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polyvalency: a promising strategy for drug design.the simultaneous binding of multiple ligands on one entity to multiple receptors on another can result in an affinity that is significantly greater than that for the binding of a single ligand to a single receptor. this concept of "polyvalency" can be used to design molecules that are potent inhibitors of toxins and pathogens. we describe the design of potent polyvalent inhibitors that neutralize anthrax toxin in vivo as well as our attempts to elucidate the relationship between inhibitor struct ...200818727104
determining the efficacy of liquid sporicides against spores of bacillus subtilis on a hard nonporous surface using the quantitative three step method: collaborative study.a collaborative study was conducted to validate the quantitative three step method (tsm), a method designed to measure the performance of liquid sporicides on a hard nonporous surface. ten laboratories agreed to participate in the collaborative study; data from 8 of 10 participating laboratories were used in the final statistical analysis. the tsm uses 5 x 5 x 1 mm glass coupons (carriers) upon which spores have been inoculated and which are introduced into liquid sporicidal agent contained in a ...200818727544
[the strategic plan for preparedness and response to bioterrorism in korea].following the anthrax bioterrorism attacks in the us in 2001, the korean government established comprehensive countermeasures against bioterrorism. these measures included the government assuming management of all infectious agents that cause diseases, including smallpox, anthrax, plaque, botulism, and the causative agents of viral hemorrhagic fevers (ebola fever, marburg fever, and lassa fever) for national security. in addition, the korean government is reinforcing the ability to prepare and r ...200818664725
stable and potent polyvalent anthrax toxin inhibitors: raft-inspired domain formation in liposomes that contain pegylated lipids. 200818666271
early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.effective prophylaxis and treatment for infections caused by biological threat agents (bta) rely upon early diagnosis and rapid initiation of therapy. most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most bta are indistinguishable flu-like signs.200818667072
intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters.the current model for virulence gene regulation in bacillus anthracis involves several trans-acting factors, the most important of which appears to be the anthrax toxin activator encoded by the atxa gene. atxa is a positive regulator of the toxin genes paga, cya and lef, and of a number of other plasmid- and chromosome-encoded genes. the atxa protein (56 kda) possesses a predicted winged-helix dna-binding domain and phosphotransferase system-regulated domains, but the mechanism for positive regu ...200818667583
the response to a specific germinant by bacillus anthracis spores in primary mouse macrophages is modulated by a protein encoded on the pxo1 plasmid.a bacillus anthracis sterne pxo1 plasmid-encoded protein designated cot43 was found in coat extracts of purified spores. cot43 is a tetratricopeptide repeat domain protein related to those which function as phosphatases in the sporulation phosphorelay and as regulators of competence and pathogenic factors. the synthesis of cot43 began in the late exponential phase downstream from a sigmaa promoter (as mapped by race) and it was present at least until the formation of phase white endospores. ther ...200818654763
recombinant bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigen.inactivated bacillus anthracis spores given with protective antigen (pa) contribute to immunity against anthrax in several animal models. antiserum raised against whole irradiated b. anthracis spores has been shown to have anti-germination and opsonic activities in vitro. based on these observations, we hypothesized that surface-exposed spore proteins might serve as supplemental components of a pa-based anthrax vaccine. the protective anti-spore serum was tested for reactivity with recombinant f ...200818657585
protein expression pattern of murine macrophages treated with anthrax lethal toxin.anthrax lethal toxin (letx; a combination of protective antigen and lethal factor) secreted by the vegetative cells of bacillus anthracis is cytotoxic for certain macrophage cell lines. the role of letx in mediating these effects is complicated largely due to the difficulty in identifying and assigning functions to the affected proteins. to analyze the protein profile of murine macrophages treated with letx, we employed two-dimensional polyacrylamide gel electrophoresis and maldi-tof ms, and int ...200818657635
characterization of the catalytic activity of the gamma-phage lysin, plyg, specific for bacillus anthracis.bacillus anthracis causes anthrax, a lethal disease affecting humans that has attracted attention due to its bioterrorism potential. plyg is a lysin of gamma-phage, which specifically infects b. anthracis and lyses its cell wall. plyg contains a t7 lysozyme-like amidase domain, which appears to be the catalytic domain, in the n-terminal region and has a high degree of sequence similarity with plyl, which is an n-acetylmuramoyl-l-alanine amidase encoded by the b. anthracis genome. here, we demons ...200818662316
effect of bacillus anthracis virulence factors on human dendritic cell activation.bacillus anthracis possesses three primary virulence factors: capsule, lethal toxin (lt), and edema toxin (et). dendritic cells (dcs) are critical to innate and acquired immunity and represent potential targets for these factors. we examined the ability of b. anthracis spores and bacilli to stimulate human monocyte-derived dc (mddc), primary myeloid dc (mdc), and plasmacytoid dc (pdc) cytokine secretion. exposure of mddcs and mdcs to spores or vegetative bacilli of the genetically complete strai ...200818662733
design and synthesis of aryl ether inhibitors of the bacillus anthracis enoyl-acp reductase.the problem of increasing bacterial resistance to the current generation of antibiotics is well documented. known resistant pathogens such as methicillin-resistant staphylococcus aureus are becoming more prevalent, while the potential exists for developing drug-resistant pathogens for use as bioweapons, such as bacillus anthracis. the biphenyl ether antibacterial agent, triclosan, exhibits broad-spectrum activity by targeting the fatty acid biosynthetic pathway through inhibition of enoyl-acyl c ...200818663709
heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin.anthrax lethal toxin (lt) rapidly kills macrophages from certain mouse strains in a mechanism dependent on the breakdown of unknown protein(s) by the proteasome, formation of the nalp1b (nlrp1b) inflammasome and subsequent activation of caspase-1. we report that heat-shocking lt-sensitive macrophages rapidly protects them against cytolysis by inhibiting caspase-1 activation without upstream effects on lt endocytosis or cleavage of the toxin's known cytosolic substrates (mitogen-activated protein ...200818671821
studies on the antifungal properties of n-thiolated beta-lactams.n-thiolated beta-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including staphylococcus aureus and bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. we now have found that these lactams also possess antifungal activity against candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. the mode of action and str ...200818672374
towards on-site pathogen detection using antibody-based sensors.in this paper, the recent progress within biosensors for plant pathogen detection will be reviewed. bio-recognition layers on sensors can be designed in various ways, however the most popular approach is to immobilise antibodies for specific capture of analytes. focus will be put on antibody surface-immobilisation strategies as well as the use of antibodies in the widely used sensors, quartz crystal microbalance, surface plasmon resonance and cantilevers. we will describe the available data on a ...200818675543
dual promoters control expression of the bacillus anthracis virulence factor atxa.the atxa virulence regulator of bacillus anthracis is required for toxin and capsule gene expression. atxa is a phosphotransferase system regulatory domain-containing protein whose activity is regulated by phosphorylation/dephosphorylation of conserved histidine residues. here we report that transcription of the atxa gene occurs from two independent promoters, p1 (previously described by dai et al. [z. dai, j. c. sirard, m. mock, and t. m. koehler, mol. microbiol. 16:1171-1181, 1995]) and p2, wh ...200818676674
the anthrax vaccine adsorbed vaccine generates protective antigen (pa)-specific cd4+ t cells with a phenotype distinct from that of naive pa t cells.cellular immune responses against protective antigen (pa) of bacillus anthracis in subjects that received the anthrax vaccine adsorbed (ava) vaccine were examined. multiple cd4(+) t-cell epitopes within pa were identified by using tetramer-guided epitope mapping. pa-reactive cd4(+) t cells with a cd45ra(-) phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (pbmc) with pa-specific tetramers. surprisingly, pa-specific t cells were also detected in pbmc of ...200818678674
solubility improvement of an anthrax toxin peptide inhibitor by rational amino acid randomization.we previously described a potent anthrax toxin inhibitor, based on a phage-library-selected peptide sequence, synthesized as a tetra-branched molecule on a lysine core and further modified for improvement of activity [pini et al., biochem. j., 2006, 395, 157]. this branched peptide had very low solubility because of several hydrophobic residues in the peptide sequence. this complicated molecule purification and manufacturing. here we report a rational modification of the peptide sequence, obtain ...200818680450
death renews biosecurity debate. 200818685659
bioterrorism. scientists seek answers, ponder future after anthrax case suicide. 200818687926
naturally acquired anthrax antibodies in a cheetah (acinonyx jubatus) in botswana.an outbreak of anthrax in the jwana game reserve in jwaneng, botswana, was first observed when three cheetahs (acinonyx jubatus) died of the disease in november 2004. in the aftermath of this event, banked serum samples collected from 23 wild-caught cheetahs were examined, by the inhibition enzyme-linked immunoassay (elisa), for antibodies to the protective antigen (pa) of bacillus anthracis. of the 23 cheetahs, 16 regularly accessed the reserve. antibodies to pa were detected in one cheetah col ...200818689661
producing, controlling, and stabilizing pasteur's anthrax vaccine: creating a new industry and a health market.when pasteur and chamberland hastily set up their small biological industry to meet the agricultural demand for the anthrax vaccine, their methods for preparation and production had not yet been stabilized. the process of learning how to standardize biological products was accelerated in 1882 when vaccination accidents required the revision of production norms as the first hypotheses on fixity, inalterability, and transportability of vaccines were invalidated and replaced by procedures for conti ...200818831139
bioterrorism and the anaesthesiologist's perspective.the use of non-conventional agents aimed at causing panic and terror among civilians has a long history. there have been uninterrupted threats and the use of biological and chemical weaponry from the time of early tribal conflicts to the iran-iraq war. the sole practical experience has come from the release of the nerve gas sarin in a tokyo subway (1994) and the inhalational anthrax discovered in florida (2001). drills that simulate scenarios of biological/chemical mass infestation have yielded ...200818831299
circular dichroism and magnetic circular dichroism studies of the biferrous site of the class ib ribonucleotide reductase from bacillus cereus: comparison to the class ia enzymes.the rate limiting step in dna biosynthesis is the reduction of ribonucleotides to form the corresponding deoxyribonucleotides. this reaction is catalyzed by ribonucleotide reductases (rnrs) and is an attractive target against rapidly proliferating pathogens. class i rnrs are binuclear non-heme iron enzymes and can be further divided into subclasses. class ia is found in many organisms, including humans, while class ib has only been found in bacteria, notably some pathogens. both bacillus anthrac ...200818831534
anthrax investigation. nas study may fail to settle anthrax case. 200818832614
effect of cpg oligonucleotides on vaccine-induced b cell memory.adding synthetic oligodeoxynucleotides containing unmethylated cpg motifs to anthrax vaccine adsorbed (ava, the licensed human vaccine) increases the speed and magnitude of the resultant ab response. ab titers persist in the protective range for >1 year, significantly longer than in animals vaccinated with ava alone. unexpectedly, a majority of mice immunized with cpg-adjuvanted ava maintained resistance to anthrax infection even after their ab titers had declined into the subprotective range. t ...200818832738
amoxicillin for postexposure inhalational anthrax in pediatrics: rationale for dosing recommendations.we reviewed information about the safety and plasma pharmacokinetic data for amoxicillin, specifically related to its potential use for postexposure inhalational anthrax. amoxicillin (45 mg/kg/d) given orally in 3 divided doses to pediatric patients <40 kg should yield an adequate time above the mic for susceptible bacillus anthracis (< or =0.5 microg/ml) over most of the dosing interval (75-100%). doses <45 mg/kg/d and dosing intervals longer than 8 hours should not be used for postexposure inh ...200818833025
the bacillus anthracis slel (yaah) protein is an n-acetylglucosaminidase involved in spore cortex depolymerization.bacillus anthracis spores, the infectious agents of anthrax, are notoriously difficult to remove from contaminated areas because they are resistant to many eradication methods. these resistance properties are due to the spore's dehydration and dormancy and to the multiple protective layers surrounding the spore core, one of which is the cortex. in order for b. anthracis spores to germinate and resume growth, the cortex peptidoglycan must be depolymerized. this study reports on analyses of slel ( ...200818835992
personalized vaccines: the emerging field of vaccinomics.the next 'golden age' in vaccinology will be ushered in by the new science of vaccinomics. in turn, this will inform and allow the development of personalized vaccines, based on our increasing understanding of immune response phenotype: genotype information. rapid advances in developing such data are already occurring for hepatitis b, influenza, measles, mumps, rubella, anthrax and smallpox vaccines. in addition, newly available data suggest that some vaccine-related adverse events may also be g ...200818847302
in vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins.there is a lot of interest towards creating therapies and vaccines for bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. systemic injection of lethal factor (lf), edema factor (ef) and protective antigen (pa) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. availability of toxins labeled with imageable radioisotopes w ...200818848660
new classes of gram-positive selective antibacterials: inhibitors of mrsa and surrogates of the causative agents of anthrax and tuberculosis.an antimicrobial phenolic stilbene, (e)-3-hydroxy-5-methoxystilbene, 1 was recently isolated from the leaves of comptonia peregrina (l.) coulter and shown to possess inhibitory activity against several gram-positive bacteria, including isolates of methicillin-resistant staphylococcus aureus (mrsa), mycobacterium bovis bcg, and avirulent bacillusanthracis (sterne strain), among others. these results prompted the design and synthesis of two new classes of compounds, phenoxystyrenes and phenothiost ...200818849164
identification of a surrogate marker for infection in the african green monkey model of inhalation anthrax.in 2001, a bioterrorism attack involving bacillus anthracis spore-laced letters resulted in 22 cases of inhalation anthrax, with five fatalities. this incident identified gaps in our health care system and precipitated a renewed interest in identifying both therapeutics and rapid diagnostic assays. to address those gaps, well-characterized animal models that resemble the human disease are needed. in addition, a rapid assay for a reliable diagnostic marker is key to the success of these efforts. ...200818852240
discovery of new therapeutic targets by the informational spectrum method.the field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. here we review the application of the informational spectrum method (ism), a virtual spectroscopy method for structure/function analysis of proteins, in identification of functional protein domains representing candidate therapeutic targets for drugs against human immunodeficiency virus (hiv)-1, anthrax, highly pathogenic ...200818855700
towards a human oral vaccine for anthrax: the utility of a salmonella typhi ty21a-based prime-boost immunization strategy.we previously demonstrated the ability of an orally administered attenuated salmonella enterica serovar typhimurium strain expressing the protective antigen (pa) of bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [stokes mg, titball rw, neeson bn, et al. oral administration of a salmonella enterica-based vaccine expressing bacillus anthracis protective antigen confers protection against aerosolized b. anthracis. infect immun 2007;75(april (4)):1827-34]. to ...200818805452
activity of the bacillus anthracis 20 kda protective antigen component.anthrax is caused by bacillus anthracis that produce two exotoxins, lethal toxin and edema toxin. the lethal toxin is composed of the lethal factor (lf) complexed with the cell binding protective antigen (pa83, 83 kda). likewise, the edema factor (ef) binds to the pa83 to form the edema toxin. once pa83 is bound to the host cell surface, a furin-like protease cleaves the full-length, inactive protein into 63 kda and 20 kda antigens (pa63 and pa20). pa63 forms a heptamer and is internalized via r ...200818808698
cytoplasmic delivery of antigens, by bacillus subtilis enhances th1 responses.endospores of the gram-positive bacterium, bacillus subtilis, have been used successfully for delivery of antigens where the immunogen is expressed on the spore surface. in this work the spore has been engineered to deliver antigens to the cytoplasm of macrophages by expressing listeriolysin o (llo) or a derivative, llo(l461t), that is stable at neutral ph, from the b. subtilis vegetative cell. following phagocytosis spores were shown to germinate in the phagosome enabling secretion of llo/llo(l ...200818809450
inhibition of bacillus anthracis spore outgrowth by nisin.the lantibiotic nisin has previously been reported to inhibit the outgrowth of spores from several bacillus species. however, the mode of action of nisin responsible for outgrowth inhibition is poorly understood. by using b. anthracis sterne 7702 as a model, nisin acted against spores with a 50% inhibitory concentration (ic(50)) and an ic(90) of 0.57 microm and 0.90 microm, respectively. viable b. anthracis organisms were not recoverable from cultures containing concentrations of nisin greater t ...200818809941
bioterrorism update--information for the dentist.the united states was awakened to the perils of bioterrorism in october 2001 with the news that letters laced with anthrax had been mailed to the media and select politicians. at that time, it became evident that a widescale attack using a bioweapon of mass destruction could rapidly overwhelm the health care system. dentists could make a tremendous contribution to the response of such an attack by gaining an understanding of the bioweapons that could be used, as well as the symptoms of their dis ...200818810910
passive administration of monoclonal antibodies to anthrolysin o prolong survival in mice lethally infected with bacillus anthracis.bacillus anthracis has two major virulence factors: a tripartite toxin that produces lethal and edema toxins and a polyglutamic acid capsule. a recent report suggested that a toxin belonging to the cholesterol dependent cytolysin (cdc) family, anthrolysin o (alo) was a new virulence factor for b. anthracis but subsequent studies have questioned its relevance in pathogenesis. in this study, we examined the immunogenicity of recombinant anthrolysin o (ralo) in mice.200818811967
ratio of lethal and edema factors in rabbit systemic anthrax.bacillus anthracis secretes two binary toxins: lethal toxin (pa + lf) and edema toxin (pa + ef) that play a major role in the pathogenesis of anthrax. their activities can synergize or interfere among each other, depending on the cell type. it is therefore fundamental to know their concentration ratio in vivo. here, we report the first determination of the concentration ratio of anthrax toxin components lf/ef in the serum of rabbits infected with b. anthracis spores.200818812184
role of the n-terminal amino acid of bacillus anthracis lethal factor in lethal toxin cytotoxicity and its effect on the lethal toxin neutralization assay.the cytotoxic activity of lethal factor (lf), a critical reagent used in the cell-based lethal toxin neutralization assay to assess anthrax vaccines, was shown to depend on the identity of its n-terminal amino acid, which plays a role in the targeting of lf to the proteasome for degradation. these results demonstrate that care must be taken to ensure that lf preparations used in standardized cell-based assays are not altered at their n-terminal ends.200818815235
immunological dynamics in response to two anthrax vaccines in mice.in order to understand the variation of humoral and cellular immune responses to a16r live spore and ava vaccine and to identify efficient immunological parameters for the early evaluation of post immunization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of balb/c mice with the anthrax vaccines. the results show that both anti-ava and anti-spore antibodies were detectable in the a16r live spore vaccinated group while high titers of anti-a ...200818815750
using molecular docking, 3d-qsar, and cluster analysis for screening structurally diverse data sets of pharmacological interest.in this study, we propose a drug design approach which includes docking, molecular fingerprints based cluster analysis, and 'induced' descriptors based receptor-dependent 3d-qsar. the method was shown to be very useful for screening and modeling structurally diverse data sets of pharmacological interest. different from other receptor-dependent 3d-qsar, no ambiguous alignments are required for the construction of the models, and the computational cost is relatively lower. moreover, 'induced' desc ...200818816024
nir spectroscopic investigation of two fluoroquinolones, levofloxacin and ofloxacin, and their tablets for qualitative identification of commercial products on the market.a rapid and nondestructive identification method for ofloxacin (oflx) and levofloxacin (lvfx) utilizing diffusion reflectance near-infrared (nir) spectroscopy was developed. an obvious difference in spectral patterns between lvfx that is used for commercial tablets and lvfx hcl that can be purchased as a reagent at a low price was also observed. these quinolones are especially important for use as drugs against bio-terrorism because of their effectiveness against anthrax infection. therefore, th ...200818819512
antibacterial activity of the fruits of iranian torilis leptophylla against some clinical pathogens.the aim of this study was to examine the antimicrobial activity of the methanolic extract of torilis leptophylla was tested on eleven bacteria (bacillus anthracis, bacillus subtilis, bacillus pumilus, staphylococcus aureus, bacillus licheniformis, brucella melitensis, escherichia coli, salmonella typhi, proteus mirabilis, bordetella bronshiseptica and pseudomonas aeruginosa). tested extract was effective against all bacteria but not b. subtilis. consequently, the ethanolic extract had antibacter ...200818819541
suppression of dendritic cell activation by anthrax lethal toxin and edema toxin depends on multiple factors including cell source, stimulus used, and function tested.bacillus anthracis produces lethal toxin (lt) and edema toxin (et), and they suppress the function of lps-stimulated dendritic cells (dcs). because dcs respond differently to various microbial stimuli, we compared toxin effects in bone marrow dcs stimulated with either lps or legionella pneumophila (lp). lt, not et, was more toxic for cells from balb/c than from c57bl/6 (b6) as measured by 7-aad uptake; however, et suppressed cd11c expression. lt suppressed il-12, il-6, and tnf-alpha in cells fr ...200818821847
[phenotypic and genetic features of cultural-morphologic variants of bacillus anthracis].comparative analysis of mvla-genotypes of 6 bacillus anthracis strains and 40 their variants differing on capsule- and toxin synthesis, hemolytic, proteolytic and lecitinase activity, nutritional requirements, susceptibility to anthrax bacteriophages, virulence, immunogenicity, and presence of genes for capsule and toxin synthesis was performed. results of phylogenetic analysis of 5 chromosome locuses and plasmid locus pxo1aat which are variable for this sample of b. anthracis cultures showed th ...200818822496
fbi to reveal anthrax data. 200818754132
pilot-scale experimental and theoretical investigations into the thermal destruction of a bacillus anthracis surrogate embedded in building decontamination residue bundles.bacillus anthracis (b. anthracis) spores were released through the u.s. mail system in 2001, highlighting the need to develop efficacious methods of decontaminating and disposing of materials contaminated with biological agents. incineration of building decontamination residue is a disposal option for such material, although the complete inactivation of bacterial spores via this technique is not a certainty. tests revealed that under some circumstances, geobacillus stearothermophilus (g. stearot ...200818754498
too close for comfort. nancy haigwood is interviewed by rex dalton. 200818756221
preparing for disaster: response matrices in the usa and uk.disasters, whether man-made or naturally occurring, require complex responses across multiple government agencies and private sector elements, including the media. these factors mandate that, for effective disaster management and because of the unpredictability of such events, response structures must be in place in advance, ready to be activated on short notice, with lines of responsibility clearly delineated and mechanisms for coordination of efforts already established. disaster response expe ...200818756376
the anthrax files. 200818756706
structural elucidation of the nonclassical secondary cell wall polysaccharide from bacillus cereus atcc 10987. comparison with the polysaccharides from bacillus anthracis and b. cereus type strain atcc 14579 reveals both unique and common structural features.nonclassical secondary cell wall polysaccharides constitute a major cell wall structure in the bacillus cereus group of bacteria. the structure of the secondary cell wall polysaccharide from bacillus cereus atcc 10987, a strain that is closely related to bacillus anthracis, was determined. this polysaccharide was released from the cell wall with aqueous hydrogen fluoride (hf) and purified by gel filtration chromatography. the purified polysaccharide, hf-ps, was characterized by glycosyl composit ...200818757856
petrobactin biosynthesis: asbb catalyzes condensation of spermidine with n8-citryl-spermidine and its n1-(3,4-dihydroxybenzoyl) derivative.the asbb enzyme, which is involved in the biosynthesis of the virulence-conferring siderophore petrobactin in bacillus anthracis, is shown to catalyze efficient atp-dependent condensation of spermidine, but not n1-(3,4-dihydroxbenzoyl)-spermidine, with n8-citryl-spermidine or n1-(3,4-dihydroxbenzoyl)-n8-citryl-spermidine, suggesting that n1-(3,4-dihydroxbenzoyl)-spermidine is very unlikely to be a significant intermediate in petrobactin biosynthesis, contrary to previous suggestions.200818758617
forensic microbiology and the reinterpretation of history. 200818759677
texas isolates closely related to bacillus anthracis ames. 200818760033
transcriptional analysis of the conjugative plasmid paw63 from bacillus thuringiensis.the broad-host range plasmid paw63 is a model for the study of molecular mechanisms associated with conjugation in the gram-positive bacillus cereus group. its main features are a conjugative apparatus that includes type iv secretion system-like components and two group ii introns, b.th.i1 and b.th.i2, located within conjugation genes, as well as a putative regulatory control circuit. furthermore, paw63 shares a common backbone with pxo2, the second virulence plasmid of bacillus anthracis, and w ...200818761035
targeting of the bcla and bclb proteins to the bacillus anthracis spore surface.the exosporium is the outermost layer of the bacillus anthracis spore. the predominant protein on the exosporium surface is bcla, a collagen-like glycoprotein. bcla is incorporated on the spore surface late in the b. anthracis sporulation pathway. a second collagen-like protein, bclb, has been shown to be surface-exposed on b. anthracis spores. we have identified sequences near the n-terminus of the bcla and bclb glycoproteins responsible for the incorporation of these proteins into the exospori ...200818761690
inhaled non-capsulated bacillus anthracis in a/j mice: nasopharynx and alveolar space as dual portals of entry, delayed dissemination, and specific organ targeting.bacillus anthracis virulence is dependent on toxins and capsule. encapsulation is associated with dissemination. we hypothesized that eliminating capsule would modify the portal of entry and the spread of bacteria. using a bioluminescent model of inhalational anthrax, we demonstrated that aerosolized spores of a capsule-deficient strain administered at moderate doses initiated infection in the nasopharynx. dissemination beyond the nasopharynx was delayed for at least 24h and then targeted the ki ...200818762267
environmental monitoring for biological threat agents using the autonomous pathogen detection system with multiplexed polymerase chain reaction.we have developed and field-tested a now operational civilian biodefense capability that continuously monitors the air in high-risk locations for biological threat agents. this stand-alone instrument, called the autonomous pathogen detection system (apds), collects and selectively concentrates particles from the air into liquid samples and analyzes the samples using multiplexed pcr amplification coupled with microsphere array detection. during laboratory testing, we evaluated the apds instrument ...200818763806
bacillus anthracis edema toxin activates nuclear glycogen synthase kinase 3beta.bacillus anthracis edema toxin (et) generates high levels of cyclic amp and impacts a complex network of signaling pathways in targeted cells. in the current study, we sought to identify kinase signaling pathways modulated by et to better understand how this toxin alters cell physiology. using a panel of small-molecule inhibitors of mammalian kinases, we found that inhibitors of glycogen synthase kinase 3 beta (gsk-3beta) protected cells from et-induced changes in the cell cycle. gsk-3beta inhib ...200818765729
expression, purification, crystallization and preliminary x-ray studies of a prolyl-4-hydroxylase protein from bacillus anthracis.collagen prolyl-4-hydroxylase (c-p4h) catalyzes the hydroxylation of specific proline residues in procollagen, which is an essential step in collagen biosynthesis. a new form of p4h from bacillus anthracis (anthrax-p4h) that shares many characteristics with the type i c-p4h from human has recently been characterized. the structure of anthrax-p4h could provide important insight into the chemistry of c-p4hs and into the function of this unique homodimeric p4h. x-ray diffraction data of selenomethi ...200818765905
an alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock.abstract:200818768085
role of n-terminal amino acids in the potency of anthrax lethal factor.anthrax lethal factor (lf) is a zn(+2)-dependent metalloprotease that cleaves several mapk kinases and is responsible for the lethality of anthrax lethal toxin (lt). we observed that a recombinant lf (lf-hma) which differs from wild type lf (lf-a) by the addition of two residues (his-met) to the native ala (a) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. we hypothesized that the "n-end rule", which relates the half-life of ...200818769623
biodefense versus bioterrorism. 200818771576
construction of bacillus thuringiensis wild-type s76 and cry- derivatives expressing a green fluorescent protein: two potential marker organisms to study bacteria-plant interactions.collectively, the species bacillus thuringiensis, bacillus cereus, and bacillus anthracis represent microorganisms of high economic, medical, and biodefense importance. although the genetic correlation and pathogenic characteristics have been extensively dissected, the ecological properties of these three species in their natural environments remain poorly understood. thus, a tractable marker for detecting these bacteria under specific environmental and physiological conditions is a valuable too ...200818772942
effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen.peptide nucleic acid (pna) is highly stable and binds to complementary rna and dna with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. we investigated whether protectiveantigen (pa, a non-toxic component of anthrax toxin) could transport antisense pna oligomers into reporter cells that contain luciferase transgenes with mutant beta-globin ivs2 intronic inserts, which permit aberrant pre-mrna splicing and impair luciferase expression. pna oligomers antisense ...200818774771
protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.in this study, the efficacy of two experimental vaccines against bacillus anthracis toxinaemia was evaluated in the rabbit model. a recombinant protective antigen (rpa) mutant and a trivalent vaccine (tv) composed by the rpa, a inactive mutant of lethal factor (mlf-y728a; e735a) and a inactive mutant of edema factor (mef-k346r), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in new zealand white rabbits. rabbits vaccinated subcutaneously with r ...200818775462
interferon protects mice against inhalation anthrax.interferons (ifns) play a role in innate immunity during many viral, bacterial, and protozoal infections. with the increasing threat of bioterrorist attacks with bacillus anthracis, its high lethality, and the limited effectiveness of antibiotics, alternative treatments are being studied. antibodies to protective antigen (pa) are promising, as is ifn. during many bacterial infections, production of and protection by ifns has been reported, including b. anthracis in vitro. in vivo, we find that ( ...200818778201
recombinant bacillus subtilis expressing the clostridium perfringens alpha toxoid is a candidate orally delivered vaccine against necrotic enteritis.recombinant bacillus subtilis endospores have been used to vaccinate against tetanus and anthrax. in this work, we have developed spores that could be used to vaccinate against clostridium perfringens alpha toxin and that could be used to protect against gas gangrene in humans and necrotic enteritis in poultry. the primary active agent in both cases is alpha toxin. a carboxy-terminal segment of the alpha toxin gene (cpa) fused to the glutathione-s-transferase (gst) gene was cloned in b. subtilis ...200818779344
evaluation of body mass index, pre-vaccination serum progesterone levels and anti-anthrax protective antigen immunoglobulin g on injection site adverse events following anthrax vaccination in women.in 2002, cdc initiated the anthrax vaccination program (avp) to provide voluntary pre-exposure anthrax vaccination for individuals at high risk for exposure to bacillus anthracis spores. the avp offered an opportunity to investigate hypothesized reasons for a reported gender difference in injection site adverse events (aes) following anthrax vaccine adsorbed (ava).200818781705
cross-contamination of clinical specimens with bacillus anthracis during a laboratory proficiency test--idaho, 2006.on july 18, 2006, the utah department of health notified epidemiologists at the idaho department of health and welfare that bacillus anthracis, the causative agent for anthrax, had been isolated from a patient. on the same day, the idaho epidemiologists were notified by the idaho bureau of laboratories of a specimen from a second patient received for anthrax testing. the two reports resulted briefly in alerts to the federal bureau of investigation (fbi) and precautionary treatment of one of the ...200818784641
probing the ph-dependent prepore to pore transition of bacillus anthracis protective antigen with differential oxidative protein footprinting.the protective antigen (pa) component of the anthrax toxin (atx) plays an essential role in the pathogenesis of the bioterrorism bacterium bacillus anthracis. after oligomerization on the cell surface and docking of lethal factor and/or edema factor, pa is internalized and undergoes a conformational change when exposed to the low ph of the endosome to form a membrane-penetrating pore. while the structure of the pa prepore has been determined, precise structural information regarding the pore sta ...200818785752
private and public economic incentives for the control of animal diseases: the case of anthrax in livestock.this study examined the roles of the public and private sectors as economic components of anthrax control with direct reference to the 2005 anthrax outbreak in livestock in north dakota. anthrax is an endemic disease in north dakota, which often causes disease outbreaks in livestock, leading to economic losses to the livestock industry. the economic incentives and interests behind public and private control of an anthrax outbreak are investigated. anthrax management is most effective with the pa ...200818786071
chimeric hepatitis b virus core particles carrying an epitope of anthrax protective antigen induce protective immunity against bacillus anthracis.the major aim of present study is to develop and evaluate chimeric virus-like particles (vlps) displaying a neutralizing epitope of anthrax protective antigen (pa) as a potential vaccine against anthrax. the truncated hepatitis b virus core (hbc) protein (aa 1-144) was used as a carrier, and the 2beta2-2beta3 loop of the pa domain 2 (aa 302-325) which has been shown contains a dominant neutralizing epitope was inserted into the major immunodominant region (mir) of the hbc. the recombinant protei ...200818786589
naturally acquired antibodies to bacillus anthracis protective antigen in vultures of southern africa.sera from 19 wild caught vultures in northern namibia and 15 (12 wild caught and three captive bred but with minimal histories) in north west province, south africa, were examined by an enzyme-linked immunosorbent assay (elisa) for antibodies to the bacillus anthracis toxin protective antigen (pa). as assessed from the baseline established with a control group of ten captive reared vultures with well-documented histories, elevated titres were found in 12 of the 19 (63%) wild caught namibian bird ...200818788202
molecular characterization of a variant of bacillus anthracis-specific phage ap50 with improved bacteriolytic activity.the genome sequence of a bacillus anthracis-specific clear plaque mutant phage, ap50c, contains 31 open reading frames spanning 14,398 bp, has two mutations compared to wild-type ap50t, and has a colinear genome architecture highly similar to that of gram-positive tectiviridae phages. spontaneous ap50c-resistant b. anthracis mutants exhibit a mucoid colony phenotype.200818791014
camp imaging of cells treated with pertussis toxin, cholera toxin, and anthrax edema toxin.the enzymatic activity of the three most studied bacterial toxins that increase the cytosolic camp level: pertussis toxin (pt), cholera toxin (ct), and anthrax edema toxin (et), was imaged by fluorescence videomicroscopy. three different cell lines were transfected with a fluorescence resonance energy transfer biosensor based on the pka regulatory and catalytic subunits fused to cfp and yfp, respectively. real-time imaging of cells expressing this camp biosensor provided time and space resolved ...200818793614
why do uk military personnel refuse the anthrax vaccination?the purpose of this study was to understand the reasons why some uk military personnel refused the anthrax vaccination. data were collected from 5,302 members of the uk armed forces who had been deployed to iraq since 2003 and had been offered the anthrax vaccination. as part of a larger questionnaire, information was collected on acceptance or refusal of the vaccination. twenty-eight percent of participants refused the anthrax vaccination; of these 51% indicated that they refused vaccination be ...200818795833
complete nucleotide sequencing and analysis of the 65-kb highly conjugative enterococcus faecium plasmid pmg1: identification of the transfer-related region and the minimum region required for replication.pmg1 (65.1 kb) is a highly conjugative, pheromone-independent enterococcus faecium plasmid that carries a tn4001-like transposon encoding gentamicin resistance. the complete nucleotide sequence (65 029 bp) of the pmg1 plasmid was determined and 73 orfs lying in the same transcription orientation were identified. sixty-one of the 73 orfs showed a high degree of similarity (90-100% identity at the amino acid level) to the orfs of the phtbeta plasmids. like the phtbeta plasmid, 22 of the pmg1 plasm ...200818795955
the symmetry rule: a seven-year study of symptoms and explanatory labels among gulf war veterans.noticing medical symptoms can cause one to search for explanatory labels such as "ate bad food" or even "exposed to anthrax," and perhaps these labels may cause new symptom reports. the present study examined whether there is empirical support for this symptom-label "symmetry rule." we interviewed veterans (n= 362) from the gulf war registry in 1995 and 2002 about their medical symptoms and about their exposure to war-related hazards and stressors. health symptom reports were strongly correlated ...200818795995
antibody-mediated targeting of the urokinase-type plasminogen activator proteolytic function neutralizes fibrinolysis in vivo.urokinase-type plasminogen activator (upa) plays a central role in tissue remodeling processes. most of our understanding of the role of upa in vivo is derived from studies using gene-targeted upa-deficient mice. to enable in vivo studies on the specific interference with upa functionality in mouse models, we have now developed murine monoclonal antibodies (mabs) directed against murine upa by immunization of upa-deficient mice with the recombinant protein. guided by enzyme-linked immunosorbent ...200818799467
cathelicidin administration protects mice from bacillus anthracis spore challenge.cathelicidins are a family of cationic peptides expressed in mammals that possess numerous bactericidal and immunomodulatory properties. in vitro analyses showed that human, mouse, and pig cathelicidins inhibited bacillus anthracis bacterial growth at micromolar concentrations in the presence or absence of capsule. combined in vitro analyses of the effects of each peptide on spore germination and vegetative outgrowth by time lapse phase contrast microscopy, transmission electron microscopy, and ...200818802102
the bicarbonate transporter is essential for bacillus anthracis lethality.in the pathogenic bacterium bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. elevated co2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. we identified a previously uncharacterized abc transporter (bas2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essen ...200819023421
enhancement of the immune responses of mice to bacillus anthracis protective antigen by cia07 combined with alum.anthrax is an acute zoonotic disease caused by infection with bacillus anthracis. b. anthracis spores are highly resistant to environmental degradation and are used as a biological weapon. in this study, we investigated the adjuvant activity of cia07 to anthrax protective antigen (pa). a/j mice were immunized intraperitoneally once, or twice with a 4-week interval, with recombinant pa alone or combined with alum, cpg1826, or cia07 as adjuvant, and serum anti-pa igg antibody responses were measur ...200819023533
[characteristics of the immune response to the lethal toxin of bacillus anthracis].we and other authors have recently shown that the pattern of the immune response to components of anthrax, the bacillus anthracis lethal toxin, is complex. in addition to neutralizing antibodies, the antitoxin antibody pool contains antibodies enhancing the toxin lethal action. we mapped the epitopes in the protective antigen that are responsible for the induction of both antibody types. in this study, we obtained new data on the cytotoxicity of the b. anthracis lethal toxin toward the j774 a.1 ...200819060938
knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in tanzania.many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-sahara african region. these include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. the current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-d ...200819046464
neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax.bacillus anthracis infection is associated with severe hemostatic disturbances but their roles and contribution to fatality remain incompletely characterized. we undertook analyses of circulating antithrombin levels during the course of infection using a comparison of lethal and nonlethal murine anthrax models. plasma samples were obtained from dba/2 mice challenged intraperitoneally with the spores of either toxigenic b. anthracis sterne strain or nontoxigenic, avirulent delta sterne strain. we ...200819049643
discrimination between biothreat agents and 'near neighbor' species using a resequencing array.timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. this study aims to evaluate the potential of resequencing arrays for this purpose. albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify bacillus anthracis, francisella tularensis, yersinia pestis and distinguish them from benign 'near neighbor' species in ...200819049648
characterization of a bacillus anthracis spore coat-surface protein that influences coat-surface morphology.bacterial spores are encased in a multilayered proteinaceous shell, called the coat. in many bacillus spp., the coat protects against environmental assault and facilitates germination. in bacillus anthracis, the spore is the etiological agent of anthrax, and the functions of the coat likely contribute to virulence. here, we characterize a b. anthracis spore protein, called cotbeta, which is encoded only in the genomes of the bacillus cereus group. we found that cotbeta is synthesized specificall ...200819054101
an essential role for the antiviral endoribonuclease, rnase-l, in antibacterial immunity.type i ifns were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. accordingly, established mediators of ifn antiviral activity may mediate previously unrecognized antibacterial functions. rnase-l is the terminal component of an rna decay pathway that is an important mediator of ifn-induced antiviral activity. here, we identify a role for rnase-l in the host antibacterial response. rnase-l(-/-) mice exhibited ...200819075243
the anthrax vaccine and research: reactions from postal workers and public health professionals.during the 2001 anthrax attacks, public health agencies faced operational and communication decisions about the use of antibiotic prophylaxis and the anthrax vaccine with affected groups, including postal workers. this communication occurred within an evolving situation with incomplete and uncertain data. guidelines for prophylactic antibiotics changed several times, contributing to confusion and mistrust. at the end of 60 days of taking antibiotics, people were offered an additional 40 days' su ...200819117431
effects of anthrax lethal toxin on human primary keratinocytes.to investigate the effects of anthrax lethal toxin (letx) on human primary keratinocytes.200819120626
investigations and control measures following a case of inhalation anthrax in east london in a drum maker and drummer, october 2008.the patient is believed to have acquired the infection from making animal hide drums. environmental investigations identified one drum and two pieces of animal skins contaminated with anthrax spores.200819094916
molecular modeling as a tool for drug discovery.with the progression of structural genomics projects, comparative modeling remains an increasingly important method of choice to obtain 3d structure of proteins. it helps to bridge the gap between the available sequence and structure information by providing reliable and accurate protein models. comparative modeling based on more than 30% sequence identity is now approaching its natural template-based limits and further improvements require the development of effective refinement techniques capa ...200819128219
protective antigen composite nanofibers as a transdermal anthrax vaccine.anthrax, a disease caused by the gram positive bacteria bacillus anthracis, has become an increasing threat to public health in the last several years, due to its use as an agent of biological warfare. the currently utilized human anthrax vaccine, which confers immunity through the host antibody recognition of protective antigen (pa), requires a three dose regimen and annual booster shots after the initial vaccination to maintain its efficacy. the long term goal of this project is to produce an ...200819162840
landscape phage as a molecular recognition interface for detection devices.filamentous phages are thread-shaped bacterial viruses. their outer coat is a tube formed by thousands equal copies of the major coat protein pviii. libraries of random peptides fused to pviii domains were used for selection of phages probes specific for a panel of test antigens and biological threat agents. because the viral carrier in the phage borne bio-selective probes is infective, they can be cloned individually and propagated indefinitely without needs of their chemical synthesis or recon ...200819190724
evaluation of 23 cutaneous anthrax patients in eastern anatolia, turkey: diagnosis and risk factors.anthrax is a potentially fatal zoonotic disease. the diagnosis of cutaneous anthrax (ca) may be very difficult, particularly in atypical presentations and nonendemic regions.200818986350
after the anthrax. 200818998336
a multi-level spatial clustering algorithm for detection of disease outbreaks.in this paper, we proposed a multi-level spatial clustering (msc) algorithm for rapid detection of emerging disease outbreaks prospectively. we used the semi-synthetic data for algorithm evaluation. we applied bard algorithm [1] to generate outbreak counts for simulation of aerosol release of anthrax. we compared msc with two spatial clustering algorithms: kulldorff's spatial scan statistic [2] and bayesian spatial scan statistic [3]. the evaluation results showed that the areas under roc had no ...200818999304
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