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early events of bacillus anthracis germination identified by time-course quantitative proteomics.germination of bacillus anthracis spores involves rehydration of the spore interior and rapid degradation of several of the protective layers, including the spore coat. here, we examine the temporal changes that occur during b. anthracis spore germination using an isobaric tagging system. over the course of 17 min from the onset of germination, the levels of at least 19 spore proteins significantly decrease. included are acid-soluble proteins, several known and predicted coat proteins, and prote ...200616927434
[isolation and identification of bacillus anthracis in an accidental case].during june to july 2005, a few farmers in chengde county of hebei province were got ill after eating beef of sick cattle. the cattle could be infected with bacillus anthracis. one beef sample and one soil sample contaminated with cattle blood were collected and used for pathogen isolation and identification in laboratory. two bacteria strains were isolated from beef and soil sample, respectively, and showed typical morphology of bacillus anthracis on blood agar and under microscope with gram st ...200616933621
the exsy protein is required for complete formation of the exosporium of bacillus anthracis.the outermost layer of the bacillus anthracis spore is the exosporium, which is composed of a paracrystalline basal layer and an external hair-like nap. the filaments of the nap are formed by a collagen-like glycoprotein called bcla, while the basal layer contains several different proteins. one of the putative basal layer proteins is exsy. in this study, we constructed a deltaexsy mutant of b. anthracis, which is devoid of exsy, and examined the assembly of the exosporium on spores produced by ...200616936017
polyvalent inhibitors of anthrax toxin that target host receptors.resistance of pathogens to antimicrobial therapeutics has become a widespread problem. resistance can emerge naturally, but it can also be engineered intentionally, which is an important consideration in designing therapeutics for bioterrorism agents. blocking host receptors used by pathogens represents a powerful strategy to overcome this problem, because extensive alterations to the pathogen may be required to enable it to switch to a new receptor that can still support pathogenesis. here, we ...200616938891
images in clinical medicine. anthrax of the cecum. 200616943406
model of the toxic complex of anthrax: responsive conformational changes in both the lethal factor and the protective antigen heptamer.the toxic complex of anthrax is formed when the monomeric protective antigen (pa) (83 kda), while bound to its cell-surface receptor, is first converted to pa63 heptamers (pa63h) following n-terminal proteolytic cleavage, and then lethal (lf) (90 kda) or edema factor (ef) binds to the heptamer. we report a "pseudoatomic" model for the complex of pa63h and full-length lf determined by applying the normal-mode flexible fitting procedure to a approximately 18 a cryo-electron microscopy (em) density ...200616943448
a case of human cutaneous anthrax. 200616948627
new-onset rheumatoid arthritis after anthrax vaccination.anthrax vaccine was licensed in 1970 and is used to protect individuals exposed to biological warfare and those who may come in contact with bacillus anthracis in infected animals or in laboratory settings. the current adsorbed anthrax vaccine is regarded as effective and safe. adverse effects reported include fever, chills, myalgia, arthralgia, and nausea. four cases of rheumatoid arthritis (ra) temporally related to anthrax vaccine have been reported. as the number of administered doses increa ...200616892791
on the use of zero-inflated and hurdle models for modeling vaccine adverse event count data.we compared several modeling strategies for vaccine adverse event count data in which the data are characterized by excess zeroes and heteroskedasticity. count data are routinely modeled using poisson and negative binomial (nb) regression but zero-inflated and hurdle models may be advantageous in this setting. here we compared the fit of the poisson, negative binomial (nb), zero-inflated poisson (zip), zero-inflated negative binomial (zinb), poisson hurdle (ph), and negative binomial hurdle (nbh ...200616892908
submicron streptavidin patterns for protein assembly.micron and submicron-scale features of aldehyde functionality were fabricated in polymer films by photolithography to develop a platform for protein immobilization and assembly at a biologically relevant scale. films containing the ph-reactive polymer poly(3,3'-diethoxypropyl methacrylate) and a photoacid generator (pag) were patterned from 500 nm to 40 mum by exposure to 365 nm (i-line) light. upon pag activation and hydrolysis of acetals, aldehyde groups formed. after the films were incubated ...200616893251
quantitative measurement of anthrax toxin receptor messenger rna in primary mononuclear phagocytes.two anthrax toxin receptors have been identified, tumor endothelial marker 8 (tem8) and capillary morphogenesis protein 2 (cmg2). both receptors have been shown to be capable of facilitating the entry of bacillus anthracis exotoxins into the cytosol of susceptible cells. the levels of tem8 and cmg2 rna transcripts present in human primary macrophages derived from multiple unrelated donors and primary mouse macrophages have not been well described. in this communication, we examined the expressio ...200616854559
characterization of bacillus anthracis-like bacteria isolated from wild great apes from cote d'ivoire and cameroon.we present the microbiological and molecular characterization of bacteria isolated from four chimpanzees and one gorilla thought to have died of an anthrax-like disease in côte d'ivoire and cameroon. these isolates differed significantly from classic bacillus anthracis by the following criteria: motility, resistance to the gamma phage, and, for isolates from cameroon, resistance to penicillin g. a capsule was expressed not only after induction by co(2) and bicarbonate but also under normal growt ...200616855222
anthrax oedema toxin induces anthrax toxin receptor expression in monocyte-derived cells.bacillus anthracis, the causative agent of anthrax, secretes two bipartite toxins that help the bacterium evade the immune system and contribute directly to pathogenesis. both toxin catalytic moieties, lethal factor (lf) and oedema factor (of), are internalized into the host-cell cytosol by a third factor, protective antigen (pa), which binds to cellular anthrax toxin receptors (antxrs). oedema factor is an adenylate cyclase that impairs host defences by raising cellular camp levels. here we dem ...200616856939
anthrax: a systematic review of atypical presentations.during the 2001 us anthrax attacks, mortality from inhalational anthrax was significantly lower than had been reported historically, which was attributed in part to early identification and timely treatment. during future attacks, clinicians will rely on published descriptions of the clinical features of inhalational anthrax to rapidly diagnose patients and institute appropriate treatment. published descriptions of typical inhalation anthrax usually include patients presenting with cough, dyspne ...200616857469
a review of the interaction of bacillus anthracis with cells of the innate immune response.bacillus anthracis spores cause natural infections and can be used as biological weapons. the innate immune response is the first line of defence against invading pathogens and is likely to play a central role in this acute infection. to date the immune evasion mechanisms of b. anthracis are not well understood. infection by inhalation with b. anthracis, the etiological agent of anthrax, is almost always lethal, yet cutaneous infections usually remain localized and resolve spontaneously in the m ...200616729468
rapid discrimination of bacillus anthracis from other members of the b. cereus group by mass and sequence of "intact" small acid soluble proteins (sasps) using mass spectrometry.the intentional contamination of buildings, e.g. anthrax in the bioterrorism attacks of 2001, demonstrated that the population can be affected rapidly and lethally if the appropriate treatment is not provided at the right time. molecular approaches, primarily involving pcr, have proved useful in characterizing "white powders" used in these attacks as well as isolated organisms. however there is a need for a simpler approach, which does not involve temperamental reagents (e.g. enzymes and primers ...200616730083
topical immunization onto mouse skin using a microemulsion incorporated with an anthrax protective antigen protein-encoding plasmid.the current anthrax vaccine in the u.s., the anthrax vaccine adsorbed, has several serious drawbacks, most notably the very lengthy and complicated dosing schedule. thus, there is a critical need to develop an alternative anthrax vaccine with a simplified immunization schedule. to address this need, we evaluated the feasibility of topically priming or boosting onto the skin using an anthrax protective antigen (pa) protein-encoding dna vaccine. to this end, we have shown that topical immunization ...200616730934
emerging infectious disease outbreaks: old lessons and new challenges for obstetrician-gynecologists.the purpose of this study was to summarize 3 recent high-profile infectious disease threats that have affected the united states: severe acute respiratory syndrome, west nile virus, and anthrax.200616731070
anthrax meningoencephalitis secondary to oral infection. 200616732167
anthrax. 200616737110
modeling the effects of a staphylococcal enterotoxin b (seb) on the apoptosis pathway.the lack of detailed understanding of the mechanism of action of many biowarfare agents poses an immediate challenge to biodefense efforts. many potential bioweapons have been shown to affect the cellular pathways controlling apoptosis 1234. for example, pathogen-produced exotoxins such as staphylococcal enterotoxin b (seb) and anthrax lethal factor (lf) have been shown to disrupt the fas-mediated apoptotic pathway 24. to evaluate how these agents affect these pathways it is first necessary to u ...200616737533
a new bacillus anthracis found in wild chimpanzees and a gorilla from west and central africa. 200616738706
resident cd11c+ lung cells are impaired by anthrax toxins after spore infection.bacillus anthracis secretes 2 toxins: lethal toxin (lt) and edema toxin (et). we investigated their role in the physiopathologic mechanisms of inhalational anthrax by evaluating murine lung dendritic cell (ldc) functions after infection with b. anthracis strains secreting lt, et, or both or with a nontoxinogenic strain. three lung cell populations gated on cd11c/cd11b expression were obtained after lung digestion: (1) cd11c(high)/cd11b(low) (alveolar macrophages), (2) cd11c(intermediate (int))/c ...200616741886
anthrax toxins: a paradigm of bacterial immune suppression.several species of microorganism have developed immune evasion and/or immunosuppression strategies. bacillus anthracis secretes two toxins, edema toxin and lethal toxin, that enter the cytosol of almost every cell type, including the cells of the innate and adaptive immune systems, and subvert cell signaling. edema toxin causes a consistent elevation of cyclic adenosine monophosphate, whereas lethal toxin cleaves most isoforms of mitogen-activated protein kinase kinases. in a concerted manner, t ...200616861036
paired bacillus anthracis dps (mini-ferritin) have different reactivities with peroxide.dps (dna protection during starvation) proteins, mini-ferritins in the ferritin superfamily, catalyze fe(2+)/h(2)o(2)/o(2) reactions and make minerals inside protein nanocages to minimize radical oxygen-chemistry (metal/osmotic/temperature/nutrient/oxidant) and sometimes to confer virulence. paired dps proteins in bacillus, rare in other bacteria, have 60% sequence identity. to explore functional differences in paired bacilli dps protein, we measured ferroxidase activity and dna protection (hydr ...200616861227
bacillus anthracis spores stimulate cytokine and chemokine innate immune responses in human alveolar macrophages through multiple mitogen-activated protein kinase pathways.contact with the human alveolar macrophage plays a key role in the innate immune response to bacillus anthracis spores. because there is a significant delay between the initial contact of the spore with the host and clinical evidence of disease, there appears to be temporary containment of the pathogen by the innate immune system. therefore, the early macrophage response to bacillus anthracis exposure is important in understanding the pathogenesis of this disease. in this paper, we studied the i ...200616861629
additional conjugation methods and immunogenicity of bacillus anthracis poly-gamma-d-glutamic acid-protein conjugates.the capsule of bacillus anthracis, composed of poly-gamma-d-glutamic acid (gammadpga), is an essential virulence factor of b. anthracis. the capsule inhibits innate host defense through its antiphagocytic action. gammadpga is a poor immunogen, but when covalently bound to a carrier protein, it elicits serum antibodies. to identify the optimal construct for clinical use, synthetic gammadpgas of different lengths were bound to carrier proteins at different densities. the advantages of the syntheti ...200616861662
pharmacokinetics, metabolism, excretion and plasma protein binding of 14c-levofloxacin after a single oral administration in the rhesus monkey.levofloxacin's metabolism, excretion, and in vitro plasma protein binding, together with its pharmacokinetics, were studied in the rhesus monkey in support of an anthrax efficacy study in this species. three males and three female rhesus monkeys were dosed with a single oral dose of 14c-levofloxacin at 15 mg kg-1 (2 mbq kg-1). following dose administration, blood samples were collected up to 48 h post-dose, and urine and faeces were quantitatively collected up to 168 h post-dose. blood, plasma, ...200616864506
preparation and evaluation of spore-specific affinity-augmented bio-imprinted beads.a novel, affinity-augmented, bacterial spore-imprinted, bead material was synthesized, based on a procedure developed for vegetative bacteria. the imprinted beads were intended as a front-end spore capture/concentration stage of an integrated biological detection system. our approach involved embedding bead surfaces with bacillus thuringiensis kurstaki (bt) spores (as a surrogate for bacillus anthracis) during synthesis. subsequent steps involved lithographic deactivation using a perfluoroether; ...200616865337
growth characteristics of virulent bacillus anthracis and potential surrogate strains.the objectives of this study were to compare generation and lag times of virulent bacillus anthracis strains with those of other bacillus strains, to identify possible surrogates for growth studies, and to determine if the b. cereus module of the u.s. department of agriculture pathogen modeling program (pmp) had predictive value for b. anthracis. growth characteristics of b. anthracis, b. cereus, b. mycoides, and b. subtilis strains in brain heart infusion broth at ph 6.5, 6.0, and 5.5 were dete ...200616865910
comparison of pcr, culture and microscopy of blood smears for the diagnosis of anthrax in sheep and cattle.to compare microscopy, culture and pcr for the diagnosis of anthrax in blood samples from sheep and cattle.200616869902
selectively guanidinylated derivatives of neamine. syntheses and inhibition of anthrax lethal factor protease.a series of mono-, di-, and tri-guanidinylated derivatives of neamine were prepared via selective guanidinylation of neamine. these molecules represent a novel scaffold as inhibitors of anthrax lethal factor zinc metalloprotease. methods for the synthesis of these compounds are described, and structure-activity relationships among the series are analyzed. in addition, initial findings regarding the mechanism of lf inhibition for these molecules are presented.200616870442
the structure of the major cell wall polysaccharide of bacillus anthracis is species-specific.in this report we describe the structure of the polysaccharide released from bacillus anthracis vegetative cell walls by aqueous hydrogen fluoride (hf). this hf-released polysaccharide (hf-ps) was isolated and structurally characterized from the ames, sterne, and pasteur strains of b. anthracis. the hf-pss were also isolated from the closely related bacillus cereus atcc 10987 strain, and from the b. cereus atcc 14579 type strain and compared with those of b. anthracis. the structure of the b. an ...200616870610
cisplatin inhibition of anthrax lethal toxin.bacillus anthracis lethal toxin (lt) produces symptoms of anthrax in mice and induces rapid lysis of macrophages derived from certain inbred strains. lt is comprised of a receptor binding component, protective antigen (pa), which delivers the enzymatic component, lethal factor (lf), into cells. we found that mouse macrophages were protected from toxin by the antitumor drug cis-diammineplatinum (ii) dichloride (cisplatin). cisplatin was shown to inhibit lt-mediated cleavage of cellular mitogen-ac ...200616870755
modulation of cytokine production and enhancement of cell viability by tlr7 and tlr9 ligands during anthrax infection of macrophages.inhalation of bacillus anthracis, a bioterrorism agent, results in a high mortality rate despite appropriate antibiotic therapy. macrophages appear to be a key factor in b. anthracis pathogenesis. the burst of pro-inflammatory cytokines from macrophages could be a major cause of death in anthrax. however, preactivation of toll-like receptors (tlrs) could modify the host response. tlr ligands stimulate the release of activating cytokines but may also down-modulate the subsequent deleterious cytok ...200616872373
production and characterization of neutralizing monoclonal antibodies that recognize an epitope in domain 2 of bacillus anthracis protective antigen.antibodies against the protective antigen (pa) of bacillus anthracis play a key role in response to infection by this important pathogen. the aim of this study was to produce and characterize monoclonal antibodies (mabs) specific for pa and to identify novel neutralizing epitopes. three murine mabs with high specificity and nanomolar affinity for b. anthracis recombinant protective antigen (rpa) were produced and characterized. western immunoblot analysis, coupled with epitope mapping using over ...200616872381
surgical infection society guidelines for vaccination after traumatic injury.recommendations for vaccination of injured patients against infection are evolving. newly-recognized infections, safety considerations, changing epidemiology, and redefinition of patient groups at risk are factors that may influence vaccine development priorities and recommendations for immunization. however, recommendations must often be formulated based on incomplete data, forcing reliance on expert opinion to address some crucial questions. these guidelines provide evidence-based recommendati ...200616875461
siderophores of bacillus anthracis, bacillus cereus, and bacillus thuringiensis.three bacillus anthracis sterne strains (usamriid, 7702, and 34f2) and bacillus cereus atcc 14579 excrete two catecholate siderophores, petrobactin (which contains 3,4-dihydroxybenzoyl moieties) and bacillibactin (which contains 2,3-dihydroxybenzoyl moieties). however, the insecticidal organism bacillus thuringiensis atcc 33679 makes only bacillibactin. analyses of siderophore production by previously isolated [cendrowski et al., mol. microbiol. 52 (2004) 407-417] b. anthracis mutant strains rev ...200616875672
nurses' beliefs about public health emergencies: fear of abandonment.since the events of september 11, 2001, subsequent anthrax mailings, world political events, and natural disasters such as hurricane katrina and the recent tsunami, public health emergencies including bioterrorism events are viewed as realistic possibilities. public health emergencies would stress the current health care system.200616877103
sepsis and pathophysiology of anthrax in a nonhuman primate model.studies that define natural responses to bacterial sepsis assumed new relevance after the lethal bioterrorist attacks with bacillus anthracis (anthrax), a spore-forming, toxigenic gram-positive bacillus. considerable effort has focused on identifying adjunctive therapeutics and vaccines to prevent future deaths, but translation of promising compounds into the clinical setting necessitates an animal model that recapitulates responses observed in humans. here we describe a nonhuman primate (papio ...200616877346
[anthrax revisited: bacillus anthracis toxins as novel actors of immune escape?].the recent bioterrorist attacks have stressed the need of a better knowledge of bacillus anthracis infection pathophysiology. we present here the increasing interests of b. anthracis studies in term of bio-defense, the main pathogen characteristics, the main clinical features of inhalational anthrax (the pulmonary form of the disease), and recent aspects of its physiopathology. next, we address the main results concerning the toxin effects on immune system through impairing the dendritic cell fu ...200616878452
ultrastable substrates for surface-enhanced raman spectroscopy: al2o3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection.a new method to stabilize and functionalize surfaces for surface-enhanced raman spectroscopy (sers) is demonstrated. atomic layer deposition (ald) is used to deposit a sub-1-nm alumina layer on silver film-over-nanosphere (agfon) substrates. the resulting overlayer maintains and stabilizes the sers activity of the underlying silver while presenting the surface chemistry of the alumina overlayer, a commonly used polar adsorbent in chromatographic separations. the relative affinity of analytes for ...200616881662
cytotoxic activity of bacillus anthracis protective antigen observed in a macrophage cell line overexpressing antxr1.anthrax toxin protective antigen (pa) binds cell surface receptors (e.g. antxr1,2), forms heptameric pores, and translocates lethal factor (lf) or oedema factor (of) into the cytoplasm of mammalian cells. in the current study, we sought to determine how receptor levels influence these events, by examining pa heptamer stability and related processes in macrophages that overexpress antxr1 (raw 264.7antxr1). in these experiments, pa-oligomers demonstrated an extended half-life in raw 264.7antxr1 ma ...200616882031
biosynthesis of antitumoral and bactericidal sanguinarine.a simple, rapid, and reliable tlc method for the separation and determination of sanguinarine has been established. this intensively studied biologically active alkaloid has a wide range of potentially useful medicinal properties, such as antimicrobial, antiinflammatory, and antitumoral activities. sanguinarine has also been incorporated into expectorant mixtures and has a strong bactericidal effect upon gram-positive bacteria, particularly bacillus anthracis and staphylococci. these medicinal p ...200616883053
forensic application of microbiological culture analysis to identify mail intentionally contaminated with bacillus anthracis spores.the discovery of a letter intentionally filled with dried bacillus anthracis spores in the office of a united states senator prompted the collection and quarantine of all mail in congressional buildings. this mail was subsequently searched for additional intentionally contaminated letters. a microbiological sampling strategy was used to locate heavy contamination within the 642 separate plastic bags containing the mail. swab sampling identified 20 bags for manual and visual examination. air samp ...200616885280
diversity of bacillus anthracis strains in georgia and of vaccine strains from the former soviet union.despite the increased number of anthrax outbreaks in georgia and the other caucasian republics of the former soviet union, no data are available on the diversity of the bacillus anthracis strains involved. there is also little data available on strains from the former soviet union, including the strains previously used for vaccine preparation. in this study we used eight-locus variable-number tandem repeat analyses to genotype 18 strains isolated from infected animals and humans at different sit ...200616885320
symptomatic predictors of influenza virus positivity in children during the influenza season.symptomatic predictors of the etiology of infectious diseases are necessary when quick action is required in treatment, as with cases of influenza or anthrax, or for when patient isolation is required, as with cases of severe acute respiratory syndrome (sars). predictors of influenza virus infection during the influenza season have previously been evaluated in adult studies of the antiviral agent zanamivir; cough and temperature > or =37.8 degrees c predicted influenza virus positivity in 79% of ...200616886147
a 43-year-old colonel with chills, diaphoresis, and headache.the objectives were to illustrate the ease with which one might attribute concomitant or subsequent illness to an exposure such as the anthrax vaccine and to demonstrate an approach that keeps the significance of such exposures in appropriate perspective. a 43-year-old, active duty, army officer presents with a variety of nonspecific common symptoms and raises concerns about the relationship of his symptoms to receipt of the anthrax vaccine. he is admitted for an evaluation that includes a serie ...200616673751
synthesis of copolymers containing an active ester of methacrylic acid by raft: controlled molecular weight scaffolds for biofunctionalization.we report the controlled radical copolymerization of n-(2-hydroxypropyl)methacrylamide (hpma) with a monomer containing an active ester, n-methacryloyloxysuccinimide (nms), by reversible addition fragmentation chain transfer (raft). the large difference in the reactivity ratios of hpma and nms resulted in significant variations in copolymer composition with increasing conversion during batch copolymerization. the use of a semi-batch copolymerization method, involving the gradual addition of the ...200616677052
sverdlovsk revisited: modeling human inhalation anthrax.several models have been proposed for the dose-response function and the incubation period distribution for human inhalation anthrax. these models give very different predictions for the severity of a hypothetical bioterror attack, when an attack might be detected from clinical cases, the efficacy of medical intervention and the requirements for decontamination. using data from the 1979 accidental atmospheric release of anthrax in sverdlovsk, russia, and limited nonhuman primate data, this paper ...200616679412
cutaneous anthrax as an occupational disease in central anatolia, turkey. 200616680276
observing local and global properties of metabolic pathways: 'load points' and 'choke points' in the metabolic networks.the local and global aspects of metabolic network analyses allow us to identify enzymes or reactions that are crucial for the survival of the organism(s), therefore directing us towards the discovery of potential drug targets.200616682421
rapid, sensitive, and specific lateral-flow immunochromatographic device to measure anti-anthrax protective antigen immunoglobulin g in serum and whole blood.evidence from animals suggests that anti-anthrax protective antigen (pa) immunoglobulin g (igg) from vaccination with anthrax vaccine adsorbed (ava) is protective against bacillus anthracis infection. measurement of anti-pa igg in human sera can be performed using either enzyme-linked immunosorbent assay or fluorescent covalent microsphere immunoassay (elisa) (r. e. biagini, d. l. sammons, j. p. smith, b. a. mackenzie, c. a. striley, v. semenova, e. steward-clark, k. stamey, a. e. freeman, c. p. ...200616682473
thump from archaeal trna:m22g10 methyltransferase, a genuine autonomously folding domain.the trna:m2(2)g10 methyltransferase of pyrococus abyssi (pab1283, a member of cog1041) catalyzes the n2,n2-dimethylation of guanosine at position 10 in trna. boundaries of its thump (thiouridine synthases, rna methyltransferases and pseudo-uridine synthases)--containing n-terminal domain [1-152] and c-terminal catalytic domain [157-329] were assessed by trypsin limited proteolysis. an inter-domain flexible region of at least six residues was revealed. the n-terminal domain was then produced as a ...200616687654
dynamics of no rebinding to the heme domain of no synthase-like proteins from bacterial pathogens.some gram-positive bacterial pathogens harbor a gene that encodes a protein (hns, heme domain of no synthase-like proteins) with striking sequence identity to the oxygenase domain of mammalian no synthases (nos). however, they lack the n-terminal and the zn-cysteine motif participating to the stability of an active dimer in the mammalian isoforms. the unique properties of hns make it an excellent model system for probing how the heme environment tunes no dynamics and for comparing it to the endo ...200616690332
environmental survey for four pathogenic bacteria and closely related species using phylogenetic and functional genes.bacterial species with high dna sequence similarity to pathogens could affect the specificity of assays designed to detect biological threat agents in environmental samples. the natural presence of four pathogenic bacteria, bacillus anthracis, clostridium perfringens, francisella tularensis, and yersinia pestis and their closely related species, was determined for a large collection of soil and aerosol samples. polymerase chain reaction (pcr) and gene sequencing were used using group-specific 16 ...200616696701
composition of bacillus species in aerosols from 11 u.s. cities.a pcr-based heteroduplex assay was used to determine the presence and composition of bacillus species in 11,059 environmental protection agency pm2.5 aerosol samples from 11 u.s. cities. the assay differentiated three groups: type a containing bacillus anthracis and very closely related, often pathogenic, bacillus cereus and bacillus thuringiensis strains; type b containing other b. cereus and b. thuringiensis strains; and a third group of more-distantly related bacillus species. eight of the 11 ...200616696702
characterization of a permissive epitope insertion site in adenovirus hexon.a robust immune response is generated against components of the adenovirus capsid. in particular, a potent and long-lived humoral response is elicited against the hexon protein. this is due to the efficient presentation of adenovirus capsid proteins to cd4+ t cells by antigen-presenting cells, in addition to the highly repetitive structure of the adenovirus capsids, which can efficiently stimulate b-cell proliferation. in the present study, we take advantage of this immune response by inserting ...200616699016
manganese transport and the role of manganese in virulence.two areas of research have recently converged to highlight important roles for mn(2+) in pathogenesis: the recognition that both bacterial nramp homologs and members of lrai family of proteins are mn(2+) transporters. their mutation is associated with decreased virulence of various bacterial species. thus, mn(2+) appears to be essential for bacterial virulence. this review describes what is currently known about mn(2+) transport in prokaryotes and how prokaryotic mn(2+) transport is regulated. s ...200616704341
the superoxide dismutases of bacillus anthracis do not cooperatively protect against endogenous superoxide stress.the bacillus anthracis chromosome encodes four unique, putative superoxide dismutase (sod) genes. during exponential growth and sporulation, soda1, soda2, and sodc are transcribed constitutively throughout the growth cycle as individual genes. in contrast, the transcription of sod15 occurs mainly during late exponential and sporulation phases as part of a four-gene operon that may be involved in spore formation. vegetative cell and spore lysates of wild-type sterne and superoxide dismutase delet ...200616707676
confronting infectious diseases is a perpetual struggle, top official says. 200616709878
cutaneous anthrax, belgian traveler. 200616710982
blocking of an ion channel by a highly charged drug: modeling the effects of applied voltage, electrolyte concentration, and drug concentration.we present a simple physical model to estimate the blocked pore probability of an ion channel that can be blocked by a highly charged drug in solution. the model is inspired by recent experimental work on the blocking of the pa(63) channel, involved in the anthrax toxin infection, by a highly charged drug [karginov pnas 102, 15075 (2005)]. the drug binding to the pore is highly specific but the strong dependence of blocking on the applied voltage and electrolyte concentration suggests that long ...200616711843
topical application of escherichia coli-vectored vaccine as a simple method for eliciting protective immunity.we report here that animals can be protected against lethal infection by clostridium tetani cells and bacillus anthracis spores following topical application of intact particles of live or gamma-irradiated escherichia coli vectors overproducing tetanus and anthrax antigens, respectively. cutaneous gammadeltat cells were rapidly recruited to the administration site. live e. coli cells were not found in nonskin tissues after topical application, although fragments of e. coli dna were disseminated ...200616714593
nasal immunization with anthrax protective antigen protein adjuvanted with polyriboinosinic-polyribocytidylic acid induced strong mucosal and systemic immunities.the current anthrax vaccine adsorbed (ava) was originally licensed for the prevention of cutaneous anthrax infection. it has many drawbacks, including the requirement for multiple injections and subsequent annual boosters. thus, an easily administrable and efficacious anthrax vaccine is needed to prevent the most lethal form of anthrax infection, inhalation anthrax. we propose to develop a nasal anthrax vaccine using anthrax protective antigen (pa) protein as the antigen and synthetic double-str ...200616718616
recombinant viral-like particles of parvovirus b19 as antigen carriers of anthrax protective antigen.viral-like particles (vlps) of parvovirus b19 were employed as an antigen carrier to present antigenic determinants of bacillus anthracis. the small-loop peptide and the full-length domain 4 of protective antigen (pa) were chosen as immunogens for presentation on the vlp-capsid surface and subsequent immunization of balb/c mice. the recombinant vlps induced anti-pa igg titers of up to 2.5 x 10(4). neutralization assays showed that the recombinant vlps elicited neutralizing anti-pa antibody titer ...200616724664
bacillus anthracis toxins inhibit human neutrophil nadph oxidase activity.bacillus anthracis, the causative agent of anthrax, is a gram-positive, spore-forming bacterium. b. anthracis virulence is ascribed mainly to a secreted tripartite ab-type toxin composed of three proteins designated protective ag (pa), lethal factor, and edema factor. pa assembles with the enzymatic portions of the toxin, the metalloprotease lethal factor, and/or the adenylate cyclase edema factor, to generate lethal toxin (ltx) and edema toxin (etx), respectively. these toxins enter cells throu ...200616751402
evaluation of a macrofoam swab protocol for the recovery of bacillus anthracis spores from a steel surface.a protocol to recover bacillus anthracis spores from a steel surface using macrofoam swabs was evaluated for its accuracy, precision, reproducibility, and limit of detection. macrofoam swabs recovered 31.7 to 49.1% of spores from 10-cm2 steel surfaces with a < or =32.7% coefficient of variation in sampling precision and reproducibility for inocula of > or =38 spores.200616751562
thermal inactivation of bacillus anthracis spores in cow's milk.decimal reduction time (time to inactivate 90% of the population) (d) values of bacillus anthracis spores in milk ranged from 3.4 to 16.7 h at 72 degrees c and from 1.6 to 3.3 s at 112 degrees c. the calculated increase of temperature needed to reduce the d value by 90% varied from 8.7 to 11.0 degrees c, and the arrhenius activation energies ranged from 227.4 to 291.3 kj/mol. six-log-unit viability reductions were achieved at 120 degrees c for 16 s. these results suggest that a thermal process s ...200616751573
simultaneous identification and verification of bacillus anthracis.specific identification of bacillus anthracis (b. anthracis) is vital for the accurate treatment of afflicted personnel during biological warfare situations and civilian terrorist attacks. in order to accomplish this, we have subjected the lysates from b. anthracis to affinity purification using monoclonal antibodies for the selected antigenic protein present in the bacteria. the bound antigenic protein was identified by multi-dimensional protein identification technology (mudpit) to be a surfac ...200616755617
[a comparative analysis of molecular-genetic peculiarities of the genomes of cholera, plague and anthrax agents and their evolutional transformations].cholera, plague, and anthrax, the diseases that have accounted for millions of human victims, still endanger the entire mankind by possible development of epidemic outbreaks due to their spread or application as bioterrorist agents. generalized results of research into the genomic features of the vibrio cholerae, yersinia pestis, and bacillus anthracis are discussed. despite different frequencies of evolutional transformations occurring in their genomes, that are likely to be associated with div ...200616755997
self-association of the transmembrane domain of an anthrax toxin receptor.protective antigen (pa), lethal factor (lf) and edema factor (ef) are secreted individually by bacillus anthracis. these components of anthrax toxin must then assemble into complexes to intoxicate mammalian cells. toxin assembly initiates when molecules of pa bind mammalian receptors antxr1/2 and are cleaved by surface proteases into 20 kda and 63 kda fragments. after pa20 dissociates, receptor-bound pa63 homo-oligomerizes into heptamers. oligomeric pa63 binds ef and lf and these complexes are i ...200616756998
long-lasting t cell responses to biological warfare vaccines in human vaccinees.medical countermeasures against biological warfare include the use of vaccines for anthrax and plague, which require repeated dosing and adjuvant to achieve adequate protection from threats such as inhalational anthrax and pneumonic plague. despite the widespread use of these measures in preparation for recent military deployments, little is known about the cell-mediated immune response that is induced by these vaccines, in comparison with conventional vaccines, such as pertussis or tetanus-diph ...200616758411
plant vs. pathogen: enlisting tobacco in the fight against anthrax. 200616759974
detection of anthrax toxin in the serum of animals infected with bacillus anthracis by using engineered immunoassays.several strategies that target anthrax toxin are being developed as therapies for infection by bacillus anthracis. although the action of the tripartite anthrax toxin has been extensively studied in vitro, relatively little is known about the presence of toxins during an infection in vivo. we developed a series of sensitive sandwich enzyme-linked immunosorbent assays (elisas) for detection of both the protective antigen (pa) and lethal factor (lf) components of the anthrax exotoxin in serum. the ...200616760326
cationic polyamines inhibit anthrax lethal factor protease.anthrax is a human disease that results from infection by the bacteria, bacillus anthracis and has recently been used as a bioterrorist agent. historically, this disease was associated with bacillus spore exposure from wool or animal carcasses. while current vaccine approaches (targeted against the protective antigen) are effective for prophylaxis, multiple doses must be injected. common antibiotics that block the germination process are effective but must be administered early in the infection ...200616762077
enhancement of an analytical method for the determination of squalene in anthrax vaccine adsorbed formulations.specific lots of anthrax vaccine adsorbed administered to members of the u.s. armed forces have been alleged to contain squalene, a chemical purported to be associated with illnesses of gulf war veterans. a method of enhanced sensitivity for determining squalene in anthrax vaccine adsorbed using high-performance liquid chromatography with photodiode array detection has been developed, validated, and applied to 44 bottles of 38 lots of anthrax vaccine. in 43 bottles of 37 lots, no squalene was de ...200616762524
anthrax: from antiquity and obscurity to a front-runner in bioterrorism. 200616762737
anthrax toxin receptor 1/tumor endothelium marker 8 mediates cell spreading by coupling extracellular ligands to the actin cytoskeleton.tumor endothelial marker 8 (tem8) is induced in tumor-associated vasculature and acts as a receptor for protective antigen (pa), the cell-binding component of the anthrax toxin determinant for toxin entrance into cells. however, the normal function for tem8 remains unknown. we show that tem8 functions as an adhesion molecule mediating cell spreading on immobilized pa and collagen i. the mechanism for tem8 interaction with collagen i was cell type-specific, because binding to collagen i was abrog ...200616762926
immunization to protect the us armed forces: heritage, current practice, and prospects.americans serving with the us armed forces need protection from the dangerous infections that they can contract during training, based on occupation, during overseas deployment, or because of underlying health status. for over 230 years, the military health-care system has immunized troops to protect them personally and to help them accomplish their missions. military researchers have invented, developed, and improved vaccines and immunization delivery methods against more than 20 diseases. this ...200616763072
vacuum sampling techniques for industrial hygienists, with emphasis on beryllium dust sampling.the u.s. department of energy (doe) chronic beryllium disease prevention program rule, 10 cfr part 850 became effective in 2000 in response to the prevalence of chronic beryllium disease (cbd) in workers. the rule requires surface and air monitoring for beryllium to determine exposure levels and the evaluation of the effectiveness of controls used to minimize or eliminate that risk. the most common methods for surface sampling use wet or dry wipes. wipe sampling techniques may be impractical for ...200616767227
anthrax vaccination and risk of optic neuritis in the united states military, 1998-2003.numerous case reports have suggested a possible association between optic neuritis and receipt of several different vaccines. the most frequently identified vaccines associated with optic neuritis in the literature are influenza and hepatitis b, and a report describing 2 us military cases suggests an association with the currently used anthrax vaccine (anthrax vaccine adsorbed).200616769869
real-time monitoring of the membrane-binding and insertion properties of the cholesterol-dependent cytolysin anthrolysin o from bacillus anthracis.bacillus anthracis has recently been shown to secrete a potently hemolytic/cytolytic protein that has been designated anthrolysin o (alo). in this work, we initiated a study of this potential anthrax virulence factor in an effort to understand the membrane-binding properties of this protein. recombinant anthrolysin o (ralo35-512) and two n-terminally truncated versions of alo (ralo390-512 and ralo403-512) from b. anthracis were overproduced in escherichia coli and purified to homogeneity. the ro ...200616775845
ornithology. vulture research soars as the scavengers' numbers decline. 200616778034
laboratory study on the immobilization of bacterial spores in arid environments.in this study, two effective, non-toxic, wind erosion palliative materials were analyzed for their efficacy in preventing the spread of bacterial spores. desert sand was employed in a laboratory setting with a non-toxic simulant bacterium in an attempt to accurately represent the spreadability of the hantavirus. spore simulants were used instead of viruses due to availability, decreased susceptibility to desiccation and detection ability without involving tissue cultures. the simulant was used t ...200616779932
trojan horse or proton force: finding the right partner(s) for toxin translocation.much is known about the structure function relationships of a large number of bacterial protein toxins, the nature of their cell surface receptors, and their enzymatic activities which lead to the inactivation of their respective cytosolic targets. despite this wealth of knowledge a detailed understanding of the mechanisms which underlie translocation of the catalytic domain across the eukaryotic cell membrane to the cytosol, the penultimate event in the intoxication process, have been slow in d ...200616785102
a loop network within the anthrax toxin pore positions the phenylalanine clamp in an active conformation.heptameric pores formed in the endosomal membrane by the protective antigen moiety of anthrax toxin serve as portals for entry of the enzymatic moieties of the toxin into the cytosol. in the aqueous lumen of each pore is a "phe clamp," a heptad of narrowly apposed phe residues (phe-427), that catalyzes the unfolding and translocation of the enzymatic moieties across the membrane. here, we provide evidence for a "loop swap" between neighboring protective antigen subunits, which is required for ef ...200616785422
morphologic, immunologic, and molecular methods to detect bacillus anthracis in formalin-fixed tissues.due to the importance of bacillus anthracis as a cause of naturally occurring infection among humans and as an agent of bioterrorism, there is a vital need for rapid and specific assays, including immunohistochemistry (ihc) and polymerase chain reaction (pcr) assays, to detect the bacterium in formalin-fixed tissues. colorimetric ihc assays were developed using a multistep indirect immunoalkaline phosphatase method with anti-b. anthracis cell wall (eaii-6g6-2-3) and anti-b. anthracis capsule (fd ...200616785797
ecology and epidemiology of anthrax in cattle and humans in zambia.anthrax is endemic in western and north-western provinces of zambia. the disease occurs throughout the year and impacts negatively on the economy of the livestock industry and public health in zambia. during 1989-1995, there were 1626 suspected cases of anthrax in cattle in western province and of these 51 were confirmed. there were 220 cases of human anthrax cases in 1990 alone and 248 cases during 1991-1998 with 19.1% and 7.7% case fatality rates, respectively. interplay of the ecology of affe ...200616786974
the bacillus anthracis cholesterol-dependent cytolysin, anthrolysin o, kills human neutrophils, monocytes and macrophages.bacillus anthracis is an animal and human pathogen whose virulence is characterized by lethal and edema toxin, as well as a poly-glutamic acid capsule. in addition to these well characterized toxins, b. anthracis secretes several proteases and phospholipases, and a newly described toxin of the cholesterol-dependent cytolysin (cdc) family, anthrolysin o (alo).200616790055
passive immunotherapy of bacillus anthracis pulmonary infection in mice with antisera produced by dna immunization.because of the high failure rate of antibiotic treatment in patients with anthrax there is a need for additional therapies such as passive immunization with therapeutic antibodies. in this study, we used codon-optimized plasmid dnas (dna vaccines) encoding bacillus anthracis protective antigen (pa) to immunize rabbits for producing anti-anthrax antibodies for use in passive immunotherapy. the antisera generated with these dna vaccines were of high titer as measured by elisa. the antisera were al ...200616790303
retrocyclins kill bacilli and germinating spores of bacillus anthracis and inactivate anthrax lethal toxin.theta-defensins are cyclic octadecapeptides encoded by the modified alpha-defensin genes of certain nonhuman primates. the recent demonstration that human alpha-defensins could prevent deleterious effects of anthrax lethal toxin in vitro and in vivo led us to examine the effects of theta-defensins on bacillus anthracis (sterne). we tested rhesus theta-defensins 1-3, retrocyclins 1-3, and several analogues of rc-1. low concentrations of theta-defensins not only killed vegetative cells of b. anthr ...200616790431
oxidized atp protection against anthrax lethal toxin.bacillus anthracis lethal toxin (lt) induces rapid lysis (<90 min) of murine macrophages from certain inbred strains. the mechanism for lt-induced cytolysis is currently unknown. we hypothesized that the atp-activated macrophage p2x7 receptors implicated in nucleotide-mediated macrophage lysis could play a role in lt-mediated cytolysis and discovered that a potent p2x7 antagonist, oxidized atp (o-atp), protects macrophages against lt. other p2x7 receptor antagonists, however, had no effect on lt ...200616790743
bacillus anthracis phospholipases c facilitate macrophage-associated growth and contribute to virulence in a murine model of inhalation anthrax.several models of anthrax pathogenesis suggest that early in the infectious process bacillus anthracis endospores germinate and outgrow into vegetative bacilli within phagocytes before being released into the blood. here, we define the respective contributions of three phospholipases c (plcs) to the pathogenesis of b. anthracis. genetic deletions of the plcs were made in the sterne 7702 background, resulting in the respective loss of their activities. the plcs were redundant both in tissue cultu ...200616790747
search for bacillus anthracis potential vaccine candidates by a functional genomic-serologic screen.bacillus anthracis proteins that possess antigenic properties and are able to evoke an immune response were identified by a reductive genomic-serologic screen of a set of in silico-preselected open reading frames (orfs). the screen included in vitro expression of the selected orfs by coupled transcription and translation of linear pcr-generated dna fragments, followed by immunoprecipitation with antisera from b. anthracis-infected animals. of the 197 selected orfs, 161 were chromosomal and 36 we ...200616790772
a monoclonal antibody to bacillus anthracis protective antigen defines a neutralizing epitope in domain 1.antibody (ab) responses to bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (mabs) have been reported. protective antigen (pa) is essential for the action of b. anthracis lethal toxin (letx) and edema toxin. in this study, we generated two mabs to pa, mabs 7.5g and 10f4. these mabs did not compete for binding to pa, consistent with specificities for different epitopes. the mabs were tested for their ability to protect a monolayer of cultured macrophag ...200616790789
a history of biological disasters of animal origin in north america.this paper examines past occurrences in north america relevant to the possibility of biological disasters with animal origins. with respect to naturally occurring animal disease outbreaks, north america, while not as adversely affected by epizootics as other regions, has had its fair share of such outbreaks of both 'traditional' and emerging animal diseases. the traditional category includes such diseases as anthrax, classical swine fever, bluetongue, brucellosis, foot and mouth disease, and the ...200616796038
achievements of the soviet biological weapons programme and implications for the future.the military-biological complex of the former union of soviet socialist republics was a true frankenstein's monster, with a powerful scientific potential--or good and for ill. this article examines both the direct scientific results of the twin biological weapons (bws) programmes run by the 'civilian' biopreparat and by the ministry of defence (mod) and the public health benefits that sprang, despite the original intent, out of those programmes. the authors will also explore the potential for bo ...200616796045
toxins of concern to animals and people.historically veterinarians have diagnosed accidental poisonings and identified possible terrorist events before they have come to the attention of public health authorities. there are many toxins that pose a threat to both humans and animals and the authors examine several of them here, namely, anthrax, tricothecenes, staphylococcal enterotoxin b, botulinum toxins, ricin, saxitoxin and dinoflagellate toxins. by discussing exposure routes, clinical signs and differential diagnoses the authors dem ...200616796059
single-step purification of recombinant anthrax lethal factor from periplasm of escherichia coli.lethal toxin (lt) that composed by protective antigen and lethal factor (lf) is the major virulence factor of bacillus anthracis. the treatments of lt in animals could reproduce most manifestations of b. anthracis infections that greatly improves our knowledge in lt-mediated pathogenesis and facilitates anthrax-related researches without having to directly contact the hazardous bacterium b. anthracis. the recombinant protein of lf (rlf), however, still lacks a simple purification method. herein, ...200616797097
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