| clinical impressions of anthrax from the 2006 outbreak in saskatchewan. | clinical signs and carcass traits observed during the 2006 saskatchewan anthrax outbreak were largely consistent with those previously published, except for cutaneous anthrax and anthrax mastitis in cows, and subcutaneous edema in bulls and horses. failure of blood to clot was the most reliable indicator of anthrax in carcasses. | 2009 | 19436482 |
| semi-automated bacterial spore detection system with micro-fluidic chips for aerosol collection, spore treatment and ican dna detection. | a semi-automated bacterial spore detection system (bsds) was developed to detect biological threat agents (e.g., bacillus anthracis) on-site. the system comprised an aerosol sampler, micro-fluidic chip-a (for spore germination and cell lysis), micro-fluidic chip-b (for extraction and detection of genomic dna) and an analyzer. an aerosol with bacterial spores was first collected in the collection chamber of chip-a with a velocity of 300 l/min, and the chip-a was taken off from the aerosol sampler ... | 2009 | 19450964 |
| evaluation of a plasmid dna-based anthrax vaccine in rabbits, nonhuman primates and healthy adults. | vcl-ab01, a cationic lipid-formulated plasmid dna (pdna)-based vaccine that contains genes encoding genetically detoxified bacillus anthracis protective antigen (pa) and lethal factor (lf), was assessed in a phase 1, dose-escalating clinical trial in healthy adults for safety and immunogenicity, and in nonhuman primates for immunogenicity and efficacy against challenge with a lethal dose of b. anthracis spores. healthy 18-45 year old subjects were randomly assigned to receive either the investig ... | 2009 | 19458488 |
| humanized immunotoxins: a new generation of immunotoxins for targeted cancer therapy. | chemotherapy, radiation, and surgery are the conventional treatment modalities for cancer. the success achieved with these approaches has been limited due to several factors like chemoresistance to drugs, non-specificity leading to peripheral toxicity, and non-resectable tumors. to combat these problems, the concept of targeted therapy using immunotoxins was developed. immunotoxins are chimeric proteins with a cell-selective ligand chemically linked or genetically fused to a toxin moiety and can ... | 2009 | 19459847 |
| plants as biofactories for the production of subunit vaccines against bio-security-related bacteria and viruses. | the development of new generation vaccines is an imperative tool to counteract accidental or intended release of bio-threat agents, such as bacillus anthracis, yersinia pestis and variola virus, and to control natural outbreaks. in the past few years, numerous data accumulated on the immunogenicity and safety of plant-made vaccines against bio-security-related organisms. in addition, expression levels achieved for these antigenic proteins are practical for the production of sufficient material f ... | 2009 | 19460602 |
| [development of a multiplex pcr-suspension array for simultaneous detection of five bioterrorism bacteria]. | to develop a rapid, high-throughput screening method of gene suspension array technique to simultaneously detect five bioterrorism bacteria: bacillus anthracis, francisella tularensis, yersinia pestis, brucella spp. and burkholderia pseudomallei. | 2009 | 19462919 |
| the mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with bacillus anthracis protective antigen. | we evaluated the safety and efficacy of the mast cell activator compound 48/80 (c48/80) when used as an adjuvant delivered intradermally (id) with recombinant anthrax protective antigen (rpa) in comparison with two well-known adjuvants. mice were vaccinated in the ear pinnae with rpa or rpa+c48/80, cpg oligodeoxynucleotides (cpg), or cholera toxin (ct). all adjuvants induced similar increases in serum anti-rpa igg and lethal toxin neutralizing antibodies. c48/80 induced a balanced cytokine produ ... | 2009 | 19464533 |
| extended multiple-locus variable-number tandem-repeat analysis of bacillus anthracis strains isolated in poland. | twenty-one variable-number tandem-repeat (vntr) marker loci were used for extended multiple locus vntr analysis (mlva) of 14 laboratory strains of bacillus anthracis isolated in poland and vaccine strain sterne 34f2a. the extended mlva (mlva-21) distinguished six genotypes clustered in three main branches. monomorphic branch 1 consisted of the vaccine strain and six isolates from distinct samples of a cow died from anthrax. this group also encompassed three haemolytic isolates of b. anthracis. b ... | 2009 | 19469279 |
| characterization of bacillus anthracis spores isolates from soil by biochemical and multiplex pcr analysis. | outbreaks of bacillus anthracis in animals are repeatedly reported in the islamic republic of iran. in this study soil samples were analysed from endemic regions of the country, and b. anthracis isolates were identified by classical bacteriological and biochemical methods. a multiplex polymerase chain reaction (pcr) assay was also developed as an alternative for identification of isolates, and was shown to be a rapid, sensitive and specific diagnostic assay. the results confirmed that 25 samples ... | 2009 | 19469438 |
| phylogenetic understanding of clonal populations in an era of whole genome sequencing. | phylogenetic hypotheses using whole genome sequences have the potential for unprecedented accuracy, yet a failure to understand issues associated with discovery bias, character sampling, and strain sampling can lead to highly erroneous conclusions. for microbial pathogens, phylogenies derived from whole genome sequences are becoming more common, as large numbers of characters distributed across entire genomes can yield extremely accurate phylogenies, particularly for strictly clonal populations. ... | 2009 | 19477301 |
| discovery, characterization and comparison of inhibitors of bacillus anthracis and staphylococcus aureus replicative dna helicases. | antibacterial compounds with new mechanisms of action are needed for effective therapy against drug-resistant pathogens in the clinic and in biodefense. screens for inhibitors of the essential replicative helicases of bacillus anthracis and staphylococcus aureus yielded 18 confirmed hits (ic(50)25 microm). several (5 of 18) of the inhibitors were also shown to inhibit dna replication in permeabilized pola-deficient b. anthracis cells. one of the most potent inhibitors also displayed antibacteria ... | 2009 | 19477652 |
| the heart is an early target of anthrax lethal toxin in mice: a protective role for neuronal nitric oxide synthase (nnos). | anthrax lethal toxin (lt) induces vascular insufficiency in experimental animals through unknown mechanisms. in this study, we show that neuronal nitric oxide synthase (nnos) deficiency in mice causes strikingly increased sensitivity to lt, while deficiencies in the two other nos enzymes (inos and enos) have no effect on lt-mediated mortality. the increased sensitivity of nnos-/- mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nnos-suffi ... | 2009 | 19478875 |
| laboratory-acquired infections. | laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that brucella species, shigella species, salmonella species, mycobacterium tuberculosis, and neisseria meningitidis are the most common causes. infections due to the bloodborne pathogens (hepatitis b virus, hepatitis c virus, and human immunodeficiency ... | 2009 | 19480580 |
| the inhibition of the interaction between the anthrax toxin and its cellular receptor by an anti-receptor monoclonal antibody. | the high affinity binding of the anthrax protective antigen (pa) to one of its receptors, capillary morphogenesis protein 2 (cmg2), is essential for the intoxication process of anthrax toxin. to acquire novel research tools to study the pa-cmg2 interaction, we generated several anti-cmg2 monoclonal antibodies (mabs). we demonstrated that one of the mabs, 4b5, could inhibit pa-cmg2 binding and could also protect the sensitive cells against an anthrax lethal toxin challenge. we identified the epit ... | 2009 | 19486894 |
| synthetic peptide vaccine targeting a cryptic neutralizing epitope in domain 2 of bacillus anthracis protective antigen. | current evidence suggests that protective antigen (pa)-based anthrax vaccines may elicit a narrow neutralizing antibody repertoire, and this may represent a vulnerability with pa-based vaccines. in an effort to identify neutralizing specificities which may complement those prevalent in pa antiserum, we evaluated whether sequences within the 2beta2-2beta3 loop of pa, which are apparent in the crystal structure of heptameric but not monomeric pa, might represent a target for an epitope-specific va ... | 2009 | 19487468 |
| proteomic technology in the design of new effective antibacterial vaccines. | infectious diseases still remain the main cause of human premature deaths, especially in developing countries. vaccines constitute the most cost-effective tool for prophylaxis of infectious diseases. elucidation of the complete genomes of many bacterial pathogens has provided a new blueprint for the search of novel vaccine candidates. at the same time, it was a turning point in the development of transcriptomics and proteomics. this article concentrates on the proteomic contribution to vaccinolo ... | 2009 | 19489702 |
| enhanced vaccine antigen delivery by salmonella using antibiotic-free operator-repressor titration-based plasmid stabilisation compared to chromosomal integration. | live attenuated bacteria provide the potential to replace traditional needle-based vaccination with an orally administered vaccine. the heterologous antigen gene is usually transformed as a multi-copy plasmid into the bacterial cell, but plasmids in live bacterial vaccine strains are often unstable, so an alternative approach is to integrate the single-copy antigen gene into the bacterial chromosome. we report a comparison between the chromosomally integrated and the plasmid-borne bacillus anthr ... | 2009 | 19490834 |
| distinct interactions of 2'- and 3'-o-(n-methyl)anthraniloyl-isomers of atp and gtp with the adenylyl cyclase toxin of bacillus anthracis, edema factor. | anthrax disease is caused by the spore-forming bacterium, bacillus anthracis. b. anthracis produces a calmodulin-activated adenylyl cyclase (ac) toxin, edema factor (ef). through excessive camp accumulation ef disrupts host defence. in a recent study [taha hm, schmidt j, göttle m, suryanarayana s, shen y, tang wj, et al. molecular analysis of the interaction of anthrax adenylyl cyclase toxin, edema factor, with 2'(3')-o-(n-(methyl)anthraniloyl)-substituted purine and pyrimidine nucleotides. mol ... | 2009 | 19492438 |
| a simple and sensitive method for detection of bacillus anthracis by loop-mediated isothermal amplification. | to develop a rapid and simple system for detection of bacillus anthracis using a loop-mediated isothermal amplification (lamp) method and determine the suitability of lamp for rapid identification of b. anthracis infection. | 2009 | 19493277 |
| direct detection of genomic dna with fluidic force discrimination assays. | herein, we describe the direct detection of genomic dna using fluidic force discrimination (ffd) assays. starting with extracted bacterial dna, samples are fragmented by restriction enzymes or sonication, then thermocycled in the presence of blocking and labeling sequences, and finally detected with microbead-based ffd assays. both strain and species identification of extracted bacillus dna have been demonstrated in <30 min, without amplification (e.g., pcr). femtomolar assays can be achieved wi ... | 2009 | 19497290 |
| anthrax of the gastrointestinal tract and oropharynx: ct findings. | anthrax is an acute infection caused by the gram-positive organism bacillus anthracis. it causes cutaneous, respiratory, and gastrointestinal (gi) infections in humans. we present the computed tomography findings of anthrax of the gi tract and oropharyngeal involvement which include inflammatory lesion in the oropharynx and gi hemorrhage. | 2010 | 19499256 |
| comparability of elisa and toxin neutralization to measure immunogenicity of protective antigen in mice, as part of a potency test for anthrax vaccines. | complexities of lethal challenge models have prompted the investigation of immunogenicity assays as potency tests of anthrax vaccines. an elisa and a lethal toxin neutralization assay (tna) were used to measure antibody response to protective antigen (pa) in mice immunized once with either a commercial or a recombinant pa (rpa) vaccine formulated in-house. even though elisa and tna results showed correlation, elisa results may not be able to accurately predict tna results in this single immuniza ... | 2009 | 19501205 |
| a new minimal replicon of bacillus anthracis plasmid pxo1. | an 8,883-bp mini-pxo1 plasmid containing a replicon from bacillus anthracis pxo1 (181.6 kb) was identified by making large deletions in the original plasmid using a newly developed cre-loxp system. portions of the truncated mini-pxo1 were cloned into an escherichia coli vector unable to replicate in b. anthracis. a 5.95-kb region encompassing three putative genes was identified as the minimal pxo1 fragment required for replication of the resulting recombinant shuttle plasmid (named pmr) in b. an ... | 2009 | 19502400 |
| detection of bacillus subtilis spores in water by means of broadband coherent anti-stokes raman spectroscopy. | broadband coherent anti-stokes raman scattering (cars) spectroscopy is used for detection of bacterial spores in aqueous solution. polarization cars spectroscopy is employed to suppress the non-resonant background. cars spectrum recorded in the spectral region from 700 to 1900 cm(-1) exhibits all the characteristic features of spontaneous raman spectrum taken for a solid powder and resembles that one of the dipicolinic acid, which is considered to be the major component of bacterial spores, incl ... | 2005 | 19503156 |
| enhanced optical chromatography in a pdms microfluidic system. | the purely refractive index driven separation of uniformly sized polystyrene, n = 1.59 and poly(methylmethacrylate), n = 1.49 in an optical chromatography system has been enhanced through the incorporation of a custom poly(dimethysiloxane) (pdms) microfluidic system. a customized channel geometry was used to create separate regions with different linear flow velocities tailored to the specific application. these separate flow regions were then used to expose the entities in the separation to dif ... | 2005 | 19503255 |
| kinetics of lethal factor and poly-d-glutamic acid antigenemia during inhalation anthrax in rhesus macaques. | systemic anthrax manifests as toxemia, rapidly disseminating septicemia, immune collapse, and death. virulence factors include the anti-phagocytic gamma-linked poly-d-glutamic acid (pga) capsule and two binary toxins, complexes of protective antigen (pa) with lethal factor (lf) and edema factor. we report the characterization of lf, pa, and pga levels during the course of inhalation anthrax in five rhesus macaques. we describe bacteremia, blood differentials, and detection of the pa gene (paga) ... | 2009 | 19506008 |
| biosensing with nanofluidic diodes. | recently reported nanofluidic diodes with highly nonlinear current-voltage characteristics offer a unique possibility to construct different biosensors. these sensors are based on local changes of the surface charge on walls of single conical nanopores induced by binding of an analyte. the analyte binding can be detected as a change of the ion-current rectification of single nanopores defined as a ratio of currents for voltages of one polarity, and currents for voltages of the opposite polarity. ... | 2009 | 19507907 |
| what sets bacillus anthracis apart from other bacillus species? | bacillus anthracis is the cause of anthrax, and two large plasmids are essential for toxicity: pxo1, which contains the toxin genes, and pxo2, which encodes a capsule. b. anthracis forms a highly monomorphic lineage within the b. cereus group, but strains of bacillus thuringiensis and b. cereus exist that are genetically closely related to the b. anthracis cluster. during the past five years b. cereus strains that contain the pxo1 virulence plasmid were discovered, and strains with both pxo1 and ... | 2009 | 19514852 |
| bacterial toxins: an overview on bacterial proteases and their action as virulence factors. | bacterial pathogenicity is a result of a combination of factors, including resistance to environmental threats and to the host's defenses, growth capability, localization in the host, tissue specificity, resource obtaining mechanisms and the bacterium's own defenses to aggression. a variety of bacterial components, often specific to each strain, are involved in the microorganism's survival, adhesion and growth in the host. many of them are harmful and, therefore, are called virulence factors. th ... | 2009 | 19519507 |
| femtomolar detection of the anthrax edema factor in human and animal plasma. | edema factor (ef), a calmodulin-activated adenylyl cyclase, is a toxin which contributes to cutaneous and systemic anthrax. as a novel strategy to detect anthrax toxins in humans or animals infected by bacillus anthracis, we have developed a sensitive enzymatic assay to be able to monitor functional ef in human and animal plasma. samples containing ef are incubated in the presence of calmodulin and atp, which is converted to camp. after oxidation and derivatization, camp is monitored by competit ... | 2009 | 19522516 |
| novel chimpanzee/human monoclonal antibodies that neutralize anthrax lethal factor, and evidence for possible synergy with anti-protective antigen antibody. | three chimpanzee fabs reactive with lethal factor (lf) of anthrax toxin were isolated and converted into complete monoclonal antibodies (mabs) with human gamma1 heavy-chain constant regions. in a macrophage toxicity assay, two of the mabs, lf10e and lf11h, neutralized lethal toxin (lt), a complex of lf and anthrax protective antigen (pa). lf10e has the highest reported affinity for a neutralizing mab against lf (dissociation constant of 0.69 nm). this antibody also efficiently neutralized lt in ... | 2009 | 19528217 |
| sample concentration using optical chromatography. | optical chromatography is a technique for the separation of particles that capitalizes on the balance between optic and fluidic forces. when microscopic particles in a fluid flow encounter a laser beam propagating in the opposite direction, they are trapped axially along the beam. they are then optically pushed upstream from the laser focal point to rest at a point where the optic and fluidic forces on the particle balance. because optical and fluid forces are sensitive to differences in the phy ... | 2007 | 19532509 |
| crystal structure of bacillus anthracis transpeptidase enzyme capd. | bacillus anthracis elaborates a poly-gamma-d-glutamic acid capsule that protects bacilli from phagocytic killing during infection. the enzyme capd generates amide bonds with peptidoglycan cross-bridges to anchor capsular material within the cell wall envelope of b. anthracis. the capsular biosynthetic pathway is essential for virulence during anthrax infections and can be targeted for anti-infective inhibition with small molecules. here, we present the crystal structures of the gamma-glutamyltra ... | 2009 | 19535342 |
| [molecular cloning, expression, and characterization of human mini-antibodies against enterotoxin c1 of staphylococcus aureus]. | we describe here the cloning, expression, and production of specific single-chain antibodies (scfv) against the recombinant enterotoxin c1 of staphylococcus aureus. high-affinity scfv were selected from the phage library of human mini antibodies; afterwards, the cells of e. coli trxa gor double mutant were infected with a product obtained by fusion of dna encoding of these mini antibodies with the trxa gene to induce soluble scfv synthesis in cell cytoplasm. the scfv obtained displayed high ente ... | 2009 | 19537170 |
| quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death. | here, we report the results of a quantitative high-throughput screen (qhts) measuring the endocytosis and translocation of a beta-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. several small molecules protect raw264.7 macrophages and cho cells from anthrax lethal toxin and protected cells from an lf-pseudomonas exotoxin fusion protein and diphtheria toxin. further efforts demonstrated that these compoun ... | 2009 | 19540764 |
| real-time public health surveillance for emergency preparedness. | | 2009 | 19542047 |
| injection of staphylococcus aureus edin by the bacillus anthracis protective antigen machinery induces vascular permeability. | systemic injection of bacillus anthracis lethal toxin (lt) produces vascular leakage and animal death. recent studies suggest that lt triggers direct endothelial cell cytotoxicity that is responsible for the vascular leakage. lt is composed of heptamers of protective antigen (pa), which drives the endocytosis and translocation into host cells of the lethal factor (lf), a mitogen-activated protein kinase kinase protease. here we investigated the consequences of injection of an endothelium-permeab ... | 2009 | 19546197 |
| a dna microarray facilitates the diagnosis of bacillus anthracis in environmental samples. | in order to improve the diagnosis of bacillus anthracis in environmental samples, we established a dna microarray based on the arraytube technology of clondiag. | 2009 | 19552771 |
| simultaneous detection of five biothreat agents in powder samples by a multiplexed suspension array. | a suspension array-based multiplexed immunoassay was developed for rapid, sensitive, specific, and simultaneous detection of multiple biothreat-associated agents in powder samples. the 5-plexed immunoassays using sets of 9-plexed coupled fluorescent beads were employed to simultaneously detect five representative biothreat agents, including b. anthracis spore, y. pestis, sars-cov, staphylococcal enterotoxin b (seb) and ricin from a single powder sample and the feasibility for field samples was d ... | 2009 | 19555207 |
| critical challenges ahead in bioterrorism preparedness training for clinicians. | a survey was distributed to determine physicians' confidence levels in recognizing potential category-a bioterrorism disease threats (e.g., smallpox, anthrax), preferred means of obtaining continuing medical education (cme) credits, and their knowledge of the connecticut department of public health's (dph) disease reporting requirements. | 2009 | 19557957 |
| the adenylyl cyclase activity of anthrax edema factor. | bacillus anthracis, the etiologic agent for anthrax, secretes edema factor (ef) to disrupt intracellular signaling pathways. upon translocation into host cells and association with a calcium sensor, calmodulin (cam), ef becomes a highly active adenylyl cyclase (ac) that raises the intracellular concentration of cyclic amp (camp). growing evidence shows that ef plays a key role in anthrax pathogenesis by affecting cellular functions vital for host defense. this strategy is also used by bordetella ... | 2009 | 19560485 |
| anthrax toxins: a weapon to systematically dismantle the host immune defenses. | successful colonization of the host by bacterial pathogens relies on their capacity to evade the complex and powerful defenses opposed by the host immune system, at least in the initial phases of infection. the two toxins of bacillus anthracis, lethal toxin and edema toxin, appear to have been shaped by evolution to assist the microorganism in this crucial function, in addition to act as general toxins acting on almost all cell types. edema toxin causes a consistent elevation of camp, an importa ... | 2009 | 19560486 |
| synthesis and assembly of a full-length human monoclonal antibody in algal chloroplasts. | monoclonal antibodies can be effective therapeutics against a variety of human diseases, but currently marketed antibody-based drugs are very expensive compared to other therapeutic options. here, we show that the eukaryotic green algae chlamydomonas reinhardtii is capable of synthesizing and assembling a full-length igg1 human monoclonal antibody (mab) in transgenic chloroplasts. this antibody, 83k7c, is derived from a human igg1 directed against anthrax protective antigen 83 (pa83), and has be ... | 2009 | 19562731 |
| membrane translocation by anthrax toxin. | much attention has been focused on anthrax toxin recently, both because of its central role in the pathogenesis of bacillus anthracis and because it has proven to be one of the most tractable toxins for studying how enzymic moieties of intracellularly acting toxins traverse membranes. the protective antigen (pa) moiety of the toxin, after being proteolytically activated at the cell surface, self-associates to form a heptameric pore precursor (prepore). the prepore binds up to three molecules of ... | 2009 | 19563824 |
| human naive and memory cd4+ t cell repertoires specific for naturally processed antigens analyzed using libraries of amplified t cells. | the enormous diversity of the naive t cell repertoire is instrumental in generating an immune response to virtually any foreign antigen that can be processed into peptides that bind to mhc molecules. the low frequency of antigen-specific naive t cells, their high activation threshold, and the constrains of antigen-processing and presentation have hampered analysis of naive repertoires to complex protein antigens. in this study, libraries of polyclonally expanded naive t cells were used to determ ... | 2009 | 19564353 |
| crystallization and initial crystallographic analysis of phosphoglucosamine mutase from bacillus anthracis. | the enzyme phosphoglucosamine mutase catalyzes the conversion of glucosamine 6-phosphate to glucosamine 1-phosphate, an early step in the formation of the nucleotide sugar udp-n-acetylglucosamine, which is involved in peptidoglycan biosynthesis. these enzymes are part of the large alpha-d-phosphohexomutase enzyme superfamily, but no proteins from the phosphoglucosamine mutase subgroup have been structurally characterized to date. here, the crystallization of phosphoglucosamine mutase from bacill ... | 2009 | 19574653 |
| participatory appraisal of foot and mouth disease in the afar pastoral area, northeast ethiopia: implications for understanding disease ecology and control strategy. | foot and mouth disease (fmd) is the most economically important disease of livestock that still affects extensive areas of the world. this study described the use of participatory appraisal tools such as pair-wise ranking, matrix scoring and proportional piling to assess the perception of livestock keepers about the clinical signs and epidemiological features of cattle diseases with particular emphasis on fmd. strong agreement among informant groups (w = 0.710; p = 0.000) in pair wise ranking in ... | 2010 | 19575306 |
| dr. jekyll and mr. hyde: a short history of anthrax. | the anthrax letters crisis, following the discovery of a major bacterial warfare program in the ussr and the realization that irak had been on the verge of using anthrax as a weapon during the first gulf war, had the consequence of putting anthrax back on the agenda of scientists. fortunately, although it was mostly unknown by the public before these events, it was far from unknown by microbiologists. already mentioned in the bible as a disease of herbivores, it remained a major cause of death f ... | 2009 | 19577591 |
| the germination-specific lytic enzymes sleb, cwlj1, and cwlj2 each contribute to bacillus anthracis spore germination and virulence. | the bacterial spore cortex is critical for spore stability and dormancy and must be hydrolyzed by germination-specific lytic enzymes (gsles), which allows complete germination and vegetative cell outgrowth. we created in-frame deletions of three genes that encode gsles that have been shown to be active in bacillus anthracis germination: sleb, cwlj1, and cwlj2. phenotypic analysis of individual null mutations showed that the removal of any one of these genes was not sufficient to disrupt spore ge ... | 2009 | 19581364 |
| human alpha-defensins inhibit hemolysis mediated by cholesterol-dependent cytolysins. | many pathogenic gram-positive bacteria release exotoxins that belong to the family of cholesterol-dependent cytolysins. here, we report that human alpha-defensins hnp-1 to hnp-3 acted in a concentration-dependent manner to protect human red blood cells from the lytic effects of three of these exotoxins: anthrolysin o (alo), listeriolysin o, and pneumolysin. hd-5 was very effective against listeriolysin o but less effective against the other toxins. human alpha-defensins hnp-4 and hd-6 and human ... | 2009 | 19581399 |
| carbohydrate metabolism differences between subgroup a1 and b2 strains of bacillus anthracis as assessed by comparative genomics and functional genetics. | in france, bacillus anthracis subgroup b2 strains do not metabolize starch or glycogen but can use gluconate, whereas subgroup a1 strains show the inverse pattern. functional genetic analysis revealed that mutations in the amys and gntk genes encoding an alpha-amylase and a gluconate kinase, respectively, were responsible for these phenotypes. | 2009 | 19581471 |
| multifunctional nanoarchitectures from dna-based abc monomers. | the ability to attach different functional moieties to a molecular building block could lead to applications in nanoelectronics, nanophotonics, intelligent sensing and drug delivery. the building unit needs to be both multivalent and anisotropic, and although many anisotropic building blocks have been created, these have not been universally applicable. recently, dna has been used to generate various nanostructures or hybrid systems, and as a generic building block for various applications. here ... | 2009 | 19581895 |
| preparative optical chromatography with external collection and analysis. | optical chromatography, used for particle separation, involves loosely focusing a laser into a fluid flowing opposite the direction of laser propagation. when microscopic particles in the flow path encounter this beam they are trapped axially along the beam and are pushed upstream from the laser focal point to rest at a point where the optical and fluid forces on the particle balance. because optical and fluid forces are sensitive to differences in the physical and chemical properties of a parti ... | 2008 | 19581966 |
| mechanisms of dna binding and regulation of bacillus anthracis dna primase. | dna primases are pivotal enzymes in chromosomal dna replication in all organisms. in this article, we report unique mechanistic characteristics of recombinant dna primase from bacillus anthracis. the mechanism of action of b. anthracis dna primase (dnag(ba)) may be described in several distinct steps as follows. its mechanism of action is initiated when it binds to single-stranded dna (ssdna) in the form of a trimer. although dnag(ba) binds to different dna sequences with moderate affinity (as e ... | 2009 | 19583259 |
| development of a pcr assay for identification of the bacillus cereus group species. | a pcr technique was developed as a reliable and rapid identification method for the bacillus cereus group species, based on a unique conserved sequence of the motb gene (encoding flagellar motor protein) from b. cereus, bacillus thuringiensis and bacillus anthracis. | 2010 | 19583794 |
| a mini-outbreak of cutaneous anthrax in vizianagaram district, andhra pradesh, india. | | 2009 | 19584478 |
| insights into the anthrax lethal factor-substrate interaction and selectivity using docking and molecular dynamics simulations. | the anthrax toxin of the bacterium bacillus anthracis consists of three distinct proteins, one of which is the anthrax lethal factor (lf). lf is a gluzincin zn-dependent, highly specific metalloprotease with a molecular mass of approximately 90 kda that cleaves most isoforms of the family of mitogen-activated protein kinase kinases (meks/mkks) close to their amino termini, resulting in the inhibition of one or more signaling pathways. previous studies on the crystal structures of uncomplexed lf ... | 2009 | 19585464 |
| raxibacumab for the treatment of inhalational anthrax. | inhalational anthrax caused by bacillus anthracis is associated with high mortality primarily due to toxin-mediated injury. raxibacumab is a human igg1lambda monoclonal antibody directed against protective antigen, a component of the anthrax toxin. | 2009 | 19587338 |
| images in clinical medicine. cutaneous anthrax. | | 2009 | 19587343 |
| protecting against future shock--inhalational anthrax. | | 2009 | 19587345 |
| comparative antimicrobial activity of granulysin against bacterial biothreat agents. | granulysin is a cationic protein produced by human t cells and natural killer cells that can kill bacterial pathogens through disruption of microbial membrane integrity. herein we demonstrate antimicrobial activity of the granulysin peptide derived from the active site against bacillus anthracis, yersinia pestis, francisella tularensis, and burkholderia mallei, and show pathogen-specific differences in granulysin peptide effects. the susceptibility of y. pestis to granulysin is temperature depen ... | 2009 | 19587798 |
| differential binding of co(ii) and zn(ii) to metallo-beta-lactamase bla2 from bacillus anthracis. | in an effort to probe the structure, mechanism, and biochemical properties of metallo-beta-lactamase bla2 from bacillus anthracis, the enzyme was overexpressed, purified, and characterized. metal analyses demonstrated that recombinant bla2 tightly binds 1 equiv of zn(ii). steady-state kinetic studies showed that mono-zn(ii) bla2 (1zn-bla2) is active, while di-zn(ii) bla2 (znzn-bla2) was unstable. catalytically, 1zn-bla2 behaves like the related enzymes ccra and l1. in contrast, di-co(ii) bla2 (c ... | 2009 | 19588962 |
| immunizations against bioterrorism: smallpox and anthrax. | | 2009 | 19589771 |
| an evaluation of suspicious powder screening tools for first responders. | field screening tools are required which would allow first responders to quickly ascertain if a suspicious powder poses a potential threat necessitating additional testing for biological pathogens such as bacillus anthracis. in this study, three commercially available generic screening technologies were evaluated for the effectiveness to accurately differentiate between a hoax powder and a true biological threat. the biocheck kit was able to detect the following biological agents 1 x 10(8)cfu of ... | 2009 | 19592160 |
| the crystal structure of a family gh25 lysozyme from bacillus anthracis implies a neighboring-group catalytic mechanism with retention of anomeric configuration. | lysozymes are found in many of the sequence-based families of glycoside hydrolases (www.cazy.org) where they show considerable structural and mechanistic diversity. lysozymes from glycoside hydrolase family gh25 adopt a (alpha/beta)(5)(beta)(3)-barrel-like fold with a proposal in the literature that these enzymes act with inversion of anomeric configuration; the lack of a suitable substrate, however, means that no group has successfully demonstrated the configuration of the product. here we repo ... | 2009 | 19595298 |
| characterisation of dihydrodipicolinate synthase (dhdps) from bacillus anthracis. | bacillus anthracis is a gram-positive spore-forming bacterium that is the causative agent of anthrax disease. the use of anthrax as a bioweapon has increased pressure for the development of an effective treatment. dihydrodipicolinate synthase (dhdps) catalyses the first committed step in the biosynthetic pathway yielding two essential bacterial metabolites, meso-diaminopimelate (dap) and (s)-lysine. dhdps is therefore a potential antibiotic target, as microbes require either lysine or dap as a c ... | 2009 | 19595801 |
| report on malignant anthrax in herds and malignant pustule in man, (on the wadsworth estate). | | 1875 | 19599924 |
| anthrax in london. | | 1896 | 19600733 |
| anthrax: the effect of tanneries in spreading the disease. | | 1898 | 19600848 |
| bioaerosol analysis with raman chemical imaging microspectroscopy. | raman chemical imaging microspectroscopy is evaluated as a technology for waterborne pathogen and bioaerosol detection. raman imaging produces a three-dimensional data cube consisting of a raman spectrum at every pixel in a microscope field of view. binary and ternary mixtures including combinations of polystyrene beads, gram-positive bacillus anthracis, b. thuringiensis, and b. atrophaeus spores, and b. cereus vegetative cells were investigated by raman imaging for differentiation and character ... | 2009 | 19601631 |
| the surface of bacillus anthracis. | bacillus anthracis is a gram positive organism possessing a complex parietal structure. an s-layer, a bi-dimensional crystalline layer, and a peptidic capsule surround the thick peptidoglycan of bacilli harvested during infection. a review of the current literature indicates that elements from each of these three structures, as well as membrane components, have been studied. so-called cell-wall secondary polymers, be they attached to the cell-wall or to the membrane play important functions, eit ... | 2009 | 19607856 |
| synthesis, spectroscopic characterization and antibacterial activity of new cobalt(ii) complexes of unsymmetrical tetradentate (osn2) schiff base ligands. | cobalt ion complexes with the schiff bases, (4-x-2-{[2-(2-pyridine-2-yl-ethylsulfanyl)ethylimino]methyl}phenol (x=methoxy (ome), phenylazo (n(2)ph), bromo (br), nitro (no(2))),were synthesized and investigated by several techniques using elemental analysis (c, h, n), ftir, electronic spectra and molar conductivity. the thermal stability of free ligands and related cobalt complexes were studied by using differential scanning calorimetry (dsc) and thermogravimetric analyses (tga). cyclic voltammet ... | 2009 | 19608303 |
| functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore. | a key step of anthrax toxin action involves the formation of a protein-translocating pore within the endosomal membrane by the protective antigen (pa) moiety. formation of this transmembrane pore by pa involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel. | 2009 | 19609431 |
| solubilization and characterization of the anthrax toxin pore in detergent micelles. | proteolytically activated protective antigen (pa) moiety of anthrax toxin self-associates to form a heptameric ring-shaped oligomer (the prepore). acidic ph within the endosome converts the prepore to a pore that serves as a passageway for the toxin's enzymatic moieties to cross the endosomal membrane. prepore is stable in solution under mildly basic conditions, and lowering the ph promotes a conformational transition to an insoluble pore-like state. n-tetradecylphosphocholine (fos14) was the on ... | 2009 | 19609933 |
| the small acid soluble proteins (sasp alpha and sasp beta) of bacillus weihenstephanensis and bacillus mycoides group 2 are the most distinct among the bacillus cereus group. | the bacillus cereus group includes bacillus anthracis, b. cereus, bacillus thuringiensis, bacillus mycoides and bacillus weihenstephanensis. the small acid soluble spore protein (sasp) beta has been previously demonstrated to be among the biomarkers differentiating b. anthracis and b. cereus; sasp beta of b. cereus most commonly exhibits one or two amino acid substitutions when compared to b. anthracis. sasp alpha is conserved in sequence among these two species. neither sasp alpha nor beta for ... | 2009 | 19616612 |
| capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo. | anthrax toxin, a major virulence factor of bacillus anthracis, gains entry into target cells by binding to either of 2 von willebrand factor a domain-containing proteins, tumor endothelium marker-8 (tem8) and capillary morphogenesis protein-2 (cmg2). the wide tissue expression of tem8 and cmg2 suggest that both receptors could play a role in anthrax pathogenesis. to explore the roles of tem8 and cmg2 in normal physiology, as well as in anthrax pathogenesis, we generated tem8- and cmg2-null mice ... | 2009 | 19617532 |
| predicting hospital surge after a large-scale anthrax attack: a model-based analysis of cdc's cities readiness initiative prophylaxis recommendations. | background: a cri-compliant prophylaxis campaign starting 2 days after exposure would protect from 86% to 87% of exposed individuals from illness (assuming, in the base case, 90% antibiotic effectiveness and a 95% attack rate). each additional day needed to complete the campaign would result in, on average, 2.4% to 2.9% more hospitalizations in the exposed population; each additional day's delay to initiating prophylaxis beyond 2 days would result in 5.2% to 6.5% additional hospitalizations. the ... | 2009 | 19617582 |
| identification of linear epitopes in bacillus anthracis protective antigen bound by neutralizing antibodies. | protective antigen (pa), the binding subunit of anthrax toxin, is the major component in the current anthrax vaccine, but the fine antigenic structure of pa is not well defined. to identify linear neutralizing epitopes of pa, 145 overlapping peptides covering the entire sequence of the protein were synthesized. six monoclonal antibodies (mabs) and antisera from mice specific for pa were tested for their reactivity to the peptides by enzyme-linked immunosorbent assays. three major linear immunodo ... | 2009 | 19617628 |
| the physiologic responses of dutch belted rabbits infected with inhalational anthrax. | bacillus anthracis, the causative agent of anthrax, is a category a priority pathogen that causes extensive damage in humans. for this reason, b. anthracis has been the focus of numerous studies using various animal models. in this study, we explored physiologic parameters in dutch belted rabbits with inhalation anthrax to characterize the disease progression in this model. to this end, we infected dutch belted rabbits with 100 ld(50) b. anthracis ames spores by nasal instillation and continuous ... | 2009 | 19619416 |
| preparedness for an anthrax attack. | bacillus anthracis is a long-known bacterial organism with a uniquely stable spore stage. its stability and the lethal disease which results when the spore is inhaled made it a favorite of state-sponsored biological weapons programs throughout the cold war era. it is also believed to be high on the list of candidate microbial agents which could be used by terrorist groups or lone actors. its unique characteristics make protection of humans, especially civilians, from an intentional biological at ... | 2009 | 19619577 |
| investigation of new dominant-negative inhibitors of anthrax protective antigen mutants for use in therapy and vaccination. | the lethal toxin (letx) of bacillus anthracis plays a key role in the pathogenesis of anthrax. the protective antigen (pa) is a primary part of the anthrax toxin and forms letx by combination with lethal factor (lf). phenylalanine-427 (f427) is crucial for pa function. this study was designed to discover potential novel therapeutic agents and vaccines for anthrax. this was done by screening pa mutants that were mutated at the f427 residue for a dominant-negative inhibitory (dni) phenotype which ... | 2009 | 19620345 |
| nod1/nod2-mediated recognition plays a critical role in induction of adaptive immunity to anthrax after aerosol exposure. | toll-like receptors and nod-like receptors (nlr) play an important role in sensing invading microorganisms for pathogen clearance and eliciting adaptive immunity for protection against rechallenge. nod1 and nod2, members of the nlr family, are capable of detecting bacterial peptidoglycan motifs in the host cytosol for triggering proinflammatory cytokine production. in the current study, we sought to determine if nod1/nod2 are involved in sensing bacillus anthracis infection and eliciting protect ... | 2009 | 19620350 |
| anthrax lethal toxin enhances ikappab kinase activation and differentially regulates pro-inflammatory genes in human endothelium. | anthrax lethal toxin (lt) was previously shown to enhance transcriptional activity of nf-kappab in tumor necrosis factor-alpha-activated primary human endothelial cells. here we show that this lt-mediated increase in nf-kappab activation is associated with the enhanced degradation of the inhibitory proteins ikappabalpha and ikappabbeta but not ikappabepsilon. moreover, this was accompanied by enhanced activation of the ikappab kinase complex (ikk), which is responsible for targeting ikappab prot ... | 2009 | 19620708 |
| [preparation and characterization of monoclonal antibodies to the cholera toxin]. | monoclonal antibodies to cholera toxin were obtained. they do not cross-react with the termolabile toxin (lt) of escherichia coli, ricin, diphtherial toxin, staphylococcus enterotoxins of sea, seb, sei, seg, or the lethal factor and protective antigen of the anthrax toxin. pairs of antibodies for the quantitative measurement of the cholera toxin in sandwich enzyme immunoassay (eia) were selected. the detection limit of the toxin is 0.2 ng/ml for plate eia and 0.44 ng/ml for microchip eia. the pr ... | 2009 | 19621051 |
| [new immunoglobulin for treatment of anthrax]. | to experimentally assess activity and safety of anti-anthrax intravenous immunoglobulin manufactured on standard technology. | 2009 | 19621821 |
| [improvement of methods for identification of atypical anthrax strains and their differentiation from closely related bacilli]. | to study biologic characteristics of atypical strains of anthrax agent in order to improve methods of identification and differentiation from closely related bacilli. | 2009 | 19621825 |
| host-derived tumor endothelial marker 8 promotes the growth of melanoma. | tumor endothelial marker 8 (tem8) was initially identified as a gene overexpressed in the vasculature of human tumors and was subsequently identified as an anthrax toxin receptor. to assess the functional role of tem8, we disrupted the tem8 gene in mice by targeted homologous recombination. tem8(-/-) mice were viable and reached adulthood without defects in physiologic angiogenesis. however, histopathologic analysis revealed an excess of extracellular matrix in several tissues, including the ova ... | 2009 | 19622764 |
| gamma-phage lysin plyg sequence-based synthetic peptides coupled with qdot-nanocrystals are useful for developing detection methods for bacillus anthracis by using its surrogates, b. anthracis-sterne and b. cereus-4342. | previous reports of site-directed deletion analysis on gamma (gamma)-phage lysin protein (plyg) have demonstrated that removal of a short amino acid sequence in the c-terminal region encompassing a 10-amino acid motif (190lkmtadfilq199) abrogates its binding activity specific to the cell wall of bacillus anthracis. whether short synthetic peptides representing the10-amino acid plyg putative binding motif flanked by surrounding n- and c-terminal residues also selectively bind to the bacterial cel ... | 2009 | 19624851 |
| the protective antigen component of anthrax toxin forms functional octameric complexes. | the assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. we begin to address this question using anthrax toxin as a model. the protective antigen (pa) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (lf) and edema factor (ef), to form toxic complexes. to disrupt the host, these toxic complexes are endocytosed, suc ... | 2009 | 19627991 |
| isolation and chimerization of a highly neutralizing antibody conferring passive protection against lethal bacillus anthracis infection. | several studies have demonstrated that the passive transfer of protective antigen (pa)-neutralizing antibodies can protect animals against bacillus anthracis infection. the standard protocol for the isolation of pa-neutralizing monoclonal antibodies is based upon a primary selection of the highest pa-binders by elisa, and usually yields only few candidates antibodies. we demonstrated that by applying a pa-neutralization functionality-based screen as the primary criterion for positive clones, it ... | 2009 | 19629185 |
| healthcare coalitions: the new foundation for national healthcare preparedness and response for catastrophic health emergencies. | after 9/11 and the 2001 anthrax letters, it was evident that our nation's healthcare system was largely underprepared to handle the unique needs and large volumes of people who would seek medical care following catastrophic health events. in response, in 2002 congress established the hospital preparedness program (hpp) in the u.s. department of health and human services (hhs) to strengthen the ability of u.s. hospitals to prepare for and respond to bioterrorism and naturally occurring epidemics ... | 2009 | 19635000 |
| protection against anthrax and plague by a combined vaccine in mice and rabbits. | the protective antigen (pa) of bacillus anthracis and the fraction 1 capsular antigen (f1 antigen), v antigen of yersinia pestis have been demonstrated to be potential immunogens and candidate vaccine sub-units against anthrax and plague respectively. in this study, the authors have investigated the antibody responses and the protective efficacy when the antigens were administered separately or in combination intramuscularly formulation adsorbed to an aluminum hydroxide adjuvant. results show th ... | 2009 | 19635609 |
| ca-074me protection against anthrax lethal toxin. | anthrax lethal toxin (lt) activates the nlrp1b (nalp1b) inflammasome and caspase-1 in macrophages from certain inbred mouse strains, but the mechanism by which this occurs is poorly understood. we report here that similar to several nlrp3 (nalp3, cryopyrin)-activating stimuli, lt activation of the nlrp1b inflammasome involves lysosomal membrane permeabilization (lmp) and subsequent cytoplasmic cathepsin b activity. ca-074me, a potent cathepsin b inhibitor, protects lt-sensitive macrophages from ... | 2009 | 19635822 |
| novel broad-spectrum bis-(imidazolinylindole) derivatives with potent antibacterial activities against antibiotic-resistant strains. | given the limited number of structural classes of clinically available antimicrobial drugs, the discovery of antibacterials with novel chemical scaffolds is an important strategy in the development of effective therapeutics for both naturally occurring and engineered resistant strains of pathogenic bacteria. in this study, several diarylamidine derivatives were evaluated for their ability to protect macrophages from cell death following infection with bacillus anthracis, a gram-positive spore-fo ... | 2009 | 19635954 |
| bacillus cereus spores release alanine that synergizes with inosine to promote germination. | the first step of the bacterial lifecycle is the germination of bacterial spores into their vegetative form, which requires the presence of specific nutrients. in contrast to closely related bacillus anthracis spores, bacillus cereus spores germinate in the presence of a single germinant, inosine, yet with a significant lag period. | 2009 | 19636427 |
| cellular and systemic effects of anthrax lethal toxin and edema toxin. | anthrax lethal toxin (lt) and edema toxin (et) are the major virulence factors of anthrax and can replicate the lethality and symptoms associated with the disease. this review provides an overview of our current understanding of anthrax toxin effects in animal models and the cytotoxicity (necrosis and apoptosis) induced by lt in different cells. a brief reexamination of early historic findings on toxin in vivo effects in the context of our current knowledge is also presented. | 2009 | 19638283 |
| retroviruses and other latent viruses: the deadliest of pathogens are not necessarily the best candidates for bioterrorism. | hiv-1 (and other viral causes of latent, chronic infections) is not a likely candidate for bioterrorism. scenarios resulting in the introduction of retroviral infections into a large population generally seem impractical and unpredictable as bioterrorist plots, especially relative to the frightening simplicity of deadly anthrax spores or smallpox virions. as evidenced in the above discussion, contaminating the blood supply would require a highly sophisticated plan resulting in effects of rather ... | 2009 | 19639767 |
| through the looking glass, mechanistic insights from enantiomeric human defensins. | despite the small size and conserved tertiary structure of defensins, little is known at a molecular level about the basis of their functional versatility. for insight into the mechanism(s) of defensin function, we prepared enantiomeric pairs of four human defensins, hnp1, hnp4, hd5, and hbd2, and studied their killing of bacteria, inhibition of anthrax lethal factor, and binding to hiv-1 gp120. unstructured hnp1, hd5, and hbd3 and several other human alpha- and beta-defensins were also examined ... | 2009 | 19640840 |
| efficient methods for large-area surface sampling of sites contaminated with pathogenic microorganisms and other hazardous agents: current state, needs, and perspectives. | the recovery operations following the 2001 attacks with bacillus anthracis spores were complicated due to the unprecedented need for large-area surface sampling and decontamination protocols. since this event, multiple reports have been published describing recovery efficiencies of several surface sampling materials. these materials include fibrous swabs of various compositions, cloth wipes, vacuum socks, and adhesive tapes. these materials have reported recovery efficiencies ranging from approx ... | 2009 | 19644689 |
| implications of limits of detection of various methods for bacillus anthracis in computing risks to human health. | used for decades for biological warfare, bacillus anthracis (category a agent) has proven to be highly stable and lethal. quantitative risk assessment modeling requires descriptive statistics of the limit of detection to assist in defining the exposure. furthermore, the sensitivities of various detection methods in environmental matrices are vital information for first responders. a literature review of peer-reviewed journal articles related to methods for detection of b. anthracis was undertake ... | 2009 | 19648357 |