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https://www.readbyqxmd.com/read/29662661/targeting-oncogenic-ras-by-the-clostridium-perfringens-toxin-tpel
#1
Björn Schorch, Hannah Heni, Nour-Imene Zahaf, Tilman Brummer, Marina Mione, Gudula Schmidt, Panagiotis Papatheodorou, Klaus Aktories
Clostridium perfringens toxin TpeL belongs to the family of large clostridial glycosylating toxins. The toxin causes N-acetylglucosaminylation of Ras proteins at threonine35 thereby inactivating the small GTPases. Here, we show that all main types of oncogenic Ras proteins (H-Ras, K-Ras and N-Ras) are modified by the toxin in vitro and in vivo . Toxin-catalyzed modification of Ras was accompanied by inhibition of the MAP kinase pathway. Importantly, TpeL inhibited the paradoxical activation of the MAP kinase pathway induced by the BRAF inhibitor Vemurafenib in the human melanoma cell line SBCL2...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661872/treating-anthrax-induced-meningitis-in-rabbits
#2
Amir Ben-Shmuel, Itai Glinert, Assa Sittner, Elad Bar-David, Josef Schlomovitz, Tal Brosh, David Kobiler, Shay Weiss, Haim Levy
Treatment of Anthrax is challenging, especially during the advanced stages of the disease. Recently the CDC updated its recommendations for post-exposure prophylaxis and treatment of exposed populations (pre and post symptoms onset). These recommendations distinguished, for the first time, between the systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic patients as meningeal unless positively proven otherwise. The treatment of patients suffering from systemic Anthrax with suspected or confirmed meningitis includes the combination of three antibiotics -- a fluoroquinolone (Levofloxacin or Ciprofloxacin), a β-lactam (Meropenem or Imipenem) and a protein-synthesis inhibitor (Linezolid or Clindamycin)...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29659495/transient-recombinant-protein-production-in-glycoengineered-nicotiana-benthamiana-cell-suspension-culture
#3
Sara C Sukenik, Kalimuthu Karuppanan, Qiongyu Li, Carlito B Lebrilla, Somen Nandi, Karen A McDonald
Transient recombinant protein production is a promising alternative to stable transgenic systems, particularly for emergency situations in which rapid production of novel therapeutics is needed. In plants, Agrobacterium tumefaciens can be used as a gene delivery vector for transient expression. A potential barrier for plant-based production of human therapeutics is that different glycosylation patterns are found on plant and mammalian proteins. Since glycosylation can affect the efficacy, safety and stability of a therapeutic protein, methods to control glycan structures and distributions in plant-based systems would be beneficial...
April 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29656957/muramyl-dipeptide-potentiates-a-bacillus-anthracis-poly-%C3%AE-d-glutamic-acid-capsule-surrogate-that-induces-maturation-and-activation-of-mouse-dendritic-cells
#4
Jun Ho Jeon, Deok-Bum Park, Sun-Je Woo, Hae-Ri Lee, Ok-Kyu Park, Jungchan Park, Gi-Eun Rhie
Poly-γ-d-glutamic acid (PGA) of anthrax is an important pathogenic factor due to its anti-phagocytic activity. Additionally, PGA has the ability to activate mouse macrophages for the secretion of cytokines through Toll-like receptor (TLR) 2. Peptidoglycan (PGN), a major bacterial cell-wall component, induces inflammatory responses in the host. We assessed whether PGA can induce maturation and cytokine expression in immature mouse dendritic cells (DCs) in the existence of muramyl dipeptide (MDP), the minimum motif of PGN with immunostimulatory activity...
April 12, 2018: Cytokine
https://www.readbyqxmd.com/read/29651670/disease-extinction-versus-persistence-in-discrete-time-epidemic-models
#5
P van den Driessche, Abdul-Aziz Yakubu
We focus on discrete-time infectious disease models in populations that are governed by constant, geometric, Beverton-Holt or Ricker demographic equations, and give a method for computing the basic reproduction number, [Formula: see text]. When [Formula: see text] and the demographic population dynamics are asymptotically constant or under geometric growth (non-oscillatory), we prove global asymptotic stability of the disease-free equilibrium of the disease models. Under the same demographic assumption, when [Formula: see text], we prove uniform persistence of the disease...
April 12, 2018: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29616046/trimethyl-chitosan-nanoparticles-encapsulated-protective-antigen-protects-the-mice-against-anthrax
#6
Anshu Malik, Manish Gupta, Rajesh Mani, Himanshu Gogoi, Rakesh Bhatnagar
Anthrax is an era old deadly disease against which there are only two currently available licensed vaccines named anthrax vaccine adsorbed and precipitated (AVP). Though they can provide a protective immunity, their multiple side-effects owing to their ill-defined composition and presence of toxic proteins (LF and EF) of Bacillus anthracis , the causative organism of anthrax, in the vaccine formulation makes their widespread use objectionable. Hence, an anthrax vaccine that contains well-defined and controlled components would be highly desirable...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615497/novel-broadly-reactive-anticapsular-antibodies-against-carbapenem-resistant-klebsiella-pneumoniae-protect-from-infection
#7
Elizabeth Diago-Navarro, Michael P Motley, Gonzalo Ruiz-Peréz, Winnie Yu, Julianne Austin, Bruna M S Seco, Guozhi Xiao, Aniska Chikhalya, Peter H Seeberger, Bettina C Fries
Carbapenem-resistant (CR) sequence type 258 (ST258) Klebsiella pneumoniae has become an urgent health care threat, causing an increasing number of high-mortality infections. Its resistance to numerous antibiotics and threat to immunocompromised patients necessitate finding new therapies to combat these infections. Previous successes in the laboratory, as well as the conservation of capsular polysaccharide (CPS) among the members of the ST258 clone, suggest that monoclonal antibody (MAb) therapy targeting the outer polysaccharide capsule of K...
April 3, 2018: MBio
https://www.readbyqxmd.com/read/29610258/certhrax-is-an-anti-virulence-factor-for-the-anthrax-like-organism-bacillus-cereus-strain-g9241
#8
Yuliya I Seldina, Courtney D Petro, Stephanie L Servetas, James M Vergis, Christy L Ventura, D Scott Merrell, Alison D O'Brien
Bacillus cereus G9241 caused a life-threatening anthrax-like lung infection in a previously healthy man. This strain harbors two large virulence plasmids, pBCXO1 and pBC210, that are absent from typical B cereus isolates. The pBCXO1 plasmid is nearly identical to pXO1 from B. anthracis and carries genes ( pagA1 , lef, and cya ) for the anthrax toxin components protective antigen (called PA1 in G9241), lethal factor (LF), and edema factor (EF), respectively. The plasmid also has an intact hyaluronic acid capsule locus...
April 2, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29608180/spore-concentration-and-modified-host-resistance-as-a-cause-of-anthrax-outbreaks-a-comment
#9
COMMENT
Janice Crook
No abstract text is available yet for this article.
April 2018: Canadian Veterinary Journal. la Revue Vétérinaire Canadienne
https://www.readbyqxmd.com/read/29599764/a-dual-role-for-the-bacillus-anthracis-master-virulence-regulator-atxa-control-of-sporulation-and-anthrax-toxin-production
#10
Jennifer L Dale, Malik J Raynor, Maureen C Ty, Maria Hadjifrangiskou, Theresa M Koehler
Bacillus anthracis is an endemic soil bacterium that exhibits two different lifestyles. In the soil environment, B. anthracis undergoes a cycle of saprophytic growth, sporulation, and germination. In mammalian hosts, the pathogenic lifestyle of B. anthracis is spore germination followed by vegetative cell replication, but cells do not sporulate. During infection, and in specific culture conditions, transcription of the structural genes for the anthrax toxin proteins and the biosynthetic operon for capsule synthesis is positively controlled by the regulatory protein AtxA...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29595948/nanoporous-hydrogels-for-the-observation-of-anthrax-exotoxin-translocation-dynamics
#11
Christopher Baker, Ben Schudel, Mangesh I Chaudhari, Kerrie Wu, Derek Dunford, Anup K Singh, Susan B Rempe, Anson V Hatch
The ability to observe lethal anthrax exotoxins translocating through size-constricting nanopores in vitro, combined with detailed sequence and structural data, has aided in eluci- dated mechanisms of exotoxin cell entry and toxicity. However, due to limited observations of anthrax exotoxins translocating through protective antigen nanopores in vitro, and the instability of protective antigen-functionalized suspended lipid bilayers, questions remain re- garding the native mechanisms of cell entry. Nanoporous hydrogel membranes oer a robust tool for studying protein translocation with ensemble measurements that complement con- ventional single molecule translocation measurements...
March 29, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29594713/ratiometric-fluorometric-determination-of-the-anthrax-biomarker-2-6-dipicolinic-acid-by-using-europium-iii-doped-carbon-dots-in-a-test-stripe
#12
Mingcong Rong, Xiangzhou Deng, Siting Chi, Longzhen Huang, Youbin Zhou, Yune Shen, Xi Chen
Europium(III)-doped carbon dots (Eu-CDs) were prepared from citric acid and europium nitrate via a one-pot pyrolytic method. The Eu-CDs emit intense blue fluorescence (with excitation/emission peaks at 365/465 nm), are water soluble and biocompatible. On addition of 2,6-dipicolinic acid (DPA; an anthrax biomarker), ligand-to-ion energy transfer occurs from DPA to Eu(III) which has a red emission peaking at 615 nm. This results in an increase of the intensity of the red fluorescence. DPA can be detected by the ratio of fluorescence intensities at 616 and 475 nm...
March 1, 2018: Mikrochimica Acta
https://www.readbyqxmd.com/read/29580944/inhibition-of-anthrax-lethal-factor-by-ssdna-aptamers
#13
Mieke Lahousse, Hae-Chul Park, Sang-Choon Lee, Na-Reum Ha, In-Pil Jung, Sara R Schlesinger, Kaylin Shackleford, Moon-Young Yoon, Sung-Kun Kim
Anthrax is caused by Bacillus anthracis, a bacterium that is able to secrete the toxins protective antigen, edema factor and lethal factor. Due to the high level of secretion from the bacteria and its severe virulence, lethal factor (LF) has been sought as a biomarker for detecting bacterial infection and as an effective target to neutralize toxicity. In this study, we found three aptamers, and binding affinity was determined by fluorescently labeled aptamers. One of the aptamers exhibited high affinity, with a Kd value of 11...
March 23, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29570493/does-anthrax-antitoxin-therapy-have-a-role-in-the-treatment-of-inhalational-anthrax
#14
Nicholas J Vietri
PURPOSE OF REVIEW: Inhalational anthrax is a rare disease and Bacillus anthracis is a likely pathogen to be used in a biological attack. The lack of clinical experience with anthrax has led experts to develop treatment guidelines. These guidelines recommend anthrax antitoxin to be used in conjunction with antibiotics for the treatment of patients with systemic anthrax infection, yet there is still a lack of human or animal data to support this recommendation. RECENT FINDINGS: The U...
March 22, 2018: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29533547/injectional-anthrax-in-human-a-new-face-of-the-old-disease
#15
REVIEW
Aleksandra A Zasada
Unusual human behavior leads to the emergence of new forms of infectious diseases and new routes of infection. In recent years, a new form of anthrax, called injectional anthrax, emerged and was related to 2 human anthrax outbreaks in Europe. The infection was caused by heroin contaminated with anthrax spores. The new form of anthrax differs from the earlier known "natural" forms of the disease in symptoms, length of the incubation period and recommended treatment. Despite medical treatment, the mortality rate in injectional anthrax is about 35%...
March 13, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29524493/generation-and-screening-of-efficient-neutralizing-single-domain-antibodies-vhhs-against-the-critical-functional-domain-of-anthrax-protective-antigen-pa
#16
Abbas Shali, Sadegh Hasannia, Fatemeh Gashtasbi, S Masoud Abdous, S Shirin Shahangian, Shirin Jalili
Since anthrax is an acute infectious disease, detection and neutralization of the toxins of pathogenic Bacillus anthracis are of great importance. The critical role of protective antigen (PA) component of tripartite anthrax toxin in toxin entry into the host cell cytosol provided a great deal of effort to generate monoclonal antibodies against this constitute. Regarding the importance of anthrax detection/neutralization and unique physicochemical and pharmacological features of VHHs as single domain antibodies, the present study aimed to generate VHHs against the receptor binding domain of PA, termed PAD4...
March 7, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29487236/role-of-the-antigen-capture-pathway-in-the-induction-of-a-neutralizing-antibody-response-to-anthrax-protective-antigen
#17
Anita Verma, Miriam M Ngundi, Gregory A Price, Kazuyo Takeda, James Yu, Drusilla L Burns
Toxin neutralizing antibodies represent the major mode of protective immunity against a number of toxin-mediated bacterial diseases, including anthrax; however, the cellular mechanisms that lead to optimal neutralizing antibody responses remain ill defined. Here we show that the cellular binding pathway of anthrax protective antigen (PA), the binding component of anthrax toxin, determines the toxin neutralizing antibody response to this antigen. PA, which binds cellular receptors and efficiently enters antigen-presenting cells by receptor-mediated endocytosis, was found to elicit robust anti-PA IgG and toxin neutralizing antibody responses...
February 27, 2018: MBio
https://www.readbyqxmd.com/read/29476407/cross-sectional-survey-of-brucellosis-and-associated-risk-factors-in-the-livestock-wildlife-interface-area-of-nechisar-national-park-ethiopia
#18
Hassen Chaka, Gezahegn Aboset, Abebe Garoma, Balako Gumi, Eric Thys
A cross-sectional survey was carried out to investigate the seroprevalence of ovine and bovine brucellosis in the livestock-wildlife interface area of Nechisar National Park, Ethiopia. Furthermore, producer's knowledge about brucellosis and its zoonotic potential was assessed using a structured questionnaire. A total of 268 cattle and 246 goat sera were collected from 50 herds and 46 flocks and subjected to Rose Bengal test (RBT) and enzyme-linked immunosorbent assay (ELISA) in parallel to detect anti-Brucella species antibodies...
February 24, 2018: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/29475476/multifunctional-fluorescent-sensing-of-chemical-and-physical-stimuli-using-smart-riboflavin-5-phosphate-eu-3-coordination-polymers
#19
Shi-Fan Xue, Jing-Fei Zhang, Zi-Han Chen, Xin-Yue Han, Min Zhang, Guoyue Shi
A novel type of stimuli-responsive fluorescent polymers has been developed via the self-assembly of riboflavin-5'-phosphate (RiP) as ligand and europium (III) (Eu3+ ) as central metal ion coordinated with the ligand. The as-prepared RiP/Eu3+ coordination polymers (RiP/Eu3+ CPs) are smart and multifunctional for respectively responding to chemical and physical stimuli, in which RiP acts as the stimuli-responsive fluorescent signal indicator. For sensing chemical stimuli, 2,6-pyridinedicarboxylic acid (DPA, an anthrax biomarker) having higher bonding force towards Eu3+ can grab it from smart RiP/Eu3+ CPs through competition reaction, resulting in the release of RiP for highly sensitive and selective DPA monitoring in a mix-and-read fluorescent enhancement format, and the detection limit is as low as 41...
July 5, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29474056/quantitative-prediction-of-multivalent-ligand-receptor-binding-affinities-for-influenza-cholera-and-anthrax-inhibition
#20
Susanne Liese, Roland R Netz
Multivalency achieves strong, yet reversible binding by the simultaneous formation of multiple weak bonds. It is a key interaction principle in biology and promising for the synthesis of high-affinity inhibitors of pathogens. We present a molecular model for the binding affinity of synthetic multivalent ligands onto multivalent receptors consisting of n receptor units arranged on a regular polygon. Ligands consist of geometrically matching rigid polygonal core to which monovalent ligand units are attached via flexible linker polymers, closely mimicking existing experimental designs...
February 23, 2018: ACS Nano
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