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[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
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
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
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
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
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
outbreak of anthrax in adults and adolescents: a review of nine cases in a regional teaching hospital in east hungary. 201726794029
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
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
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
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
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
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
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
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
crisis standard needed for anthrax medical countermeasure screening. 201626836584
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
structural hot spots for the solubility of globular proteins.natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. this raises the question whether the solubility of natural protein sequences can be improved. we here show an anti-correlation between the number of aggregation prone regions (aprs) in a protein sequence and its solubility, suggesting that mutational suppression of aprs provides a simple strategy to increase protein solubility. w ...201626905391
inhibition of interleukin 1β (il-1β) expression by anthrax lethal toxin (letx) is reversed by histone deacetylase 8 (hdac8) inhibition in murine macrophages.many pathogenic microbes often release toxins that subvert the host's immune responses to render the environment suitable for their survival and proliferation. letx is one of the toxins causing immune paralysis by cleaving and inactivating the mitogen-activated protein kinase (mapk) kinases (meks). here, we show that inhibition of the histone deacetylase 8 (hdac8) by either the hdac8-specific inhibitor pci-34051 or small interference (si)rnas rendered letx-exposed murine macrophages responsive t ...201626912657
mechanistic analysis of the effect of deamidation on the immunogenicity of anthrax protective antigen.the spontaneous modification of proteins, such as deamidation of asparagine residues, can significantly affect the immunogenicity of protein-based vaccines. using a "genetically deamidated" form of recombinant protective antigen (rpa), we have previously shown that deamidation can decrease the immunogenicity of rpa, the primary component of new-generation anthrax vaccines. in this study, we investigated the biochemical and immunological mechanisms by which deamidation of rpa might decrease the i ...201626912784
culturability of bacillus spores on aerosol collection filters exposed to airborne combustion products of al, mg, and b·ti.destruction of bioweapon facilities due to explosion or fire could aerosolize highly pathogenic microorganisms. the post-event air quality assessment is conducted through air sampling. a bioaerosol sample (often collected on a filter for further culture-based analysis) also contains combustion products, which may influence the microbial culturability and, thus, impact the outcome. we have examined the interaction between spores deposited on collection filters using two simulants of bacillus anth ...201626914458
crystal structure of the bacillus-conserved mazg protein, a nucleotide pyrophosphohydrolase.ba1544 from bacillus anthracis was previously annotated as a transcription factor for the gene cluster ba1554 - ba1558, but has not been experimentally characterized. b. anthracis is an obligate pathogen causing fatal inhalational anthrax, and ba1544 is absolutely conserved in bacillus species, including bacillus cereus, bacillus thuringiensis and bacillus mycoides, with 100% sequence identity. to address the function of ba1544, we performed structural and biochemical studies, which revealed tha ...201626920050
dimerization of bacterial diaminopimelate decarboxylase is essential for catalysis.diaminopimelate decarboxylase (dapdc) catalyzes the final step in the diaminopimelate biosynthesis pathway of bacteria. the product of the reaction is the essential amino acid l-lysine, which is an important precursor for the synthesis of the peptidoglycan cell wall, housekeeping proteins, and virulence factors of bacteria. accordingly, the enzyme is a promising antibacterial target. previous structural studies demonstrate that dapdc exists as monomers, dimers, and tetramers in the crystal state ...201626921318
glycosylation of bcla glycoprotein from bacillus cereus and bacillus anthracis exosporium is domain-specific.the spores of the bacillus cereus group (b. cereus, bacillus anthracis, and bacillus thuringiensis) are surrounded by a paracrystalline flexible yet resistant layer called exosporium that plays a major role in spore adhesion and virulence. the major constituent of its hairlike surface, the trimerized glycoprotein bcla, is attached to the basal layer through an n-terminal domain. it is then followed by a repetitive collagen-like neck bearing a globular head (c-terminal domain) that promotes glyco ...201626921321
identification of novel raft marker protein, flotp in bacillus anthracis.lipid rafts are dynamic, nanoscale assemblies of specific proteins and lipids, distributed heterogeneously on eukaryotic membrane. flotillin-1, a conserved eukaryotic raft marker protein (rmp) harbor spfh (stomatin, prohibitin, flotillin, and hflk/c) and oligomerization domains to regulate various cellular processes through its interactions with other signaling or transport proteins. rafts were thought to be absent in prokaryotes hitherto, but recent report of its presence and significance in ph ...201626925042
quantitative determination of lethal toxin proteins in culture supernatant of human live anthrax vaccine bacillus anthracis a16r.bacillus anthracis (b. anthracis) is the etiological agent of anthrax affecting both humans and animals. anthrax toxin (at) plays a major role in pathogenesis. it includes lethal toxin (lt) and edema toxin (et), which are formed by the combination of protective antigen (pa) and lethal factor (lf) or edema factor (ef), respectively. the currently used human anthrax vaccine in china utilizes live-attenuated b. anthracis spores (a16r; pxo1+, pxo2-) that produce anthrax toxin but cannot produce the ...201626927174
nad+-glycohydrolase promotes intracellular survival of group a streptococcus.a global increase in invasive infections due to group a streptococcus (s. pyogenes or gas) has been observed since the 1980s, associated with emergence of a clonal group of strains of the m1t1 serotype. among other virulence attributes, the m1t1 clone secretes nad+-glycohydrolase (nadase). when gas binds to epithelial cells in vitro, nadase is translocated into the cytosol in a process mediated by streptolysin o (slo), and expression of these two toxins is associated with enhanced gas intracellu ...201626938870
a case report of inhalation anthrax acquired naturally.anthrax is a zoonotic occupational disease caused by bacillus anthracis, a rod-shaped immobile aerobic gram-positive bacteria with spore. anthrax occurs in humans randomly and with low frequency. most cases of anthrax are acquired through contact with infected animals or contaminated animal products. this old disease became particularly important since 2001 that the biological spores were exploited in america. depending on the transmission method of the disease, clinical manifestations occur in ...201626939756
recent developments in the understanding and use of anthrax vaccine adsorbed: achieving more with less.anthrax vaccine adsorbed (ava, biothrax™) is the only food and drug administration (fda) approved vaccine for the prevention of anthrax in humans. recent improvements in pre-exposure prophylaxis (prep) use of ava include intramuscular (im) administration and simplification of the priming series to three doses over 6 months. administration im markedly reduced the frequency, severity and duration of injection site reactions. refinement of animal models for inhalation anthrax, identification of imm ...201626942655
mixed methods survey of zoonotic disease awareness and practice among animal and human healthcare providers in moshi, tanzania.zoonoses are common causes of human and livestock illness in tanzania. previous studies have shown that brucellosis, leptospirosis, and q fever account for a large proportion of human febrile illness in northern tanzania, yet they are infrequently diagnosed. we conducted this study to assess awareness and knowledge regarding selected zoonoses among healthcare providers in moshi, tanzania; to determine what diagnostic and treatment protocols are utilized; and obtain insights into contextual facto ...201626943334
use of multiple peptide-based sers probes binding to different epitopes on a protein biomarker to improve detection sensitivity.we propose an analytical strategy to improve the sensitivity for detecting a protein biomarker through signal multiplication by manipulating multiple peptide-based surface-enhanced raman scattering (sers) probes to bind the biomarker. protective antigen (pa) was used as an anthrax biomarker in this study. for this purpose, five small peptides selective to various pa epitopes with different binding affinities were chosen and peptide-conjugated au nanoparticle (aunp) sers probes were individually ...201626948277
complex antigens drive permissive clonal selection in germinal centers.germinal center (gc) b cells evolve toward increased affinity by a darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. we explored the population dynamics of genetically diverse gc responses to two complex antigens-bacillus anthracis protective antigen and influenza hemagglutinin-in which b cells competed both intra- and interclonally for distinct epitopes. preferred vh rearrangements among antigen-binding, naive b cells were similarly abundant ...201626948373
ultrafast, sensitive and large-volume on-chip real-time pcr for the molecular diagnosis of bacterial and viral infections.to control future infectious disease outbreaks, like the 2014 ebola epidemic, it is necessary to develop ultrafast molecular assays enabling rapid and sensitive diagnoses. to that end, several ultrafast real-time pcr systems have been previously developed, but they present issues that hinder their wide adoption, notably regarding their sensitivity and detection volume. an ultrafast, sensitive and large-volume real-time pcr system based on microfluidic thermalization is presented herein. the meth ...201626952334
development of potential broad spectrum antimicrobials using c2-symmetric 9-fluorenone alkyl amine.dna-dependent rna primase is essential for de novo primer synthesis during dna replication in all living organisms. bacterial dnag primase is an attractive target for inhibition because it is essential, low in copy number and structurally distinct from eukaryotic and archaeal primases. dnag primase is sensitive to known inhibitors including suramin and doxorubicin. recently, tilorone was discovered by high throughput screening to be an inhibitor of bacillus anthracis primase dnag but it failed t ...201626965856
soluble expression and characterization of biologically active bacillus anthracis protective antigen in escherichia coli.bacillus anthracis secretory protein protective antigen (pa) is primary candidate for subunit vaccine against anthrax. attempts to obtain large quantity of pa from escherichia coli expression system often result in the formation of insoluble inclusion bodies. therefore, it is always better to produce recombinant proteins in a soluble form. in the present study, we have obtained biologically active recombinant pa in small scale e. coli shake culture system using three different expression constru ...201626966576
nanomechanical characterization of bacillus anthracis spores by atomic force microscopy.the study of structures and properties of bacterial spores is important to understanding spore formation and biological responses to environmental stresses. while significant progress has been made over the years in elucidating the multilayer architecture of spores, the mechanical properties of the spore interior are not known. here, we present a thermal atomic force microscopy (afm) study of the nanomechanical properties of internal structures of bacillus anthracis spores. we developed a nanosu ...201626969703
ebselen and analogs as inhibitors of bacillus anthracis thioredoxin reductase and bactericidal antibacterials targeting bacillus species, staphylococcus aureus and mycobacterium tuberculosis.bacillus anthracis is the causative agent of anthrax, a disease associated with a very high mortality rate in its invasive forms.201626971857
false-negative rate, limit of detection and recovery efficiency performance of a validated macrofoam-swab sampling method for low surface concentrations of bacillus anthracis sterne and bacillus atrophaeus spores.we sought to evaluate the effects of bacillus species, low surface concentrations, and surface material on recovery efficiency (re), false-negative rate (fnr) and limit of detection for recovering bacillus spores using a validated macrofoam-swab sampling procedure.201626972788
physical sequestration of bacillus anthracis in the pulmonary capillaries in terminal infection.the lung is the terminal target of bacillus anthracis before death, whatever the route of infection (cutaneous, inhalational, or digestive). during a cutaneous infection in absence of toxins, we observed encapsulated bacteria colonizing the alveolar capillary network, bacteria and hemorrhages in alveolar and bronchiolar spaces, and hypoxic foci in the lung (endothelial cells) and brain (neurons and neuropil). circulating encapsulated bacteria were as chains of approximately 13 µm in length. bact ...201626977051
the ins and outs of anthrax toxin.anthrax is a severe, although rather rare, infectious disease that is caused by the gram-positive, spore-forming bacterium bacillus anthracis. the infectious form is the spore and the major virulence factors of the bacterium are its poly-γ-d-glutamic acid capsule and the tripartite anthrax toxin. the discovery of the anthrax toxin receptors in the early 2000s has allowed in-depth studies on the mechanisms of anthrax toxin cellular entry and translocation from the endocytic compartment to the cyt ...201626978402
randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of av7909 vaccine for anthrax post-exposure prophylaxis in healthy adults.av7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over biothrax(®) (anthrax vaccine adsorbed). a phase 2, randomized, double-blind, biothrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of av7909 in 168 healthy adults. subjects were randomized at a 4:3:2:4:2 ratio ...201626979136
targeting the map kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion.malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. understanding and targeting cancer cell invasion is an important therapeutic approach. cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (map) kinase (mapk). in many cell lines, the use of mapk-targeted drugs proved to be a potential method to inhibit cancer cell motility. in the present study, we use a recombinant anthrax lethal toxin ...201626984023
rapid antimicrobial susceptibility testing of bacillus anthracis, yersinia pestis, and burkholderia pseudomallei by use of laser light scattering technology.rapid methods to determine antimicrobial susceptibility would assist in the timely distribution of effective treatment or postexposure prophylaxis in the aftermath of the release of bacterial biothreat agents such as bacillus anthracis, yersinia pestis, or burkholderia pseudomallei conventional susceptibility tests require 16 to 48 h of incubation, depending on the bacterial species. we evaluated a method that is based on laser light scattering technology that measures cell density in real time. ...201626984973
extracellular synthesis of silver and gold nanoparticles by sporosarcina koreensis dc4 and their biological applications.the present study highlights the microbial synthesis of silver and gold nanoparticles by sporosarcina koreensis dc4 strain, in an efficient way. the synthesized nanoparticles were characterized by ultraviolet-visible spectrophotometry, which displayed maximum absorbance at 424nm and 531nm for silver and gold nanoparticles, respectively. the spherical shape of nanoparticles was characterized by field emission transmission electron microscopy. the energy dispersive x-ray spectroscopy and elemental ...201626992796
in vivo dynamics of active edema and lethal factors during anthrax.lethal and edema toxins are critical virulence factors of bacillus anthracis. however, little is known about their in vivo dynamics of production during anthrax. in this study, we unraveled for the first time the in vivo kinetics of production of the toxin components ef (edema factor) and lf (lethal factor) during cutaneous infection with a wild-type toxinogenic encapsulated strain in immuno-competent mice. we stratified the asynchronous infection process into defined stages through bioluminesce ...201626996161
the phylogeny of bacillus cereus sensu lato.the three main species of the bacillus cereus sensu lato, b. cereus, b. thuringiensis, and b. anthracis, were recognized and established by the early 1900 s because they each exhibited distinct phenotypic traits. b. thuringiensis isolates and their parasporal crystal proteins have long been established as a natural pesticide and insect pathogen. b. anthracis, the etiological agent for anthrax, was used by robert koch in the 19th century as a model to develop the germ theory of disease, and b. ce ...201626999390
aggregation of chameleon peptides: implications of α-helicity in fibril formation.we investigate the relationship between the inherent secondary structure and aggregation propensity of peptides containing chameleon sequences (i.e., sequences that can adopt either α or β structure depending on context) using a combination of replica exchange molecular dynamics simulations, ion-mobility mass spectrometry, circular dichroism, and transmission electron microscopy. we focus on an eight-residue long chameleon sequence that can adopt an α-helical structure in the context of the iron ...201627001160
ab5 preassembly is not required for shiga toxin activity.shiga toxin (stx)-producing escherichia coli (stec) is a major cause of foodborne illness, including the life-threatening complication hemolytic-uremic syndrome. the german outbreak in 2011 resulted in nearly 4,000 cases of infection, with 54 deaths. two forms of stx, stx1 and stx2, differ in potency, and subtype stx2a is most commonly associated with fatal human disease. stx is considered to be an ab5 toxin. the single a (enzymatically active) subunit inhibits protein synthesis by cleaving a ca ...201627002129
a comparison of the adaptive immune response between recovered anthrax patients and individuals receiving three different anthrax vaccines.several different human vaccines are available to protect against anthrax. we compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. adaptive immunity was measured by elispot to count cells that produce interferon (ifn)-γ in response to restimulation ex vivo with the anthrax toxin components pa, lf and ef and by measuring circulating igg specific to these antigens. neutralising activity of antisera against anthrax ...201627007118
identifying meningitis during an anthrax mass casualty incident: systematic review of systemic anthrax since 1880.bacillus anthracis, the causative agent of anthrax, is a potential bioterrorism agent. anthrax meningitis is a common manifestation of b. anthracis infection, has high mortality, and requires more aggressive treatment than anthrax without meningitis. its rapid identification and treatment are essential for successful management of an anthrax mass casualty incident.201627025833
[perspectives of development of live recombinant anthrax vaccines based on opportunistic and apathogenic microorganisms].live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-organisms are a safe and adequate alternative to preparations based on attenuated bacillus anthracis strains. mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs arid tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. live recombinant anthrax vacc ...201627029122
identification of the pxo1 plasmid in attenuated bacillus anthracis vaccine strains.anthrax toxins and capsule are the major virulence factors of bacillus anthracis. they are encoded by genes located on the plasmids pxo1 and pxo2, respectively. the vaccine strain pasteur ii was produced from high temperature subcultures of b. anthracis, which resulted in virulence attenuation through the loss of the plasmid pxo1. however, it is unclear whether the high temperature culture completely abolishes the plasmid dna or affects the replication of the plasmid pxo1. in this study, we test ...201627029580
administration of dna plasmid coding protein aggregating domain induces inflammatory bone loss.plasmids coding protein aggregation polypeptides from different sources have been proposed as genetic adjuvants for dna vaccines. we reported that a plasmid (patrex), encompassing the dna sequence for the von willebrand a (vwa/a) domain of the anthrax toxin receptor-1 (antxr-1, alias tem8, tumor endothelial marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates and subsequent cell death.201627029946
identification and pathogenic potential of clinical bacillus and paenibacillus isolates.the soil-related bacillus and paenibacillus species have increasingly been implicated in various human diseases. nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of bacillus anthracis and bacillus cereus, little is known on their pathogenicity for humans. in this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (maldi-tof ms) in the identification of clinical isolates ...201627031639
profiling lethal factor interacting proteins from human stomach using t7 phage display screening.the anthrax lethal factor (lf) is a zinc dependent metalloproteinase that cleaves the majority of mitogen-activated protein kinase kinases and a member of nod-like receptor proteins, inducing cell apoptosis. despite efforts to fully understand the bacillus anthracis toxin components, the gastrointestinal (gi) anthrax mechanisms have not been fully elucidated. previous studies demonstrated gastric ulceration, and a substantial bacterial growth rate in peyer's patches. however, the complete molecu ...201627035230
electrophysiological evidences of interaction between calcium channels and pa of anthrax. 201627045324
awareness, knowledge, and risks of zoonotic diseases among livestock farmers in punjab.the present study was conducted to assess the awareness, knowledge, and risks of zoonotic diseases among livestock farmers in punjab.201627051206
delivery of non-native cargo into mammalian cells using anthrax lethal toxin.the intracellular delivery of peptide and protein therapeutics is a major challenge due to the plasma membrane, which acts as a barrier between the extracellular environment and the intracellular milieu. over the past two decades, a nontoxic pa/lfn delivery platform derived from anthrax lethal toxin has been developed for the transport of non-native cargo into the cytosol of cells in order to understand the translocation process through a protective antigen (pa) pore and to probe intracellular b ...201627055654
genome sequence of bacillus anthracis strain stendal, isolated from an anthrax outbreak in cattle in germany.in july 2012, an anthrax outbreak occurred among cattle in northern germany resulting in ten losses. here, we report the draft genome sequence ofbacillus anthracisstrain stendal, isolated from one of the diseased cows.201627056225
c/ebpβ-thr217 phosphorylation stimulates macrophage inflammasome activation and liver injury.amplification of liver injury is mediated by macrophages but the signaling by which the macrophage inflammasome enhances liver injury is not completely understood. the ccaat/enhancer binding protein-β (c/ebpβ) is a critical signaling molecule for macrophages because expression of a dominant inhibitor of c/ebpβ dna-binding sites or a targeted deletion of c/ebpβ results in impaired macrophage differentiation. we reported that expression of the phosphorylation-mutant c/ebpβ-glu217, which mimics pho ...201627067260
inhibitors of the metalloproteinase anthrax lethal factor.bacillus anthracis, a rod shaped, spore forming, gram positive bacteria, is the etiological agent of anthrax. b. anthracis virulence is partly attributable to two secreted bipartite protein toxins, which act inside host cells to disrupt signaling pathways important for host defense against infection. these toxins may also directly contribute to mortality in late stage infection. the zinc-dependent metalloproteinase anthrax lethal factor (lf) is a critical component of one of these protein toxins ...201627072692
optimization, production, and characterization of a cpg-oligonucleotide-ficoll conjugate nanoparticle adjuvant for enhanced immunogenicity of anthrax protective antigen.we have synthesized and characterized a novel phosphorothioate cpg oligodeoxynucleotide (cpg odn)-ficoll conjugated nanoparticulate adjuvant, termed dv230-ficoll. this adjuvant was constructed from an amine-functionalized-ficoll, a heterobifunctional linker (succinimidyl-[(n-maleimidopropionamido)-hexaethylene glycol] ester) and the cpg-odn dv230. herein, we describe the evaluation of the purity and reactivity of linkers of different lengths for cpg-odn-ficoll conjugation, optimization of linker ...201627074387
genotype analysis of bacillus anthracis strains circulating in bangladesh.in bangladesh, anthrax, caused by the bacterium bacillus anthracis, is considered an endemic disease affecting ruminants with sporadic zoonotic occurrences in humans. due to the lack of knowledge about risks from an incorrect removal of infected carcasses, the disease is not properly monitored, and because of the socio-economic conditions, the situation is under-reported and under-diagnosed. for sensitive species, anthrax represents a fatal outcome with sudden death and sometimes bleeding from n ...201627082248
obiltoxaximab: first global approval.obiltoxaximab (anthim(®), eti-204) is a monoclonal antibody that is being developed by elusys therapeutics and the us department of health and human services' biomedical advanced research and development authority for the prevention and treatment of inhalational anthrax due to bacillus anthracis. obiltoxaximab has been designed to neutralize the free protective antigen of b. anthracis, thereby inhibiting the lethal effects of anthrax toxins. in march 2016, intravenous obiltoxaximab was approved ...201627085536
sensing and inactivation of bacillus anthracis sterne by polymer-bromine complexes.we report on the performance of brominated poly(n-vinylpyrrolidone) (pvp-br), brominated poly(ethylene glycol) (peg-br), and brominated poly(allylamine-co-4-aminopyridine) (paam-apy-br) for their ability to decontaminate bacillus anthracis sterne spores in solution while also allowing for the sensing of the spores. the polymers were brominated by bromine using carbon tetrachloride or potassium tribromide as solvents, with bromine loadings ranging from 1.6 to 4.2 meq/g of polymer. b. anthracis st ...201627087522
study of surveillance data for class b notifiable disease in china from 2005 to 2014.the surveillance of infection is very important for public health management and disease control. it has been 10 years since china implemented its new web-based infection surveillance system, which covers the largest population in the world.201627094249
mapping the distribution of anthrax in mainland china, 2005-2013.anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland china. despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood.201627097318
outer membrane vesicles of lysobacter sp. xl1: biogenesis, functions, and applied prospects.outer membrane vesicles (omvs) produced by gram-negative bacteria have been intensively investigated in recent times. vesicle formation models have been proposed, some factors affecting the process were established, and important roles vesicles play in vital activities of their producing cells were determined. studies of pathogenic bacterial vesicles contribute to understanding the causes of acute infection and developing drugs on their basis. despite intensive research, issues associated with t ...201627098257
production of functionally active and immunogenic non-glycosylated protective antigen from bacillus anthracis in nicotiana benthamiana by co-expression with peptide-n-glycosidase f (pngase f) of flavobacterium meningosepticum.bacillus anthracis has long been considered a potential biological warfare agent, and therefore, there is a need for a safe, low-cost and highly efficient anthrax vaccine with demonstrated long-term stability for mass vaccination in case of an emergency. many efforts have been made towards developing an anthrax vaccine based on recombinant protective antigen (rpa) of b. anthracis, a key component of the anthrax toxin, produced using different expression systems. plants represent a promising reco ...201627101370
chloroquine derivatives block the translocation pores and inhibit cellular entry of clostridium botulinum c2 toxin and bacillus anthracis lethal toxin.the pathogenic bacteria clostridium botulinum and bacillus anthracis produce the binary protein toxins c2 and lethal toxin (lt), respectively. these toxins consist of a binding/transport (b7) component that delivers the separate enzyme (a) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. the b7 components of c2 toxin and lt, c2iia and pa63, respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes wi ...201727106023
cyclic diguanylate regulation of bacillus cereus group biofilm formation.biofilm formation can be considered a bacterial virulence mechanism. in a range of gram-negatives, increased levels of the second messenger cyclic diguanylate (c-di-gmp) promotes biofilm formation and reduces motility. other bacterial processes known to be regulated by c-di-gmp include cell division, differentiation and virulence. among gram-positive bacteria, where the function of c-di-gmp signalling is less well characterized, c-di-gmp was reported to regulate swarming motility in bacillus sub ...201627116468
multigeneration cross-contamination of mail with bacillus anthracis spores.the release of biological agents, including those which could be used in biowarfare or bioterrorism in large urban areas, has been a concern for governments for nearly three decades. previous incidents from sverdlosk and the postal anthrax attack of 2001 have raised questions on the mechanism of spread of bacillus anthracis spores as an aerosol or contaminant. prior studies have demonstrated that bacillus atrophaeus is easily transferred through simulated mail handing, but no reports have demons ...201627123934
bacillus anthracis prolyl 4-hydroxylase modifies collagen-like substrates in asymmetric patterns.proline hydroxylation is the most prevalent post-translational modification in collagen. the resulting product trans-4-hydroxyproline (hyp) is of critical importance for the stability and thus function of collagen, with defects leading to several diseases. prolyl 4-hydroxylases (p4hs) are mononuclear non-heme iron α-ketoglutarate (αkg)-dependent dioxygenases that catalyze hyp formation. although animal and plant p4hs target peptidyl proline, prokaryotes have been known to use free l-proline as a ...201627129244
lack of evidence for plague or anthrax on the new york city subway.ackelsberg et al. point out a lack of evidence in the dataset of afshinekoo et al. for the presence of plague and anthrax on the new york city subway.201527135683
the intxo-psl recombination system is a key component of the second maintenance system for bacillus anthracis plasmid pxo1.we previously identified three noncontiguous regions on bacillus anthracis plasmid pxo1 that comprise a system for accurate plasmid partitioning and maintenance. however, deletion of these regions did not decrease retention of certain shortened pxo1 plasmids during vegetative growth. using two genetic tools developed for dna manipulation in b. anthracis (the cre-loxp and flp-frt systems), we found two other noncontiguous pxo1 regions that together are sufficient for plasmid stability. this secon ...201627137503
structural analysis of cofactor binding for a prolyl 4-hydroxylase from the pathogenic bacterium bacillus anthracis.the prolyl 4-hydroxylases (p4hs) are mononuclear nonheme iron enzymes that catalyze the formation of 4r-hydroxyproline from many different substrates, with various biological implications. p4h is a key player in collagen accumulation, which has implications in fibrotic disorders. the stabilization of collagen triple-helical structure via prolyl hydroxylation is the rate-limiting step in collagen biosynthesis, and therefore p4h has been extensively investigated as a potential therapeutic target o ...201627139630
correction: mapping the distribution of anthrax in mainland china, 2005-2013.[this corrects the article doi: 10.1371/journal.pntd.0004637.].201627145181
biothrax and anthrasil for anthrax. 201627148924
plantazolicin is an ultra-narrow spectrum antibiotic that targets the bacillus anthracis membrane.plantazolicin (pzn) is a ribosomally synthesized and post-translationally modified natural product from bacillus methylotrophicus fzb42 and bacillus pumilus. extensive tailoring to twelve of the fourteen amino acid residues in the mature natural product endows pzn with not only a rigid, polyheterocyclic structure, but also antibacterial activity. here we report a remarkably discriminatory activity of pzn toward bacillus anthracis, which rivals a previously-described gamma (γ) phage lysis assay i ...201627152321
evaluation of early immune response-survival relationship in cynomolgus macaques after anthrax vaccine adsorbed vaccination and bacillus anthracis spore challenge.anthrax vaccine adsorbed (ava, biothrax) is approved by the us food and drug administration for post-exposure prophylaxis (pep) of anthrax in adults. the pep schedule is 3 subcutaneous (sc) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. the objectives of this study were to understand the onset of protection from ava pep vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/preparedness/mcm/phemce/docu ...201627155494
pasteur revisited: an unexpected finding in bacillus anthracis vaccine strains. 201627163362
cxcl10 acts as a bifunctional antimicrobial molecule against bacillus anthracis.bacillus anthracis is killed by the interferon-inducible, elr(-) cxc chemokine cxcl10. previous studies showed that disruption of the gene encoding ftsx, a conserved membrane component of the atp-binding cassette transporter-like complex ftse/x, resulted in resistance to cxcl10. ftsx exhibits some sequence similarity to the mammalian cxcl10 receptor, cxcr3, suggesting that the cxcl10 n-terminal region that interacts with cxcr3 may also interact with ftsx. a c-terminal truncated cxcl10 was tested ...201627165799
predicting disease risk, identifying stakeholders, and informing control strategies: a case study of anthrax in montana.infectious diseases that affect wildlife and livestock are challenging to manage and can lead to large-scale die-offs, economic losses, and threats to human health. the management of infectious diseases in wildlife and livestock is made easier with knowledge of disease risk across space and identifying stakeholders associated with high-risk landscapes. this study focuses on anthrax, caused by the bacterium bacillus anthracis, risk to wildlife and livestock in montana. there is a history of anthr ...201627169560
antxr-1 and -2 independent modulation of a cytotoxicity mediated by anthrax toxin in human cells.several animal models have shown that anthrax toxin (atx) elicits a cytotoxic effect on host cells through anthrax toxin receptor (antxr) function. in this study, compared with mouse cells, cells obtained from humans exhibited low sensitivity to atx-mediated cytotoxicity, and the sensitivity was not correlated with expression levels of antxrs. atx treatment also induced a cytotoxic effect in other cultured human cells, human embryonic kidney (hek) 293 cells, that express antxrs at undetectable l ...201627170489
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