Publications

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role of purine biosynthesis in bacillus anthracis pathogenesis and virulence.bacillus anthracis, the etiological agent of anthrax, is a spore-forming, gram-positive bacterium and a category a biothreat agent. screening of a library of transposon-mutagenized b. anthracis spores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme purh. purh is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine imp. we constructed and characterized defined purh mutants of the virulent b ...201021041498
structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers.the protein transporter anthrax lethal toxin is composed of protective antigen (pa), a transmembrane translocase, and lethal factor (lf), a cytotoxic enzyme. after its assembly into holotoxin complexes, pa forms an oligomeric channel that unfolds lf and translocates it into the host cell. we report the crystal structure of the core of a lethal toxin complex to 3.1-å resolution; the structure contains a pa octamer bound to four lf pa-binding domains (lf(n)). the first α-helix and β-strand of each ...201021037566
photocatalytic inactivation of spores of bacillus anthracis using titania nanomaterials.studies on photocatalytic inactivation of spores of bacillus anthracis have been carried out using nanosized titania materials and uva light or sun light. results demonstrated pseudo first order behaviour of spore inactivation kinetics. the value of kinetic rate constant increased from 0.4h(-1) to 1.4h(-1) indicating photocatalysis facilitated by addition of nanosized titania. nanosized titania exhibited superior inactivation kinetics on par with large sized titania. the value of kinetic rate co ...201021035260
cd and mcd spectroscopic studies of the two dps miniferritin proteins from bacillus anthracis: role of o2 and h2o2 substrates in reactivity of the diiron catalytic centers.dna protection during starvation (dps) proteins are miniferritins found in bacteria and archaea that provide protection from uncontrolled fe(ii)/o radical chemistry; thus the catalytic sites are targets for antibiotics against pathogens, such as anthrax. ferritin protein cages synthesize ferric oxymineral from fe(ii) and o(2)/h(2)o(2), which accumulates in the large central cavity; for dps, h(2)o(2) is the more common fe(ii) oxidant contrasting with eukaryotic maxiferritins that often prefer dio ...201021028901
treatment of human anthrax with penicillin. 194521026573
[not available]. 194621025026
[not available]. 194521021176
anthrax. 194521015371
anthrax treated with sulfadiazine; report of a case. 194621013959
[not available]. 194521013359
[not available]. 194521011460
a note on the efficacy of commercial anti-anthrax bacterins. 194521009458
[on the chemotherapy of experimental infection by anthrax]. 194521008748
[treatment of anthrax]. 194521008645
observations on the resistance of anthrax spores to heat. 194521005511
chemotherapy of experimental anthrax infections. 194620998820
anthrax; its diagnosis and treatment. 194620994281
cutaneous anthrax; report of twenty-five cases. 194620992839
avirulent anthrax vaccine. 194620990776
[not available]. 194620990196
[not available]. 194620989755
the capsular substance of bacillus anthracis. 194620989455
the capsular substance of bacillus anthracis. 194620989452
application of nutritional studies for development of practical culture media for bacillus anthracis. 194620983282
studies on the nutritional requirements of bacillus anthracis. 194620983281
a modeled structure for amidase-03 from bacillus anthracis.homology models of amidase-03 from bacillus anthracis were constructed using modeller (9v2). modeller constructs protein models using an automated approach for comparative protein structure modeling by the satisfaction of spatial restraints. a template structure of listeria monocytogenes bacteriophage psa endolysin plypsa (pdb id: 1xov) was selected from protein databank (pdb) using blastp with blosum62 sequence alignment scoring matrix. we generated five models using the modeller default routin ...200920975917
myd88-dependent signaling protects against anthrax lethal toxin-induced impairment of intestinal barrier function.myd88-deficient mice were previously shown to have increased susceptibility to bacillus anthracis infection relative to wild-type animals. to determine the mechanism by which myd88 protects against b. anthracis infection, knockout mice were challenged with nonencapsulated, toxigenic b. anthracis or with anthrax toxins. myd88-deficient mice had increased susceptibility to b. anthracis and anthrax lethal toxin but not to edema toxin. lethal toxin alone induced marked multifocal intestinal ulcers i ...201020974827
glucose-dependent activation of bacillus anthracis toxin gene expression and virulence requires the carbon catabolite protein ccpa.sensing environmental conditions is an essential aspect of bacterial physiology and virulence. in bacillus anthracis, the causative agent of anthrax, transcription of the two major virulence factors, toxin and capsule, is triggered by bicarbonate, a major compound in the mammalian body. here it is shown that glucose is an additional signaling molecule recognized by b. anthracis for toxin synthesis. the presence of glucose increased the expression of the protective antigen toxin component-encodin ...201020971911
in vitro studies of peptidoglycan binding and hydrolysis by the bacillus anthracis germination-specific lytic enzyme sleb.the bacillus anthracis endospore loses resistance properties during germination when its cortex peptidoglycan is degraded by germination-specific lytic enzymes (gsles). although this event normally employs several gsles for complete cortex removal, the sleb protein alone can facilitate enough cortex hydrolysis to produce vulnerable spores. as a means to better understand its enzymatic function, sleb was overexpressed, purified, and tested in vitro for depolymerization of cortex by measurement of ...201020971910
deciphering the role of glucosamine-6-phosphate in the riboswitch action of glms ribozyme.the glms ribozyme is believed to exploit a general acid-base catalytic mechanism in the presence of glucosamine-6-phosphate (glcn6p) to accelerate self-cleavage by approximately six orders of magnitude. the general acid and general base are not known, and the role of the glcn6p cofactor is even less well understood. the amine group of glcn6p has the ability to either accept or donate a proton and could therefore potentially act as an acid or a base. in order to decipher the role of glcn6p in the ...201020971809
anthrax lethal toxin suppresses murine cardiomyocyte contractile function and intracellular ca2+ handling via a nadph oxidase-dependent mechanism.anthrax infection is associated with devastating cardiovascular sequelae, suggesting unfavorable cardiovascular effects of toxins originated from bacillus anthracis namely lethal and edema toxins. this study was designed to examine the direct effect of lethal toxins on cardiomyocyte contractile and intracellular ca(2+) properties.201020967205
decontamination of bacillus anthracis spores: evaluation of various disinfectants.the present study compares the efficacy of various disinfectants against bacillus anthracis spores. while bleach rite(®) and 10% bleach reduce spore numbers by 90% within 10 minutes, a long contact time is required for complete disinfection. by contrast, although sporgon(®) did not initially reduce the number of spores as quickly as bleach rite or 10% bleach, shorter contact times were required for complete eradication of viable spores.200920967138
hapalindole-related alkaloids from the cultured cyanobacterium fischerella ambigua.four hapalindole-related alkaloids, namely fischambiguines a and b, ambiguine p, ambiguine q nitrile as well as ambiguine g nitrile were identified from the cultured cyanobacterium fischerella ambigua (utex 1903). the structures were determined by spectroscopic analysis including ms, 1d and 2d nmr and x-ray crystallography. the alkaloids possessed fused pentacyclic and hexacyclic carbon skeletons. fischambiguine b displayed a strong inhibitory activity against mycobacterium tuberculosis with an ...201020965528
a bayesian approach for estimating bioterror attacks from patient data.terrorist attacks using an aerosolized pathogen have gained credibility as a national security concern after the anthrax attacks of 2001. inferring some important details of the attack quickly, for example, the number of people infected, the time of infection, and a representative dose received can be crucial to planning a medical response. we use a bayesian approach, based on a short time series of diagnosed patients, to estimate a joint probability density for these parameters. we first test t ...201020963771
yhgc protects bacillus anthracis from oxidative stress.bacillus anthracis can cause lethal inhalational anthrax and can be used as a bioweapon due to its ability to form spores and to survive under various environmental stress conditions. yhgc in bacilli are structural homologues of trap, a protein involved in stress response in staphylococci. to test the role of yhgc in b. anthracis, yhgc gene was deleted in b. anthracis strain sterne and parent and mutant strains tested. immunolocalization studies indicated that yhgc is clustered both on the cell ...201020963726
anthrax: modern exposure science combats a deadly, ancient disease. 201020959831
the plague of the philistines and other pestilences in the ancient world: exploring relations between the religious-literary tradition, artistic evidence and scientific proof.in ancient times the term pestilence referred not only to infectious disease caused by yersinia pestis, but also to several different epidemics. we explore the relations between references in the bible and recent scientific evidence concerning some infectious diseases, especially the so-called plague of the philistines and leprosy. in addition, some considerations regarding possible connections among likely infectious epidemic diseases and the ten plagues of egypt are reported. evidence suggesti ...201020956880
recombinant anthrax toxin receptor-fc fusion proteins produced in plants protect rabbits against inhalational anthrax.inhalational anthrax, a zoonotic disease caused by the inhalation of bacillus anthracis spores, has a ∼50% fatality rate even when treated with antibiotics. pathogenesis is dependent on the activity of two toxic noncovalent complexes: edema toxin (edtx) and lethal toxin (letx). protective antigen (pa), an essential component of both complexes, binds with high affinity to the major receptor mediating the lethality of anthrax toxin in vivo, capillary morphogenesis protein 2 (cmg2). certain antibod ...201020956592
bacillus anthracis produces membrane-derived vesicles containing biologically active toxins.extracellular vesicle production is a ubiquitous process in gram-negative bacteria, but little is known about such process in gram-positive bacteria. we report the isolation of extracellular vesicles from the supernatants of bacillus anthracis, a gram-positive bacillus that is a powerful agent for biological warfare. b. anthracis vesicles formed at the outer layer of the bacterial cell had double-membrane spheres and ranged from 50 to 150 nm in diameter. immunoelectron microscopy with mabs to pr ...201020956325
contributions of edema factor and protective antigen to the induction of protective immunity by bacillus anthracis edema toxin as an intranasal adjuvant.we have shown that intranasal coapplication of bacillus anthracis protective ag (pa) together with a b. anthracis edema factor (ef) mutant having reduced adenylate cyclase activity (i.e., ef-s414n) enhances anti-pa ab responses, but also acts as a mucosal adjuvant for coadministered unrelated ags. to elucidate the role of edema toxin (edtx) components in its adjuvanticity, we examined how a pa mutant lacking the ability to bind ef (pa-u7) or another mutant that allows the cellular uptake of ef, ...201020952678
[recombinant antibodies for medical protection against bioterrorism agents: the example of anthrax].recombinant antibodies are a highly successful class of therapeutic molecules, they are well adapted for use against bio-weapons (bw) as they act immediately, are often synergistic with other therapeutic molecules, have a long half-life and are well tolerated. anthrax is regarded at high risk of being used as bw, and its pathogenic properties depend on toxins, which might be neutralized by antibodies. these toxins are made of three different types of sub-units (pa, lf, ef). several anti-pa have ...201020950579
anthrolysin o and fermentation products mediate the toxicity of bacillus anthracis to lung epithelial cells under microaerobic conditions.bacillus anthracis generates virulence factors such as lethal and edema toxins, capsule, and hemolytic proteins under conditions of reduced oxygenation. here, we report on the acute cytotoxicity of culture supernatants (sups) of six nonencapsulated b. anthracis strains grown till the stationary phase under static microaerobic conditions. human small airway epithelial, umbilical vein endothelial, caco-2, and hep-g2 cells were found to be susceptible. sups displayed a reduction of ph to 5.3-5.5, i ...201020946354
cell cycle arrest induced by the bacterial adenylate cyclase toxins from bacillus anthracis and bordetella pertussis.bacillus anthracis oedema toxin (et) and bordetella pertussis adenylate cyclase toxin (act) enter host cells and produce camp. to understand the cellular consequences, we exposed j774 cells to these toxins at ng ml(-1) (pm) concentrations, then followed cell number and changes in cell signalling pathways. under these conditions, both toxins produce a concentration-dependent inhibition of cell proliferation without cytotoxicity. et and act increase the proportion of cells in g(1) /g(0) and reduce ...201020946259
role of cypa and hsp90 in membrane translocation mediated by anthrax protective antigen.bacillus anthracis lethal toxin consists of the protective antigen (pa) and the metalloprotease lethal factor (lf). during cellular uptake pa forms pores in membranes of endosomes, and unfolded lf translocates through the pores into the cytosol. we have investigated whether host cell chaperones facilitate translocation of lf and the fusion protein lf(n)dta. lf(n) mediates uptake of lf(n)dta into the cytosol, where dta, the catalytic domain of diphtheria toxin, adp-ribosylates elongation factor-2 ...201020946244
anthrax toxins cooperatively inhibit endocytic recycling by the rab11/sec15 exocyst.bacillus anthracis is the causative agent of anthrax in humans and other mammals. in lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (lf) and oedema factor (ef), leading to widespread vascular leakage and shock. whereas host targets of lf (mitogen-activated protein-kinase kinases) and ef (camp-dependent processes) have been implicated in the initial phase of anthrax, less is understood about toxin action during the final stage of infection. her ...201020944747
curing the plasmid pxo2 from bacillus anthracis a16 using plasmid incompatibility.plasmid incompatibility, which has no effect on other plasmids or chromosomal genes, can be used to cure a target plasmid. in this report, we successfully cured the plasmid pxo2 from bacillus anthracis a16 with a newly constructed, incompatible plasmid pksv7-oriiv and obtained a new pxo2-cured strain, designated a16pi2. this is the first time that a plasmid was cured from the b. anthracis wild-type strain a16 utilizing this principle, which could be considered as an efficacious method to cure la ...201020927628
yhgc protects bacillus anthracis from oxidative stress.bacillus anthracis can cause lethal inhalational anthrax and can be used as a bioweapon due to its ability to form spores and to survive under various environmental stress conditions. yhgc in bacilli are structural homologues of trap, a protein involved in stress response in staphylococci. to test the role of yhgc in b. anthracis, yhgc gene was deleted in b. anthracis strain sterne and parent and mutant strains tested. immunolocalization studies indicated that yhgc is clustered both on the cell ...201020925037
psychosocial considerations for mass decontamination.mass exposure to explosions, infectious agents, foodborne illnesses, chemicals or radiological materials may require mass decontamination that have critical psychosocial implications for the public and for both traditional and non-traditional responders in terms of impact and of response. five main issues are common to mass decontamination events: (i) perception, (ii) somatisation, (iii) media role and communication, (iv) information sharing, (v) behavioural guidance and (vi) organisational issu ...201020924122
activation of the edema factor of bacillus anthracis by calmodulin: evidence of an interplay between the ef-calmodulin interaction and calcium binding.calmodulin (cam) is a remarkably flexible protein which can bind multiple targets in response to changes in intracellular calcium concentration. it contains four calcium-binding sites, arranged in two globular domains. the calcium affinity of cam n-terminal domain (n-cam) is dramatically reduced when the complex with the edema factor (ef) of bacillus anthracis is formed. here, an atomic explanation for this reduced affinity is proposed through molecular dynamics simulations and free energy pertu ...201020923661
a review of sentinel laboratory performance: identification and notification of bioterrorism agents.the anthrax incident of 2001 in the united states prompted the college of american pathologists (cap), the association of public health laboratories, and the centers for disease control and prevention to develop exercises for laboratory response network (lrn) sentinel laboratories.201020923306
neutrophil elastase mediates pathogenic effects of anthrax lethal toxin in the murine intestinal tract.neutrophils isolated from balb/c or c57bl/6 mice and treated in vitro with anthrax lethal toxin release bioactive neutrophil elastase, a proinflammatory mediator of tissue destruction. similarly, neutrophils isolated from mice treated with anthrax lethal toxin in vivo and cultured ex vivo release greater amounts of elastase than neutrophils from vehicle-treated controls. direct measurements from murine intestinal tissue samples demonstrate an anthrax lethal toxin-dependent increase in neutrophil ...201020921524
development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities.bioterrorism poses a daunting challenge to global security and public health in the 21st century. variola major virus, the etiological agent of smallpox, and bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as ...201020921397
testing nucleoside analogues as inhibitors of bacillus anthracis spore germination in vitro and in macrophage cell culture.bacillus anthracis, the etiological agent of anthrax, has a dormant stage in its life cycle known as the endospore. when conditions become favorable, spores germinate and transform into vegetative bacteria. in inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory tract and germinate in phagosomes of alveolar macrophages. germinated cells can then produce toxins and establish infection. thus, germination is a crucial step for the init ...201020921305
a requirement for fcγr in antibody-mediated bacterial toxin neutralization.one important function of humoral immunity is toxin neutralization. the current view posits that neutralization results from antibody-mediated interference with the binding of toxins to their targets, a phenomenon viewed as dependent only on antibody specificity. to investigate the role of antibody constant region function in toxin neutralization, we generated igg2a and igg2b variants of the bacillus anthracis protective antigen-binding igg1 monoclonal antibody (mab) 19d9. these antibodies expre ...201020921285
multi-species integrative biclustering.we describe an algorithm, multi-species cmonkey, for the simultaneous biclustering of heterogeneous multiple-species data collections and apply the algorithm to a group of bacteria containing bacillus subtilis, bacillus anthracis, and listeria monocytogenes. the algorithm reveals evolutionary insights into the surprisingly high degree of conservation of regulatory modules across these three species and allows data and insights from well-studied organisms to complement the analysis of related but ...201020920250
on some points regarding the distribution of bacillus anthracis in the human skin in malignant pustule. 188620896665
spatial analysis of an anthrax outbreak in saskatchewan, 2006.an outbreak of anthrax in saskatchewan in 2006 affected more than 800 animals at 150 locations. the purpose of this study was to assess the spatial and temporal patterns among the cases to determine if there were any significant trends associated with this outbreak. case and population data were first analyzed for each individual farm location and then again as aggregate data per rural municipality using spatial and spatiotemporal statistical methods such as oden's ipop, cuzick-edwards' test, sp ...201020885827
identification and characterization of clinical bacillus spp. isolates phenotypically similar to bacillus anthracis.bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming rod, with colonies exhibiting a unique ground-glass appearance, and lacking hemolysis and motility. in addition to these phenotypes, several others traits are characteristic of b. anthracis such as susceptibility to gamma phage, the presence of two virulence plasmids (px01 and px02), and specific cell wall and capsular antigens that are commonly detected by direct fluorescent-antibody assays. we report on the ...201020883499
targeted mutations of bacillus anthracis dihydrofolate reductase condense complex structure−activity relationships.several antifolates, including trimethoprim (tmp) and a series of propargyl-linked analogues, bind dihydrofolate reductase from bacillus anthracis (badhfr) with lower affinity than is typical in other bacterial species. to guide lead optimization for badhfr, we explored a new approach to determine structure-activity relationships whereby the enzyme is altered and the analogues remain constant, essentially reversing the standard experimental design. active site mutants of the enzyme, ba(f96i)dhfr ...201020882962
recognition of community-acquired anthrax: has anything changed since 2001?to compare responses of practicing military and civilian primary care physicians to a series of standardized inhalational anthrax cases.201020882930
enrichment of escherichia coli spheroplasts displaying scfv antibodies specific for antigens expressed on the human cell surface.anchored periplasmic expression (apex) is a method for isolating high affinity ligand-binding proteins from large combinatorial libraries, and antibodies highly specific for soluble antigens were successfully isolated from apex antibody libraries in combination with flow cytometric sorting (harvey et al., proc natl acad sci usa 101(25):9193-9198, 2004). however, many disease markers and drug targets are localized on the cell surface, and often, unique posttranslational modifications and/or prope ...201020878322
a two-stage, multilevel quality control system for serological assays in anthrax vaccine clinical trials.a two-stage, multilevel assay quality control (qc) system was designed and implemented for two high stringency qc anthrax serological assays; a quantitative anti-pa igg enzyme-linked immunosorbent assay (elisa) and an anthrax lethal toxin neutralization activity (tna) assay. the qc system and the assays were applied for the congressionally mandated centers for disease control and prevention (cdc) phase 4 human clinical trial of anthrax vaccine adsorbed (ava, biothrax). a total of 57,284 human se ...201020875951
a review of cutaneous anthrax and its outcome.anthrax is still an endemic disease in some countries in the world and has become a re-emerging disease in western countries with recent intentional outbreak. the aim of this study was to review our clinical experience with cutaneous anthrax cases. from the patient's files, transmission of the diseases, clinical findings and severity of infection, treatment and outcome of patients were recorded. twenty-two cases were diagnosed as cutaneous anthrax in the last 7 years. of these cases, 10 cases we ...201020869669
simultaneous pathogen detection and antibiotic resistance characterization using snp-based multiplexed oligonucleotide ligation-pcr (mol-pcr).extensive use of antibiotics in both public health and animal husbandry has resulted in rapid emergence of antibiotic resistance in almost all human pathogens, including biothreat pathogens. antibiotic resistance has thus become a major concern for both public health and national security. we developed multiplexed assays for rapid, simultaneous pathogen detection and characterization of ciprofloxacin and doxycycline resistance in bacillus anthracis, yersinia pestis, and francisella tularensis. t ...201020865530
antidotes to anthrax lethal factor intoxication. part 1: discovery of potent lethal factor inhibitors with in vivo efficacy.sub-nanomolar small molecule inhibitors of anthrax lethal factor have been identified using sar and merck l915 (4) as a model compound. one of these compounds (16) provided 100% protection in a rat lethal toxin model of anthrax disease.201020864339
electrically active magnetic nanoparticles as novel concentrator and electrochemical redox transducer in bacillus anthracis dna detection.magnetic polymer nanostructures are a new class of multifunctional nanomaterials that are recently being explored in biosensor devices. in this paper, for the first time we report the novel application of electrically active magnetic (eam) nanoparticles as concentrator of dna targets as well as electrochemical transducers for detection of the bacillus anthracis protective antigen a (pag a) gene. the eam nanoparticles are synthesized by chemical polymerization and have dimensions of 80-100 nm. th ...201020864333
atxa, a bacillus anthracis global virulence regulator.fifteen years ago, atxa was isolated as a toxin gene activator and five years later it was shown to be a bacillus anthracis master regulator. atxa controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. atxa can activate or repress gene expression. the mechanism by which atxa exerts its control is unknown; it is indirect on some genes but may be direct on others. the ...201020863885
principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents.the use of biological agents has generally been confined to military-led conflicts. however, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. there are a wide range of prophylactics and treatments being ...201020860656
chemical probing reveals insights into the signaling mechanism of inflammasome activation.caspase-1-mediated il-1β production is generally controlled by two pathways. toll-like receptors (tlrs) recognize pathogen-derived products and induce nf-κb-dependent pro-il-1β transcription; nod-like receptors (nlrs) assemble caspase-1-activating inflammasome complexes that sense bacterial products/danger signals. through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specific and potent inhibitor of the caspase-1 pathway. bromoxone is effective over diverse i ...201020856264
constitutive mek1 activation rescues anthrax lethal toxin-induced vascular effects in vivo.anthrax lethal toxin (lt) increases vascular leakage in a number of mammalian models and in human anthrax disease. using a zebrafish model, we determined that vascular delivery of lt increased permeability, which was phenocopied by treatment with a selective chemical inhibitor of mek1 and mek2 (also known as mitogen-activated protein kinase [mapk] kinase, mek, or mkk). here we investigate further the role of mek1/phospho-erk (perk) in the action of lt. overexpression of wild-type zebrafish mek1 ...201020855511
distinct immune responses of recombinant plasmid dna replicon vaccines expressing two types of antigens with or without signal sequences.here, dna replicon vaccines encoding the hc domain of botulinum neurotoxin serotype a (ahc) or the receptor binding domain of anthrax protective antigen (pa4) with or without signal sequences were evaluated in mice. strong antibody and protective responses were elicited only from ahc dna vaccines with an ig κ signal sequence or tissue plasminogen activator signal sequence. meanwhile, there were no differences in total antibody responses or isotypes, lymphocyte proliferative responses, cytokine p ...201020854897
identifying active phage lysins through functional viral metagenomics.recent metagenomic sequencing studies of uncultured viral populations have provided novel insights into the ecology of environmental bacteriophage. at the same time, viral metagenomes could also represent a potential source of recombinant proteins with biotechnological value. in order to identify such proteins, a novel two-step screening technique was devised for cloning phage lytic enzymes from uncultured viral dna. this plasmid-based approach first involves a primary screen in which transforme ...201020851985
sampling port for real-time analysis of bioaerosol in whole body exposure system for animal aerosol model development.multiple factors influence the viability of aerosolized bacteria. the delivery of aerosols is affected by chamber conditions (humidity, temperature, and pressure) and bioaerosol characteristics (particle number, particle size distribution, and viable aerosol concentration). measurement of viable aerosol concentration and particle size is essential to optimize viability and lung delivery. the madison chamber is widely used to expose small animals to infectious aerosols.201120849964
the effect of anthrax bioterrorism on emergency department presentation.from september through december 2001, 22 americans were diagnosed with anthrax, prompting widespread national media attention and public concern over bioterrorism. the purpose of this study was to determine the effect of the threat of anthrax bioterrorism on patient presentation to a west coast emergency department (ed).200520847852
adsorption of chlorine dioxide gas on activated carbons.research and field experience with chlorine dioxide (clo2) gas to decontaminate structures contaminated with bacillus anthracis spores and other microorganisms have demonstrated the effectiveness of this sterilant technology. however, because of its hazardous properties, the unreacted clo2, gas must be contained and captured during fumigation events. although activated carbon has been used during some decontamination events to capture the clo2 gas, no data are available to quantify the performan ...201020842929
residue histidine 669 is essential for the catalytic activity of bacillus anthracis lethal factor.the lethal factor (lf) of bacillus anthracis is a zn(2+)-dependent metalloprotease which plays an important role in anthrax virulence. this study was aimed at identifying the histidine residues that are essential to the catalytic activities of lf. the site-directed mutagenesis was employed to replace the 10 histidine residues in domains ii, iii, and iv of lf with alanine residues, respectively. the cytotoxicity of these mutants was tested, and the results revealed that the alanine substitution f ...201020833809
groel provides protection against bacillus anthracis infection in balb/c mice.heat shock proteins (hsps) of the hsp60 and hsp70 family are highly conserved and essential to all living organisms. hsps are immunodominant in numerous microbial infections and have been investigated for their vaccine potential. we investigated the immunogenicity and protective efficacy of groel and dnak of b. anthracis in murine model. both hsps were found to be highly immunogenic with mixed antibody response (both igg1 and igg2a), indicating stimulation of both humoral and cell-mediated immun ...201020832865
high-resolution crystal structures of the flavoprotein nrdi in oxidized and reduced states--an unusual flavodoxin. structural biology.the small flavoprotein nrdi is an essential component of the class ib ribonucleotide reductase system in many bacteria. nrdi interacts with the class ib radical generating protein nrdf. it is suggested to be involved in the rescue of inactivated diferric centres or generation of active dimanganese centres in nrdf. although nrdi bears a superficial resemblance to flavodoxin, its redox properties have been demonstrated to be strikingly different. in particular, nrdi is capable of two-electron redu ...201020831589
survival of bacillus anthracis spores in fruit juices and wine.foods have been identified as a potential target for bioterrorism due to their essential nature and global distribution. foods produced in bulk have the potential to have large batches of product intentionally contaminated, which could affect hundreds or thousands of individuals. bacillus anthracis spores are one potential bioterrorism agent that may survive pasteurization and remain viable throughout the shelf life of fruit juices and cause disease if consumed. this project examined b. anthraci ...201020828478
development and validation of a real-time quantitative pcr assay for rapid identification of bacillus anthracis in environmental samples.a real-time polymerase chain reaction (pcr) assay was developed for rapid identification of bacillus anthracis in environmental samples. these samples often harbor bacillus cereus bacteria closely related to b. anthracis, which may hinder its specific identification by resulting in false positive signals. the assay consists of two duplex real-time pcr: the first pcr allows amplification of a sequence specific of the b. cereus group (b. anthracis, b. cereus, bacillus thuringiensis, bacillus weihe ...201020827474
a multiplex real-time pcr for identifying and differentiating b. anthracis virulent types.bacillus anthracis is closely related to the endospore forming bacteria bacillus cereus and bacillus thuringiensis. for accurate detection of the life threatening pathogen b. anthracis, it is essential to distinguish between these three species. here we present a novel multiplex real-time pcr for simultaneous specific identification of b. anthracis and discrimination of different b. anthracis virulence types. specific b. anthracis markers were selected by whole genome comparison and different se ...201120826037
bioinformatic tools for using whole genome sequencing as a rapid high resolution diagnostic typing tool when tracing bioterror organisms in the food and feed chain.the rapid technological development in the field of parallel sequencing offers new opportunities when tracing and tracking microorganisms in the food and feed chain. if a bioterror organism is deliberately spread it is of crucial importance to get as much information as possible regarding the strain as fast as possible to aid the decision process and select suitable controls, tracing and tracking tools. a lot of efforts have been made to sequence multiple strains of potential bioterror organisms ...201120826036
matrix-assisted laser desorption ionization time-of-flight mass spectrometry: usefulness for taxonomy and epidemiology.matrix-assisted laser desorption ionization time-of-flight (maldi-tof) mass spectrometry (ms) is a powerful tool for the species and subspecies classification of a broad spectrum of bacteria, including gram-positive bacteria such as staphylococcus, streptococcus and listeria, and gram-negative bacteria such as neisseria, salmonella, aeromonas, campylobacter and helicobacter. maldi-tof ms has also been used for the rapid identification and typing of potential bioterrorism agents, including coxiel ...201020825435
public compliance with mass prophylaxis guidance.in 2008, the new york city department of health and mental hygiene (nyc dohmh) conducted a series of 8 focus groups to determine what improvements could be made to existing plans to ensure that the public would adhere to instructions issued during an emergency that required mass antibiotic distribution following an aerosolized anthrax attack. discussion focused on perceptions surrounding public health emergencies, overall point-of dispensing (pod) strategy, willingness to pick up medications for ...201020825336
structural study and thermodynamic characterization of inhibitor binding to lumazine synthase from bacillus anthracis.the crystal structure of lumazine synthase from bacillus anthracis was solved by molecular replacement and refined to r(cryst) = 23.7% (r(free) = 28.4%) at a resolution of 3.5 a. the structure reveals the icosahedral symmetry of the enzyme and specific features of the active site that are unique in comparison with previously determined orthologues. the application of isothermal titration calorimetry in combination with enzyme kinetics showed that three designed pyrimidine derivatives bind to lum ...201020823551
case records of the massachusetts general hospital. case 25-2010. a 24-year-old woman with abdominal pain and shock. 201020818879
a bacteriophage-based platform for rapid trace detection of proteases.sensitive, inexpensive, and rapid protease activity assays are of great merit for clinical diagnostics. detection of protease-based toxins produced by clostridium botulinum and bacillus anthracis represents a particularly challenging task, as exceptional sensitivity is a prerequisite because of the extreme potency of the toxins. here we present an inexpensive and sensitive assay platform for activity-based protease quantification utilizing filamentous bacteriophage as an exponentially amplifiabl ...201020812737
rapid identification of genetic modifications in bacillus anthracis using whole genome draft sequences generated by 454 pyrosequencing.the anthrax letter attacks of 2001 highlighted the need for rapid identification of biothreat agents not only for epidemiological surveillance of the intentional outbreak but also for implementing appropriate countermeasures, such as antibiotic treatment, in a timely manner to prevent further casualties. it is clear from the 2001 cases that survival may be markedly improved by administration of antimicrobial therapy during the early symptomatic phase of the illness; i.e., within 3 days of appear ...201020811637
a multiplex nanoparticle-based bio-barcoded dna sensor for the simultaneous detection of multiple pathogens.a highly amplified, nanoparticle-based, bio-barcoded electrochemical biosensor for the simultaneous multiple detection of the protective antigen a (paga) gene (accession number, m22589) of bacillus anthracis and the insertion element (iel) gene (accession number, z83734) of salmonella enteritidis is reported in this paper. the biosensor system is mainly composed of three nanoparticles: gold nanoparticles (aunps), magnetic nanoparticles (mnps), and nanoparticle tracers (nts, such as pbs and cds). ...201020810267
evaluation of the house fly musca domestica as a mechanical vector for an anthrax.anthrax is a disease of human beings and animals caused by the encapsulated, spore-forming, bacillus anthracis. the potential role of insects in the spread of b. anthracis to humans and domestic animals during an anthrax outbreak has been confirmed by many studies. among insect vectors, the house fly musca domestica is considered a potential agent for disease transmission. in this study, laboratory-bred specimens of musca domestica were infected by feeding on anthrax-infected rabbit carcass or a ...201020808920
two rare presentations of fatal anthrax: meningeal and intestinal.anthrax is an ancient disease of animals and men, caused by bacillus anthracis. the diagnosis of cutaneous infection is relatively easy, but other clinical forms might escape recognition. we present two rare and fatal forms of anthrax: meningeal in a 33-year-old male shepherd and intestinal in a 4-year-old boy. the former was admitted to the hospital with complaints of headache, vomiting, fever, and decreased level of consciousness. the latter presented with abdominal pain and distension, vomiti ...201020804313
suspected outbreak of cutaneous anthrax in kasese district, the investigation and response, april to may 2007.a report of suspected anthrax was submitted by the kasese district health office to the epidemiology surveillance division of ministry of health. a joint team comprising officers from moh, iph and mph officers proceeded to the district to investigate the reported threat of anthrax. the investigations were conducted in bwera hsd, bukonjo west county, in communities bordering queen elizabeth national park.200920803911
evaluation of bacillus strains as model systems for the work on bacillus anthracis spores.available strain collections of bacillus anthracis and bacillus cereus were screened for b. cereus strains sharing major genotypic characteristics with b. anthracis. based on the comparison of partial spoiiiab sequences, whole genome sequences and mlst, a strain set representing different lineages including candidate model strains for b. anthracis was compiled. spores from the selected strain set and two b. anthracis strains were prepared according to a newly optimized protocol transferable to b ...201120800917
characterization of the n-acetyl-α-d-glucosaminyl l-malate synthase and deacetylase functions for bacillithiol biosynthesis in bacillus anthracis .bacillithiol (cys-glcn-malate, bsh) has recently been identified as a novel low-molecular weight thiol in bacillus anthracis, staphylococcus aureus, and several other gram-positive bacteria lacking glutathione and mycothiol. we have now characterized the first two enzymes for the bsh biosynthetic pathway in b. anthracis, which combine to produce α-d-glucosaminyl l-malate (glcn-malate) from udp-glcnac and l-malate. the structure of the glcnac-malate intermediate has been determined, as have the k ...201020799687
[anthrax cattle burial grounds in russia and their biosafety].to develop standard operating procedure for assessment level of biohazard for population living near existing cattle burial grounds.201020799398
influence of particle size on the pathology and efficacy of vaccination in a murine model of inhalational anthrax.deposition of bacillus anthracis endospores within either the lungs or nasal passages of a/j mice after aerosol exposure was influenced by different particle sized aerosols and resulted in different infection kinetics. the infection resulting from the inhalation of endospores within a 12 μm particle aerosol was prolonged compared to that from a 1 μm particle aerosol with a mean time-to-death of 161 ± 16.1 h and 101.6 ± 10.4 h, respectively. inhalation of endospores within 1 μm or 12 μm particle ...201020798216
cemovis on a pathogen: analysis of bacillus anthracis spores.background information: under conditions of starvation, bacteria of bacillus ssp. are able to form a highly structured cell type, the dormant spore. when the environment presents more favourable conditions, the spore starts to germinate, which will lead to the release of the vegetative form in the life cycle, the bacillus. for bacillus anthracis, the aetiological agent of anthrax, germination is normally linked to host uptake and represents an important step in the onset of anthrax disease. morp ...201020795943
treatment of human cutaneous anthrax with penicillin. 194520786196
cutaneous anthrax treated with penicillin. 194520786103
cutaneous anthrax treated by arsenicals and sulphapyridine. 194120783972
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