm is a focal dystonia involving chiefly the orbicularis oculi and periocular muscles resulting in involuntary sustained eyelid closure. Botulinum toxin injection is the mainstay of treatment with meaningful improvement in over 85% of patients, but the effects often wear off within 3-4months. Apraclonidine is an alpha-2 adrenergic receptor agonist, which causes contraction of superior tarsal (Müller) muscle which may improve blepharospasm-related eyelid closure...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28010961/synthetic-peptide-antigens-derived-from-long-chain-alpha-neurotoxins-immunogenicity-effect-against-elapid-venoms
#13
Guillermo de la Rosa, Nina Pastor, Alejandro Alagón, Gerardo Corzo
Three-finger toxins (3FTXs), especially α-neurotoxins, are the most poorly neutralized elapid snake toxins by current antivenoms. In this work, the conserved structural similarity and motif arrangements of long-chain α-neurotoxins led us to design peptides with consensus sequences. Eight long-chain α-neurotoxins (also known as Type II) were used to generate a consensus sequence from which two peptides were chemically synthesized, LCP1 and LCP2. Rabbit sera raised against them were able to generate partially-neutralizing antibodies, which delayed mice mortality in neutralization assays against Naja haje, Dendrospis polylepis and Ophiophagus hannah venoms...
February 2017: Peptides
https://www.readbyqxmd.com/read/28007643/synergistic-effect-of-olfactory-ensheathing-cells-and-alpha-crystallin-on-restoration-of-adult-rat-optic-nerve-injury
#14
Yan Hua Wang, Zheng Qin Yin, Yi Wang
Olfactory enshesathing cells (OECs) and α-crystallin all can promote axonal regeneration after optic nerve injury. However, their mechanisms were different. Here, we study the synergistic effect of OECs and α-crystallin on the optic nerve regeneration. α-Crystallin was injected into vitreous cavity, and OECs were transplanted to the optic nerve injury area. The regeneration length of optic nerve were measured by anterograde tracing using cholera toxin subunit B (CTB). The survival of RGCs were assessed by counting the numbers of βIII-tubulin-labeled RGCs in a retinal whole mount...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27984062/rbaltmip-a-recombinant-alpha-type-myotoxin-inhibitor-from-bothrops-alternatus-rhinocerophis-alternatus-snake-as-a-potential-candidate-to-complement-the-antivenom-therapy
#15
Norival A Santos-Filho, Tiago S Sousa, Johara Boldrini-França, Ludier K Santos-Silva, Danilo L Menaldo, Flávio Henrique-Silva, Adélia C O Cintra, Helen J Laure, Carla C N Mamede, Fábio de Oliveira, Thalita B Riul, Marcelo Dias-Baruffi, José C Rosa, Suely V Sampaio
Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors...
October 28, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27930371/effect-of-low-concentration-nonmydriatic-selective-alpha-adrenergic-agonist-eyedrops-on-upper-eyelid-position
#16
Taís B Mendonça, Atauíne P Lummertz, Francisco J L Bocaccio, Fernando Procianoy
BACKGROUND: Ptosis after botulinum toxin injection is a disturbing complication. Decongestant and antiglaucoma eyedrops are frequently prescribed for temporary improvement of eyelid ptosis. Although frequently cited on informal communications, the effect of these drugs on eyelid position has never been compared in a formal study. OBJECTIVE: To measure the effect of low-concentration, nonmydriatic selective alpha agonist eyedrops on upper eyelid position. METHODS AND MATERIALS: This nonrandomized clinical trial enrolled 20 healthy subjects aged 18 to 50 years...
February 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/27929417/atp-release-from-human-airway-epithelial-cells-exposed-to-staphylococcus-aureus-alpha-toxin
#17
Romina Baaske, Mandy Richter, Nils Möller, Sabine Ziesemer, Ina Eiffler, Christian Müller, Jan-Peter Hildebrandt
Airway epithelial cells reduce cytosolic ATP content in response to treatment with S. aureus alpha-toxin (hemolysin A, Hla). This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e...
December 6, 2016: Toxins
https://www.readbyqxmd.com/read/27887025/design-and-expression-of-a-chimeric-vaccine-candidate-for-avian-necrotic-enteritis
#18
Amin Rostami, Fatemeh Goshadrou, Reza Pilehchian Langroudi, S Zahra Bathaie, Ali Riazi, Jafar Amani, Gholamreza Ahmadian
Necrotic enteritis is an economically important disease of poultry mainly caused by Clostridium perfringens The bacteria release multiple toxins of which NetB, alpha toxin and TpeL have been reported to play important roles in pathogenicity and/or severity of the disease. In this study, the sequence of clostridial toxins NetB, alpha toxin and TpeL were analyzed using bioinformatics tools to determine protein domains with high immunogenicity factor. Several chimeric trivalent proteins consisting of the immunogenic regions of the three toxins were designed and evaluated...
January 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27879630/recombinant-alpha-beta-and-epsilon-toxins-of-clostridium-perfringens-production-strategies-and-applications-as-veterinary-vaccines
#19
REVIEW
Marcos Roberto A Ferreira, Gustavo Marçal S G Moreira, Carlos Eduardo P da Cunha, Marcelo Mendonça, Felipe M Salvarani, Ângela N Moreira, Fabricio R Conceição
Clostridium perfringens is a spore-forming, commensal, ubiquitous bacterium that is present in the gastrointestinal tract of healthy humans and animals. This bacterium produces up to 18 toxins. The species is classified into five toxinotypes (A-E) according to the toxins that the bacterium produces: alpha, beta, epsilon, or iota. Each of these toxinotypes is associated with myriad different, frequently fatal, illnesses that affect a range of farm animals and humans. Alpha, beta, and epsilon toxins are the main causes of disease...
November 21, 2016: Toxins
https://www.readbyqxmd.com/read/27863510/establishing-a-reference-array-for-the-cs-%C3%AE-%C3%AE-superfamily-of-defensive-peptides
#20
D Ellen K Tarr
BACKGROUND: "Invertebrate defensins" belong to the cysteine-stabilized alpha-beta (CS-αβ), also known as the scorpion toxin-like, superfamily. Some other peptides belonging to this superfamily of defensive peptides are indistinguishable from "defensins," but have been assigned other names, making it unclear what, if any, criteria must be met to qualify as an "invertebrate defensin." In addition, there are other groups of defensins in invertebrates and vertebrates that are considered to be evolutionarily unrelated to those in the CS-αβ superfamily...
November 18, 2016: BMC Research Notes
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