| structure-activity relationships of bacillus cereus and bacillus anthracis dihydrofolate reductase: toward the identification of new potent drug leads. | new and improved therapeutics are needed for bacillus anthracis, the etiological agent of anthrax. to date, antimicrobial agents have not been developed against the well-validated target dihydrofolate reductase (dhfr). in order to address whether dhfr inhibitors could have potential use as clinical agents against bacillus, 27 compounds were screened against this enzyme from bacillus cereus, which is identical to the enzyme from b. anthracis at the active site. several 2,4-diamino-5-deazapteridin ... | 2006 | 17005826 |
| comparative analysis of two-component signal transduction systems of bacillus cereus, bacillus thuringiensis and bacillus anthracis. | members of the bacillus cereus group are ubiquitously present in the environment and can adapt to a wide range of environmental fluctuations. in bacteria, these adaptive responses are generally mediated by two-component signal transduction systems (tcss), which consist of a histidine kinase (hk) and its cognate response regulator (rr). with the use of in silico techniques, a complete set of hks and rrs was recovered from eight completely sequenced b. cereus group genomes. by applying a bidirecti ... | 2006 | 17005984 |
| significant passive protective effect against anthrax by antibody to bacillus anthracis inactivated spores that lack two virulence plasmids. | the protective-antigen (pa)-based cell-free vaccine is the only vaccine licensed for use against bacillus anthracis infection in humans. although the pa shows strong immunogenicity, the capsule or spore-associated somatic antigens may be important as additional vaccine targets for full protection against anthrax. in this study, the protective effect of spore-associated antigens against b. anthracis infection was determined. rabbits were immunized with formalin-fixed spores of a non-toxigenic une ... | 2006 | 17005989 |
| immunization against anthrax using bacillus subtilis spores expressing the anthrax protective antigen. | protective immunity to anthrax can be achieved by antibodies raised against the secreted protective antigen (pa) and this forms the basis of the current acellular vaccines for human use. bacillus subtilis spores have previously been used for delivery of heterologous antigens by the oral and nasal routes and their intrinsic heat-stability make them attractive vaccine vehicles. in this study we have expressed pa, or segments of pa, in b. subtilis using two strategies. first, display on the spore c ... | 2007 | 17007969 |
| bacillus anthracis: a multi-faceted role for anthrax lethal toxin in thwarting host immune defenses. | lethal factor (lf), along with its receptor-binding partner protective antigen (pa), forms lethal toxin (lt), a critical virulence factor for bacillus anthracis. lf is a zn(2+) protease that cleaves specific mitogen activated protein kinase kinases (mapkks), inactivating signal transduction intermediates required for normal immune function. initial research emphasized the role of lt in attenuating pro-inflammatory responses by macrophages, the primary targets of infection. more recent studies ha ... | 2007 | 17008119 |
| application of paramagnetic beads for purifying bacillus anthracis protective antigen. | paramagnetic beads coated with protein g and tosylactivated-280 dynabeads have been used to purify bacillus anthracis protective antigen from a liquid culture. the obtained protein was used in the enzyme-linked immunosorbent assay test to detect b. anthracis protective antigen antibodies in human sera collected from immunized individuals. the purification method using paramagnetic beads is very effective. it is fast, easy and may be carried out practically in any laboratory. | 2006 | 17010044 |
| surface protein isdc and sortase b are required for heme-iron scavenging of bacillus anthracis. | bacillus anthracis, the spore-forming agent of anthrax, requires iron for growth and is capable of scavenging heme-iron during infection. we show here that the b. anthracis iron-regulated surface determinants (isd) locus encompasses isdc, specifying a heme-iron binding surface protein. anchoring of isdc to the cell wall envelopes of vegetative bacilli requires srtb, which encodes sortase b. purified sortase b cleaves isdc between the threonine and the glycine of its npktg motif sorting signal. b ... | 2006 | 17012401 |
| destruction of spores on building decontamination residue in a commercial autoclave. | the u.s. environmental protection agency conducted an experiment to evaluate the effectiveness of a commercial autoclave for treating simulated building decontamination residue (bdr). the bdr was intended to simulate porous materials removed from a building deliberately contaminated with biological agents such as bacillus anthracis (anthrax) in a terrorist attack. the purpose of the tests was to assess whether the standard operating procedure for a commercial autoclave provided sufficiently robu ... | 2006 | 17012597 |
| investigation in a model system of the effects of combinations of anthrax and pertussis vaccines administered to service personnel in the 1991 gulf war. | the toxicity and immunogenicity of the anthrax and pertussis vaccine combinations used in the 1991 gulf war was assessed in nih, a/j and balb/c mice. inoculation of pertussis vaccines, vaccine combinations, or aluminium salt caused illness, splenomegaly and significant weight loss. although some animals recovered eventually, a lethal form of ascites developed in some nih mice and body weights of a/j and balb/c mice remained below normal levels. inoculation of anthrax vaccine produced little effe ... | 2005 | 17012879 |
| military hospitalizations among deployed us service members following anthrax vaccination, 1998-2001. | safety concerns have confronted the department of defense anthrax vaccine immunization program since inception in 1998. to determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken and analyzed with cox proportional hazards models. the study population consisted of 170,723 active duty us service members who were anthrax-vaccinated and deployed during the time per ... | 2006 | 17012889 |
| generalized cutaneous reactions to the anthrax vaccine: preliminary results of anthrax vaccine-specific cell mediated immunity and cytokine profiles. | over two years, the vaccine adverse event reporting system reported that 0.042% of all anthrax vaccine (biothrax, bioport corporation) doses administered were associated with cutaneous reactions, half of which were eczematous. this case series attempts to immunologically detail this eczematous reaction in four patients by measuring anthrax vaccine-specific cell mediated immunity (ascmi), profiling th1 and th2 cytokine response to the anthrax vaccine in vitro, and analyzing of skin biopsy specime ... | 2006 | 17012907 |
| evaluation of promed-mail as an electronic early warning system for emerging animal diseases: 1996 to 2004. | to identify emerging animal and zoonotic diseases and associated geographic distribution, disease agents, animal hosts, and seasonality of reporting in the program for monitoring emerging diseases (promed)-mail electronic early warning system. | 2006 | 17014355 |
| hypersensitivity reactions to quinolones. | quinolones are one of the most important classes of antimicrobial agents discovered in the recent years and one of the most widely used classes of antibiotics in clinical medicine. their broad spectrum of activity and pharmacokinetic properties make them ideal agents for treating a variety of infections. their clinical importance is further demonstrated by their activity against a wide range of diseases of public health importance such as anthrax, tuberculosis, bacterial pneumonia, and sexually ... | 2006 | 17017926 |
| structure and action of the binary c2 toxin from clostridium botulinum. | c2 toxin from clostridium botulinum is composed of the enzyme component c2-i, which adp-ribosylates actin, and the binding and translocation component c2-ii, responsible for the interaction with eukaryotic cell receptors and the following endocytosis. three c2-i crystal structures at resolutions of up to 1.75 a are presented together with a crystal structure of c2-ii at an appreciably lower resolution and a model of the prepore formed by fragment c2-iia. the c2-i structure was determined at ph 3 ... | 2006 | 17027031 |
| microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine. | the recombinant protective antigen (rpa) of bacillus anthracis is a promising anthrax vaccine. we compared serum immunoglobulin g levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following pri ... | 2006 | 17030580 |
| flow cytometry sorting protocol of bacillus spore using ultraviolet laser and autofluorescence as main sorting criterion. | the ultraviolet (uv) fluorescent aerodynamic particle sizer (flaps), a flow cytometer-like apparatus was developed by the canadian department of national defence for real-time detection of autofluorescence of biological aerosol particles such as bacterial spores. the direct relation between autofluorescence intensity and viability has recently been reported and viable spore are more autofluorescent in uv (laflamme, frontiers in bioscience). the goal of this manuscript is to describe a flow cytom ... | 2006 | 17031569 |
| unique aggregation of anthrax (bacillus anthracis) spores by sugar-coated single-walled carbon nanotubes. | there has been significant interest in the binding of anthrax spores by molecular species, but with only limited success. proteins and more recently peptides were used. however, despite the known presence of carbohydrates on the spore surface, carbohydrate-carbohydrate interactions have hardly been explored likely because of the lack of required specific platform for synthetic carbohydrates. we report the successful use of single-walled carbon nanotubes as a truly unique scaffold for displaying ... | 2006 | 17031942 |
| a preliminary assessment of bacillus anthracis spore inactivation using an electrochemically activated solution (ecasol). | to evaluate the efficacy of electrochemically activated solution (ecasol) in decontaminating bacillus anthracis ames and vollum 1b spores, with and without changing the source water hardness and final ecasol ph. | 2006 | 17032220 |
| complete sequence analysis of novel plasmids from emetic and periodontal bacillus cereus isolates reveals a common evolutionary history among the b. cereus-group plasmids, including bacillus anthracis pxo1. | the plasmids of the members of the bacillus cereus sensu lato group of organisms are essential in defining the phenotypic traits associated with pathogenesis and ecology. for example, bacillus anthracis contains two plasmids, pxo1 and pxo2, encoding toxin production and encapsulation, respectively, that define this species pathogenic potential, whereas the presence of a bt toxin-encoding plasmid defines bacillus thuringiensis isolates. in this study the plasmids from b. cereus isolates that prod ... | 2007 | 17041058 |
| a urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types. | urokinase plasminogen activator (upa) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. these have mostly led to tumor growth inhibition rather than tumor regression. a different approach was adopted by replacing the furin activation site on a recombinant anthrax toxin with a urok ... | 2006 | 17041100 |
| systemic hyalinosis: a distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (antrx2). | we sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood. | 2006 | 17043134 |
| cloning and expression in e. coli of a functional fab fragment obtained from single human lymphocyte against anthrax toxin. | human lymphocytes derived from the blood of a donor immunized with anthrax vaccine were isolated and enriched for b-cells by nycoprep density centrifugation. individual anti-anthrax protective antigen (pa) b-cells were isolated by fluorescence activated cell sorting with fluorescence-labeled recombinant pa (rpa). the rna from sorted single b-cells was extracted using plant total rna as the carrier prior to purification by nanoprep rna isolation columns and then cdna was prepared. donor specific ... | 2007 | 17045651 |
| evaluation of the rapid analyte measurement platform (ramp) for the detection of bacillus anthracis at a crime scene. | the aim of this study was to evaluate the accuracy and reliability of the rapid analyte measurement platform (ramp) for presumptive identification of bacillus anthracis spores. test samples consisted of serial dilutions of spore preparations of several bacillus species, including b. anthracis, which were tested, using the ramp anthrax test cartridge, according to the manufacturer's instructions. the fluorescence labelled antibody-antigen complexes were detected in the portable reader after 15 mi ... | 2007 | 17049777 |
| a linguistic model for the rational design of antimicrobial peptides. | antimicrobial peptides (amps) are small proteins that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. there is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and could form the basis for a new class of therapeutic agents. here we report the rational design of new amps that show limited homology to naturally occurring proteins but have strong bacteriostatic activity against several spe ... | 2006 | 17051220 |
| development of methods to measure humoral immune responses against selected antigens in the common marmoset (callithrix jacchus) and the effect of pyridostigmine bromide administration. | this methodological study was carried out in preparation for a major long term study, also reported in this volume, which was designed to investigate whether the combination of vaccines and pyridostigmine bromide (pb) could have been responsible for adverse signs and symptoms reported by a number of veterans of the 1990/1991 gulf conflict. in this context, the marmoset has been used to model aspects of the human immune system. the purposes of this methodological study were to select appropriate ... | 2006 | 17052666 |
| multiple vaccine and pyridostigmine bromide interactions in the common marmoset callithrix jacchus: immunological and endocrinological effects. | following active service during the 1990/1991 gulf conflict, a number of uk and us veterans presented with a diverse range of symptoms, collectively known as gulf veterans illnesses (gvi). the administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (pb), given to armed forces personnel during the gulf conflict has been implicated as a possible factor in the aetiology of these illnesses. the possibility that adverse health effects may resu ... | 2006 | 17052667 |
| anthrax toxin receptor 2-dependent lethal toxin killing in vivo. | anthrax toxin receptors 1 and 2 (antxr1 and antxr2) have a related integrin-like inserted (i) domain which interacts with a metal cation that is coordinated by residue d683 of the protective antigen (pa) subunit of anthrax toxin. the receptor-bound metal ion and pa residue d683 are critical for antxr1-pa binding. since pa can bind to antxr2 with reduced affinity in the absence of metal ions, we reasoned that d683 mutant forms of pa might specifically interact with antxr2. we show here that this ... | 2006 | 17054395 |
| heat activation/shock temperatures for bacillus anthracis spores and the issue of spore plate counts versus true numbers of spores. | assessing true numbers of viable anthrax spores is complex. optimal heat activation conditions vary with species, media and germinants. published time/temperature combinations for bacillus anthracis spores range from 60 degrees c for <or=90 min to boiling for 1 min. results presented here indicate that temperatures are best kept to <or=70 degrees c and holding times need not exceed 15-30 min. under conditions of 60 degrees c for 90 min, 62-23 degrees c for 15 min and 70 degrees c for 15 or 30 mi ... | 2007 | 17055602 |
| the hc fragment of tetanus toxin forms stable, concentration-dependent dimers via an intermolecular disulphide bond. | protein oligomerisation is a prerequisite for the toxicity of a number of bacterial toxins. examples include the pore-forming cytotoxin streptolysin o, which oligomerises to form large pores in the membrane and the protective antigen of anthrax toxin, where a heptameric complex is essential for the delivery of lethal factor and edema factor to the cell cytosol. binding of the clostridial neurotoxins to receptors on neuronal cells is well characterised, but little is known regarding the quaternar ... | 2007 | 17056064 |
| united states biodefense, international law, and the problem of intent. | since the anthrax attacks of 2001 in the united states, annual u.s. government spending on biodefense programs has increased enormously. u.s. biodefense was once exclusively the domain of military agencies and was aimed principally at protecting battlefield troops against the products of state-run biological warfare programs. today, it is engaged in and promoted by a variety of government agencies contemplating "bioterrorism," and it is aimed principally at protecting the american civilian popul ... | 2006 | 17059319 |
| protective and immunochemical activities of monoclonal antibodies reactive with the bacillus anthracis polypeptide capsule. | bacillus anthracis is surrounded by a polypeptide capsule composed of poly-gamma-d-glutamic acid (gammadpga). in a previous study, we reported that a monoclonal antibody (mab f26g3) reactive with the capsular polypeptide is protective in a murine model of pulmonary anthrax. the present study examined a library of six mabs generated from mice immunized with gammadpga. evaluation of mab binding to the capsule by a capsular "quellung" type reaction showed a striking diversity in capsular effects. m ... | 2007 | 17060470 |
| the gordon wilson lecture: using genetic medicine to regenerate diseased organs and protect against the hostile environment. | | 2004 | 17060966 |
| houston biosecurity: building a national model. | on september 11, 2001, al qaeda terrorists committed an atrocity when they used domestic jetliners to crash into buildings in new york city and washington, dc, killing thousands of people. in october 2001, another act of savagery occurred, this time using anthrax, not airplanes, to take innocent lives. each incident demonstrates the vulnerability of an open society, and americans are left to wonder how such acts can be prevented. two years later, al qaeda operatives are reportedly regrouping, re ... | 2004 | 17060983 |
| bioethics, bioweapons and the microbiologist. | the analysis of behavior of man in the field of biology is carried out through bioethics, considered the science of the survival. in the microbiology, there are numerous discoveries related with pathogenic microorganisms, including those that can be used as weapons in a biological war or in an attack considered bioterrorism. the scientist involved in microbiology can participate with his knowledge in the development and improvement of bioweapons, however from the point of view of bioethics it is ... | 2002 | 17061514 |
| structure of a carbohydrate esterase from bacillus anthracis. | | 2007 | 17063474 |
| pharmacokinetic considerations and efficacy of levofloxacin in an inhalational anthrax (postexposure) rhesus monkey model. | because the treatment of inhalational anthrax cannot be studied in human clinical trials, it is necessary to conduct efficacy studies using a rhesus monkey model. however, the half-life of levofloxacin was approximately three times shorter in rhesus monkeys than in humans. computer simulations to match plasma concentration profile, area under the concentration-time curve (auc), and time above mic for a human oral dose of 500 mg levofloxacin once a day identified a dosing regimen in rhesus monkey ... | 2006 | 17065619 |
| anthrax in south africa: economics, experiment and the mass vaccination of animals, c. 1910-1945. | | 2006 | 17066129 |
| inhibition of bacillus anthracis and potential surrogate bacilli growth from spore inocula by nisin and other antimicrobial peptides. | the ability of nisin, synthetic temporin analogs, magainins, defensins, and cecropins to inhibit bacillus anthracis, bacillus cereus, bacillus thuringiensis, bacillus mycoides, and bacillus subtilis growth from spore inocula was determined using well diffusion assays. nisin, magainin ii amide, and defensins were inhibitory in screening against b. anthracis sterne or b. cereus atcc 7004, but only nisin inhibited virulent b. anthracis strains. the mics of nisin against the 10 bacillus strains exam ... | 2006 | 17066940 |
| multicomponent anthrax toxin display and delivery using bacteriophage t4. | we describe a multicomponent antigen display and delivery system using bacteriophage t4. two dispensable outer capsid proteins, hoc (highly antigenic outer capsid protein, 155 copies) and soc (small outer capsid protein, 810 copies), decorate phage t4 capsid. these proteins bind to the symmetrically localized capsid sites, which appear following prohead assembly and expansion. we hypothesized that multiple antigens fused to hoc can be displayed on the same capsid and such particles can elicit br ... | 2007 | 17069938 |
| qualification and performance characteristics of a quantitative enzyme-linked immunosorbent assay for human lgg antibodies to anthrax lethal factor antigen. | the contribution of bacillus anthracis lethal factor (lf)-specific immune responses to protection against anthrax disease in humans remains incompletely defined due, in part, to a paucity of qualified reagents and a lack of standardized serological assays. toward this end, we have identified and characterized suitable positive quality control and standard reference sera and developed, optimized, and qualified an enzyme-linked immunosorbent assay (elisa) to measure lf-binding igg. herein we descr ... | 2007 | 17071101 |
| targeting proteins to the cell wall of sporulating bacillus anthracis. | dormant spores of bacillus anthracis germinate during host infection and their vegetative growth and dissemination precipitate anthrax disease. upon host death, bacilli engage a developmental programme to generate infectious spores within carcasses. hallmark of sporulation in bacillus spp. is the formation of an asymmetric division septum between mother cell and forespore compartments. we show here that sortase c (srtc) cleaves the lpnta sorting signal of bash and basi, thereby targeting both po ... | 2006 | 17074072 |
| inhibition of anthrax protective antigen outside and inside the cell. | in the course of bacillus anthracis infection, b. anthracis lethal factor (lf) and edema factor bind to a protective antigen (pa) associated with cellular receptors antxr1 (tem8) or antxr2 (cmg2), followed by internalization of the complex via receptor-mediated endocytosis. a new group of potential antianthrax drugs, beta-cyclodextrins, has recently been described. a member of this group, per-6-(3-aminopropylthio)-beta-cyclodextrin (amprbetacd), was shown to inhibit the toxicity of lf in vitro a ... | 2007 | 17074791 |
| poly-gamma-glutamate capsule-degrading enzyme treatment enhances phagocytosis and killing of encapsulated bacillus anthracis. | the poly-gamma-d-glutamic acid capsule confers antiphagocytic properties on bacillus anthracis and is essential for virulence. in this study, we showed that capd, a gamma-polyglutamic acid depolymerase encoded on the b. anthracis capsule plasmid, degraded purified capsule and removed the capsule from the surface of anthrax bacilli. treatment with capd induced macrophage phagocytosis of encapsulated b. anthracis and enabled human neutrophils to kill encapsulated organisms. a second glutamylase, p ... | 2007 | 17074794 |
| fully virulent bacillus anthracis does not require the immunodominant protein bcla for pathogenesis. | the bcla protein is the immunodominant epitope on the surface of bacillus anthracis spores; however, its roles in pathogenesis are unclear. we constructed a bcla deletion mutant (bcla) of the fully virulent ames strain. this derivative retained full virulence in several small-animal models of infection despite the bcla deletion. | 2007 | 17074844 |
| cell entry and camp imaging of anthrax edema toxin. | the entry and enzymatic activity of the anthrax edema factor (ef) in different cell types was studied by monitoring ef-induced changes in intracellular camp with biochemical and microscopic methods. camp was imaged in live cells, transfected with a fluorescence resonance energy transfer biosensor based on the protein kinase a regulatory and catalytic subunits fused to cfp and yfp, respectively. the camp biosensor was located either in the cytosol or was membrane-bound owing to the addition of a ... | 2006 | 17082768 |
| evaluation of the ability of n-terminal fragment of lethal factor of bacillus anthracis for delivery of mycobacterium t cell antigen esat-6 into cytosol of antigen presenting cells to elicit effective cytotoxic t lymphocyte response. | we report the ability of n-terminal fragment of lethal factor of bacillus anthracis to deliver genetically fused esat-6 (early secretory antigen target), a potent t cell antigen of mycobacterium tuberculosis, into cytosol to elicit cytotoxic t lymphocyte (ctl) response. in vitro th1 cytokines data and ctl assay proved that efficient delivery of lfn.esat-6 occurs in cytosol, in the presence of protective antigen (pa), and leads to generation of effective ctl response. since ctl response is essent ... | 2006 | 17084814 |
| analogies and surprising differences between recombinant nitric oxide synthase-like proteins from staphylococcus aureus and bacillus anthracis in their interactions with l-arginine analogs and iron ligands. | genome sequencing has recently shown the presence of genes coding for no-synthase (nos)-like proteins in bacteria. the roles of these proteins remain unclear. the interactions of a series of l-arginine (l-arg) analogs and iron ligands with two recombinant nos-like proteins from staphylococcus aureus (sanos) and bacillus anthracis (banos) have been studied by uv-visible spectroscopy. sanos and banos in their ferric native state, as well as their complexes with l-arg analogs and with various ligan ... | 2006 | 17084900 |
| structure and molecular mechanism of bacillus anthracis cofactor-independent phosphoglycerate mutase: a crucial enzyme for spores and growing cells of bacillus species. | phosphoglycerate mutases (pgms) catalyze the isomerization of 2- and 3-phosphoglycerates and are essential for glucose metabolism in most organisms. this study reports the production, structure, and molecular dynamics analysis of bacillus anthracis cofactor-independent pgm (ipgm). the three-dimensional structure of b. anthracis pgm is composed of two structural and functional domains, the phosphatase and transferase. the structural relationship between these two domains is different than in the ... | 2007 | 17085493 |
| anthrax toxins inhibit immune cell chemotaxis by perturbing chemokine receptor signalling. | pathogenic strains of bacillus anthracis produce two potent toxins, lethal toxin (lt), a metalloprotease that cleaves mitogen-activated protein kinase kinases, and oedema toxin (et), a calcium/calmodulin-dependent adenylate cyclase. emerging evidence indicates a role for both toxins in suppressing the initiation of both innate and adaptive immune responses, which are essential to keep the infection under control. here we show that lt and et inhibit chemotaxis of t-cells and macrophages by subver ... | 2007 | 17087730 |
| assessing surveillance using sensitivity, specificity and timeliness. | monitoring ongoing processes of illness to detect sudden changes is an important aspect of practical epidemiology and medicine more generally. most commonly, the monitoring has been restricted to a unidimensional stream of data over time. in such situations, analytic results from the industrial process monitoring have suggested optimal approaches to monitor the data streams. data streams including spatial location as well as temporal sequence are becoming available. monitoring methods that incor ... | 2006 | 17089948 |
| strain-specific single-nucleotide polymorphism assays for the bacillus anthracis ames strain. | highly precise diagnostics and forensic assays can be developed through a combination of evolutionary analysis and the exhaustive examination of genomic sequences. in bacillus anthracis, whole-genome sequencing efforts revealed ca. 3,500 single-nucleotide polymorphisms (snps) among eight different strains and evolutionary analysis provides the identification of canonical snps. we have previously shown that snps are highly evolutionarily stable, and the clonal nature of b. anthracis makes them id ... | 2007 | 17093023 |
| high throughput screening for spores and vegetative forms of pathogenic b. anthracis by an internally controlled real-time pcr assay with automated dna preparation. | human infections with bacillus anthracis have become rare but in cases of intentional release, masses of samples would have to be expected. current pcr assays for anthrax are appropriate for use in single cases, but they have not been formulated for high throughput screening. this article describes a high throughput real-time pcr for anthrax, including automated sample preparation without the need for pre-culturing of samples. the assay detects single copies of target gene. an internal control m ... | 2007 | 17093976 |
| lethal and edema toxins in the pathogenesis of bacillus anthracis septic shock: implications for therapy. | recent research regarding the structure and function of bacillus anthracis lethal (letx) and edema (etx) toxins provides growing insights into the pathophysiology and treatment of shock with this lethal bacteria. these are both binary-type toxins composed of protective antigen necessary for their cellular uptake and either lethal or edema factors, the toxigenic moieties. the primary cellular receptors for protective antigen have been identified and constructed and key steps in the extracellular ... | 2007 | 17095744 |
| crystal structure of bacillus cereus hlyiir, a transcriptional regulator of the gene for pore-forming toxin hemolysin ii. | production of bacillus cereus and bacillus anthracis toxins is controlled by a number of transcriptional regulators. here we report the crystal structure of b. cereus hlyiir, a regulator of the gene encoding the pore-forming toxin hemolysin ii. we show that hlyiir forms a tight dimer with a fold and overall architecture similar to the tetr family of repressors. a remarkable feature of the structure is a large internal cavity with a volume of 550 a(3) suggesting that the activity of hlyiir is mod ... | 2007 | 17097673 |
| complement and the multifaceted functions of vwa and integrin i domains. | the recent crystal structure of complement protein component c2a reveals an interface between its vwa and serine protease domains that could not exist in the zymogen c2. the implied change in vwa domain conformation between c2 and c2a differs from that described for other vwa domains, including the i domains in integrins. here, the remarkable diversity in both conformational regulation and ligand binding among vwa domains that function in complement, hemostasis, cell adhesion, anthrax toxin bind ... | 2006 | 17098186 |
| lysine methylation as a routine rescue strategy for protein crystallization. | crystallization remains a critical step in x-ray structure determination. because it is not generally possible to rationally predict crystallization conditions, commercial screens have been developed which sample a wide range of crystallization space. while this approach has proved successful in many cases, a significant number of proteins fail to crystallize despite being soluble and monodispersed. it is established that chemical modification can facilitate the crystallization of otherwise intr ... | 2006 | 17098187 |
| n/c-4 substituted azetidin-2-ones: synthesis and preliminary evaluation as new class of antimicrobial agents. | a series of 3-chloro-4-(3-methoxy-4-acetyloxyphenyl)-1-[3-oxo-3-(phenylamino)propanamido] azetidin-2-ones 3a-g and 3-chloro-4-[2-hydroxy-5-(nitro substituted phenylazo)phenyl]-1-phenylazetidin-2-ones 6a-h were synthesized using appropriate synthetic route. structures of all the synthesized compounds were established on the basis of elemental analysis and spectroscopic data. the antimicrobial activity of the synthesized compounds was screened against several microbes. several of these molecules s ... | 2007 | 17098426 |
| anthrax: a disease in waiting? | anthrax was a relatively unknown disease in the western world until 2001, when spores were maliciously mailed in the us, causing five deaths. the mortality of the disease, the stability of its spores and the subsequent lack of person-to-person spread make anthrax an attractive biological weapon for terrorists with a desire for targeted mass destruction. | 2006 | 17099096 |
| sentencing. enhanced sentence for hiv-positive inmate affirmed. | | 2006 | 17099962 |
| insertion of anthrax protective antigen into liposomal membranes: effects of a receptor. | protective antigen (pa), the receptor-binding component of anthrax toxin, heptamerizes and inserts into the endosomal membrane at acidic ph, forming a pore that mediates translocation of the enzymic components of the toxin to the cytosol. when the heptameric pre-insertion form of pa (the prepore) is acidified in solution, it rapidly loses the ability to insert into membranes. to maximize insertion into model membranes, we examined two ways to bind the protein to large unilamellar vesicles (luv). ... | 2007 | 17107945 |
| inhalational anthrax. | inhalational anthrax is a lethal infection acquired from the inhalation of bacillus anthracis, a pathogen classified as a category a bioterrorist agent by the centers for disease control and prevention. the recent 2001 attack in which weaponized spores were delivered by mail to several us cities exposed our vulnerability to bioterrorism, and taught us important lessons in the timely diagnosis of this devastating disease. it is clear that patient mortality is significantly decreased by early reco ... | 2006 | 17110848 |
| morphogenesis of the bacillus anthracis spore. | bacillus spp. and clostridium spp. form a specialized cell type, called a spore, during a multistep differentiation process that is initiated in response to starvation. spores are protected by a morphologically complex protein coat. the bacillus anthracis coat is of particular interest because the spore is the infective particle of anthrax. we determined the roles of several b. anthracis orthologues of bacillus subtilis coat protein genes in spore assembly and virulence. one of these, cote, has ... | 2007 | 17114257 |
| aluminum adjuvant linked to gulf war illness induces motor neuron death in mice. | gulf war illness (gwi) affects a significant percentage of veterans of the 1991 conflict, but its origin remains unknown. associated with some cases of gwi are increased incidences of amyotrophic lateral sclerosis and other neurological disorders. whereas many environmental factors have been linked to gwi, the role of the anthrax vaccine has come under increasing scrutiny. among the vaccine's potentially toxic components are the adjuvants aluminum hydroxide and squalene. to examine whether these ... | 2007 | 17114826 |
| [wedding and anthrax]. | | 2006 | 17117209 |
| dna microarray for detection of antibiotic resistance determinants in bacillus anthracis and closely related bacillus cereus. | we developed a multiplex pcr for amplification of ten genes involved in resistance to ciprofloxacin, doxycycline, rifampin, and vancomycin in bacillus anthracis and closely related bacillus cereus. enzymatic labelling of pcr products followed by hybridization to oligonucleotide probes on a dna microarray enabled simultaneous detection of resistance genes tetk, tetl, tetm, teto, vana, and vanb and resistance-mediating point mutations in genes gyra, gyrb, parc, and rpob. the presented assay allows ... | 2007 | 17118627 |
| anthrax, but not bacillus anthracis? | | 2006 | 17121463 |
| operon prediction for sequenced bacterial genomes without experimental information. | various computational approaches have been proposed for operon prediction, but most algorithms rely on experimental or functional data that are only available for a small subset of sequenced genomes. in this study, we explored the possibility of using phylogenetic information to aid in operon prediction, and we constructed a bayesian hidden markov model that incorporates comparative genomic data with traditional predictors, such as intergenic distances. the prediction algorithm performs as well ... | 2007 | 17122389 |
| evaluation of a wipe surface sample method for collection of bacillus spores from nonporous surfaces. | polyester-rayon blend wipes were evaluated for efficiency of extraction and recovery of powdered bacillus atrophaeus spores from stainless steel and painted wallboard surfaces. method limits of detection were also estimated for both surfaces. the observed mean efficiency of polyester-rayon blend wipe recovery from stainless steel was 0.35 with a standard deviation of +/-0.12, and for painted wallboard it was 0.29 with a standard deviation of +/-0.15. evaluation of a sonication extraction method ... | 2007 | 17122390 |
| maasai perception of the impact and incidence of malignant catarrhal fever (mcf) in southern kenya. | we investigated the perceived impact of malignant catarrhal fever (mcf) to pastoralists in isinya division, a wildlife dispersal area of nairobi national park, and used a range of participatory epidemiology methodologies. we compared the relative importance, incidence and impact of mcf compared to other locally defined important diseases with a total of 158 respondents in 11 group meetings and 21 household meetings in july 2004. direct losses due to disease were investigated through lowered pric ... | 2007 | 17123651 |
| evaluation of bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs. | bacillus anthracis, which causes anthrax, has attracted attention because of its potential use as a biological weapon. the risk of multidrug resistance against b. anthracis increases the need for antibiotics with new molecular targets. nucleoside analogs are well-known antiviral and anticancer prodrugs, and thymidine kinase catalyzes the rate-limiting step in the activation of pyrimidine nucleoside analogs used in chemotherapy. the thymidine kinase gene from b. anthracis sterne strain (34f2) (ba ... | 2006 | 17132103 |
| anthrax pathogen evades the mammalian immune system through stealth siderophore production. | systemic anthrax, caused by inhalation or ingestion of bacillus anthracis spores, is characterized by rapid microbial growth stages that require iron. tightly bound and highly regulated in a mammalian host, iron is scarce during an infection. to scavenge iron from its environment, b. anthracis synthesizes by independent pathways two small molecules, the siderophores bacillibactin (bb) and petrobactin (pb). despite the great efficiency of bb at chelating iron, pb may be the only siderophore neces ... | 2006 | 17132740 |
| plasmid: a centralized repository for plasmid clone information and distribution. | the plasmid information database (plasmid; http://plasmid.hms.harvard.edu) was developed as a community-based resource portal to facilitate search and request of plasmid clones shared with the dana-farber/harvard cancer center (df/hcc) dna resource core. plasmid serves as a central data repository and enables researchers to search the collection online using common gene names and identifiers, keywords, vector features, author names and pubmed ids. as of october 2006, the repository contains >46 ... | 2007 | 17132831 |
| synthesis and antigenic analysis of the bcla glycoprotein oligosaccharide from the bacillus anthracis exosporium. | the glycoprotein bcla is an important constituent of the exosporium of bacillus anthracis spores. this glycoprotein is substituted with an oligosaccharide composed of a beta-l-rhamnoside substituted with the previously unknown terminal saccharide, 2-o-methyl-4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-d-glucopyranose, also referred to as anthrose. anthrose has not been found in spores of b. cereus and b. thuringiensis, making it a potential species-specific marker for b. anthracis. in order to ... | 2006 | 17133642 |
| ecopathological approach in tropical countries: a challenge in intensified production systems. | from the 1960s, in developed countries, epidemiological approach widened in veterinary sciences in order to understand and analyze the emergence of "production diseases" in "modern farms" where animal management was compared to industrial process. this approach was linked to "productivism" in livestock farming system. in france, this approach included formerly the understanding of farmers' practices and considered the health disorders as an output of farming system. this theory was known as "eco ... | 2006 | 17135503 |
| cpg oligonucleotides improve the protective immune response induced by the licensed anthrax vaccine. | synthetic oligodeoxynucleotides (odn) containing unmethylated cpg motifs act as immune adjuvants, improving the response elicited by a coadministered vaccine. combining cpg odn with anthrax vaccine adsorbed (ava, the licensed human vaccine) increases the speed, magnitude, and avidity of the resultant antibody response. igg abs against anthrax protective antigen (pa) protect mice, guinuea pigs, and rhesus macaques from infection. | 2006 | 17145935 |
| oral administration of a salmonella enterica-based vaccine expressing bacillus anthracis protective antigen confers protection against aerosolized b. anthracis. | bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. protection against anthrax is primarily afforded by immunity to the b. anthracis protective antigen (pa), particularly pa domains 4 and 1. to further the development of an orally delivered human vaccine for mass vaccination against anthrax, we produced salmonella enterica serovar typhimurium expressing full-length pa, pa domains 1 and 4, or pa domain 4 using codon-optimized pa dna fused ... | 2007 | 17145938 |
| the impact of incomplete vaccination schedules on the magnitude and duration of protective antigen-specific igg responses in recipients of the us licensed anthrax vaccine. | using a cross-sectional analysis design, we measured serum anti-protective antigen (pa) concentrations in individuals receiving six or fewer us licensed anthrax vaccinations. samples were collected from 363 individuals with a mean of 29.6+/-8.42 months after their last vaccination (range 3-57 months). an enzyme-linked immunosorbent assay (elisa) developed and validated by the centers for disease control and prevention (cdc) was used to evaluate the range and status of anthrax vaccine-induced ser ... | 2007 | 17150286 |
| discontinued drugs in 2005: anti-infectives. | this perspective is the fifth in a series discussing drugs dropped from development in 2005, of which 11 were being developed for infectious diseases. of these, eight were antivirals and were dropped in phase ii or iii: medivir's alovudine, ono pharmaceuticals' aplaviroc hydrochloride and excite's immunotherapeutic xcellerate for hiv; boehringer ingelheim's ciluprevir, viropharma's hcv-086, isis pharmaceuticals' antisense oligonucleotide isis-14803, japan tobacco's jtk-003 and rigel's r803 for h ... | 2007 | 17155849 |
| a fully integrated microfluidic genetic analysis system with sample-in-answer-out capability. | we describe a microfluidic genetic analysis system that represents a previously undescribed integrated microfluidic device capable of accepting whole blood as a crude biological sample with the endpoint generation of a genetic profile. upon loading the sample, the glass microfluidic genetic analysis system device carries out on-chip dna purification and pcr-based amplification, followed by separation and detection in a manner that allows for microliter samples to be screened for infectious patho ... | 2006 | 17159153 |
| the design of inhibitors for medicinally relevant metalloproteins. | a number of metalloproteins are important medicinal targets for conditions ranging from pathogenic infections to cancer. many but not all of these metalloproteins contain a zinc(ii) ion in the protein active site. small-molecule inhibitors of these metalloproteins are designed to bind directly to the active site metal ions. in this review several metalloproteins of interest are discussed, including matrix metalloproteinases (mmps), histone deacetylases (hdacs), anthrax lethal factor (lf), and ot ... | 2007 | 17163561 |
| adenovirus-based prime-boost immunization for rapid vaccination against anthrax. | prime-boost vaccination using plasmid dna and replication-defective adenovirus vectors has emerged as a highly effective strategy for vaccinating against viral pathogens. however, its ability to provide protection against bacterial disease has never been assessed. here we evaluate prime-boost vaccination approaches for immunizing against anthrax. we show that mice primed with dna and boosted with an adenovirus vector, both expressing domain four of bacillus anthracis protective antigen (pa), hav ... | 2007 | 17164792 |
| [use of variable-number tandem repeats to examine genetic diversity of bacillus anthracis]. | to study the genotyping of bacillus anthracis based on multiple-locus variable-number tandem repeats(vntr) in the b. anthracis genome. | 2006 | 17172115 |
| data vs conclusions in the optic neuritis vaccination investigation. | | 2006 | 17172627 |
| radiology of biological weapons--old and the new? | | 2007 | 17174174 |
| metal binding studies and epr spectroscopy of the manganese transport regulator mntr. | manganese transport regulator (mntr) is a member of the diphtheria toxin repressor (dtxr) family of transcription factors that is responsible for manganese homeostasis in bacillus subtilis. prior biophysical studies have focused on the metal-mediated dna binding of mntr [lieser, s. a., davis, t. c., helmann, j. d., and cohen, s. m. (2003) biochemistry 42, 12634-12642], as well as metal stabilization of the mntr structure [golynskiy, m. v., davis, t. c., helmann, j. d., and cohen, s. m. (2005) bi ... | 2006 | 17176058 |
| synthetic small molecule furin inhibitors derived from 2,5-dideoxystreptamine. | furin plays a crucial role in embryogenesis and homeostasis and in diseases such as alzheimer's disease, cancer, and viral and bacterial infections. thus, inhibition of furin may provide a feasible and promising approach for therapeutic intervention of furin-mediated disease mechanisms. here, we report on a class of small molecule furin inhibitors based on 2,5-dideoxystreptamine. derivatization of 2,5-dideoxystreptamine by the addition of guanidinylated aryl groups yielded a set of furin inhibit ... | 2006 | 17179036 |
| silence: a new forward genetic technology. | silencing induced by long terminal repeat (ltr)-encoded cis-acting response element, termed silence, is a forward genetic system that allows for conditional, epigenetic control of host-gene transcription. this new research tool is independent of gene mutation or disruption, does not require complementation, and conditional gene repression appears complete at the level of protein function. silence functions in hypodiploid cells and is a platform technology with broad applications in gene discover ... | 2007 | 17179935 |
| ultrastructural features of lymphocyte suppression induced by anthrax lethal toxin and treated with chloroquine. | antibacterial therapy does not fully protect against anthrax because of severe systemic intoxication. lysosomal processing of anthrax lethal toxin (ltx) is a key event in the disease pathogenesis, and agents interfering with this process, like chloroquine (cq), may have practical applications. although ltx is known to induce t-cell suppression, precise mechanisms of this phenomenon are not completely characterized. in the present study, we investigated alterations of lymphocyte ultrastructure ca ... | 2007 | 17179957 |
| the rule of law and bioterrorism. | bioterrorism is multi-faceted. its impact will extend beyond the victims, the agent used, and the perpetrator(s). the rule of law must be considered in the wake of september 11 and the fall 2001 anthrax attacks. bioterrorism preparedness should address rule of law and social issues. laboratory professionals must be prepared for professional, civil justice, and social impact in the event of a future major bioweapons event. | 2006 | 17181122 |
| the 1.6 a crystal structure of the catalytic domain of plyb, a bacteriophage lysin active against bacillus anthracis. | lysins are peptidoglycan hydrolases that are produced by bacteriophage and act to lyse the bacterial host cell wall during progeny phage release. here, we describe the structure and function of a novel bacteriophage-derived lysin, plyb, which displays potent lytic activity against the bacillus anthracis-like strain atcc 4342. this molecule comprises an n-terminal catalytic domain (plyb(cat)) and a c-terminal bacterial sh3-like domain, sh3b. it is shown that both domains are required for effectiv ... | 2007 | 17182056 |
| divalent metal ion coordination by residue t118 of anthrax toxin receptor 2 is not essential for protective antigen binding. | the protective antigen (pa) subunit of anthrax toxin interacts with the integrin-like i domains of either of two cellular receptors, antxr1 or antxr2. these i domains contain a metal ion-dependent adhesion site (midas) made up of five non-consecutive amino acid residues that coordinate a divalent metal ion that is important for pa-binding. the midas residues of integrin i domains shift depending upon whether the domain exists in a closed (ligand-unbound) or open (ligand-bound) conformation. of r ... | 2006 | 17183731 |
| chloroplast-derived anthrax and other vaccine antigens: their immunogenic and immunoprotective properties. | transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation, heat stability, absence of human pathogens, protection of antigens in the stomach through bioencapsulation (when delivered orally), elimination of the need for expensive purification and sterile injections and generation of both systemic and mucosal immunity. recent studies have demonstrated that chloroplast-derived anthrax-protective antigen elicits effective imm ... | 2006 | 17184221 |
| virulent spores of bacillus anthracis and other bacillus species deposited on solid surfaces have similar sensitivity to chemical decontaminants. | to compare the relative sensitivity of bacillus anthracis and spores of other bacillus spp. deposited on different solid surfaces to inactivation by liquid chemical disinfecting agents. | 2007 | 17184315 |
| biosynthetic analysis of the petrobactin siderophore pathway from bacillus anthracis. | the asbabcdef gene cluster from bacillus anthracis is responsible for biosynthesis of petrobactin, a catecholate siderophore that functions in both iron acquisition and virulence in a murine model of anthrax. we initiated studies to determine the biosynthetic details of petrobactin assembly based on mutational analysis of the asb operon, identification of accumulated intermediates, and addition of exogenous siderophores to asb mutant strains. as a starting point, in-frame deletions of each of th ... | 2007 | 17189355 |
| the alternative sigma factor sigmah is required for toxin gene expression by bacillus anthracis. | expression of the structural genes for the anthrax toxin proteins is coordinately controlled by host-related signals, such as elevated co(2), and the trans-acting positive regulator atxa. in addition to these requirements, toxin gene expression is under growth phase regulation. the transition state regulator abrb represses atxa expression to influence toxin synthesis. during the late exponential phase of growth, when abrb levels begin to decrease, toxin synthesis increases. here we report that t ... | 2007 | 17189374 |
| systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. | anthrax lethal toxin (letx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (mapk) kinases and inhibits the mapk signaling pathways. the majority of metastatic melanomas possess the v599e braf mutation, which constitutively activates mapk1/2 signaling. letx is cytotoxic to braf mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. in this study, we determine the in vivo potency and safety of systemica ... | 2006 | 17189417 |
| learning from the 2001 anthrax attacks: immunological characteristics. | | 2007 | 17191158 |
| the us capitol bioterrorism anthrax exposures: clinical epidemiological and immunological characteristics. | bioterrorism-related anthrax exposures occurred at the us capitol in 2001. exposed individuals received antibiotics and anthrax vaccine adsorbed immunization. | 2007 | 17191162 |
| anticipating demand for emergency health services due to medication-related adverse events after rapid mass prophylaxis campaigns. | mass prophylaxis against infectious disease outbreaks carries the risk of medication-related adverse events (mraes). the authors sought to define the relationship between the rapidity of mass prophylaxis dispensing and the subsequent demand for emergency health services due to predictable mraes. | 2007 | 17192445 |
| structural investigation of the glms ribozyme bound to its catalytic cofactor. | the glms riboswitch is located in the 5'-untranslated region of the gene encoding glucosamine-6-phosphate (glcn6p) synthetase. the glms riboswitch is a ribozyme with activity triggered by binding of the metabolite glcn6p. presented here is the structure of the glms ribozyme (2.5 a resolution) with glcn6p bound in the active site. the glms ribozyme adopts a compact double pseudoknot tertiary structure, with two closely packed helical stacks. recognition of glcn6p is achieved through coordination ... | 2007 | 17196404 |