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pharmacodynamically guided levofloxacin dosing for pediatric community-acquired pneumonia.oral levofloxacin is recommended as a preferred treatment for pediatric community-acquired penicillin-resistant streptococcus pneumoniae pneumonia. this article describes a pharmacodynamically guided levofloxacin regimen and the probability of the pharmacodynamic target being attained in s pneumoniae isolates collected from pediatric patients.201626903555
comparison of french and worldwide bacillus anthracis strains favors a recent, post-columbian origin of the predominant north-american clade.bacillus anthracis, the highly dangerous zoonotic bacterial pathogen species is currently composed of three genetic groups, called a, b and c. group a is represented worldwide whereas group b is present essentially in western europe and southern africa. only three strains from group c have been reported. this knowledge is derived from the genotyping of more than 2000 strains collected worldwide. strains from both group a and group b are present in france. previous investigations showed that the ...201626901621
development of a zealand white rabbit deposition model to study inhalation anthrax.despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. such information allows dosimetric extrapolation to humans to inform human outcomes. the lung geometry of the new zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scann ...201626895308
dose-response modeling for inhalational anthrax in rabbits following single or multiple exposures.there is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. the exposure scenario most often considered is a single exposure that occurs during an attack. however, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. on ...201626889937
childhood-onset eosinophilic granulomatosis with polyangiitis: a rare childhood vasculitis mimicking anthrax and eosinophilic leukaemia.a 14-year-old boy previously misdiagnosed as having cutaneous anthrax was referred with a 2-month history of multiple wide and deep ulceronecrotic lesions in the lower extremities, which occurred after contact with animals. skin biopsy was compatible with vasculitis. further examination at our hospital elicited eosinophilia and a history of asthma. on the second day of hospitalisation, he developed deep vein thrombosis. a diagnosis of eosinophilic granulomatosis with polyangiitis (egpa) was esta ...201626887883
a cumulative spore killing approach: synergistic sporicidal activity of dilute peracetic acid and ethanol at low ph against clostridium difficile and bacillus subtilis spores.background.  alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with ph 1.5-2 that were as effective as soap and water washing in reducing levels of c difficile spores on hands. we hypothesized that the addit ...201626885539
gene control of tyrosine kinase tie2 and vascular manifestations of infections.ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. here, we show that tie2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. f ...201626884170
considerations for estimating microbial environmental data concentrations collected from a field setting.in the event of an indoor release of an environmentally persistent microbial pathogen such as bacillus anthracis, the potential for human exposure will be considered when remedial decisions are made. microbial site characterization and clearance sampling data collected in the field might be used to estimate exposure. however, there are many challenges associated with estimating environmental concentrations of b. anthracis or other spore-forming organisms after such an event before being able to ...201726883476
ultrasensitive electrochemical immunoassay for surface array protein, a bacillus anthracis biomarker using au-pd nanocrystals loaded on boron-nitride nanosheets as catalytic labels.bacillus anthracis, the causative agent of anthrax, is a well known bioterrorism agent. the determination of surface array protein (sap), a unique biomarker for b. anthracis can offer an opportunity for specific detection of b. anthracis in culture broth. in this study, we designed a new catalytic bionanolabel and fabricated a novel electrochemical immunosensor for ultrasensitive detection of b. anthracis sap antigen. bimetallic gold-palladium nanoparticles were in-situ grown on poly (diallyldim ...201626874112
rapid detection of viable bacillus anthracis spores in environmental samples by using engineered reporter phages.bacillus anthracis, the causative agent of anthrax, was utilized as a bioterrorism agent in 2001 when spores were distributed via the u.s. postal system. in responding to this event, the federal bureau of investigation used traditional bacterial culture viability assays to ascertain the extent of contamination of the postal facilities within 24 to 48 h of environmental sample acquisition. here, we describe a low-complexity, second-generation reporter phage assay for the rapid detection of viable ...201626873316
whole genome analysis of injectional anthrax identifies two disease clusters spanning more than 13 years.anthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple european countries and this outbreak has been difficult to trace back to a source.201526870786
cytotoxic potential of bacillus cereus strains atcc 11778 and 14579 against human lung epithelial cells under microaerobic growth conditions.bacillus cereus, a food poisoning bacterium closely related to bacillus anthracis, secretes a multitude of virulence factors including enterotoxins, hemolysins, and phospholipases. however, the majority of the in vitro experiments evaluating the cytotoxic potential of b. cereus were carried out in the conditions of aeration, and the impact of the oxygen limitation in conditions encountered by the microbe in natural environment such as gastrointestinal tract remains poorly understood. this resear ...201626870026
genome sequence of bacillus pumilus strain bonn, isolated from an anthrax-like necrotic skin infection site of a child.we report the draft genome sequence of bacillus pumilus strain bonn associated with human skin infection. b. pumilus bonn was isolated from a carbuncle-like necrotic site, resembling cutaneous anthrax, on the back of the hand of a 10-year-old child.201626868410
humoral and cell-mediated immune responses to alternate booster schedules of anthrax vaccine adsorbed in humans.protective antigen (pa)-specific antibody and cell-mediated immune (cmi) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (ava; biothrax) were characterized in humans over 43 months. study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (im) priming series (0, 1, and 6 months) with a single booster at 42 months (4-im); 3-dose im priming with boosters at 18 and 42 months (5-im); 3-dose im priming with boosters at 12, 18, 30, and 42 months ...201626865594
development of a sterne-based complement fixation test to monitor the humoral response induced by anthrax vaccines.anthrax is a zoonotic disease caused by bacillus anthracis spore-forming bacterium. since it is primarily a disease of animals, the control in animals, and humans depend on the prevention in livestock, principally cattle, sheep, and goats. most veterinary vaccines utilize the toxigenic, uncapsulated (pxo1+/pxo2-) b. anthracis strain 34f2 which affords protection through the production of neutralizing antibodies directed to the toxin components protective antigen (pa), lethal factor (lf), and ede ...201626858700
the use of germinants to potentiate the sensitivity of bacillus anthracis spores to peracetic acid.elimination of bacillus anthracis spores from the environment is a difficult and costly process due in part to the toxicity of current sporicidal agents. for this reason we investigated the ability of the spore germinants l-alanine (100 mm) and inosine (5 mm) to reduce the concentration of peracetic acid (paa) required to inactivate b. anthracis spores. while l-alanine significantly enhanced (p = 0.0085) the bactericidal activity of 500 ppm paa the same was not true for inosine suggesting some f ...201626858699
diminished but not abolished effect of two his351 mutants of anthrax edema factor in a murine model.edema toxin (et), which is composed of a potent adenylate cyclase (ac), edema factor (ef), and protective antigen (pa), is one of the major toxicity factors of bacillus anthracis. in this study, we introduced mutations in full-length ef to generate alanine ef(h351a) and arginine ef(h351r) variants. in vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type ef. when the native and mutant toxins were administ ...201626848687
crisis standard needed for anthrax medical countermeasure screening. 201626836584
the role of dna restriction-modification systems in the biology of bacillus anthracis.restriction-modification (r-m) systems are widespread among prokaryotes and, depending on their type, may be viewed as selfish genetic elements that persist as toxin-antitoxin modules, or as cellular defense systems against phage infection that confer a selective advantage to the host bacterium. studies in the last decade have made it amply clear that these two options do not exhaust the list of possible biological roles for r-m systems. their presence in a cell may also have a bearing on other ...201626834729
living at the edge of an interface area in zimbabwe: cattle owners, commodity chain and health workers' awareness, perceptions and practices on zoonoses.in the great limpopo transfrontier conservation area (gltfca), there is an increased interface between wildlife and domestic animals, because rural households move their cattle into the game park in search of grazing and watering resources. this creates opportunities for inter-species transmission of infectious diseases, including zoonoses like brucellosis and tuberculosis, which may also pose a health risk to the local rural communities. this study investigated the awareness, perceptions and pr ...201626822888
a d-amino acid at the n-terminus of a protein abrogates its degradation by the n-end rule pathway.eukaryotes have evolved the ubiquitin (ub)/proteasome system to degrade polypeptides. the ub/proteasome system is one way that cells regulate cytosolic protein and amino acids levels through the recognition and ubiquitination of a protein's n-terminus via e1, e2, and e3 enzymes. the process by which the n-terminus stimulates intracellular protein degradation is referred to as the n-end rule. characterization of the n-end rule has been limited to only the natural l-amino acids. using a cytosolic ...201526807441
roles of anthrax toxin receptor 2 in anthrax toxin membrane insertion and pore formation.interaction between bacterial toxins and cellular surface receptors is an important component of the host-pathogen interaction. anthrax toxin protective antigen (pa) binds to the cell surface receptor, enters the cell through receptor-mediated endocytosis, and forms a pore on the endosomal membrane that translocates toxin enzymes into the cytosol of the host cell. as the major receptor for anthrax toxin in vivo, anthrax toxin receptor 2 (antxr2) plays an essential role in anthrax toxin action by ...201626805886
recombinant hsa-cmg2 is a promising anthrax toxin inhibitor.anthrax toxin is the major virulence factor produced by bacillus anthracis. protective antigen (pa) is the key component of the toxin and has been confirmed as the main target for the development of toxin inhibitors. the inhibition of the binding of pa to its receptor, capillary morphogenesis protein-2 (cmg2), can effectively block anthrax intoxication. the recombinant, soluble von willebrand factor type a (vwa) domain of cmg2 (scmg2) has demonstrated potency against anthrax toxin. however, the ...201626805881
the regulation of exosporium-related genes in bacillus thuringiensis.bacillus anthracis, bacillus cereus, and bacillus thuringiensis (bt) are spore-forming members of the bacillus cereus group. spores of b. cereus group species are encircled by exosporium, which is composed of an external hair-like nap and a paracrystalline basal layer. despite the extensive studies on the structure of the exosporium-related proteins, little is known about the transcription and regulation of exosporium gene expression in the b. cereus group. herein, we studied the regulation of s ...201626805020
evaluation of the efficacy of methyl bromide in the decontamination of building and interior materials contaminated with bacillus anthracis spores.the primary goal of this study was to determine the conditions required for the effective inactivation of bacillus anthracis spores on materials by using methyl bromide (mebr) gas. another objective was to obtain comparative decontamination efficacy data with three avirulent microorganisms to assess their potential for use as surrogates for b. anthracis ames. decontamination tests were conducted with spores of b. anthracis ames and geobacillus stearothermophilus, b. anthracis nnr1δ1, and b. anth ...201626801580
bacillus anthracis ω-amino acid:pyruvate transaminase employs a different mechanism for dual substrate recognition than other amine transaminases.understanding the metabolic potential of organisms or a bacterial community based on their (meta) genome requires the reliable prediction of an enzyme's function from its amino acid sequence. besides a remarkable development in prediction algorithms, the substrate scope of sequences with low identity to well-characterized enzymes remains often very elusive. from a recently conducted structure function analysis study of plp-dependent enzymes, we identified a putative transaminase from bacillus an ...201626795966
outbreak of anthrax in adults and adolescents: a review of nine cases in a regional teaching hospital in east hungary. 201726794029
hot, humid air decontamination of a c-130 aircraft contaminated with spores of two acrystalliferous bacillus thuringiensis strains, surrogates for bacillus anthracis.to develop test methods and evaluate survival of bacillus thuringiensis kurstaki cry(-) hd-1 and b. thuringiensis al hakam spores after exposure to hot, humid air inside of a c-130 aircraft.201626786717
anthrax toxin receptor 1 is essential for arteriogenesis in a mouse model of hindlimb ischemia.anthrax toxin receptor 1/tumor endothelial marker 8 (antxr1 or tem8) is up-regulated in tumor vasculature and serves as a receptor for anthrax toxin, but its physiologic function is unclear. the objective of this study was to evaluate the role of antxr1 in arteriogenesis. the role of antxr1 in arteriogenesis was tested by measuring gene expression and immunohistochemistry in a mouse model of hindlimb ischemia using wild-type and antxr1(-/-) mice. additional tests were performed by measuring gene ...201626785120
applying science: opportunities to inform disease management policy with cooperative research within a one health framework.the ongoing ebola outbreak in west africa and the current saiga antelope die off in kazakhstan each represent very real and difficult to manage public or veterinary health crises. they also illustrate the importance of stable and funded surveillance and sound policy for intervention or disease control. while these two events highlight extreme cases of infectious disease (ebola) or (possible) environmental exposure (saiga), diseases such as anthrax, brucellosis, tularemia, and plague are all zoon ...201526779471
cd4+ t cells targeting dominant and cryptic epitopes from bacillus anthracis lethal factor.anthrax is an endemic infection in many countries, particularly in the developing world. the causative agent, bacillus anthracis, mediates disease through the secretion of binary exotoxins. until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. there is, however, growing recognition that cellular immune responses involving ifnγ producing cd4+ t cells also contribute significantly to a protective memory respon ...201526779161
expression and refolding of the protective antigen of bacillus anthracis: a model for high-throughput screening of antigenic recombinant protein refolding.bacillus anthracis protective antigen (pa) is a well known and relevant immunogenic protein that is the basis for both anthrax vaccines and diagnostic methods. properly folded antigenic pa is necessary for these applications. in this study a high level of pa was obtained in recombinant escherichia coli. the protein was initially accumulated in inclusion bodies, which facilitated its efficient purification by simple washing steps; however, it could not be recognized by specific antibodies. refold ...201626777581
[screening and antibacterial function of bacillus amyloliquefaciens x030].we isolated 339 bacillus strains from 72 soil samples all over the country, then purified their antimicrobial compounds and studied the antibacterial activity, to enrich bacillus resources and explore their second metabolites.201526762026
antigen binding and site-directed labeling of biosilica-immobilized fusion proteins expressed in diatoms.the diatom thalassiosira pseudonana was genetically modified to express biosilica-targeted fusion proteins comprising either enhanced green fluorescent protein (egfp) or single chain antibodies engineered with a tetracysteine tagging sequence. of interest were the site-specific binding of (1) the fluorescent biarsenical probe ascy3 and ascy3e to the tetracysteine tagged fusion proteins and (2) high and low molecular mass antigens, the bacillus anthracis surface layer protein ea1 or small molecul ...201626746113
structural basis for latency and function of immune inhibitor a metallopeptidase, a modulator of the bacillus anthracis secretome.immune inhibitor a(inha)-type metallopeptidases are potential virulence factors secreted by members of the bacillus cereus group. two paralogs from anthrax-causing bacillus anthracis (bainha1 and bainha2) were shown to degrade host tissue proteins with broad substrate specificity. analysis of their activation mechanism and the crystal structure of a zymogenic bainha2 variant revealed a ∼750-residue four-domain structure featuring a pro-peptide, a catalytic domain, a domain reminiscent of viral e ...201626745529
feeding anthrax: the crystal structure of bacillus anthracis inha protease.pathogenic bacteria secrete proteases to evade host defense and to acquire nutrients. in this issue of structure, arolas et al. (2016) describe the structural basis of activation and latency of inha, a major secreted protease of bacillus anthracis.201626745525
loss of σi affects heat-shock response and virulence gene expression in bacillus anthracis.the pathogenesis of bacillus anthracis depends on several virulence factors, including the anthrax toxin. loss of the alternative sigma factor σi results in a coordinate decrease in expression of all three toxin subunits. our observations suggest that loss of σi alters the activity of the master virulence regulator atxa, but atxa transcription is unaffected by loss of σi. σi-containing rna polymerase does not appear to directly transcribe either atxa or the toxin gene paga. as in bacillus subtil ...201626744224
the efficacy and safety of nine south african medicinal plants in controlling bacillus anthracis sterne vaccine strain.anthrax is a zoonotic disease caused by bacillus anthracis, a gram-positive spore-forming bacterium. the presence of the bacteria and the toxins in the blood of infected hosts trigger a cascade of pathological events leading to death. nine medicinal plants with good activities against other bacteria were selected to determine their in vitro antibacterial activity against bacillus anthracis sterne strain. the cytotoxicity of the extracts on vero kidney cells was also determined.201626742484
adenoviral expression of a bispecific vhh-based neutralizing agent that targets protective antigen provides prophylactic protection from anthrax in mice.bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (lt and et, respectively). the common component in these toxins, protective antigen (pa), is responsible for binding to cellular receptors and translocating the lethal factor (lf) and edema factor (ef) enzymatic moieties to the cytosol. antibodies against pa protect against anthrax. we previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only ...201626740390
identification of b. anthracis n(5)-carboxyaminoimidazole ribonucleotide mutase (pure) active site binding compounds via fragment library screening.the de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and pure from this pathway has been identified to be crucial for bacillus anthracis survival in serum. in this study we adopted a fragment-based hit discovery approach, using three screening methods-saturation transfer difference nucleus magnetic resonance (std-nmr), water-ligand observed via gradient spectroscopy (waterlogsy) nmr, and surface plasmon resonance (spr), against b. anthracis pure (bapure) ...201626740153
technical note: simple, scalable, and sensitive protocol for retrieving bacillus anthracis (and other live bacteria) from heroin.we describe a culture-based method suitable for isolating bacillus anthracis and other live bacteria from heroin. this protocol was developed as a consequence of the bioforensic need to retrieve bacteria from batches of the drug associated with cases of injectional anthrax among heroin-consumers in europe. this uncommon manifestation of infection with the notorious pathogen b. anthracis has resulted in 26 deaths between the years 2000 to 2013. thus far, no life disease agent has been isolated fr ...201626734987
next-generation bacillus anthracis live attenuated spore vaccine based on the htra(-) (high temperature requirement a) sterne strain.anthrax is a lethal disease caused by the gram-positive spore-producing bacterium bacillus anthracis. live attenuated vaccines, such as the nonencapsulated sterne strain, do not meet the safety standards mandated for human use in the western world and are approved for veterinary purposes only. here we demonstrate that disrupting the htra gene, encoding the chaperone/protease htra (high temperature requirement a), in the virulent bacillus anthracis vollum strain results in significant virulence a ...201626732659
a complex role of anthrax toxin receptor 2 polymorphisms and capillary morphogenesis protein 2 in ankylosing spondylitis pathogenesis.this study investigated the role of anthrax toxin receptor 2 (antxr2) gene polymorphisms and capillary morphogenesis protein 2 (cmg2) expression in susceptibility and pathogenesis to ankylosing spondylitis (as) in the han chinese in beijing. a case-control study was performed using 602 as patient samples meeting the revised new york criterion and 619 matched controls from han chinese individuals. nineteen single-nucleotide polymorphisms (snps) of antxr2 genes were selected and genotyped using th ...201626728147
human cutaneous anthrax, the east anatolian region of turkey 2008-2014.anthrax is a zoonotic infectious disease caused by bacillus anthracis. while anthrax is rare in developed countries, it is endemic in turkey. the names of the different forms of the disease refer to the manner of entry of the spores into the body-cutaneous, gastrointestinal, inhalation, and injection. the purpose of this study was to evaluate the clinical characteristics, epidemiological history, treatment, and outcomes of patients with anthrax. eighty-two cases of anthrax hospitalized at atatür ...201626720232
antibody-based biologics and their promise to combat staphylococcus aureus infections.the growing incidence of serious infections mediated by methicillin-resistant staphylococcus aureus (mrsa) strains poses a significant risk to public health. this risk is exacerbated by a prolonged void in the discovery and development of truly novel antibiotics and the absence of a vaccine. these gaps have created renewed interest in the use of biologics in the prevention and treatment of serious staphylococcal infections. in this review, we focus on efforts towards the discovery and developmen ...201626719219
composite sampling approaches for bacillus anthracis surrogate extracted from soil.any release of anthrax spores in the u.s. would require action to decontaminate the site and restore its use and operations as rapidly as possible. the remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples c ...201526714315
structural characterization of zinc-bound zmp1, a zinc-dependent metalloprotease secreted by clostridium difficile.proteases are commonly secreted by microorganisms. in some pathogens, they can play a series of functional roles during infection, including maturation of cell surface or extracellular virulence factors, interference with host cell signaling, massive host tissue destruction, and dissolution of infection-limiting clots through degradation of the host proteins devoted to the coagulation cascade. we previously reported the identification and characterization of zmp1, a zinc-dependent metalloproteas ...201626711661
[development of specific therapy to category a toxic infections].category a select agents continue to be major threat to human population both as naturally occurring diseases and as potential weapon of bioterrorists. anthrax and botulism are probably the most threatening agents as both have virtually uncontrolled natural reservoirs from which they can be isolated and propagated. available specific antitoxin therapy of both diseases is outdated; its efficiency is questionable as well as safety of reactogenic or human-derived components used in treatment. highl ...201526710525
anthrax susceptibility: human genetic polymorphisms modulating antxr2 expression.anthrax toxin causes anthrax pathogenesis and expression levels of antxr2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. previous studies found that antxr2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eqtls (expression quantitative trait loci) have been identified. by using 3c (chromatin conformation capture), crispr-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing ...201526703731
does bacillus anthracis lethal toxin directly depress myocardial function? a review of clinical cases and preclinical studies.the us outbreak of b.anthracis infection in 2001 and subsequent cases in the us and europe demonstrate that anthrax is a continuing risk for the developed world. while several bacterial components contribute to the pathogenesis of b. anthracis, production of lethal toxin (lt) is strongly associated with the development of hypotension and lethality. however, the mechanisms underlying the cardiovascular instability lt produces are unclear. some evidence suggests that lt causes shock by impairing t ...201526703730
cutaneous anthrax in an unusual location: case report.cutaneous anthrax is well known, unlike anthrax of the lumbar region, which is not reported elsewhere. we present a case of anthrax of the lumbar region in a 50-year-old man. the infection was characterised by a wide, black eschar and oedema on an erythematous ground. after isolation of the gram-positive bacilli from the skin lesions, prompt antibiotic treatment (intravenous sulbactam-ampicillin 1.5 g every six hours) was initiated. following eradication of the bacilli after 14 days of antibioti ...201526700091
a strategic approach for rapid synthesis of gold and silver nanoparticles by panax ginseng leaves.the study highlights the synthesis of gold nanoparticles and silver nanoparticles by fresh leaves of panax ginseng, an herbal medicinal plant. the reduction of auric chloride and silver nitrate led to the formation of gold and silver nanoparticles within 3 and 45 min, at 80°c, respectively. the developed methodology was rapid, facile, ecofriendly and the utmost significant is quite economical, which did not require subsequent processing for reduction or stabilization of nanoparticles. the nanopa ...201626698271
antitoxin treatment of inhalation anthrax: a systematic review.concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. we conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recom ...201726690378
overexpression of the pleiotropic regulator cody decreases sporulation, attachment and pellicle formation in bacillus anthracis.cody, a global transcriptional regulator, primarily functions as a nutrient and energy sensor. it is activated by metabolic effectors like bcaa and gtp. in low g + c gram positive bacteria, it facilitates coupling of changes in the cellular metabolite pool with those required in the transcriptome of the cell. this pleiotropic regulator controls the expression of a vast number of genes as the cell transits from exponential to the stationary phase. earlier studies have shown that cody is required ...201626686421
detection and management of the first human anthrax outbreak in togo.the aim of this study was to describe and define an outbreak of human anthrax in two villages in the northern savannah region of togo.201626672006
historical cases of anthrax in sweden 1916-1961.as in most european countries, anthrax was common in swedish livestock during the centuries leading up to the mid-twentieth century. after 1957, the disease was regarded as practically extinct. however, in the past 7 years, three outbreaks have caused public alarm because of the risk of environmental contamination. properly buried carcasses should present little risk of spore contamination, and instructions were in place to ensure this since the 1890s. however, as has been demonstrated in recent ...201526671241
spatio-temporal patterns of an anthrax outbreak in white-tailed deer, odocoileus virginanus, and associated genetic diversity of bacillus anthracis.anthrax, a soil-borne zoonosis caused by the bacterium bacillus anthracis, is enzootic in areas of north america with frequent outbreaks in west texas. despite a long history of study, pathogen transmission during natural outbreaks remains poorly understood. here we combined case-level spatio-temporal analysis and high resolution genotyping to investigate anthrax transmission dynamics. carcass locations from a single white-tailed deer, odocoileus virginanus, outbreak were analyzed for spatial cl ...201526669305
infantile systemic hyalinosis in identical twins.infantile systemic hyalinosis (ish) is a rare disorder belonging to the heterogeneous group of genetic fibromatoses. it is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues caused by mutations in the anthrax toxin receptor 2 gene - antxr2. it presents hyperpigmented skin over bony prominences. characteristic purplish patches develop over the medial and lateral malleoli of the ankles, the metacarpophalangeal joints, ...201526668783
genetic characterization of bacillus anthracis 17 jb strain.bacillus anthracis is one of the most homogenous bacteria ever described. some level of diversity. bacillus anthracis 17jb is a laboratory strain it is broadly used as a challenge strain in guinea pigs for potency test of anthrax vaccine.201526668705
real-time pcr identification of unique bacillus anthracis sequences.bacillus anthracis is a spore-forming, gram-positive microorganism. it is a causative agent of anthrax, a highly infectious disease. it belongs to the "bacillus cereus group", which contains other closely related species, including bacillus cereus, bacillus thuringiensis, bacillus mycoides, bacillus weihenstephanensis, and bacillus pseudomycoides. b. anthracis naturally occurs in soil environments. the ba5345 genetic marker was used for highly specific detection of b. anthracis with taqman probe ...201526667574
[optimization of labeling and localizing bacterial membrane and nucleus with fm4-64 and hoechst dyes].to observe cell membrane and nucleus in bacteria for subcellular localization.201526665605
molecular assembly of lethal factor enzyme and pre-pore heptameric protective antigen in early stage of translocation.during intoxication, the anthrax toxin lethal (lf) and edema (ef) factors initially assemble with the protective antigen (pa) on the plasma membrane of cells expressing the membrane-bound surface-exposed anthrax toxin receptor (atr). this takes place at the physiological ph prior to entering the acidic environment of the endosome. we elucidated the molecular dynamics (md) behaviors of the three-dimensional structure of the (pa63)7lf3 complex in various conformations and analyzed the dynamical pr ...201626659402
chemo-enzymatic synthesis of site-specific isotopically labeled nucleotides for use in nmr resonance assignment, dynamics and structural characterizations.stable isotope labeling is central to nmr studies of nucleic acids. development of methods that incorporate labels at specific atomic positions within each nucleotide promises to expand the size range of rnas that can be studied by nmr. using recombinantly expressed enzymes and chemically synthesized ribose and nucleobase, we have developed an inexpensive, rapid chemo-enzymatic method to label atp and gtp site specifically and in high yields of up to 90%. we incorporated these nucleotides into r ...201626657632
smallpox, anthrax, and the historiography of cutaneous diseases. 201526650656
approval of raxibacumab for the treatment of inhalation anthrax under the us food and drug administration "animal rule".on december 14, 2012, the fda approved raxibacumab, the first monoclonal antibody product developed under project bioshield to achieve this milestone, and the first biologic product to be approved through the fda animal efficacy rule (or "animal rule"). raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies ...201526648915
"in-house" production of dna size marker from a vaccinal bacillus anthracis strain.dna molecular weight marker is widely used in molecular biology experiments incurring considerable costs on low-budget settings.201526644873
observations on the inactivation efficacy of a maldi-tof ms chemical extraction method on bacillus anthracis vegetative cells and spores.a chemical (ethanol; formic acid; acetonitrile) protein extraction method for the preparation of bacterial samples for matrix assisted laser desorption ionisation time-of-flight mass spectrometry (maldi-tof ms) identification was evaluated for its ability to inactivate bacterial species. initial viability tests (with and without double filtration of the extract through 0.2 μm filters), indicated that the method could inactivate escherichia coli mre 162 and klebsiella pneumoniae atcc 35657, with ...201526633884
clinical framework and medical countermeasure use during an anthrax mass-casualty incident.in 2014, cdc published updated guidelines for the prevention and treatment of anthrax (hendricks ka, wright me, shadomy sv, et al. centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. emerg infect dis 2014;20[2]. available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). these guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax ...201526632963
improvements to a markerless allelic exchange system for bacillus anthracis.a system was previously developed for conducting i-scei-mediated allelic exchange in bacillus anthracis. in this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease i-scei. although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in b. anthracis, researchers are nonetheless required to "pick and patch" colon ...201526624016
antimicrobial treatment for systemic anthrax: analysis of cases from 1945 to 2014 identified through a systematic literature review.systemic anthrax is associated with high mortality. current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of 2 weeks, bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax, and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. however, in an anthrax mass casualty incident, large numbers of anthrax cases ma ...201726623698
anthrax lethal factor investigated by molecular simulations.the anthrax disease is caused by the lethal toxin secreted by the bacterium bacillus anthracis. the toxin is a protein aggregate which contains a zn-based hydrolase called anthrax lethal factor (lf). in this work, we investigate the structure of its michaelis complex with an optimized mapkk-like substrate using several computational methods including density functional theory, molecular dynamics, and coarse grained techniques. our calculations suggest that (i) the presence of second-shell ligand ...200826620178
ultrasensitive detection of protease activity of anthrax and botulinum toxins by a new pcr-based assay.anthrax and botulism are dangerous infectious diseases that can be fatal unless detected and treated quickly. fatalities from these diseases are primarily due to endopeptidase toxins secreted by the pathogens. rapid and sensitive detection of the presence of active toxins is the key element for protection from natural outbreaks of anthrax and botulism, as well as from the threat of bioterrorism. we describe an ultrasensitive polymerase chain reaction (pcr)-based assay for detecting proteolytic a ...201626620058
bacterial exotoxins and the inflammasome.the inflammasomes are intracellular protein complexes that play an important role in innate immune sensing. activation of inflammasomes leads to activation of caspase-1 and maturation and secretion of the pro-inflammatory cytokines interleukin (il)-1β and il-18. in certain myeloid cells, this activation can also lead to an inflammatory cell death (pyroptosis). inflammasome sensor proteins have evolved to detect a range of microbial ligands and bacterial exotoxins either through direct interactio ...201526617605
highly predictive support vector machine (svm) models for anthrax toxin lethal factor (lf) inhibitors.anthrax is a highly lethal, acute infectious disease caused by the rod-shaped, gram-positive bacterium bacillus anthracis. the anthrax toxin lethal factor (lf), a zinc metalloprotease secreted by the bacilli, plays a key role in anthrax pathogenesis and is chiefly responsible for anthrax-related toxemia and host death, partly via inactivation of mitogen-activated protein kinase kinase (mapkk) enzymes and consequent disruption of key cellular signaling pathways. antibiotics such as fluoroquinolon ...201626615468
neutralizing antibody and functional mapping of bacillus anthracis protective antigen-the first step toward a rationally designed anthrax vaccine.anthrax is defined by the centers for disease control and prevention as a category a pathogen for its potential use as a bioweapon. current prevention treatments include anthrax vaccine adsorbed (ava). ava is an undefined formulation of bacillus anthracis culture supernatant adsorbed to aluminum hydroxide. it has an onerous vaccination schedule, is slow and cumbersome to produce and is slightly reactogenic. next-generation vaccines are focused on producing recombinant forms of anthrax toxin in a ...201626611201
a cpg-ficoll nanoparticle adjuvant for anthrax protective antigen enhances immunogenicity and provides single-immunization protection against inhaled anthrax in monkeys.nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of apcs, have shown substantial promise for enhanced immunopotentiation. we investigated the adjuvant activity of synthetic oligonucleotides containing cpg-rich motifs linked to the sucrose polymer ficoll, forming soluble 50-nm particles (dv230-ficoll), each containing >100 molecules of the tlr9 ligand, dv230. dv230-ficoll was evaluated as an adjuvant for a candidate ...201626608924
anti-infectious human vaccination in historical perspective.a brief history of vaccination is presented since the jenner's observation, through the first golden age of vaccinology (from pasteur's era to 1938), the second golden age (from 1940 to 1970), until the current period. in the first golden age, live, such as bacille calmette guérin (bcg), and yellow fever, inactivated, such as typhoid, cholera, plague, and influenza, and subunit vaccines, such as tetanus and diphtheria toxoids, have been developed. in the second golden age, the cell culture techn ...201626606466
differential detection of a surrogate biological threat agent (bacillus globigii) with a portable surface plasmon resonance biosensor.new methods and technology are needed to quickly and accurately detect potential biological warfare agents, such as bacillus anthracis, causal agent of anthrax in humans and animals. here, we report the detection of a simulant of b. anthracis (b. globigii) alone and in a mixture with a different species of bacillus to test non-specific interference using a portable surface plasmon resonance (spr) biosensor (spirit 4.0, seattle sensor systems). both direct capture and antibody amplification were ...201626606307
serologic evidence of the geographic distribution of bacterial zoonotic agents in kenya, 2007.diseases of zoonotic origin contribute to the burden of febrile illnesses in developing countries. we evaluated serologic evidence of exposure to bacillus anthracis, brucella spp., spotted fever group rickettsioses (sfgr), and typhus group rickettsioses (tgr) from samples of persons aged 15-64 years collected during a nationwide human immunodeficiency virus (hiv) serosurvey conducted in 2007 in kenya. the seropositivity observed for pathogens was b. anthracis 11.3%, brucella spp. 3.0%, sfgr 23.3 ...201626598574
characterization and antimicrobial application of biosynthesized gold and silver nanoparticles by using microbacterium resistens.various microorganisms were found to be cable of synthesizing gold and silver nanoparticles when gold and silver salts were supplied in the reaction system. the main objective of this study was to evaluate the extracellular synthesis of gold and silver nanoparticles by the type strain microbacterium resistens(t) [kacc14505]. the biosynthesized gold and silver nanoparticles were characterized by ultraviolet-visible spectroscopy (uv-vis), field emission transmission electron micrograph (fe-tem), e ...201626597594
geospatial resolution of human and bacterial diversity with city-scale metagenomics.the panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. we sequenced dna from surfaces across the entire new york city (nyc) subway system, the gowanus canal, and public parks. nearly half of the dna (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmles ...201526594662
are we prepared for emerging and re-emerging diseases? experience and lessons from epidemics that occurred in tanzania during the last five decades.this paper reviews preparedness for containing and controlling emerging and re-emerging diseases drawing lessons from disease events that occurred in animal and human populations in the last five decades (1961-2011). a comprehensive analysis based on retrieval and analysis of grey and published literature as well as reported cases was carried out to document type and trend of occurrence of emerging and re-emerging infectious diseases in different parts of tanzania. overall, the majority of disea ...201126591993
[selection of disposable personal protective equipment for work with samples containing highly pathogenic microorganisms].emerging microbiological threats, such as sars, ebola, mers-cov, anthrax, cause necessity of considering how effectively protect laboratory workers against dangerous pathogens which might be present in clinical samples. the article presents requirements for personal protective equipment (ppe) in microbiological laboratories and examples of selection and application of disposable ppe.201526591666
determination of il1 r2, antxr2, card9, and snapc4 single nucleotide polymorphisms in iranian patients with ankylosing spondylitis.ankylosing spondylitis (as) is a chronic inflammatory disease of unknown origin, while both genetic and environmental factors have been demonstrated to be etiologically involved. recent genome-wide association and replication studies have suggested that anthrax toxin receptor 2 (antxr2), interleukin-1 receptor 2 (il1r2), caspase recruitment domain-containing protein 9 (card9), and small nuclear rna-activating complex polypeptide 4 (snapc4) seem to be associated with as pathogenesis. this case-co ...201626590821
draft genome sequences of two south african bacillus anthracis strains.bacillus anthracis is a gram-positive bacterium that causes anthrax, mainly in herbivores through exotoxins and capsule produced on plasmids, pxo1 and pxo2. this paper compares the whole-genome sequences of two b. anthracis strains from an endemic region and a sporadic outbreak in south africa. sequencing was done using next-generation sequencing technologies.201526586878
an anthrax toxin variant with an improved activity in tumor targeting.anthrax lethal toxin (lt) is an a-b type toxin secreted by bacillus anthracis, consisting of the cellular binding moiety, protective antigen (pa), and the catalytic moiety, lethal factor (lf). to target cells, pa binds to cell-surface receptors and is then proteolytically processed forming a lf-binding competent pa oligomer where each lf binding site is comprised of three subsites on two adjacent pa monomers. we previously generated pa-u2-r200a, a urokinase-activated pa variant with lf-binding s ...201526584669
suspected anthrax outbreak: investigation in a rural block of west bengal and public health response.anthrax is one of the top 10 diseases reported in india and also one of the major causes of death in livestock. this study was conducted to confirm the outbreak of suspected anthrax, determine the transmission mechanism, and implement control measures in bhatar block of burdwan district, west bengal, india. a cross-sectional descriptive study was conducted through house-to-house visits in oregram and kathaldanga villages during the period from may 30, 2013 to june 8, 2013. out of the 93 persons ...201726584171
characterization of protein-protein interfaces through a protein contact network approach.anthrax toxin comprises three different proteins, jointly acting to exert toxic activity: a non-toxic protective agent (pa), toxic edema factor (ef), and lethal factor (lf). binding of pa to anthrax receptors promotes oligomerization of pa, binding of ef and lf, and then endocytosis of the complex. homomeric forms of pa, complexes of pa bound to lf and to the endogenous receptor capillary morphogenesis gene 2 (cmg2) were analyzed. in this work, we characterized protein-protein interfaces (ppis) ...201526579512
ligand-induced expansion of the s1' site in the anthrax toxin lethal factor.the bacillus anthracis lethal factor (lf) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but lf is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. these structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific in ...201526578066
immunotherapy for infectious diseases: past, present, and future.passive immunotherapy for established infections, as opposed to active immunization to prevent disease, remains a tiny niche in the world of antimicrobial therapies. many of the passive immunotherapies currently available are directed against bacterial toxins, such as botulism, or are intended for agents of bioterrorism such as anthrax, which fortunately has remained rare. the emergence of ebola virus and multi-drug resistant pathogens, however, may breathe new life into the immunotherapy field ...201526575462
genome sequence of bacillus anthracis larissa, associated with a case of cutaneous anthrax in greece.we report the genome sequence of bacillus anthracis strain larissa, isolated from a diseased sheep associated with a human case of cutaneous anthrax in central greece from 2012. genome sequence analysis of strain larissa may aid in describing phylogenetic relationships of b. anthracis isolates in southeastern european countries.201526564034
new anthrax vaccine underway with hhs support. 201526563045
diverse mechanisms for inflammasome sensing of cytosolic bacteria and bacterial virulence.the inflammasomes are emerging cytosolic defenses against bacterial infections. the inflammasomes converge on inflammatory caspases activation that triggers pyroptosis, and interleukin-1β/18 maturation in the case of caspase-1 activation. the inflammasomes not only detect major bacterial molecules but also sense bacterial virulence activity. among the canonical caspase-1-activating inflammasomes, the naip subfamily of nlr proteins serves as the receptors for bacterial flagellin and type iii secr ...201626562791
cell-to-cell propagation of the bacterial toxin cnf1 via extracellular vesicles: potential impact on the therapeutic use of the toxin.eukaryotic cells secrete extracellular vesicles (evs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. evs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and rna. furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via evs. we have herein demonstrated that eukaryotic evs represent an additional route of cell-to-cell propagation ...201526556375
massive horizontal gene transfer, strictly vertical inheritance and ancient duplications differentially shape the evolution of bacillus cereus enterotoxin operons hbl, cytk and nhe.bacillus cereus sensu lato comprises eight closely related species including the human pathogens bacillus anthracis and bacillus cereus. within b. cereus sensu lato, chromosomally and plasmid-encoded toxins exist. while plasmid-mediated horizontal gene transfer of the emetic toxin, anthrax and insecticidal toxins is known, evolution of enterotoxin genes within the group has not been studied.201526555390
nano/micromotors for security/defense applications. a review.the new capabilities of man-made micro/nanomotors open up considerable opportunities for diverse security and defense applications. this review highlights new micromotor-based strategies for enhanced security monitoring and detoxification of chemical and biological warfare agents (cbwa). the movement of receptor-functionalized nanomotors offers great potential for sensing and isolating target bio-threats from complex samples. new mobile reactive materials based on zeolite or activated carbon off ...201526554557
disarmed anthrax toxin delivers antisense oligonucleotides and sirna with high efficiency and low toxicity.inefficient cytosolic delivery and vector toxicity contribute to the limited use of antisense oligonucleotides (asos) and sirna as therapeutics. as anthrax toxin (atx) accesses the cytosol, the purpose of this study was to evaluate the potential of disarmed atx to deliver either asos or sirna. we hypothesized that this delivery strategy would facilitate improved transfection efficiency while eliminating the toxicity seen for many vectors due to membrane destabilization. atx complex formation wit ...201526546271
the bacillus anthracis exosporium: what's the big "hairy" deal?in some bacillus species, including bacillus subtilis, the coat is the outermost layer of the spore. in others, such as the bacillus cereus family, there is an additional layer that envelops the coat, called the exosporium. in the case of bacillus anthracis, a series of fine hair-like projections, also referred to as a "hairy" nap, extends from the exosporium basal layer. the exact role of the exosporium in b. anthracis, or for any of the bacillus species possessing this structure, remains uncle ...201526542035
the saccharomyces boulardii cncm i-745 strain shows protective effects against the b. anthracis lt toxin.the probiotic yeast saccharomyces boulardii (s. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. gastrointestinal anthrax causes fatal systemic disease. in the present study, we investigated the protective effects conferred by saccharomyces boulardii cncm i-745 strain on polarized t84 columnar epithelial cells intoxicated by the lethal toxin (lt) of bacillus anthracis. exposure of polarized t84 cells to lt affected cell monolayer integrit ...201526529015
evaluation of tools for environmental sampling of bacillus anthracis spores.this study describes the validation of sampling techniques used to detect biological warfare agents used in terror attacks. for this purpose, we tested the efficiencies of different sampling media and extraction solutions for the recovery of bacterial pathogens. we first used bacillus cereus atcc 4342 spores as a surrogate for highly pathogenic b. anthracis to compare recovery efficiencies of spores from four different surfaces. we used three different types of sampling swabs and four different ...201526528669
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