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microrna-124 involves in ankylosing spondylitis by targeting antxr2.a recent genome-wide association study or gwas identified that anthrax roxin receptor 2 (antxr2) was one of the risk loci for ankylosing spondylitis (as). previous study also showed that antxr2 could potentially affect new bone formation. this study aimed to investigate the possible mechanisms of antxr2 involved in as pathogenesis.201525736362
affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilized protein a for removal of anthrax toxin protective antigen.polymeric cryogels are efficient carriers for the immobilization of biomolecules because of their unique macroporous structure, permeability, mechanical stability and different surface chemical functionalities. the aim of the study was to demonstrate the potential use of macroporous monolithic cryogels for biotoxin removal using anthrax toxin protective antigen (pa), the central cell-binding component of the anthrax exotoxins, and covalent immobilization of monoclonal antibodies. the affinity li ...201525736504
identification of bacillus anthracis pure inhibitors with antimicrobial activity.n(5)-carboxy-amino-imidazole ribonucleotide (n(5)-cair) mutase (pure), a bacterial enzyme in the de novo purine biosynthetic pathway, has been suggested to be a target for antimicrobial agent development. we have optimized a thermal shift method for high-throughput screening of compounds binding to bacillus anthracis pure. we used a low ionic strength buffer condition to accentuate the thermal shift stabilization induced by compound binding to bacillus anthracis pure. the compounds identified we ...201525737087
[clustered regularly interspaced short palindromic repeats (crispr) site in bacillus anthracis].to investigate the polymorphism of clustered regularly interspaced short palindromic repeats (crispr) in bacillu santhracis and the application to molecular typing based on the polymorphism of crispr in b. anthracis.201425752143
walrk two component system of bacillus anthracis responds to temperature and antibiotic stress.walrk two component system (tcs) of bacillus anthracis forms a functional tcs. this report elaborates upon the walrk genomic architecture, promoter structure, promoter activity and expression under various stress conditions in b. anthracis. 5' race located the walrk functional promoter within 317 bp region upstream of walr. reporter gene assays demonstrated maximal promoter activity during early growth phases indicating utility in exponential stages of growth. qrt-pcr showed upregulation of walr ...201525753206
periorbital cellulitis due to cutaneous anthrax.virgil's plague of the ancient world, bacillus anthracis, is rare in developed nations. unfortunately rural communities across the globe continue to be exposed to this potentially lethal bacterium. herein we report a case of periorbital cutaneous anthrax infection in a 3-year-old girl from the rural area surrounding harare, zimbabwe with a brief review of the literature.201525763844
the development of a green approach for the biosynthesis of silver and gold nanoparticles by using panax ginseng root extract, and their biological applications.the biosynthesis of nanoparticles has received attention because of the development of economic and environmentally friendly technology for the synthesis of nanoparticles. the study develops a convenient method for the green synthesis of silver and gold nanoparticles by utilizing fresh root extract of the four-year old panax ginseng plant, and evaluated the antimicrobial applications of silver nanoparticles against pathogenic microorganisms. p. ginseng is a well-known herbal medicinal plant, and ...201625771716
a novel multiplex pcr discriminates bacillus anthracis and its genetically related strains from other bacillus cereus group species.anthrax is an important zoonotic disease worldwide that is caused by bacillus anthracis, a spore-forming pathogenic bacterium. a rapid and sensitive method to detect b. anthracis is important for anthrax risk management and control in animal cases to address public health issues. however, it has recently become difficult to identify b. anthracis by using previously reported molecular-based methods because of the emergence of b. cereus, which causes severe extra-intestinal infection, as well as t ...201525774512
glutamate racemase mutants of bacillus anthracis.d-glutamate is an essential component of bacterial peptidoglycan and a building block of the poly-γ-d-glutamic acid (pdga) capsule of bacillus anthracis, the causative agent of anthrax. earlier work suggested that two glutamate racemases, encoded by race1 and race2, are each essential for growth of b. anthracis, supplying d-glutamic acid for the synthesis of peptidoglycan and pdga capsule. earlier work could not explain, however, why two enzymes that catalyze the same reaction may be needed for ...201525777674
atomic structure of anthrax protective antigen pore elucidates toxin translocation.anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of bacillus anthracis, an agent that causes high mortality in humans and animals. protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. protective antigen is not only a vaccine component and therapeutic target for ...201525778700
differential dependence on n-glycosylation of anthrax toxin receptors cmg2 and tem8.antxr 1 and 2, also known as tem8 and cmg2, are two type i membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. here we have analyzed the importance of n-glycosylation on folding, trafficking and ligand binding of these closely related proteins. we find that tem8 has a stringent dependence on n-glycosylation. the presence of at least one glycan on each of its two extracellular domains, the vwa and ig-li ...201525781883
generation and characterization of human monoclonal antibodies targeting anthrax protective antigen following vaccination with a recombinant protective antigen vaccine.the anthrax protective antigen (pa) is the central component of the three-part anthrax toxin, and it is the primary immunogenic component in the approved ava anthrax vaccine and the "next-generation" recombinant pa (rpa) anthrax vaccines. animal models have indicated that pa-specific antibodies (ab) are sufficient to protect against infection with bacillus anthracis. in this study, we investigated the pa domain specificity, affinity, mechanisms of neutralization, and synergistic effects of pa-sp ...201525787135
laboratory-acquired lethal infections by potential bioweapons pathogens including ebola in 2014.researchers studying both cellular and viral disease agents in the laboratory have become infected since the early days of microbiology 150 years ago. however, in the early 21st century, new concerns about bioweapons being used to generate terror and also with a series of newly emerging or newly understood disease-causing microbes have resulted in infections and deaths of workers studying these microbes in the laboratory, generally to gain understanding and to develop treatments and vaccines. he ...201525790490
applications of commercial biosensors in clinical, food, environmental, and biothreat/biowarfare analyses.the lack of specific, low-cost, rapid, sensitive, and easy detection of biomolecules has resulted in the development of biosensor technology. innovations in biosensor technology have enabled many biosensors to be commercialized and have enabled biomolecules to be detected onsite. moreover, the emerging technologies of lab-on-a-chip microdevices and nanosensors offer opportunities for the development of new biosensors with much better performance. biosensors were first introduced into the laborat ...201525790902
genome sequence of bacillus anthracis isolated from an anthrax burial site in pollino national park, basilicata region (southern italy).a bacillus anthracis strain was isolated from a burial-site in pollino national park where a bovine died of anthrax and was buried in 2004. we report the first genome sequence of b. anthracis isolated in the basilicata region (southern italy), which is the highest risk area of anthrax infection in italy.201525792059
bacillus cereus from the environment is genetically related to the highly pathogenic b. cereus in zambia.to follow-up anthrax in zambia since the outbreak in 2011, we have collected samples from the environment and the carcasses of anthrax-suspected animals, and have tried to isolate bacillus anthracis. in the process of identification of b. anthracis, we collected two isolates, of which colonies were similar to b. anthracis; however, from the results of identification using the molecular-based methods, two isolates were genetically related to the highly pathogenic b. cereus, of which clinical mani ...201525797134
human infection with a zoonotic orthopoxvirus in the country of georgia.during 2013, cutaneous lesions developed in two men in the country of georgia after they were exposed to ill cows. the men had never received vaccination against smallpox. tests of lesion material with the use of a quantitative real-time polymerase-chain-reaction assay for non-variola virus orthopoxviruses were positive, and dna sequence analysis implicated a novel orthopoxvirus species. during the ensuing epidemiologic investigation, no additional human cases were identified. however, serologic ...201525806914
us disaster planners' attitudes regarding preevent vaccine for first responders and point-of-dispensing workers.disaster planners' attitudes toward pre-event anthrax and smallpox vaccine for first responders and point-of-dispensing (pod) workers have not been examined. an online questionnaire was sent to us cities readiness initiative (cri) and non-cri public health disaster planners in 2013. multivariate logistic regressions were used to assess determinants of belief that first responders and pod workers should be offered the anthrax and/or smallpox vaccine before an event. a total of 301 disaster planne ...201625812426
the 49th hour: analysis of a follow-up medication and vaccine dispensing field test.anthrax response plans, exercises, and assessments over the past decade have focused almost exclusively on the first 48 hours of the public health response following a jurisdiction-wide exposure and provision of an initial 10-day supply of antibiotics from the strategic national stockpile (sns). but mass dispensing of the subsequent 50-day course of antibiotics and administration of the 3-dose vaccine series have received considerably less attention, although these follow-up activities may prove ...201625812429
gcogsa-ba: a global core genome snp analysis for bacillus anthracis.as an issue of biosecurity, it is important to identify the origin of a suspected sample to distinguish whether it originated from the release of a bioterrorism agent or from environmental contamination with a virulent agent. here we have developed an analytical pipeline that can infer the phylogenetic position of bacillus cereus group species, including b. anthracis, from next-generation sequencing reads without extensive genomics skills. gcogsa-ba can also detect the existence of anthrax plasm ...201625812430
multiplex pcr for species-level identification of bacillus anthracis and detection of pxo1, pxo2, and related plasmids.the bacillus anthracis virulence plasmids pxo1 and pxo2 have critical implications for biosafety and select agent status. the proper identification and characterization of b. anthracis and its plasmid profile is important to the biodefense research community. multiplex pcr was used to simultaneously detect a b. anthracis-specific chromosomal mutation, 4 targets distributed across pxo1, 3 targets distributed across pxo2, and highly conserved regions of the 16s gene, allowing an internal positive ...201725813976
development of a novel adjuvanted nasal vaccine: c48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity.in a time in which mucosal vaccines development has been delayed by the lack of safe and effective mucosal adjuvants, the combination of adjuvants has started to be explored as a strategy to obtain potent vaccine formulations. this study describes a novel adjuvant combination as an effective approach for a nasal vaccine - the association of the mast cell activator compound 48/80 with chitosan based nanoparticles. it was hypothesized that mucoadhesive nanoparticles would promote the cellular upta ...201525818119
anthrax vaccine recipients lack antibody against the loop neutralizing determinant: a protective neutralizing epitope from bacillus anthracis protective antigen.epitope-focused immunogens can elicit antibody against the loop neutralizing determinant (lnd), a neutralizing epitope found within the 2β2-2β3 loop of protective antigen (pa), which can protect rabbits from high-dose inhalation challenge with bacillus anthracis ames strain. interestingly, data suggests that this epitope is relatively immunosilent in rabbits and non-human primates immunized with full length pa.201525820066
assessing the sporicidal activity of oligo-p-phenylene ethynylenes and their role as bacillus germinants.a wide range of oligo-p-phenylene ethynylenes has been shown to exhibit good biocidal activity against both gram-negative and gram-positive bacteria. while cell death may occur in the dark, these biocidal compounds are far more effective in the light as a result of their ability to sensitize the production of cell-damaging reactive oxygen species. in these studies, the interactions of a specific cationic oligo-p-phenylene ethynylene with spore-forming bacillus atrophaeus and bacillus anthracis s ...201525822668
anthrax: a case report.anthrax is a zoonotic disease caused by a bacterium called bacillus anthracis. in humans, it causes a cutaneous, gastro-intestinal and inhalation form of disease. the in-cutaneous form progresses along with skin necrosis and oedema. since the necroses in the skin are not quite superficial, they can affect the tendon sheaths progressing close to the skin. therefore, in surgical treatment, the closure in the areas where tendons are surfaced must be provided by a flap instead of a graft.the repair ...201425823167
two putative polysaccharide deacetylases are required for osmotic stability and cell shape maintenance in bacillus anthracis.membrane-anchored lipoproteins have a broad range of functions and play key roles in several cellular processes in gram-positive bacteria. ba0330 and ba0331 are the only lipoproteins among the 11 known or putative polysaccharide deacetylases of bacillus anthracis. we found that both lipoproteins exhibit unique characteristics. ba0330 and ba0331 interact with peptidoglycan, and ba0330 is important for the adaptation of the bacterium to grow in the presence of a high concentration of salt, whereas ...201525825488
anthrax vaccine associated deaths in miniature horses.during a widespread anthrax outbreak in canada, miniature horses were vaccinated using a live spore anthrax vaccine. several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. during the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found.201525829553
capsules, toxins and atxa as virulence factors of emerging bacillus cereus biovar anthracis.emerging b. cereus strains that cause anthrax-like disease have been isolated in cameroon (ca strain) and côte d'ivoire (ci strain). these strains are unusual, because their genomic characterisation shows that they belong to the b. cereus species, although they harbour two plasmids, pbcxo1 and pbcxo2, that are highly similar to the pxo1 and pxo2 plasmids of b. anthracis that encode the toxins and the polyglutamate capsule respectively. the virulence factors implicated in the pathogenicity of the ...201525830379
anthrax in injecting drug users: the need for increased vigilance in the clinic.the emergence of a previously unrecognized route of bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern europe have demonstrated the severe pathology associated with the newly described 'injectional anthrax'. with a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. lack of awareness of this syndrome among emergency room clinicians can lead to a delayed d ...201525831413
the angiopoietin-tie2 signaling axis in the vascular leakage of systemic inflammation.the ability of small blood vessels to undergo rapid, reversible morphological changes is essential for the adaptive response to tissue injury or local infection. a canonical feature of this response is transient hyperpermeability. however, when leakiness is profound or persistent, adverse consequences accrue to the host, including organ dysfunction and shock. a growing body of literature identifies the tie2 receptor, a transmembrane tyrosine kinase highly enriched in the endothelium, as an impor ...201525838975
development of receptor-based inhibitory rna aptamers for anthrax toxin neutralization.anthrax toxin excreted by bacillus anthracis is the key causative agent of infectious anthrax disease. in the present study, we targeted the binding of pa to the atr/tem8 von willebrand factor type a (vwa) domain, which we cloned into escherichia coli and purified to homogeneity under denaturing conditions. to develop an anthrax toxin inhibitor, we selected and identified short single strand rna aptamers (approximately 30mer) consisting of different sequences of nucleic acids with a high binding ...201525841381
[characteristics of isogenic variants of bacillus anthracis with various content of virulence plasmids].production and characteristics by main cultural-morphologic and antigenic properties of isogenic variants bacillus anthracis, that differ by the presence of virulence plasmids.201525842948
molecular diversity of bacillus anthracis in the netherlands: investigating the relationship to the worldwide population using whole-genome snp discovery.bacillus anthracis, the causative agent of anthrax, has been widely described as a clonal species. here we report the use of both canonical snp analysis and whole-genome sequencing to characterize the phylogenetic lineages of b. anthracis from the netherlands. eleven strains isolated over a 25-years period (1968-1993) were paired-end sequenced using parallel sequencing technology. five cansnp groups or lineages, i.e. a.br.001/002 (n=6), a.br.aust94 (n=2), a.br.008/011 (n=1), a.br.011/009 (n=1) a ...201525843650
biosynthesis, characterization, and antimicrobial applications of silver nanoparticles.in the present study, the strain brevibacterium frigoritolerans dc2 was explored for the efficient and extracellular synthesis of silver nanoparticles. these biosynthesized silver nanoparticles were characterized by ultraviolet-visible spectrophotometry, which detected the formation of silver nanoparticles in the reaction mixture and showed a maximum absorbance at 420 nm. in addition, field emission transmission electron microscopy revealed the spherical shape of the nanoparticles. the dynamic l ...201525848272
retrospective review of the case of cutaneous anthrax-malignant pustule from 1995 in 15-year old girl.a 15-year-old girl was admitted to our department with cutaneous lesion resembling black eschar. anamnesis revealed that before getting ill she was wearing pullover made of rough sheep's wool and ornaments made of leather like straps. cutaneous anthrax was confirmed by identification of b. anthracis in specimens from weeping ulceration, culture from black eschar, thermoprecipitation test, and bioassay on guinea pig. the girl was treated with crystalline penicillin. she responded well to the ther ...201425848786
protein composition of the outermost exosporium-like layer of clostridium difficile 630 spores.clostridium difficile spores are considered the morphotype of infection, transmission and persistence of c. difficile infections. there is a lack of information on the composition of the outermost exosporium layer of c. difficile spores. using recently developed exosporium removal methods combined with ms/ms, we have established a gel-free approach to analyze the proteome of the exosporium of c. difficile spores of strain 630. a total of 184 proteins were found in the exosporium layer of c. diff ...201525849250
evaluation of anthrax vaccine safety in 18 to 20 year olds: a first step towards age de-escalation studies in adolescents.anthrax vaccine adsorbed (ava, biothrax(®)) is recommended for post-exposure prophylaxis administration for the us population in response to large-scale bacillus anthracis spore exposure. however, no information exists on ava use in children and ethical barriers exist to performing pre-event pediatric ava studies. a presidential ethics commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds t ...201525850022
human anthrax as a re-emerging disease.anthrax is primarily a disease of herbivores and the etiological agent is b. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. for these reasons, b. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. soil is the main reservoir for the infectious agent. the disease most ...201525851429
chemical feasibility of the general acid/base mechanism of glms ribozyme self-cleavage.in numerous gram-positive bacteria, the glms ribozyme or catalytic riboswitch regulates the expression of glucosamine-6-phosphate (glcn6p) synthase via site-specific cleavage of its sugar-phosphate backbone in response to glcn6p ligand binding. biochemical data have suggested a crucial catalytic role for an active site guanine (g40 in thermoanaerobacter tengcongensis, g33 in bacillus anthracis). we used hybrid quantum chemical/molecular mechanical (qm/mm) calculations to probe the mechanism wher ...201525858644
using light scattering to determine the stoichiometry of protein complexes.the stoichiometry of a protein complex can be calculated from an accurate measurement of the complex's molecular weight. multiangle laser light scattering in combination with size exclusion chromatography and interferometric refractometry provides a powerful means for determining the molecular weights of proteins and protein complexes. in contrast to conventional size exclusion chromatography and analytical centrifugation, measurements do not rely on the use of molecular weight standards and are ...201525859953
biosensors for monitoring airborne pathogens.airborne pathogens affect both humans and animals and are often highly and rapidly transmittable. many problematic airborne pathogens, both viral (influenza a/h1n1, rubella, and avian influenza/h5n1) and bacterial (mycobacterium tuberculosis, streptococcus pneumoniae, and bacillus anthracis), have huge impacts on health care and agricultural applications, and can potentially be used as bioterrorism agents. many different laboratory-based methods have been introduced and are currently being used. ...201525862683
recent developments in understanding the iron acquisition strategies of gram positive pathogens.iron is a versatile redox-active catalyst and a required cofactor within a diverse array of biological processes. to almost all organisms, iron is both essential and potentially toxic, where homeostatic concentrations must be stringently maintained. within the iron-restricted host, the survival and proliferation of microbial invaders is contingent upon exploiting the host iron pool. bacteria express a multitude of complex, and often redundant means of acquiring iron, including surface-associated ...201525862688
bacillus anthracis edema but not lethal toxin challenge in rats is associated with depressed myocardial function in hearts isolated and tested in a langendorff system.although direct myocardial depression has been implicated in the lethal effects of bacillus anthracis lethal toxin (lt), in hearts isolated from healthy rats and perfused under constant pressure, neither lt or edema toxin (et) in typically lethal concentrations depressed myocardial function. in the present study, we challenged rats with lt and et and performed in vivo and ex vivo heart measures. sprague-dawley rats infused over 24 h with lt (n = 94), et (n = 99), or diluent (controls; n = 50) we ...201525862834
regulation and rna-binding properties of hfq-like rna chaperones in bacillus anthracis.small rnas (srnas) are important modulators of gene expression in bacteria. regulation by srnas is yet to be established in bacillus anthracis. here, regulation and rna-binding properties of hfq-like rna chaperones in b. anthracis are investigated.201525863287
deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma fadu cell.for decades, despite the advancement of medical science, the prognosis of head and neck squamous cell carcinoma (hnscc), has not improved. deltonin is one of the major active components of dioscorea zingiberensis wright that has been used for anthrax, rheumatic heart disease, rheumatoid arthritis etc. by employing hnscc fadu cell and normal human epidermal keratinocyte, we investigate deltonin efficacy and associated mechanism in both cell culture and nude mice xenografts. deltonin treatment sel ...201525866222
diverse supramolecular structures formed by self-assembling proteins of the bacillus subtilis spore coat.bacterial spores (endospores), such as those of the pathogens clostridium difficile and bacillus anthracis, are uniquely stable cell forms, highly resistant to harsh environmental insults. bacillus subtilis is the best studied spore-former and we have used it to address the question of how the spore coat is assembled from multiple components to form a robust, protective superstructure. b. subtilis coat proteins (coty, cote, cotv and cotw) expressed in escherichia coli can arrange intracellularly ...201525872412
seasonal patterns of hormones, macroparasites, and microparasites in wild african ungulates: the interplay among stress, reproduction, and disease.sex hormones, reproductive status, and pathogen load all affect stress. together with stress, these factors can modulate the immune system and affect disease incidence. thus, it is important to concurrently measure these factors, along with their seasonal fluctuations, to better understand their complex interactions. using steroid hormone metabolites from fecal samples, we examined seasonal correlations among zebra and springbok stress, reproduction, gastrointestinal (gi) parasite infections, an ...201525875647
[development and comparative evaluation of up-converting phosphor technology based lateral flow assay for rapid detection of yersinia pestis, bacillus anthracis spore and brucella spp].to develop an up-converting phosphor technology based lateral flow (upt-lf) assay for rapid and quantitative detection of yersinia pestis, bacillus anthracis spore and brucella spp.and make the comparison with biothreat alert (bta) test strips (tetracore inc., usa).201525876487
the nlrp1 inflammasomes.inflammasomes are cytosolic protein complexes that serve as platforms for the recruitment and activation of the pro-inflammatory caspase-1 protease. caspase-1 activation leads to processing and maturation of the cytokines interleukin-1β and interleukin-18 and a lytic form of cell death termed pyroptosis. inflammasome assembly is initiated by cytosolic sensors in response to microbial infections. many of these sensors, including nlrp1 (nlr family, pyrin domain containing 1), are described to form ...201525879281
genetic characterization of bacillus anthracis in guizhou province, southwest of china.bacillus (b.) anthracis is the pathogen that causes fatal anthrax. guizhou province is an old foci of anthrax in the southwest of china. human anthrax has also been frequently reported in guizhou in recent year. however, there is limited information on the genetic background of local b. anthracis isolates in guizhou province. strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial genetics. in the present study, we employed multiple locus va ...201525887647
tertiary amides of salinomycin: a new group of antibacterial agents against bacillus anthracis and methicillin-resistant staphylococcus epidermidis.for the first time, a series of tertiary amides of polyether antibiotic-salinomycin have been obtained and screened for their antibacterial activity against different strains of bacteria, including bacillus anthracis and clinical methicillin-resistant staphylococcus epidermidis (mrse). moreover, biofilm inhibition of mrse and genotoxicity tests against bacillus subtilis have been performed. our studies show that salinomycin and its some derivatives are active against tested bacteria and exhibite ...201525891104
[molecular model of anthrax toxin translocation into target-cells].anthrax toxin is formed from three components: protective antigen (pa), lethal (lf) and edema (ef) factors. pa83 is cleaved by cell surface protease furin to produce a 63-kda fragment (pa63). pa63 and lf/ef molecules are assembled to anthrax toxin complexes: oligomer pa63 x 7 + lf/ef x 3. assembly is occurred during of binding with cellular receptor or near surface of target-cell. this toxin complex forms pore and induces receptor-mediated endocytosis. formed endosome consists extracellular liqu ...201525898749
survey of uk health care first responders' knowledge of personal protective equipment requirements.an adequate level of personal protective equipment (ppe) is necessary when treating patients with highly infectious diseases or those contaminated with hazardous substances.201525901721
evaluation of new dihydrophthalazine-appended 2,4-diaminopyrimidines against bacillus anthracis: improved syntheses using a new pincer complex.the synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat bacillus anthracis is reported. an improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(ii), allows the final heck coupling to be performed at 90 °c using triethylamine as the base. these milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that deg ...201525905602
acquired coagulant factor viii deficiency induced by bacillus anthracis lethal toxin in mice.mice treated with anthrax lethal toxin (lt) exhibit hemorrhage caused by unknown mechanisms. moreover, lt treatment in mice induced liver damage. in this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. the hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to lt. in agreement with our hypothesis, lt induces ...201525906166
the neglected zoonoses--the case for integrated control and advocacy.the neglected zoonotic diseases (nzds) have been all but eradicated in wealthier countries, but remain major causes of ill-health and mortality across africa, asia, and latin america. this neglect is, in part, a consequence of under-reporting, resulting in an underestimation of their global burden that downgrades their relevance to policy-makers and funding agencies. increasing awareness about the causes of nzds and how they can be prevented could reduce the incidence of many endemic zoonoses. a ...201525911990
bcla and toxin antigens augment each other to protect nmri mice from lethal bacillus anthracis challenge.while proving highly effective in controlling anthrax in farm animals all over the world currently attenuated live anthrax vaccines employed in a veterinary context suffer from drawbacks such as residual virulence, short term protection, variation in quality and, most importantly, lack of efficacy if administered simultaneously with antibiotics. these limitations have stimulated the development of non-living component vaccines which induce a broad spectrum immune response capable of targeting bo ...201525917676
a case of fatal gastrointestinal anthrax in north eastern iran.background. bacillus species are aerobic or facultative anaerobic, gram-positive, or gram-variable spore-forming rods. they are ubiquitous in the environmental sources. bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal, and cutaneous. the gastrointestinal (gi) anthrax develops after eating contaminated meat. in this paper we report septic intestinal anthrax. case presentation. we report an isolation of bacillus anthracis from blood culture of patient with ...201525918652
an overview of investigational toxin-directed therapies for the adjunctive management of bacillus anthracis infection and sepsis.sepsis with bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. over the past 15 years, recent outbreaks in the us and in europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to improve clinical outcomes. since lethal toxin and edema toxin (lt and et) make central contributions to the pathogenesis of b. anthracis, these have been major targets in this effort.201525920540
targeting intracellular bacteria with an extended cationic amphiphilic polyproline helix.an extended cationic and amphiphilic polyproline helix (caph) is described with a dual mode of action: effective cell penetration of human macrophages, and potent antimicrobial activity in vitro against both gram-positive and negative pathogens, including acinetobacter baumannii, escherichia coli o157 and bacillus anthracis. this dual action was successfully combined to clear pathogenic bacteria (brucella and salmonella) residing within macrophages.201525925008
biochemical and structural analysis of an eis family aminoglycoside acetyltransferase from bacillus anthracis.proteins from the enhanced intracellular survival (eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (ags). their upregulation confers drug resistance. homologues of eis are present in diverse bacteria, including many pathogens. eis from mycobacterium tuberculosis (eis_mtb) has been well characterized. in this study, we explored the ag specificity and catalytic efficiency of the eis family protein from bacillus anthracis (eis_ban) ...201525928210
membrane-targeting dcap analogues with broad-spectrum antibiotic activity against pathogenic bacteria.we performed a structure-activity relationship study of 2-((3-(3,6-dichloro-9h-carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol (dcap), which is an antibacterial agent that disrupts the membrane potential and permeability of bacteria. the stereochemistry of dcap had no effect on the biological activity of dcap. the aromaticity and electronegativity of the chlorine-substituted carbazole was required for activity, suggesting that its planar and dipolar characteristics orient ...201525941556
immunoassay for capsular antigen of bacillus anthracis enables rapid diagnosis in a rabbit model of inhalational anthrax.inhalational anthrax is a serious biothreat. effective antibiotic treatment of inhalational anthrax requires early diagnosis; the further the disease has progressed, the less the likelihood for cure. current means for diagnosis such as blood culture require several days to a result and require advanced laboratory infrastructure. an alternative approach to diagnosis is detection of a bacillus anthracis antigen that is shed into blood and can be detected by rapid immunoassay. the goal of the study ...201525942409
effects of 39 compounds on calmodulin-regulated adenylyl cyclases ac1 and bacillus anthracis edema factor.adenylyl cyclases (acs) catalyze the conversion of atp into the second messenger camp. membranous ac1 (ac1) is involved in processes of memory and learning and in muscle pain. the ac toxin edema factor (ef) of bacillus anthracis is involved in the development of anthrax. both acs are stimulated by the eukaryotic ca(2+)-sensor calmodulin (cam). the cam-ac interaction could constitute a potential target to enhance or impair the ac activity of ac1 and ef to intervene in above (patho)physiological m ...201525946093
risk-based decision making for reoccupation of contaminated areas following a wide-area anthrax release.this article presents an analysis of postattack response strategies to mitigate the risks of reoccupying contaminated areas following a release of bacillus anthracis spores (the bacterium responsible for causing anthrax) in an urban setting. the analysis is based on a hypothetical attack scenario in which individuals are exposed to b. anthracis spores during an initial aerosol release and then placed on prophylactic antibiotics that successfully protect them against the initial aerosol exposure. ...201525946233
capture of methyl bromide emissions with activated carbon following the fumigation of a small building contaminated with a bacillus anthracis spore simulant.a wide-area bacillus anthracis spore contamination incident will present immense challenges related to decontamination capacity. for this reason, fumigation with methyl bromide (mebr) has been proposed as a potential remediation option. although a few bench-scale laboratory studies have been conducted to evaluate activated carbon for the capture of mebr, these studies were conducted at conditions replicating commodity fumigation using relatively low mebr concentrations, temperatures, and/or rela ...201525947050
rapid detection of bacillus anthracis in complex food matrices using phage-mediated bioluminescence.bacillus anthracis, the causative agent of anthrax, is considered a high-priority agent that may be used in a food-related terrorist attack because it can be contracted by ingestion and it also forms spores with heat and chemical resistance. thus, novel surveillance methodologies to detect b. anthracis on adulterated foods are important for bioterrorism preparedness. we describe the development of a phage-based bioluminescence assay for the detection of b. anthracis on deliberately contaminated ...201525951391
surrogate testing suggests that chlorine dioxide gas exposure would not inactivate ebola virus contained in environmental blood contamination.the ability to decontaminate a room potentially containing the ebola virus is important to healthcare facilities in the united states. ebola virus remains viable in body fluids, a room that has housed a patient with ebola virus disease must have all surfaces manually wiped with an approved disinfectant, which increases occupational exposure risk. this study evaluated the efficacy of gaseous chlorine dioxide inactivation of bacterial organisms in blood as ebola virus surrogates and as the organis ...201525955403
diagnostic performance characteristics of a rapid field test for anthrax in cattle.although diagnosis of anthrax can be made in the field with a peripheral blood smear, and in the laboratory with bacterial culture or molecular based tests, these tests require either considerable experience or specialised equipment. here we report on the evaluation of the diagnostic sensitivity and specificity of a simple and rapid in-field diagnostic test for anthrax, the anthrax immunochromatographic test (aict). the aict detects the protective antigen (pa) component of the anthrax toxin pres ...201525956134
updating a b. anthracis risk model with field data from a bioterrorism incident.in this study, a bayesian framework was applied to update a model of pathogen fate and transport in the indoor environment. distributions for model parameters (e.g., release quantity of b. anthracis spores, risk of illness, spore setting velocity, resuspension rate, sample recovery efficiency, etc.) were updated by comparing model predictions with measurements of b. anthracis spores made after one of the 2001 anthrax letter attacks. the updating process, which was implemented by using markov cha ...201525961107
bacillus anthracis overcomes an amino acid auxotrophy by cleaving host serum proteins.bacteria sustain an infection by acquiring nutrients from the host to support replication. the host sequesters these nutrients as a growth-restricting strategy, a concept termed "nutritional immunity." historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. we emplo ...201525962917
lytic enzyme-assisted germination of bacillus anthracis and bacillus subtilis spores.the goal of this work was to determine conditions under which external application of a spore germination-specific lytic enzyme (gsle) can increase the germination efficiency of spore populations.201525963559
[general procedures in response to suspected attacks with highly contagious and pathogenic agents].the discovery of undefined powders that are content of letters or parcels with or without threats in writing addressed to institutions, groups or persons, often raises the suspicion of an attack involving biological agents such as anthrax. subsequent investigations and analyses by local authorities often aim at excluding anthrax or anthrax spores. suspicion and actions are then mistakenly justified by referring to the 2001 anthrax letter attacks in the usa, which now lie more than 10 years in th ...201525963640
novel furin inhibitors with potent anti-infectious activity.new peptidomimetic furin inhibitors with unnatural amino acid residues in the p3 position were synthesized. the most potent compound 4-guanidinomethyl-phenylacteyl-arg-tle-arg-4-amidinobenzylamide (mi-1148) inhibits furin with a ki value of 5.5 pm. the derivatives also strongly inhibit pc1/3, whereas pc2 is less affected. selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. a significant protec ...201525974265
a review of back-calculation techniques and their potential to inform mitigation strategies with application to non-transmissible acute infectious diseases.back-calculation is a process whereby generally unobservable features of an event leading to a disease outbreak can be inferred either in real-time or shortly after the end of the outbreak. these features might include the time when persons were exposed and the source of the outbreak. such inferences are important as they can help to guide the targeting of mitigation strategies and to evaluate the potential effectiveness of such strategies. this article reviews the process of back-calculation wi ...201525977955
reaerosolization of spores from flooring surfaces to assess the risk of dissemination and transmission of infections.the aim of this study was to quantify reaerosolization of microorganisms caused by walking on contaminated flooring to assess the risk to individuals accessing areas contaminated with pathogenic organisms, for example, spores of bacillus anthracis. industrial carpet and polyvinyl chloride (pvc) floor coverings were contaminated with aerosolized spores of bacillus atrophaeus by using an artist airbrush to produce deposition of ∼10(3) to 10(4) cfu · cm(-2). microbiological air samplers were used t ...201525979883
effects of metalloprotease anthrax lethal factor on its peptide-based inhibitor r9lf-1.the metalloprotease lethal factor (lf) from bacillus anthracis plays a vital role in anthrax toxin action, and thus becomes a target for anti-anthrax therapy. following the guidelines based on existing metalloprotease inhibitors, we designed a 'first-generation' lf inhibitor r9lf-1. this inhibitor was shown to be very stable by itself in a wide range of ph and temperature and able to inhibit lf activity in vitro. however, as we reported previously in the presence of lf, this inhibitor was degrad ...201525981534
fast and sensitive detection of an anthrax biomarker using sers-based solenoid microfluidic sensor.we report the application of a fully automated surface-enhanced raman scattering (sers)-based solenoid-embedded microfluidic device to the quantitative and sensitive detection of anthrax biomarker poly-γ-d-glutamic acid (pga) in solution. analysis is based on the competitive reaction between pga and pga-conjugated gold nanoparticles with anti-pga-immobilized magnetic beads within a microfluidic environment. magnetic immunocomplexes are trapped by yoke-type solenoids embedded within the device, a ...201525985198
an optimized coupled assay for quantifying diaminopimelate decarboxylase activity.diaminopimelate decarboxylase (dapdc) catalyzes the conversion of meso-dap to lysine and carbon dioxide in the final step of the diaminopimelate (dap) pathway in plants and bacteria. given its absence in humans, dapdc is a promising antibacterial target, particularly considering the rise in drug-resistant strains from pathogens such as escherichia coli and mycobacterium tuberculosis. here, we report the optimization of a simple quantitative assay for measuring dapdc catalytic activity using sacc ...201525986217
advances in anthrax detection: overview of bioprobes and biosensors.anthrax is an infectious disease caused by bacillus anthracis. although anthrax commonly affects domestic and wild animals, it causes a rare but lethal infection in humans. a variety of techniques have been introduced and evaluated to detect anthrax using cultures, polymerase chain reaction, and immunoassays to address the potential threat of anthrax being used as a bioweapon. the high-potential harm of anthrax in bioterrorism requires sensitive and specific detection systems that are rapid, fie ...201525987133
the function of plcr in bacillus anthracis vaccine strain a16r.bacillus anthracis, b. thuringiensis and b. cereus are members of the b. cereus group. they share high genetic similarity. whereas plcr (phospholipase c regulator) usually encodes a functional pleiotropic activator protein in b. cereus and b. thuringiensis isolates, a characteristic nonsense mutation is found in all b. anthracis strains investigated, making the gene dysfunctional. to study the function of plcr in b. anthracis, we used the b. cereus cmcc63301 genome as a template and constructed ...201525998439
identification of potent and compartment-selective small molecule furin inhibitors using cell-based assays.the proprotein convertase furin is implicated in a variety of pathogenic processes such as bacterial toxin activation, viral propagation, and cancer. several groups have identified non-peptide compounds with high inhibitory potency against furin in vitro, although their efficacy in various cell-based assays is largely unknown. in this study we show that certain guanidinylated 2,5-dideoxystreptamine derivatives exhibit interesting ex vivo properties. compound 1b (1,1'-(4-((2,4-diguanidino-5-(4-gu ...201526003844
micropatterned macrophage analysis reveals global cytoskeleton constraints induced by bacillus anthracis edema toxin.bacillus anthracis secretes the edema toxin (et) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. the effects of et on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. in this study, we have developed different adhesive micropatterned surfaces (l and crossbow) to control the shape of bone marrow-derived macrophages (bmdms ...201526015478
[the epidemiological situation in the republic of abkhazia in 2013-2014 and rospotrebnadzor participation in activities for its stabilization].official statistics of republican ses on infectious diseases are used. the characteristics of the current epidemiological situation in the republic of abkhazia is given. the analysis of infectious dis- eases from 2012 to 2014 is presented. it was found that the most widespread infectious diseases are acute respiratory viral and acute intestinal infection. during the analyzed period in the country outbreaks of dysentery, whooping cough and measles were reported. epidemic threat is the presence of ...201526016353
immobilization and orientation-dependent activity of a naturally occurring antimicrobial peptide.a naturally occurring antimicrobial peptide, smap-29, was synthesized with an n-terminal or c-terminal cysteine, termed c_smap and smap_c, respectively, for site-directed immobilization to superparamagnetic beads. immobilized smap orientation-dependent activity was probed against multiple bacteria of clinical interest including acinetobacter baumannii, pseudomonas aeruginosa, bacillus anthracis sterne and staphylococcus aureus. a kinetic microplate assay was employed to reveal both concentration ...201526018607
esxb, a secreted protein from bacillus anthracis forms two distinct helical bundles.the esxb protein from bacillus anthracis belongs to the wxg100 family, a group of proteins secreted by a specialized secretion system. we have determined the crystal structures of recombinant esxb and discovered that the small protein (∼10 kda), comprised of a helix-loop-helix (hlh) hairpin, is capable of associating into two different helical bundles. the two basic quaternary assemblies of esxb are an antiparallel (ap) dimer and a rarely observed bisecting u (bu) dimer. this structural duality ...201526032645
bacillus anthracis meningitis during an outbreak of injectional anthrax, scotland, uk. 201526033672
the worldwide distribution of genetically and phylogenetically diverse bacillus cereus isolates harbouring bacillus anthracis-like plasmids.bacillus cereus is a close relative of b. anthracis, the causative agent of anthrax whose pathogenic determinants are located on pxo1 and pxo2 plasmids. bacillus anthracis-like plasmids have been also noted among b. cereus, however, genetic features of b. cereus harbouring these elements remain largely undescribed, especially from the global perspective. herein, we present the genetic polymorphism, population structure and phylogeny of b. cereus with pxo1-/pxo2-like plasmids originating from arg ...201526033739
russian vaccines against especially dangerous bacterial pathogens.in response to the epidemiological situation, live attenuated or killed vaccines against anthrax, brucellosis, cholera, glanders, plague and tularemia were developed and used for immunization of at-risk populations in the former soviet union. certain of these vaccines have been updated and currently they are used on a selective basis, mainly for high risk occupations, in the russian federation. except for anthrax and cholera these vaccines currently are the only licensed products available for p ...201426038506
bacillus anthracis capsular conjugates elicit chimpanzee polyclonal antibodies that protect mice from pulmonary anthrax.the immunogenicity of bacillus anthracis capsule (poly-γ-d-glutamic acid [pga]) conjugated to recombinant b. anthracis protective antigen (rpa) or to tetanus toxoid (tt) was evaluated in two anthrax-naive juvenile chimpanzees. in a previous study of these conjugates, highly protective monoclonal antibodies (mabs) against pga were generated. this study examines the polyclonal antibody response of the same animals. preimmune antibodies to pga with titers of >10(3) were detected in the chimpanzees. ...201526041039
monitoring biothreat agents (francisella tularensis, bacillus anthracis and yersinia pestis) with a portable real-time pcr instrument.in the event of suspected releases or natural outbreaks of contagious pathogens, rapid identification of the infectious agent is essential for appropriate medical intervention and disease containment. the purpose of this study was to compare the performance of a novel portable real-time pcr thermocycler, pikoreal™, to the standard real-time pcr thermocycler, applied biosystems® 7300 (abi 7300), for the detection of three high-risk biothreat bacterial pathogens: francisella tularensis, bacillus a ...201526043838
pharmaceutical approval update.ivabradine (corlanor) for heart failure, anthrax immune globulin intravenous (human) (anthrasil) for inhalational anthrax, and glatiramer acetate (glatopa) for relapsing forms of multiple sclerosis.201526045644
loss of homogentisate 1,2-dioxygenase activity in bacillus anthracis results in accumulation of protective pigment.melanin production is important to the pathogenicity and survival of some bacterial pathogens. in bacillus anthracis, loss of hmga, encoding homogentisate 1,2-dioxygenase, results in accumulation of a melanin-like pigment called pyomelanin. pyomelanin is produced in the mutant as a byproduct of disrupted catabolism of l-tyrosine and l-phenylalanine. accumulation of pyomelanin protects b. anthracis cells from uv damage but not from oxidative damage. neither loss of hmga nor accumulation of pyomel ...201526047497
analysis of pregnancy and infant health outcomes among women in the national smallpox vaccine in pregnancy registry who received anthrax vaccine adsorbed.the national smallpox vaccine in pregnancy registry (nsvipr) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. approximately 65% of nsvipr participants also inadvertently received anthrax vaccine adsorbed (ava) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. ava-exposed pregnancies were ascertained using nsvipr and electronic hea ...201526049005
curing both virulent mega-plasmids from bacillus anthracis wild-type strain a16 simultaneously using plasmid incompatibility.plasmid-cured derivative strains of bacillus anthracis are frequently used in laboratory studies. plasmid incompatibility, which does not increase the risk of chromosomal mutation, is a useful method for plasmid curing. however, in bacteria containing multiple plasmids, it often requires the sequential introduction of multiple, specific incompatibility plasmids. this lengthy process renders the traditional plasmid incompatibility method inefficient and mutation-prone. in this study, we successfu ...201526059513
inhibitor bound crystal structures of bacterial nitric oxide synthase.nitric oxide generated by bacterial nitric oxide synthase (nos) increases the susceptibility of gram-positive pathogens staphylococcus aureus and bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. not surprisingly, nos inhibitors also improve the effectiveness of antimicrobials. development of potent and selective bacterial nos inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian nos isoforms. to expl ...201526062720
identification of highly pathogenic microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry: results of an interlaboratory ring trial.in the case of a release of highly pathogenic bacteria (hpb), there is an urgent need for rapid, accurate, and reliable diagnostics. maldi-tof mass spectrometry is a rapid, accurate, and relatively inexpensive technique that is becoming increasingly important in microbiological diagnostics to complement classical microbiology, pcr, and genotyping of hpb. in the present study, the results of a joint exercise with 11 partner institutions from nine european countries are presented. in this exercise ...201526063856
anthrax lethal toxin-induced lung injury and treatment by activating mk2.anthrax is associated with severe vascular leak, which is caused by the bacterial lethal toxin (letx). pleural effusions and pulmonary edema that occur in anthrax are believed to reflect endothelial injury caused by the anthrax toxin. since vascular leak can also be observed consistently in rats injected intravenously with letx, the latter might present a simple physiologically relevant animal model of acute lung injury (ali). such a model could be utilized in evaluating and developing better tr ...201526066827
bridging non-human primate correlates of protection to reassess the anthrax vaccine adsorbed booster schedule in humans.anthrax vaccine adsorbed (ava, biothrax) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-im) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. a reduction in ava booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. because human inhalatio ...201526072016
natural cutaneous anthrax infection, but not vaccination, induces a cd4(+) t cell response involving diverse cytokines.whilst there have been a number of insights into the subsets of cd4(+) t cells induced by pathogenic bacillus anthracis infections in animal models, how these findings relate to responses generated in naturally infected and vaccinated humans has yet to be fully established. we describe the cytokine profile produced in response to t cell stimulation with a previously defined immunodominant antigen of anthrax, lethal factor (lf), domain iv, in cohorts of individuals with a history of cutaneous ant ...201526075052
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