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https://www.readbyqxmd.com/read/28094982/bacterial-genome-editing-via-a-designed-toxin-antitoxin-cassette
#1
Jie Wu, Aihua Deng, Qinyun Sun, Hua Bai, Zhaopeng Sun, Xiuling Shang, Yun Zhang, Qian Liu, Yong Liang, Shuwen Liu, Yongsheng Che, Tingyi Wen
Manipulating the bacterial genomes in an efficient manner is essential to biological and biotechnological research. Despite usage of various modules for genomic editing with counter-selectable markers including the toxin genes, an easy-to-use and highly designable toxin-antitoxin (TA) cassette without causing any leakages is urgently needed for efficient genome editing of the Gram-positive bacteria. Here, we reprogramed the bacterial TA systems as a toxin counter-selectable cassette regulated by an antitoxin switch (TCCRAS) for genetic modifications in the extensively studied and utilized Gram-positive bacteria, B...
January 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28087047/rational-design-of-low-immunogenic-anti-cd25-recombinant-immunotoxin-for-t-cell-malignancies-by-elimination-of-t-cell-epitopes-in-pe38
#2
Ronit Mazor, Gilad Kaplan, Dong Park, Youjin Jang, Fred Lee, Robert Kreitman, Ira Pastan
LMB-2, is a potent recombinant immunotoxin (RIT) that is composed of scFv antibody that targets CD25 (Tac) and a toxin fragment (PE38). It is used to treat T cell leukemias and lymphomas. To make LMB-2 less immunogenic, we introduced a large deletion in domain II and six point mutations in domain III that were previously shown to reduce T cell activation in other RITs. We found that unlike other RITs, deletion of domain II from LMB-2 severely compromised its activity. Rather than deletion, we identified T cell epitopes in domain II and used alanine substitutions to identify point mutations that diminished those epitopes...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28081446/host-to-host-transmission-of-streptococcus-pneumoniae-is-driven-by-its-inflammatory-toxin-pneumolysin
#3
M Ammar Zafar, Yang Wang, Shigeto Hamaguchi, Jeffrey N Weiser
Host-to-host transmission is a critical step for infection. Here we studied transmission of the opportunistic pathogen Streptococcus pneumoniae in an infant mouse model. Transmission from nasally colonized pups required high levels of bacterial shedding in nasal secretions and was temporally correlated with, and dependent upon, the acute inflammatory response. Pneumolysin, a pore-forming cytotoxin and major virulence determinant, was both necessary and sufficient to promote inflammation, which increased shedding and allowed for intralitter transmission...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28079531/the-effect-of-albumin-and-platelet-poor-plasma-supplemented-botulinum-a-toxin-on-bioavaliability-an-experimental-rabbit-model
#4
Serhat Sibar, Kemal Findikcioglu, Murat Zinnuroglu, Seyhan Cenetoglu
Today, botulinum toxin is commonly used for cosmetic purposes throughout the world. Despite various agents reducing the efficiency of toxin are well defined, the studies related to increasing the bioavailability are limited. The purpose of our study is to assess the effect of the preparation of toxin by diluting with platelet-poor plasma (PPP) and/or albumin instead of standard dilution (saline) on bioavailability in cosmetic-purpose botulinum toxin applications.In the study, 24 New Zealand rabbits were used...
January 10, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28045959/the-impact-of-detoxification-costs-and-predation-risk-on-foraging-implications-for-mimicry-dynamics
#5
Christina G Halpin, John Skelhorn, Candy Rowe, Graeme D Ruxton, Andrew D Higginson
Prey often evolve defences to deter predators, such as noxious chemicals including toxins. Toxic species often advertise their defence to potential predators by distinctive sensory signals. Predators learn to associate toxicity with the signals of these so-called aposematic prey, and may avoid them in future. In turn, this selects for mildly toxic prey to mimic the appearance of more toxic prey. Empirical evidence shows that mimicry could be either beneficial ('Mullerian') or detrimental ('quasi-Batesian') to the highly toxic prey, but the factors determining which are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/27999281/probiotic-microorganisms-inhibit-epithelial-cell-internalization-of-botulinum-neurotoxin-serotype-a
#6
Tina I Lam, Christina C Tam, Larry H Stanker, Luisa W Cheng
Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins...
December 16, 2016: Toxins
https://www.readbyqxmd.com/read/27999204/mesothelin-targeted-immunotoxin-rg7787-has-synergistic-anti-tumor-activity-when-combined-with-taxanes
#7
Emily Kolyvas, Michael Rudloff, Marianne Poruchynsky, Rebekah Landsman, Kevin Hollevoet, David Venzon, Christine Alewine
Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27997854/the-emerging-metabolic-view-of-clostridium-difficile-pathogenesis
#8
REVIEW
Andrew J Hryckowian, Kali M Pruss, Justin L Sonnenburg
It is widely accepted that Clostridium difficile exploits dysbiosis and leverages inflammation to thrive in the gut environment, where it can asymptomatically colonize humans or cause a toxin-mediated disease ranging in severity from frequent watery diarrhea to pseudomembranous colitis or toxic megacolon. Here, we synthesize recent findings from the gut microbiota and enteric pathogenesis fields to inform the next steps toward a better understanding of C. difficile infection (CDI). In this review, we present a model in which the lifestyle of C...
December 17, 2016: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/27974078/operation-canine-lifeline-recommendations-for-enhancing-prehospital-care-for-government-working-dogs
#9
Teija Corse, Chelsea Firth, John Burke, Kenneth Schor, James F Koterski, Sabrina McGraw, Nancy Vincent-Johnson, Lori Gordon
Operation Canine Lifeline was a tabletop exercise developed by students and faculty of Boston University School of Medicine's Healthcare Emergency Management master's program. The tabletop exercise led to discussion on current protocols for canines working in the field, what occurs if a canine encounters a toxin in the field, and what to do in situations of national security that require working with civilian agencies. This discussion led to the creation of a set of recommendations around providing prehospital veterinary care to government working dogs...
December 15, 2016: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/27967234/alternative-progenitor-lineages-regenerate-the-adult-lung-depleted-of-type-ii-cells
#10
Min Yee, William Domm, Robert Gelein, Karen L de Mesy Bentley, R Matthew Kottmann, Patricia J Sime, B Paige Lawrence, Michael A O'Reilly
An aberrant oxygen environment at birth increases the severity of respiratory viral infections later in life through poorly understood mechanisms. Here we show that alveolar epithelial type II (AEC2) cells, a progenitor for AEC1 cells are depleted in adult mice exposed to neonatal hypoxia or hyperoxia. Airway cells expressing SP-C and ABCA3, alveolar pod cells expressing KRT5, and pulmonary fibrosis was observed when these mice were infected with a sublethal dose of HKx31, H3N2 influenza A virus (IAV). This was not seen in infected siblings birthed into room air...
December 14, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27958325/onabotulinumtoxina-urethral-sphincter-injection-as-treatment-for-non-neurogenic-voiding-dysfunction-a-randomized-double-blind-placebo-controlled-study
#11
Yuan-Hong Jiang, Chung-Cheng Wang, Hann-Chorng Kuo
Non-neurogenic voiding dysfunction including dysfunctional voiding and detrusor underactivity caused by a spastic or non-relaxing external urethral sphincter can theoretically be treated by injections of botulinum A toxin into the external urethral sphincter. This randomized, double-blind, placebo-controlled trial was designed to determine the clinical efficacy of onabotulinumtoxinA urethral sphincter injections in patients with dysfunctional voiding or detrusor underactivity. Patients with medically refractory dysfunctional voiding (n = 31) or detrusor underactivity (n = 31) were randomly allocated in a 2:1 ratio to receive either onabotulinumtoxinA (100 U) (n = 38) or placebo (normal saline) (n = 24)...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928382/isolated-fourth-nerve-palsy-in-tuberculous-meningitis
#12
María García-Zamora, Hortensia Sánchez-Tocino, Ana Villanueva-Gómez, José Miguel Angles-Deza, Elena Pérez-Gutierrez
Tuberculous meningitis is a type of subacute meningitis and like other intracranial processes can compromise ocular motor nerves, causing palsies. Trochlear nerve is an unusual isolated manifestation in this type of pathology. The authors report a 5-year-old boy presented in their clinic with a trochlear nerve palsy as unique neurological manifestation of tuberculous meningitis. Treatment with complete anti-tuberculous therapy and botulinum A toxin was needed to get the complete resolution of the nerve palsy...
February 2016: Neuro-ophthalmology
https://www.readbyqxmd.com/read/27924350/-use-of-intracutaneous-or-subcutaneous-botulinum-toxin-for-postherpetic-neuralgia
#13
L Halb, B J Amann, H Bornemann-Cimenti
BACKGROUND: Botulinum neurotoxin (BoNT), a toxin of the anaerobic spore-forming bacterium Clostridium botulinum is used as a drug for alleviating muscle spasticity. Other indications include the cosmetic application in facial muscles, hyperhidrosis and neurogenic bladder disorders. It has been approved since 2010 as the first prophylactic treatment for chronic migraine. The analgesic effect of BoNT was observed early on and is currently the subject of intensive research. Painful postherpetic neuralgia is a common complication of an infection with herpes zoster virus...
December 6, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27920769/transcriptional-profiling-of-type-ii-toxin-antitoxin-genes-of-helicobacter-pylori-under-different-environmental-conditions-identification-of-hp0967-hp0968-system
#14
María G Cárdenas-Mondragón, Miguel A Ares, Leonardo G Panunzi, Sabino Pacheco, Margarita Camorlinga-Ponce, Jorge A Girón, Javier Torres, Miguel A De la Cruz
Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence of H. pylori in the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin-antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome of H. pylori 26695: HP0315-HP0316, HP0892-HP0893, and HP0894-HP0895...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27917833/crystal-structure-of-the-toxin-msmeg_6760-the-structural-homolog-of-mycobacterium-tuberculosis-rv2035-a-novel-type-ii-toxin-involved-in-the-hypoxic-response
#15
R Alexandra Bajaj, Mark A Arbing, Annie Shin, Duilio Cascio, Linda Miallau
The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin-antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate-latch mechanism...
December 1, 2016: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/27916477/modulation-of-a-circulating-uremic-solute-via-rational-genetic-manipulation-of-the-gut-microbiota
#16
A Sloan Devlin, Angela Marcobal, Dylan Dodd, Stephen Nayfach, Natalie Plummer, Tim Meyer, Katherine S Pollard, Justin L Sonnenburg, Michael A Fischbach
Renal disease is growing in prevalence and has striking co-morbidities with metabolic and cardiovascular disease. Indoxyl sulfate (IS) is a toxin that accumulates in plasma when kidney function declines and contributes to the progression of chronic kidney disease. IS derives exclusively from the gut microbiota. Bacterial tryptophanases convert tryptophan to indole, which is absorbed and modified by the host to produce IS. Here, we identify a widely distributed family of tryptophanases in the gut commensal Bacteroides and find that deleting this gene eliminates the production of indole in vitro...
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27915984/structure-function-and-evolution-of-clostridium-botulinum-c2-and-c3-toxins-insight-to-poultry-and-veterinary-vaccines
#17
P Chellapandi, A Prisilla
Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines...
December 1, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27910884/the-hha-tomb-toxin-antitoxin-system-shows-conditional-toxicity-and-promotes-persister-cell-formation-by-inhibiting-apoptosis-like-death-in-s-typhimurium
#18
Sangeeta Jaiswal, Prajita Paul, Chandrashekhar Padhi, Shilpa Ray, Daniel Ryan, Shantoshini Dash, Mrutyunjay Suar
Toxin-antitoxin (TA) modules are two component "addictive" genetic elements found on either plasmid or bacterial chromosome, sometimes on both. TA systems perform a wide range of functions like biofilm formation, persistence, programmed cell death, phage abortive infection etc. Salmonella has been reported to contain several such TA systems. However, the hemolysin expression modulating protein (Hha) and its adjacent uncharacterized hypothetical protein TomB (previously known as YbaJ), have not been listed as a TA module in Salmonella...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902436/exploring-the-parameters-of-post-segregation-killing-using-heterologous-expression-of-secreted-toxin-barnase-and-antitoxin-barstar-in-an-e-coli-case-study
#19
Dorien S Coray, Brigitta Kurenbach, Jack A Heinemann
Post-segregational killing (PSK) is a phenotype determined by plasmids using a toxin and an antitoxin (TA) gene pair. Loss of the genes depletes the cell's reserve of antitoxin and allows the toxin to act upon the cell. PSK benefits mobile elements when it increases reproductive success relative to other mobile competitors. A side effect of PSK is that plasmids become refractory to displacement from the cell during growth as a monoculture. Most PSK systems use a cytoplasmic toxin, but the external toxins of bacteriocins also have a PSK-like effect...
November 16, 2016: Microbiology
https://www.readbyqxmd.com/read/27879113/dynamical-analysis-of-a-toxin-producing-phytoplankton-zooplankton-model-with-refuge
#20
Juan Li, Yongzhong Song, Hui Wan
To study the impacts of toxin produced by phytoplankton and refuges provided for phytoplankton on phytoplankton-zooplankton interactions in lakes, we establish a simple phytoplankton-zooplankton system with Holling type II response function. The existence and stability of positive equilibria are discussed. Bifurcation analyses are given by using normal form theory which reveals reasonably the mechanisms and nonlinear dynamics of the effects of toxin and refuges, including Hopf bifurcation, Bogdanov-Takens bifurcation of co-dimension 2 and 3...
April 1, 2017: Mathematical Biosciences and Engineering: MBE
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