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applications of docking and molecular dynamic studies on the search for new drugs against the biological warfare agents bacillus anthracis and yersinia pestis.the fear of biological warfare agents (bwa) use by terrorists is the major concern of the security agencies and health authorities worldwide today. the non-existence of vaccines or drugs against most bwa and the possibility of genetic modified strains has turned the search for new drugs to a state of urgency. fast in silico techniques are, therefore, perfect tools for this task once they can quickly provide structures of several new lead compounds for further experimental work. here we try to pr ...201324341424
haem-based sensors: a still growing old superfamily.the haem-based sensors are chimeric multi-domain proteins responsible for the cellular adaptive responses to environmental changes. the signal transduction is mediated by the sensing capability of the haem-binding domain, which transmits a usable signal to the cognate transmitter domain, responsible for providing the adequate answer. four major families of haem-based sensors can be recognized, depending on the nature of the haem-binding domain: (i) the haem-binding pas domain, (ii) the co-sensit ...201324054793
rapid targeted gene disruption in bacillus anthracis.anthrax is a zoonotic disease recognized to affect herbivores since biblical times and has the widest range of susceptible host species of any known pathogen. the ease with which the bacterium can be weaponized and its recent deliberate use as an agent of terror, have highlighted the importance of gaining a deeper understanding and effective countermeasures for this important pathogen. high quality sequence data has opened the possibility of systematic dissection of how genes distributed on both ...201324047152
bacillus anthracis has two independent bottlenecks that are dependent on the portal of entry in an intranasal model of inhalational infection.bacillus anthracis can cause inhalational anthrax. murine inhalational b. anthracis infections have two portals of entry, the nasal mucosa-associated lymphoid tissue (nalt) and the lumen of the lungs. analysis of the dissemination from these sites is hindered because infections are asynchronous and asymptomatic until the hosts near death. to further understand and compare how b. anthracis disseminates from these two different environments, clonal analysis was employed using a library of equally ...201324042112
hollow-fiber pharmacodynamic studies and mathematical modeling to predict the efficacy of amoxicillin for anthrax postexposure prophylaxis in pregnant women and children.amoxicillin is considered an option for postexposure prophylaxis of bacillus anthracis in pregnant and postpartum women who are breastfeeding and in children because of the potential toxicities of ciprofloxacin and doxycycline to the fetus and child. the amoxicillin regimen that effectively kills b. anthracis and prevents resistance is unknown. fourteen-day dose range and dose fractionation studies were conducted in in vitro pharmacodynamic models to identify the exposure intensity and pharmacod ...201324041894
infectious diseases in poland in 2011.the aim of the study was assessment of the epidemiological situation of infectious and parasitic diseases in poland in 2011 materials and methods: the main source of data to develop the statistical overview was the annual bulletin "infectious diseases in poland in 2011," and "vaccinations in poland in 2011,"/niph-nih, csi, 2011 and information contained in the articles of epidemiological journal in which authors depth discussion of the epidemiological situation of 27 diseases or groups of diseas ...201324040711
evidence of local persistence of human anthrax in the country of georgia associated with environmental and anthropogenic factors.anthrax is a soil-borne disease caused by the bacterium bacillus anthracis and is considered a neglected zoonosis. in the country of georgia, recent reports have indicated an increase in the incidence of human anthrax. identifying sub-national areas of increased risk may help direct appropriate public health control measures. the purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters.201324040426
effect of delayed anthrax vaccine dose on bacillus anthracis protective antigen igg response and lethal toxin neutralization activity.we describe the bacillus anthracis protective antigen igg antibody response and the b. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (ava, biothrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of ava. overall, 23.6% of subjects showed detectable anti-pa igg before the boost, compared to 99.2% (p<0.0001) 28 days after the boost. geometric mean anti-pa igg concentra ...201324026013
[current situation of endemic status, prevention and control of neglected zoonotic diseases in china].neglected zoonotic diseases not only threaten the health of human, especially to the livestock keepers in poverty-stricken areas but also cause great economic losses to the animal husbandry. this paper reviews the current situation of the endemic status, prevention and control of neglected zoonotic diseases existing in china including rabies, bovine tuberculosis, brucellosis, anthrax, leptospirosis, echinococcosis, cysticercosis, leishmaniasis and fascioliasis, so as to provide the basic informa ...201324024457
beetroot-pigment-derived colorimetric sensor for detection of calcium dipicolinate in bacterial spores.in this proof-of-concept study, we describe the use of the main red beet pigment betanin for the quantification of calcium dipicolinate in bacterial spores, including bacillus anthracis. in the presence of europium(iii) ions, betanin is converted to a water-soluble, non-luminescent orange 1∶1 complex with a stability constant of 1.4 × 10(5) l mol(-1). the addition of calcium dipicolinate, largely found in bacterial spores, changes the color of the aqueous solution of [eu(bn)(+)] from orange to m ...201324019934
anthrax edema factor toxicity is strongly mediated by the n-end rule.anthrax edema factor (ef) is a calmodulin-dependent adenylate cyclase that converts adenosine triphosphate (atp) into 3'-5'-cyclic adenosine monophosphate (camp), contributing to the establishment of bacillus anthracis infections and the resulting pathophysiology. we show that ef adenylate cyclase toxin activity is strongly mediated by the n-end rule, and thus is dependent on the identity of the n-terminal amino acid. ef variants having different n-terminal residues varied by more than 100-fold ...201324015319
cyclodextrin derivatives as anti-infectives.cyclodextrin derivatives can be utilized as anti-infectives with pore-forming proteins as the targets. the highly efficient selection of potent inhibitors was achieved because per-substituted cyclodextrins have the same symmetry as the target pores. inhibitors of several bacterial toxins produced by bacillus anthracis, staphylococcus aureus, clostridium perfringens, clostridium botulinum, and clostridium difficile were identified from a library of ∼200 cd derivatives. it was demonstrated that mu ...201324011515
gastrointestinal anthrax: clinical experience in 5 cases.bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal and cutaneous. the gastrointestinal (gi) anthrax develops after eating contaminated meat. thus, in this paper were report 5 cases of intestinal anthrax.201324009958
in silico and in vitro evaluation of pcr-based assays for the detection of bacillus anthracis chromosomal signature sequences.bacillus anthracis, the causative agent of anthrax, is a zoonotic pathogen that is relatively common throughout the world and may cause life threatening diseases in animals and humans. there are many pcr-based assays in use for the detection of b. anthracis. while most of the developed assays rely on unique markers present on virulence plasmids pxo1 and pxo2, relatively few assays incorporate chromosomal dna markers due to the close relatedness of b. anthracis to the b. cereus group strains. for ...201324005110
two anthrax cases with soft tissue infection, severe oedema and sepsis in danish heroin users.anthrax had become extremely rare in europe, but in 2010 an outbreak of anthrax among heroin users in scotland increased awareness of contaminated heroin as a source of anthrax. we present the first two danish cases of injectional anthrax and discuss the clinical presentations, which included both typical and more unusual manifestations.201324004900
discovery of inhibitors of bacillus anthracis primase dnag.primase dnag is an essential bacterial enzyme that synthesizes short ribonucleotide primers required for chromosomal dna replication. inhibitors of dnag can serve as leads for development of new antibacterials and biochemical probes. we recently developed a nonradioactive in vitro primase-pyrophosphatase assay to identify and analyze dnag inhibitors. application of this assay to dnag from bacillus anthracis (ba dnag), a dangerous pathogen, yielded several inhibitors, which include agents with dn ...201324004110
key tissue targets responsible for anthrax-toxin-induced lethality.bacillus anthracis, the causative agent of anthrax disease, is lethal owing to the actions of two exotoxins: anthrax lethal toxin (lt) and oedema toxin (et). the key tissue targets responsible for the lethal effects of these toxins are unknown. here we generated cell-type-specific anthrax toxin receptor capillary morphogenesis protein-2 (cmg2)-null mice and cell-type-specific cmg2-expressing mice and challenged them with the toxins. our results show that lethality induced by lt and et occurs thr ...201323995686
bacillus anthracis diagnostic detection and rapid antibiotic susceptibility determination using 'bioluminescent' reporter phage.genetically modified phages have the potential to detect pathogenic bacteria from clinical, environmental, or food-related sources. herein we assess an engineered 'bioluminescent' reporter phage (wß::luxab) as a clinical diagnostic tool for bacillus anthracis, the etiological agent of anthrax. wß::luxab is able to rapidly (within minutes) detect a panel of b. anthracis strains by transducing a bioluminescent phenotype. the reporter phage displays species specificity by its inability, or signific ...201323994352
structure of isochorismate synthase dhbc from bacillus anthracis.the isochorismate synthase dhbc from bacillus anthracis is essential for the biosynthesis of the siderophore bacillibactin by this pathogenic bacterium. the structure of the selenomethionine-substituted protein was determined to 2.4 å resolution using single-wavelength anomalous diffraction. b. anthracis dhbc bears the strongest resemblance to the escherichia coli isochorismate synthase entc, which is involved in the biosynthesis of another siderophore, namely enterobactin. both proteins adopt t ...201323989140
increasing the potency of an alhydrogel-formulated anthrax vaccine by minimizing antigen-adjuvant interactions.aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. here we report an unexpected role for phosphate buffer in an anthrax vaccine (sparvax) containing recombinant protective antigen (rpa) and aluminum oxyhydroxide (aloh) adjuvant (alhydrogel). phosphate ions bind to aloh to produce an aluminum phosphate surface with a reduced rpa adsorption coefficient and binding capacity. however, these effects continued to increase as the ...201323986317
anthrax vaccines: present status and future prospects.the management of anthrax remains a top priority among the biowarfare/bioterror agents. it was the bacillus anthracis spore attack through the us mail system after the september 11, 2001, terrorist attacks in the usa that highlighted the potential of b. anthracis as a bioterrorism agent and the threat posed by its deliberate dissemination. these attacks invigorated the efforts toward understanding the anthrax pathogenesis and development of more comprehensive medical intervention strategies for ...201323984963
effect of anthrax immune globulin on response to biothrax (anthrax vaccine adsorbed) in new zealand white rabbits.development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. anthrax immune globulin intravenous (aigiv) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (pa), a component of anthrax toxins. we evaluated the interaction between aigiv and biothrax (anthrax vaccine adsorbed) in rabbits. while pharmacokinetics of aigiv were not altered by vaccinati ...201323979740
evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax.bacillus anthracis toxins can be neutralized by antibodies against protective antigen (pa), a component of anthrax toxins. anthrivig (human anthrax immunoglobulin), also known as aigiv, derived from plasma of humans immunized with biothrax (anthrax vaccine adsorbed), is under development for the treatment of toxemia following exposure to anthrax spores. the pharmacokinetics (pk) of aigiv was assessed in naive animals and healthy human volunteers, and the efficacy of aigiv was assessed in animals ...201323979731
the interdependence of antibody c and v regions on specificity and affinity: significant implications for the engineering of therapeutic antibodies. 201323979029
ecological niche modeling of bacillus anthracis on three continents: evidence for genetic-ecological divergence?we modeled the ecological niche of a globally successful bacillus anthracis sublineage in the united states, italy and kazakhstan to better understand the geographic distribution of anthrax and potential associations between regional populations and ecology. country-specific ecological-niche models were developed and reciprocally transferred to the other countries to determine if pathogen presence could be accurately predicted on novel landscapes. native models accurately predicted endemic areas ...201323977300
erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.anthrax is a disease caused by the bacterium bacillus anthracis, which results in high mortality in animals and humans. although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. lethal toxin (lt) is a major virulence factor of b. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (mapkks). anthrax lt causes lethality and induces certain ...201323977125
[four cases of cutaneous anthrax in diyarbakir, turkey].anthrax which is a rare disease in developed countries, is still a serious public health problem in countries like turkey where livestock is common. in this report, four cases of cutaneous anthrax detected in kirkira village of diyarbakir, southeast anatolia, turkey, were presented. three female and one male patients were admitted to our hospital with the complaints of skin lesions and high fever lasting for 10 days. their history indicated that they injured their fingers during slaughtering of ...201323971932
[a severe cutaneous anthrax case complicated with sepsis in bursa, turkey].anthrax is a zoonotic infection caused by bacillus anthracis. although the incidence of disease has been decreasing in turkey, it is still endemic in some regions of the country. the cutaneous form of disease is the most common clinical form, usually benign and rarely causes bacteriemia and sepsis. in this report, a case of cutaneous anthrax complicated with sepsis where b.anthracis was isolated from blood and wound cultures, was presented. a 53-years-old male living in bursa province (northwest ...201323971931
decontamination of a hospital room using gaseous chlorine dioxide: bacillus anthracis, francisella tularensis, and yersinia pestis.this study assessed the efficacy of gaseous chlorine dioxide for inactivation of bacillus anthracis, francisella tularensis, and yersinia pestis in a hospital patient care suite. spore and vegetative cells of bacillus anthracis sterne 34f2, spores of bacillus atrophaeus atcc 9372 and vegetative cells of both francisella tularensis atcc 6223 and yersinia pestis a1122 were exposed to gaseous chlorine dioxide in a patient care suite. organism inactivation was then assessed by log reduction in viabl ...201323971883
thermally modulated porous silica multispectral filters and their application in remote imaging.we report a thermally tunable multispectral imaging filter based on reversible condensation of volatile organic fluids within a nanoporous one-dimensional photonic crystal. the photonic crystal (optical rugate filter) comprises oxidized porous silicon, prepared by electrochemical etch of silicon and subsequent air oxidation (porous silica rugate filter, psif). the reflectance spectrum of the psif is designed and constructed to match two of the red emission bands of the luminescent complex europi ...201323968219
dual effects of single-walled carbon nanotubes coupled with near-infrared radiation on bacillus anthracis spores: inactivates spores and stimulates the germination of surviving spores.bacillus anthracis is a pathogen that causes life-threatening disease--anthrax. b. anthracis spores are highly resistant to extreme temperatures and harsh chemicals. inactivation of b. anthracis spores is important to ensure the environmental safety and public health. the 2001 bioterrorism attack involving anthrax spores has brought acute public attention and triggered extensive research on inactivation of b. anthracis spores. single-walled carbon nanotubes (swcnts) as a class of emerging nanoma ...201323965258
high throughput detection of human neutrophil peptides from serum, saliva, and tear by anthrax lethal factor-modified nanoparticles.human α defensins human neutrophil peptide 1-3 (hnp 1-3) are potential prognostic cancer biomarkers. metalloprotein anthrax lethal factor (alf) binds to hnp 1-3 in a zn2+-dependent manner. we conjugated alf to the surface of magnetic nanoparticles (mnp) to magnetically isolate the hnps, and used zn2+ to control the capture and release hnps.201323965149
monitoring the kinetics of the ph-driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance.domain 2 of the anthrax protective antigen (pa) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 å β barrel pore that inserts into the endosomal membrane. the pa pore facilitates the ph-dependent unfolding and translocation of bound toxin enzymic components, lethal factor (lf) and/or edema factor, from the endosome to the cytoplasm. we constructed immobilized complexes of the prepore with the pa-binding domain of lf (lfn) to monitor the real-time pre ...201323964683
equivalent t cell epitope promiscuity in ecologically diverse human pathogens.the hla (human leukocyte antigen) molecules that present pathogen-derived epitopes to t cells are highly diverse. correspondingly, many pathogens such as hiv evolve epitope variants in order to evade immune recognition. in contrast, another persistent human pathogen, mycobacterium tuberculosis, has highly conserved epitope sequences. this raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse hla alleles, referred to as an epitope's bin ...201323951341
anthrax toxin-induced rupture of artificial lipid bilayer membranes.we demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. when the solution ph is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. the results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm.201323947891
characterization of amiba2446, a novel bacteriolytic enzyme active against bacillus species.there continues to be a need for developing efficient and environmentally friendly treatments for bacillus anthracis, the causative agent of anthrax. one emerging approach for inactivation of vegetative b. anthracis is the use of bacteriophage endolysins or lytic enzymes encoded by bacterial genomes (autolysins) with highly evolved specificity toward bacterium-specific peptidoglycan cell walls. in this work, we performed in silico analysis of the genome of bacillus anthracis strain ames, using a ...201323872558
optimizing snp microarray probe design for high accuracy microbial genotyping.microarrays to characterize single nucleotide polymorphisms (snps) provide a cost-effective and rapid method (under 24h) to genotype microbes as an alternative to sequencing. we developed a pipeline for snp discovery and microarray design that scales to 100's of microbial genomes. here we tested various snp probe design strategies against 8 sequenced isolates of bacillus anthracis to compare sequence and microarray data. the best strategy allowed probe length to vary within 32-40 bp to equalize ...201323871857
selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses.pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. one common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. to identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. here we report that 4-bromobenzaldehyde n-( ...201324191014
quantitative models of the dose-response and time course of inhalational anthrax in humans.anthrax poses a community health risk due to accidental or intentional aerosol release. reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. analyses of available data from exposures and infections of humans and non-human primates are often contradictory. we review existing quantitative inhalational anthrax dose-response models in light of criter ...201324058320
a sensitive & specific multiplex pcr assay for simultaneous detection of bacillus anthracis, yersinia pestis, burkholderia pseudomallei & brucella species.bacillus anthracis, yersinia pestis, burkholderia pseudomallei and brucella species are potential biowarfare agents. classical bacteriological methods for their identification are cumbersome, time consuming and of potential risk to the handler.201324056564
the two ccda proteins of bacillus anthracis differentially affect virulence gene expression and sporulation.the cytochrome c maturation system influences the expression of virulence factors in bacillus anthracis. b. anthracis carries two copies of the ccda gene, encoding predicted thiol-disulfide oxidoreductases that contribute to cytochrome c maturation, while the closely related organism bacillus subtilis carries only one copy of ccda. to investigate the roles of the two ccda gene copies in b. anthracis, strains were constructed without each ccda gene, and one strain was constructed without both cop ...201324056109
bacillus cereus sensu lato genomes: basis for identifying anthrax disease strain sources. 201324092785
whole-genome sequences of 94 environmental isolates of bacillus cereus sensu lato.bacillus cereus sensu lato is a species complex that includes the anthrax pathogen bacillus anthracis and other bacterial species of medical, industrial, and ecological importance. their phenotypes of interest are typically linked to large plasmids that are closely related to the anthrax plasmids pxo1 and pxo2. here, we present the draft genome sequences of 94 isolates of b. cereus sensu lato, which were chosen for their plasmid content and environmental origins.201324092776
calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis.the protective antigen component of bacillus anthracis toxins can interact with at least three distinct proteins on the host cell surface, capillary morphogenesis gene 2 (cmg2), tumor endothelial marker 8, and β1-integrin, and, with the assistance of other host proteins, enters targeted cells by receptor-mediated endocytosis. using an antisense-based phenotypic screen, we discovered the role of calpains in this process. we show that functions of a ubiquitous ca(2+)-dependent cysteine protease, c ...201324085852
prophylaxis and treatment of anthrax in pregnant women.to review the safety and pharmacokinetics of antimicrobials recommended for anthrax postexposure prophylaxis and treatment in pregnant women.201324084549
influence of temperature and organic load on chemical disinfection of geobacillus steareothermophilus spores, a surrogate for bacillus anthracis.this study evaluated the influence of temperature and organic load on the effectiveness of domestic bleach (db), surface decontamination foam (sdf), and virkon in inactivating geobacillus stearothermophilus spores, which are a surrogate for bacillus anthracis spores. the spores were suspended in light or heavy organic preparations and the suspension was applied to stainless steel carrier disks. the dried spore inoculum was covered with the disinfectants and the disks were then incubated at vario ...201324082400
bacillus anthracis, virulence factors, pcr, and interpretation of results. 201324067452
a chemically synthesized capture agent enables the selective, sensitive, and robust electrochemical detection of anthrax protective antigen.we report on a robust and sensitive approach for detecting protective antigen (pa) exotoxin from bacillus anthracis in complex media. a peptide-based capture agent against pa was developed by improving a bacteria display-developed peptide into a highly selective biligand through in situ click screening against a large, chemically synthesized peptide library. this biligand was coupled with an electrochemical enzyme-linked immunosorbent assay utilizing nanostructured gold electrodes. the resultant ...201324063758
receptor-directed chimeric toxins created by sortase-mediated protein fusion.chimeric protein toxins that act selectively on cells expressing a designated receptor may serve as investigational probes and/or antitumor agents. here, we report use of the enzyme sortase a (srta) to create four chimeric toxins designed to selectively kill cells bearing the tumor marker her2. we first expressed and purified: (i) a receptor recognition-deficient form of diphtheria toxin that lacks its receptor-binding domain and (ii) a mutated, receptor-binding-deficient form of anthrax-protect ...201323945077
co-infection of an animal with more than one genotype can occur in anthrax.during the routine fingerprinting of outbreak strains of bacillus anthracis of european and african origin by means of a 31-marker multi-locus variable number of tandem repeats analysis (mlva), four cultures, two from the etosha national park (enp), namibia, and two from an outbreak in the pyrenees in 1997, were found to harbour different genotypes (gts). to investigate this further, isolates from 10 samples of blood-soaked soil from beneath anthrax carcasses and 18 clinical swabs taken from car ...201323937393
field-based pcr for rapid diagnosis of cutaneous anthrax in the deployed setting using the joint biological agent identification and diagnostic system.anthrax is occasionally encountered by u.s. military physicians in the deployed setting, where limited resources make it difficult to obtain laboratory confirmation. we present a case of cutaneous anthrax diagnosed using a ruggedized polymerase chain reaction device in austere combat conditions.201323929060
d-cycloserine or similar physiochemical compounds may be uniquely suited for use in bacillus anthracis spore decontamination strategies.as observed in the aftermath of the anthrax attacks of 2001, decontamination and remediation of a site contaminated by the accidental or intentional release of bacillus anthracis spores is difficult, costly and potentially damaging to the environment. the identification of novel strategies that neutralize the threat of spores while minimizing environmental damage remains a high priority. we investigated the efficacy of d-cycloserine (dcs), an antibiotic and inhibitor of the spore-associated enzy ...201323927578
biophysical characterization and immunization studies of dominant negative inhibitor (dni), a candidate anthrax toxin subunit vaccine.dominant negative inhibitor (dni) is a translocation-deficient homolog of recombinant protective antigen of bacillus anthracis that is a candidate for a next generation anthrax vaccine. this study demonstrates that the biophysical characteristics of the dni protein stored in lyophilized form at 4°c for 8 y were similar to recombinant protective antigen (rpa). to provide information on the accelerated stability of dni, samples in the lyophilized form were subjected to thermal stress (40°c and 70° ...201323925275
periocular cutaneous anthrax in jimma zone, southwest ethiopia: a case series.anthrax is a zoonotic disease caused by bacillus anthracis. naturally occurring human infection is rare and is generally the result of contact with anthrax-infected animals or animal products.201323924443
anthrax lethal toxin induces acute diastolic dysfunction in rats through disruption of the phospholamban signaling network.anthrax lethal toxin (lt), secreted by bacillus anthracis, causes severe cardiac dysfunction by unknown mechanisms. lt specifically cleaves the docking domains of mapkk (meks); thus, we hypothesized that lt directly impairs cardiac function through dysregulation of mapk signaling mechanisms.201323907041
assessing agreement of repeated binary measurements with an application to the cdc's anthrax vaccine clinical trial.cohen's kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. however, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. this study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions ...201323898025
regulation of bacillus subtilis bacillithiol biosynthesis operons by spx.bacillithiol is the major low molecular mass thiol produced by many firmicutes bacteria, including the model organism bacillus subtilis and pathogens such as bacillus anthracis and staphylococcus aureus. we have previously shown that four genes (bsha, bshb1, bshb2 and bshc) are involved in bacillithiol biosynthesis. here, we report that these four genes are encoded within three, unlinked operons all expressed from canonical σ(a)-dependent promoters as determined by 5'race (rapid amplification of ...201323894131
differentiation of strains from the bacillus cereus group by rflp-pfge genomic fingerprinting.bacillus mycoides, bacillus pseudomycoides, bacillus weihenstephanensis, bacillus anthracis, bacillus thuringiensis, and bacillus cereus belong to the b. cereus group. the last three species are characterized by different phenotype features and pathogenicity spectrum, but it has been shown that these species are genetically closely related. the macrorestriction analysis of the genomic dna with the noti enzyme was used to generate polymorphism of restriction profiles for 39 food-borne isolates (b ...201323893780
identification of a ligand on the wip1 bacteriophage highly specific for a receptor on bacillus anthracis.tectiviridae is a family of tailless bacteriophages with gram-negative and gram-positive hosts. the family model prd1 and its close relatives all infect a broad range of enterobacteria by recognizing a plasmid-encoded conjugal transfer complex as a receptor. in contrast, tectiviruses with gram-positive hosts are highly specific to only a few hosts within the same bacterial species. the cellular determinants that account for the observed specificity remain unknown. here we present the genome sequ ...201323893110
present-day conservative treatment retinopathy of prematurity.retinopathy of prematurity occurs in prematurely born babies. etiology of disease is multifactorial and frequency of retinopathy of prematurity diagnosis increases. retinopathy is one of causes for major loss of vision and amaurosis in newborns around the world. low efficacy of treatment leads to necessity for looking for new solutions and modern therapy use in treatment of this disease. so far, therapies used are: laser and cryotherapy and cases of retina detachment, the course is combined with ...201323882745
in vitro and in vivo activities of recombinant anthrax protective antigen co-expressed with thioredoxin in escherichia coli.because of the central role it plays in the formation of lethal toxin and edema toxin, protective antigen (pa) is the principal target for the development of vaccines against anthrax. in the present study, we explored and compared the in vitro and in vivo activities of recombinant anthrax protective antigen (rpa) and receptor binding domain of protective antigen (pa4). as a result, the fully soluble rpa and pa4 proteins were successfully expressed in escherichia coli by co-expression with thiore ...201323880942
toxin inhibition of antimicrobial factors induced by bacillus anthracis peptidoglycan in human blood.here, we describe the capacity of bacillus anthracis peptidoglycan (bapgn) to trigger an antimicrobial response in human white blood cells (wbcs). analysis of freshly isolated human blood cells found that monocytes and neutrophils, but not b and t cells, were highly responsive to bapgn and produced a variety of cytokines and chemokines. this bapgn-induced response was suppressed by anthrax lethal toxin (lt) and edema toxin (et), with the most pronounced effect on human monocytes, and this corres ...201323876807
engineering biomaterial-associated complement activation to improve vaccine efficacy.the complement system plays an important role in innate and adaptive immunity, which suggests that complement activation could be exploited as a potential strategy for vaccine adjuvants. here we explored the potential of chitosan-based microparticles (cs-nh2 mps) as a vaccine adjuvant with an active surface for complement activation due to the abundance of amino groups. in vaccination studies, using recombinant anthrax protective antigen as a model antigen, compared with the control microparticl ...201323875970
transcriptomic and phenotypic analysis of paralogous spx gene function in bacillus anthracis sterne.spx of bacillus subtilis is a redox-sensitive protein, which, under disulfide stress, interacts with rna polymerase to activate genes required for maintaining thiol homeostasis. spx orthologs are highly conserved among low %gc gram-positive bacteria, and often exist in multiple paralogous forms. in this study, we used b. anthracis sterne, which harbors two paralogous spx genes, spxa1 and spxa2, to examine the phenotypes of spx null mutations and to identify the genes regulated by each spx paralo ...201323873705
[bioterrorism and pathogenic microorganisms].in recent years the use of pathogenic microorganisms in acts of bioterrorism has been the subject of major concern in many countries. this paper presents a possible application of viruses and bacteria for warfare and terrorist purposes, as well as a laboratory diagnosis to identify those agents. the viruses of smallpox (orthopoxvirus), of hemorrhagic fever and those belonging to filovirus have been highlighted, inter alia, as agents of human infection with bioterrorist intent. among the bacteria ...201324473660
historical review of the list of occupational diseases recommended by the international labour organization (ilo).the list of occupational diseases established in the international and national legal system has played important roles in both prevention of and compensation for workers' diseases. this report reviewed the historical development in the ilo list of occupational diseases and suggested implications of the trends. since the first establishment of the ilo list of occupational diseases in 1925, the list has played a key role in harmonizing the development of policies on occupational diseases at the i ...201324472440
ante- and postmortem diagnostic techniques for anthrax: rethinking pathogen exposure and the geographic extent of the disease in wildlife.although antemortem approaches in wildlife disease surveillance are common for most zoonoses, they have been used infrequently in anthrax surveillance. classically, anthrax is considered a disease with extremely high mortality. this is because anthrax outbreaks are often detected ex post facto through wildlife or livestock fatalities or spillover transmission to humans. as a result, the natural prevalence of anthrax infection in animal populations is largely unknown. however, in the past 20 yr, ...201324502707
[the experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated against plague and anthrax].the article deals with experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated with plague and anthrax live dry vaccines. it is established that the introduction of plague and anthrax live dry vaccines into organism of vaccinated persons ignites immunologic rearrangement manifested by reliable increase of level of blood concentration of th1-lymphocytes (immunologic memory cells) against the background of vaccination. the highe ...201324640112
serological correlate of protection in guinea pigs for a recombinant protective antigen anthrax vaccine produced from bacillus brevis.recombinant protective antigen (rpa) is the active pharmaceutical ingredient of a second generation anthrax vaccine undergoing clinical trials both in korea and the usa. by using the rpa produced from bacillus brevis pnu212 expression system, correlations of serological immune response to anthrax protection efficacy were analyzed in a guinea pig model.201224159510
the african buffalo: a villain for inter-species spread of infectious diseases in southern africa.the african buffalo (syncerus caffer) is a large wild bovid which until recently ranged across all but the driest parts of sub-saharan africa, and their local range being limited to about 20 km from surface water. they are of high ecological value due to their important role as bulk feeders in the grazing hierarchy. they also have high economic value, because they are one of the sought after 'big five' in the eco-tourism industry. in africa, buffaloes have been recognised for some time as an imp ...201223327373
[safe from biothreats? legislation protects you and society].the 9/11 terror attacks, followed by mailing of letters containing anthrax spores, changed our comprehension on threats towards modern society. finland is committed by international treaties to develop biosafety and biosecurity legislation, and general awareness of the legislation. however, the rapidly developing field of biosciences cannot be extensively regulated by legislation. awareness of the risks and challenges involved in handling of biological agents is an important tool in threat preve ...201223210284
analysing the spatial patterns of livestock anthrax in kazakhstan in relation to environmental factors: a comparison of local (gi*) and morphology cluster statistics.we compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle) and small (sheep and goats) domestic ruminants across kazakhstan. the getis-ord (gi*) statistic and a multidirectional optimal ecotope algorithm (amoeba) were compared using 1st, 2nd and 3rd order rook contiguity matrices. multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the amoeba and gi* tests. a logistic regression ...201223242686
critical challenges and impediments affecting rural physicians during a public health emergency.disaster preparedness has become a health policy priority for the united states in the aftermath of the anthrax attacks, 9/11, and other calamities. it is important for rural health care professionals to be prepared for a bioterrorist attack or other public health emergency. we sought to determine the barriers impeding rural physicians from being prepared for a human-induced disaster such as a bioterrorist attack.201223241464
the differential susceptibility of spores from virulent and attenuated bacillus anthracis strains to aldehyde- and hypochlorite-based disinfectants.this study compared the sensitivity of spores from virulent and attenuated bacillus anthracis strains in suspension to inactivation by various chemical disinfectants. spore suspensions from two virulent strains (a0256 and a0372) and two attenuated strains (sterne and a0141) of b. anthracis were tested against two aldehyde-based disinfectants and one hypochlorite-based disinfectant. a novel statistical model was used to estimate 4-log(10) reduction times for each disinfectant/strain combination. ...201223233190
coumarin-based inhibitors of bacillus anthracis and staphylococcus aureus replicative dna helicase: chemical optimization, biological evaluation, and antibacterial activities.the increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9-18-fold increased potency against staphylococcus aureus (sa) and bacillus anthracis (ba) helicases. compounds 20 and ...201223231076
[detection and identification of highly pathogenic bacteria within the framework of the eqadeba project--part ii: samples containing inactivated pathogens].the aim of the studies was analysis of methods applied and results of detection and identification of bacillus anthracis, yersinia pestis, francisella tularensis, brucella sp., bulkholderia mallei and b. pseudomallei in inactivated samples obtained within the framework of the third external quality assessment exercise (eqae) in the project ,,establishment of quality assurances for detection of highly pathogenic bacteria of potential bioterrorism risk (eqadeba)".201223230707
public response to an anthrax attack: a multiethnic perspective.the 2001 anthrax attacks emphasized the need to develop outreach that would more effectively support racial/ethnic minority populations during a bioterrorism incident. given the importance of antibiotic prophylaxis in a future anthrax attack, it should be a priority to better support racial/ethnic minorities in mass dispensing programs. to examine the needs and perspectives of racial/ethnic minorities, this study used a nationally representative poll of 1,852 adults, including 1,240 whites, 261 ...201223244501
injection anthrax--a new outbreak in heroin users.injection anthrax is a rare disease that affects heroin users and is caused by bacillus anthracis. in 2012, there were four cases in germany, one of which was fatal, as well as a small number of cases in other european countries, including denmark, france, and the united kingdom. three cases among drug users occurred in germany in 2009/2010, in the setting of a larger outbreak centered on scotland, where there were 119 cases. case presentation and clinical course: we present three cases of injec ...201223267409
effects of epidemic diseases on the distribution of bonobos.this study examined how outbreaks and the occurrence of anthrax, ebola, monkeypox and trypanosomiasis may differentially affect the distribution of bonobos (pan paniscus). using a combination of mapping, jaccard overlapping coefficients and binary regressions, the study determined how each disease correlated with the extent of occurrence of, and the areas occupied by, bonobos. anthrax has only been reported to occur outside the range of bonobos and so was not considered further. ebola, monkeypox ...201223251431
genetic populations of bacillus anthracis isolates from korea.bacillus (b.) anthracis is the pathogen that causes fatal anthrax. strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial population genetics. in the present study, we employed molecular approaches including multiple-locus variable-number tandem repeat analysis (mlva) and canonical single-nucleotide polymorphism (cansnp) analysis to perform molecular typing of b. anthracis strains isolated in korea. according to the mlva, 17 b. anthracis is ...201223271180
development of a high throughput assay for indirectly measuring phage growth using the omnilog(tm) system.the conventional and most accepted method of measuring the lytic activity of a phage against its bacterial host is the plaque assay. this method is laborious, time consuming and expensive, especially in high throughput analyses where multiple phage-bacterial interactions are required to be monitored simultaneously. it can also vary considerably with the experimenter and by the growth and plating conditions. alternatively, the lytic activity can be measured indirectly by following the decrease in ...201223275867
computational studies on molecular interactions of 6-thioguanosine analogs with anthrax toxin receptor 1.dormant endospores of bacillus anthracis are the causative agent of anthrax, which is an acute disease for both human and animals. anthrax has been practised as biological weapon because of two attributes: i) short duration of spore germination, and ii) lethal toxaemia of the vegetative stage. pathogenesis is caused by the activity of edema toxin and lethal toxin. protective antigen (pa), is an essential component of both complexes, binds to anthrax toxin receptor (atr) and mediates the lethalit ...201223292691
new aspects of the infection mechanisms of bacillus anthracis.articles concerning new aspects of b. anthracis mechanisms of infection were reviewed. it was found, that the hair follicle plays an important role in the spore germination process. the hair follicle represent an important portal of entry in the course of the cutaneous form of disease infections. after mouse exposition to aerosol of spores prepared from b. anthracis strains, an increase in the level of tnf-α cytokines was observed. the tnf-α cytokines were produced after intrusion into the host ...201223311776
inhibition of anthrax lethal factor: lability of hydroxamate as a chelating group.the metalloprotease activity of lethal factor (lf) from bacillus anthracis (b. anthracis) is a main source of toxicity in the lethality of anthrax infection. thus, the understanding of the enzymatic activity and inhibition of b. anthracis lf is of scientific and clinical interests. we have designed, synthesized, and studied a peptide inhibitor of lf, r9lf-1, with the structure nh(2)-(d: -arg)(9)-val-leu-arg-co-nhoh in which the c-terminal hydroxamic acid is commonly used in the inhibitors of met ...201222270239
rapid detection methods for bacillus anthracis in environmental samples: a review.bacillus anthracis is a gram-positive, spore-forming bacterium, which causes anthrax, an often lethal disease of animals and humans. although the disease has been well studied since the nineteenth century, it has witnessed a renewed interest during the past decade, due to its use as a bioterrorist agent in the fall of 2001 in the usa. a number of techniques aimed at rapidly detecting b. anthracis, in environmental samples as well as in point-of-care settings for humans suspected of exposure to t ...201222262227
hiv vaccine candidates generate in vitro t cell response to putative epitopes in chinese-origin rhesus macaques.the indian rhesus macaque is the established animal model for hiv infection and vaccine research. growing evidence suggests that the more readily available chinese rhesus macaque may be a more relevant option. as increasing numbers of novel chinese rhesus mhc alleles are reported, we decided to explore potential hiv vaccine epitopes in this model. we immunized forty chinese rhesus macaques with three different hiv vaccine candidates either individually or following a prime/boost strategy. we use ...201222261410
pharmacological inhibition of the clpxp protease increases bacterial susceptibility to host cathelicidin antimicrobial peptides and cell envelope-active antibiotics.the clpxp protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. here we identified a pharmacological inhibitor of the clpxp protease, f2, and evaluated its action in bacillus anthracis and staphylococcus aureus. we found that f2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane, such as penicillin and daptomycin, in b. anthracis and drug- ...201222252821
gc/ms method for positive detection of bacillus anthracis endospores.a simple method was developed for detection of bacillus anthracis (ba) endospores and for differentiation of them from other species in the bacillus cereus group. chemical profiles that include lipids (i.e., fatty acids), carbohydrates (i.e., sugars), and the spore-specific biomarker, dipicolinic acid, were generated by one-step thermochemolysis (tcm) at 140 °c in 5 min to provide specific biomarker signatures. anthrose, which is a biomarker characteristic of the b. cereus group of bacteria, was ...201222243393
comparison of quantitative pcr and culture-based methods for evaluating dispersal of bacillus thuringiensis endospores at a bioterrorism hoax crime scene.since the anthrax mail attacks of 2001, law enforcement agencies have processed thousands of suspicious mail incidents globally, many of which are hoax bioterrorism threats. bio-insecticide preparations containing bacillus thuringiensis (bt) spores have been involved in several such threats in australia, leading to the requirement for rapid and sensitive detection techniques for this organism, a close relative of bacillus anthracis. here we describe the development of a quantitative pcr (qpcr) m ...201222227150
apoptosis, antimicrobial and antioxidant activities of phytochemicals from garcinia malaccensis hk.f.to study the chemical constituents of stembark of garcinia malaccensis (g. malaccensis) together with apoptotic, antimicrobial and antioxidant activities.201222221758
binding and cell intoxication studies of anthrax lethal toxin.anthrax lethal toxin (lt) is a major virulence factor of bacillus anthracis. the vast majority of the anthrax toxin-related literature describes the assembly of lt as a cell-dependent process. however, some reports have provided evidence for the existence of a fully assembled lt, either in vitro or in the bloodstream of anthrax-infected animals. to follow up on this work, we present studies on fully-assembled lt. we first demonstrate facile and cell-free assembly and purification of lt. we then ...201222219086
development of aptamer beacons for rapid presumptive detection of bacillus spores.a library of 92 dna aptamer sequences was developed against bacillus anthracis (nonpathogenic sterne strain) spores and anthrose sugar immobilized on magnetic beads. the selected dna sequences were studied for similarities and potential binding pockets between the b. anthracis spore and anthrose aptamers. several recurring loop structures were identified and tested for their potential to act as aptamer beacons when labeled with tye 665 dye on their 5' ends and iowa black quencher on their 3' end ...201222218972
frequency of epitope-specific naive cd4(+) t cells correlates with immunodominance in the human memory repertoire.the frequency of epitope-specific naive cd4(+) t cells in humans has not been extensively examined. in this study, a systematic approach was used to examine the frequency of cd4(+) t cells that recognize the protective ag of bacillus anthracis in both anthrax vaccine-adsorbed vaccinees and nonvaccinees with hla-drb1*01:01 haplotypes. three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine. average naive precursor frequencies of t cell ...201222327072
synthetic studies toward the anthrax tetrasaccharide: alternative synthesis of this antigen.the synthesis of the anthrax tetrasaccharide, amenable for conjugation, has been envisaged by both [2+2] and [1+3] approaches from d-fucose and l-rhamnose. the successful route reported herein relies on a [1+3] strategy in which the 1,2-trans-glycosidic linkages have been secured using a participating group at the 2-position of the donors using conventional thio as well as trichloroacetimidate glycosylation chemistry. the exchange of the ester to benzyl protective groups on the rhamnosyl moiety ...201222356927
role of n-terminal his6-tags in binding and efficient translocation of polypeptides into cells using anthrax protective antigen (pa).it is of interest to define bacterial toxin biochemical properties to use them as molecular-syringe devices in order to deliver enzymatic activities into host cells. binary toxins of the ab(7/8)-type are among the most potent and specialized bacterial protein toxins. the b subunits oligomerize to form a pore that binds with high affinity host cell receptors and the enzymatic a subunit. this allows the endocytosis of the complex and subsequent injection of the a subunit into the cytosol of the ho ...201223056543
draft genome sequence of bacillus anthracis ur-1, isolated from a german heroin user.we report the draft genome sequence of bacillus anthracis ur-1, isolated from a fatal case of injectional anthrax in a german heroin user. analysis of the genome sequence of strain ur-1 may aid in describing phylogenetic relationships between virulent heroin-associated isolates of b. anthracis isolated in the united kingdom, germany, and other european countries.201223045504
effect of the bacillus atrophaeus subsp. globigii spo0f h101r mutation on strain fitness.sporulation is a critical developmental process in bacillus spp. that, once initiated, removes the possibility of further growth until germination. therefore, the threshold conditions triggering sporulation are likely to be subject to evolutionary constraint. our previous studies revealed two spontaneous hypersporulating mutants of bacillus atrophaeus subsp. globigii, both containing point mutations in the spo0f gene. one of these strains (detrick-2; contains the spo0f101 allele with a c:t [his1 ...201223042165
debridement increases survival in a mouse model of subcutaneous anthrax.anthrax is caused by infection with bacillus anthracis, a spore-forming gram-positive bacterium. a major virulence factor for b. anthracis is an immunomodulatory tripartite exotoxin that has been reported to alter immune cell chemotaxis and activation. it has been proposed that b. anthracis infections initiate through entry of spores into the regional draining lymph nodes where they germinate, grow, and disseminate systemically via the efferent lymphatics. if this model holds true, it would be p ...201222393351
the aminoglycoside antibiotic kanamycin damages dna bases in escherichia coli: caffeine potentiates the dna-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in escherichia coli and bacillus anthracis.the distribution of mutants in the keio collection of escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. strains lacking one of a number of glycosylases (e.g., alka, yzab, ogt, ksga) or other specific repair proteins (alkb, phrb, smbc) are more sensitive to these antibiotics. mutants lacking alkb display the strongest sensitivity among the gly ...201222391551
identification of 2 novel antxr2 mutations in patients with hyaline fibromatosis syndrome and proposal of a modified grading system.juvenile hyaline fibromatosis (jhf) and infantile systemic hyalinosis (ish) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (antxr2) located on chromosome 4q21. characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. the present report describes a pair o ...201222383261
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