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evaluation of substituted triazol-1-yl-pyrimidines as inhibitors of bacillus anthracis acetohydroxyacid synthase.acetohydroxyacid synthase (ahas), a potential target for antimicrobial agents, catalyzes the first common step in the biosynthesis of the branched-chain amino acids. the genes of both catalytic and regulatory subunits of ahas from bacillus anthracis (bantx), a causative agent of anthrax, were cloned, overexpressed in escherichia coli, and purified to homogeneity. to develop novel anti-anthracis drugs that inhibit ahas, a chemical library was screened, and four chemicals, avs2087, avs2093, avs238 ...201020170757
role of the gerp operon in germination and outgrowth of bacillus anthracis spores.germination of bacillus anthracis spores occurs when nutrients such as amino acids or purine nucleosides stimulate specific germinant receptors located in the spore inner membrane. the gerp(abcdef) operon has been suggested to play a role in facilitating the interaction between germinants and their receptors in spores of bacillus subtilis and bacillus cereus. b. anthracis mutants containing deletions in each of the six genes belonging to the orthologue of the gerp(abcdef) operon, or deletion of ...201020161744
synthesis and in vitro efficacy studies of silver carbene complexes on biosafety level 3 bacteria.a series of n-heterocyclic carbene silver complexes have been synthesized and tested against the select group of bio-safety level 3 bacteria burkholderia pseudomallei, burkholderia mallei, bacillus anthracis, methicillin-resistant staphylococcus aureus and yersinia pestis. minimal inhibitory concentrations, minimal bactericidal and killing assays demonstrated the exceptional efficacy of the complexes against these potentially weaponizable pathogens.200920160993
heroin contaminated with anthrax has killed 11 people. 201020156915
synthesis and biological evaluation of botulinum neurotoxin a protease inhibitors.nsc 240898 was previously identified as a botulinum neurotoxin a light chain (bont/a lc) endopeptidase inhibitor by screening the national cancer institute open repository diversity set. two types of analogues have been synthesized and shown to inhibit bont/a lc in a fret-based enzyme assay, with confirmation in an hplc-based assay. these two series of compounds have also been evaluated for inhibition of anthrax lethal factor (lf), an unrelated metalloprotease, to examine enzyme specificity of t ...201020155918
a tnf-like trimeric lectin domain from burkholderia cenocepacia with specificity for fucosylated human histo-blood group antigens.the opportunistic pathogen burkholderia cenocepacia expresses several soluble lectins, among them bc2l-c. this lectin exhibits two domains: a c-terminal domain with high sequence similarity to the recently described calcium-dependent mannose-binding lectin bc2l-a, and an n-terminal domain of 156 amino acids without similarity to any known protein. the recombinant n-terminal bc2l-c domain is a new lectin with specificity for fucosylated human histo-blood group epitopes h-type 1, lewis b, and lewi ...201020152153
pharmacokinetic-pharmacodynamic assessment of faropenem in a lethal murine bacillus anthracis inhalation postexposure prophylaxis model.there are few options for prophylaxis after exposure to bacillus anthracis, especially in children and women of childbearing potential. faropenem is a beta-lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. faropenem was shown to have in vitro activity against b. anthracis strains that variably express the bla1 beta-lactamase (mic range, <or=0.06 to 1 microg/ml). in this study we evaluated the pharmacok ...201020145081
type-iia secreted phospholipase a2 is an endogenous antibiotic-like protein of the host.type-iia secreted phospholipase a(2) (spla(2)-iia) has been proposed to play a role in the development of inflammatory diseases. it has been shown to release arachidonic acid, the precursor of proinflammatory eicosanoids, to hydrolyze phospholipids of pulmonary surfactant, and to bind to specific receptors located on cell surface membranes. however, the most established biological role of spla(2)-iia is related to its potent bactericidal property in particular toward gram-positive bacteria. this ...201020144678
three-dimensional structure of the anthrax toxin pore inserted into lipid nanodiscs and lipid vesicles.a major goal in understanding the pathogenesis of the anthrax bacillus is to determine how the protective antigen (pa) pore mediates translocation of the enzymatic components of anthrax toxin across membranes. to obtain structural insights into this mechanism, we constructed pa-pore membrane complexes and visualized them by using negative-stain electron microscopy. two populations of pa pores were visualized in membranes, vesicle-inserted and nanodisc-inserted, allowing us to reconstruct two vir ...201020142512
the overlap of small molecule and protein binding sites within families of protein structures.protein-protein interactions are challenging targets for modulation by small molecules. here, we propose an approach that harnesses the increasing structural coverage of protein complexes to identify small molecules that may target protein interactions. specifically, we identify ligand and protein binding sites that overlap upon alignment of homologous proteins. of the 2,619 protein structure families observed to bind proteins, 1,028 also bind small molecules (250-1000 da), and 197 exhibit a sta ...201020140189
[development of a universal primers pcr-coupled liquid bead array to detect biothreat bacteria].to develop a fast, high-throughput screening method with suspension array technique for simultaneous detection of biothreat bacteria.200920137470
nano aptasensor for protective antigen toxin of anthrax.we demonstrate a highly sensitive nano aptasensor for anthrax toxin through the detection of its polypeptide entity, protective antigen (pa toxin) using a pa toxin ssdna aptamer functionalized single-walled carbon nanotubes (swnts) device. the aptamer was developed in-house by capillary electrophoresis systematic evolution of ligands by exponential enrichment (ce-selex) and had a dissociation constant (k(d)) of 112 nm. the aptasensor displayed a wide dynamic range spanning up to 800 nm with a de ...201020136122
rapid field detection assays for bacillus anthracis, brucella spp., francisella tularensis and yersinia pestis.rapid detection is essential for timely initiation of medical post-exposure prophylactic measures in the event of intentional release of biological threat agents. we compared real-time pcr assay performance between the applied biosystems 7300/7500 and the razor instruments for specific detection of the causative agents of anthrax, brucellosis, tularemia and plague. furthermore, an assay detecting bacillus thuringiensis, a bacillus anthracis surrogate, was developed for field-training purposes. a ...201120132255
the role of heterologous chloroplast sequence elements in transgene integration and expression.heterologous regulatory elements and flanking sequences have been used in chloroplast transformation of several crop species, but their roles and mechanisms have not yet been investigated. nucleotide sequence identity in the photosystem ii protein d1 (psba) upstream region is 59% across all taxa; similar variation was consistent across all genes and taxa examined. secondary structure and predicted gibbs free energy values of the psba 5' untranslated region (utr) among different families reflecte ...201020130101
cd1d-dependent b-cell help by nk-like t cells leads to enhanced and sustained production of bacillus anthracis lethal toxin-neutralizing antibodies.the current bacillus anthracis vaccine consists largely of protective antigen (pa), the protein of anthrax toxin that mediates entry of edema factor (ef) or lethal factor (lf) into cells. pa induces protective antibody (ab)-mediated immunity against bacillus anthracis but has limited efficacy and duration. we previously demonstrated that activation of cd1d-restricted natural killer-like t cells (nkt) with a cd1d-binding glycolipid led to enhanced ab titers specific for foreign antigen (ag). we t ...201020123711
anthrax outbreak in a swedish beef cattle herd--1st case in 27 years: case report.after 27 years with no detected cases, an outbreak of anthrax occurred in a beef cattle herd in the south of sweden. the outbreak was unusual as it occurred in winter, in animals not exposed to meat-and-bone meal, in a non-endemic country. the affected herd consisted of 90 animals, including calves and young stock. the animals were kept in a barn on deep straw bedding and fed only roughage. seven animals died during 10 days, with no typical previous clinical signs except fever. the carcasses wer ...201020122147
[selected research problems of anthrax vaccine development].the threat of bioterrorism with b. anthracis against civilian population is one of major concern. after successful bioterroristic attack in 2001 in us renewed research interest has prompted in the development of new and more effective vaccine against anthrax. there are two licensed vaccines against anthrax--ava-bio-thrax us and uk--sterile culture filtrate prepared by alum precipitation. both vaccines are based on pa antigen. there are several concerns regarding pa based vaccines. they require s ...200920120948
prevalence of bacillus anthracis-like organisms and bacteriophages in the intestinal tract of the earthworm eisenia fetida.stable infection of bacillus anthracis laboratory strains with environmental bacteriophages confers survival phenotypes in soil and earthworm intestinal niches (r. schuch and v. a. fischetti, plos one 4:e6532, 2009). here, the natural occurrence of two such b. anthracis-infective bacteriophages, wip1 and wip4, was examined in the intestines of eisenia fetida earthworms as part of a 6-year longitudinal study at a pennsylvania forest site. the wip1 tectivirus was initially dominant before being su ...201020118353
capsule depolymerase overexpression reduces bacillus anthracis virulence.capsule depolymerase (capd) is a gamma-glutamyl transpeptidase and a product of the bacillus anthracis capsule biosynthesis operon. in this study, we examined the effect of modulating capd expression on b. anthracis capsule phenotype, interaction with phagocytic cells and virulence in guinea pigs. transcriptional fusions of capd were made to the genes encoding heat-shock protein 60 (hsp60) and elongation factor tu (eftu), and to capa, a b. anthracis capsule biosynthesis gene. translation signals ...201020110296
pulling the plug on anthrax research: wild horses and "the doctor's dilemma". 201020110270
current and future medical approaches to combat the anthrax threat. 201020102155
identification of ciprofloxacin resistance by simpleprobe, high resolution melt and pyrosequencing nucleic acid analysis in biothreat agents: bacillus anthracis, yersinia pestis and francisella tularensis.the potential for genetic modification of biological warfare agents makes rapid identification of antibiotic resistant strains critical for the implementation of suitable infection control measures. the fluorinated quinolone, ciprofloxacin, is an antibiotic effective for treating bacterial infections by inhibiting the enzyme activity of the dna type ii topoisomerases dna gyrase and topoisomerase iv. the genes that encode the subunits of dna gyrase (gyra and gyrb) and topo iv (par c and pare) con ...201020100564
[doxycycline].doxycycline is a semi-synthetic derivative of tetracycline family exhibiting an interesting pharmacokinetic profile since no dosage adjustment is required for renal failure. doxycycline displays good bacteriostatic activity against most bacteria as well as anti-inflammatory activity. bacterial resistance is mainly acquired. many infectious diseases can be treated with doxycycline including brucellosis, pasteurellosis, borreliosis, rickettsioses, trepanomatosis, cholera, leptospirosis, q fever, p ...200920099667
two-photon luminescence imaging of bacillus spores using peptide-functionalized gold nanorods.bacillus subtilis spores (a simulant of bacillus anthracis) have been imaged by two-photon luminescence (tpl) microscopy, using gold nanorods (gnrs) functionalized with a cysteine-terminated homing peptide. control experiments using a peptide with a scrambled amino acid sequence confirmed that the gnr targeting was highly selective for the spore surfaces. the high sensitivity of tpl combined with the high affinity of the peptide labels enables spores to be detected with high fidelity using gnrs ...200820098661
effects of l-alanine and inosine germinants on the elasticity of bacillus anthracis spores.the surface of dormant bacillus anthracis spores consists of a multilayer of protein coats and a thick peptidoglycan layer that allow the cells to resist chemical and environmental insults. during germination, the spore coat is degraded, making the spore susceptible to chemical inactivation by antisporal agents as well as to mechanical inactivation by high-pressure or mechanical abrasion processes. while chemical changes during germination, especially the release of the germination marker, dipic ...201020095533
lamp using a disposable pocket warmer for anthrax detection, a highly mobile and reliable method for anti-bioterrorism.a quick, reliable detection system is necessary to deal with bioterrorism. loop-mediated isothermal amplification (lamp) is a dna amplification method that can amplify specific dna fragments in isothermal conditions. we developed a new highly mobile and practical lamp anthrax detection system that uses a disposable pocket warmer without the need for electricity (pocket-warmer lamp). in our tests, the detection limit of the pocket-warmer lamp was 1,000 copies of bacillus anthracis pag and capb ge ...201020093760
transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity.we have investigated how bacillus anthracis lethal toxin (lt) triggers caspase-3 activation and the formation of thick actin cables in human endothelial cells. by dna array analysis we show that lt has a major impact on the cell transcriptome and we identify key host genes involved in lt cytotoxic effects. indeed, upregulation of trail and downregulation of xiap both participate in lt-induced caspase-3 activation. lt induces a downregulation of the immediate early gene and master regulator of tr ...201020088950
an outbreak of infection with bacillus anthracis in injecting drug users in scotland.an investigation is currently underway to explore and control an outbreak of bacillus anthracis among drug users (mainly injecting) in scotland. contaminated heroin or a contaminated cutting agent mixed with the heroin is considered to be the most likely source and vehicle of infection. heroin users have been advised of the risk. the risk to the general public is regarded as very low.201020085694
preliminary case report of fatal anthrax in an injecting drug user in north-rhine-westphalia, germany, december 2009.a fatal case of anthrax occurred in an injecting drug user in germany, in december 2009. a potential link to similar cases in scotland in the same time period is currently under investigation.201020085693
[anthrax meningoencephalitis: a case report and review of turkish literature].the incidence of anthrax is decreasing in turkey, however, it is still endemic in some regions of the country. although central nervous system involvement is rare in cases with anthrax, high mortality rates are significant. here, we report a 46-years old woman who was anthrax meningoencephalitis. the patient was from yozgat located in central anatolia, turkey. her history revealed that following peeling the skin of sheeps and consuming their meat a week ago, a lesion developed in her left forear ...200920084923
evaluation of surface sampling techniques for collection of bacillus spores on common drinking water pipe materials.drinking water utilities may face biological contamination of the distribution system from a natural incident or deliberate contamination. determining the extent of contamination or the efficacy of decontamination is a challenge, because it may require sampling of the wetted surfaces of distribution infrastructure. this study evaluated two sampling techniques that utilities might use to sample exhumed pipe sections. polyvinyl chloride (pvc), cement-lined ductile iron, and ductile iron pipe coupo ...201020082033
anthrax toxin triggers the activation of src-like kinases to mediate its own uptake.ab-type toxins, like other bacterial toxins, are notably opportunistic molecules. they rely on target cell receptors to reach the appropriate location within the target cell where translocation of their enzymatic subunits occurs. the anthrax toxin, however, times its own uptake, suggesting that toxin binding triggers specific signaling events. here we show that the anthrax toxin triggers tyrosine phosphorylation of its own receptors, capillary morphogenesis gene 2 and tumor endothelial marker 8, ...201020080640
bacillus anthracis and bacillus subtilis spore surface properties and transport.effective decontamination of environments contaminated by bacillus spores remains a significant challenge since bacillus spores are highly resistant to killing and could plausibly adhere to many non-biological as well as biological surfaces. decontamination of bacillus spores can be significantly improved if the chemical basis of spore adherence is understood. in this research, we investigated the surface adhesive properties of bacillus subtilis and bacillus anthracis spores. the spore thermodyn ...201020074921
a "dock and lock" approach to preparation of targeted liposomes.we developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. this strategy is based on "dock and lock" the interactions between two mutated fragments of human rnase i, a 1-15-aa fragment with the r4c amino acid substitution, (cys-tag), and a 21-127-aa fragment with the v118c substitution, (ad-c). upon binding to each other, cys-tag and ad-c spontaneously form a disulfide bond between the complimentary 4c and 118c residues. therefore, ...201020072886
statistical assessment of dna extraction reagent lot variability in real-time quantitative pcr.the aim of this study was to evaluate the variability in lots of a dna extraction kit using real-time pcr assays for bacillus anthracis, francisella tularensis and vibrio cholerae.201020070509
raxibacumab.raxibacumab (abthrax) is a human igg1 monoclonal antibody against bacillus anthracis protective antigen. hgs is currently providing stockpiles of the agent to the us government for use in the prevention and treatment of inhalation anthrax. as of may 2009, the candidate was undergoing review by the us food and drug administration. the availability of bioterrorism countermeasures has become more important since the september 2001 anthrax attacks, and development of raxibacumab is a significant adv ...200920068396
microbial threat lists: obstacles in the quest for biosecurity?anxiety about threats from the microbial world and about the deliberate misuse of microorganisms has led to efforts to define and control these dangers using lists and regulations. one list with tremendous legal implications and a potentially huge impact on research is the select agents and toxins list, which was created by the us government to limit the possession of and access to particular microorganisms and toxins. in this article, in addition to highlighting general problems with taxonomy-b ...201020065941
effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen.multimeric pores formed in the endosomal membrane by the protective antigen moiety of anthrax toxin translocate the enzymatic moieties of the toxin to the cytosolic compartment of mammalian cells. there is evidence that the side chains of the phe(427) residues come into close proximity with one another in the lumen of the pore and form a structure, termed the phe clamp, that catalyzes the translocation process. in this report we describe the effects of replacing phe(427) in a single subunit of t ...201020061382
analysis of the sporicidal activity of chlorine dioxide disinfectant against bacillus anthracis (sterne strain).routine surface decontamination is an essential hospital and laboratory procedure, but the list of effective, noncorrosive disinfectants that kill spores is limited. we investigated the sporicidal potential of an aqueous chlorine dioxide solution and encountered some unanticipated problems. quantitative bacteriological culture methods were used to determine the log(10) reduction of bacillus anthracis (sterne strain) spores following 3min exposure to various concentrations of aqueous chlorine dio ...201020061062
genetic analysis of petrobactin transport in bacillus anthracis.summary iron acquisition mechanisms play an important role in the pathogenesis of many infectious microbes. in bacillus anthracis, the siderophore petrobactin is required for both growth in iron depleted conditions and for full virulence of the bacterium. here we demonstrate the roles of two putative petrobactin binding proteins fatb and fpua (encoded by gbaa5330 and gbaa4766, respectively) in bacillus anthracis iron acquisition and pathogenesis. markerless deletion mutants were created using al ...201020059694
array lead zirconate titanate/glass piezoelectric microcantilevers for real-time detection of bacillus anthracis with 10 spores/ml sensitivity and 1/1000 selectivity in bacterial mixtures.an array of three identical piezoelectric microcantilever sensors (pemss) consisting of a lead zirconate titanate layer bonded to a glass layer was fabricated and examined for simultaneous, in situ, real-time, all-electrical detection of bacillus anthracis (ba) spores in an aqueous suspension using the first longitudinal extension mode of resonance. with anti-ba antibody immobilized on the sensor surfaces all three pems exhibited identical ba detection resonance frequency shifts at all tested co ...200920059167
crystallization and preliminary x-ray diffraction analysis of diaminopimelate epimerase from escherichia coli.diaminopimelate (dap) epimerase (ec 5.1.1.7) catalyzes the penultimate step of lysine biosynthesis in bacteria and plants, converting l,l-diaminopimelate to meso-diaminopimelate. here, the cloning, expression, purification, crystallization and preliminary x-ray diffraction analysis of dap epimerase from escherichia coli are presented. crystals were obtained in space group p4(1)2(1)2 and diffracted to 2.0 a resolution, with unit-cell parameters a = b = 89.4, c = 179.6 a. molecular replacement was ...201020057066
structure of dihydrodipicolinate synthase from methanocaldococcus jannaschii.in bacteria and plants, dihydrodipicolinate synthase (dhdps) plays a key role in the (s)-lysine biosynthesis pathway. dhdps catalyzes the first step of the condensation of (s)-aspartate-beta-semialdehyde and pyruvate to form an unstable compound, (4s)-4-hydroxy-2,3,4,5-tetrahydro-(2s)-dipicolinic acid. the activity of dhdps is allosterically regulated by (s)-lysine, a feedback inhibitor. the crystal structure of dhdps from methanocaldococcus jannaschii (mjdhdps) was solved by the molecular-repla ...200920054116
inhibition of tumor angiogenesis by the matrix metalloproteinase-activated anthrax lethal toxin in an orthotopic model of anaplastic thyroid carcinoma.patients with anaplastic thyroid carcinoma (atc) typically succumb to their disease months after diagnosis despite aggressive therapy. a large percentage of atcs have been shown to harbor the v600e b-raf point mutation, leading to the constitutive activation of the mitogen-activated protein kinase pathway. atc invasion, metastasis, and angiogenesis are in part dependent on the gelatinase class of matrix metalloproteinases (mmp). the explicit targeting of these two tumor markers may provide a nov ...201020053778
preparedness for terrorism: managing nuclear, biological and chemical threats.the management of nuclear, biological and chemical (nbc) terrorism events is critical to reducing morbidity and mortality in the next decade; however, initial patient care considerations and protective actions for staff are unfamiliar to most front-line clinicians. high explosive events (bomb and blast) remain the most common type of terrorism and are easy to detect. conversely, some types of terrorist attacks are more likely to be unsuspected or covert. this paper explains the current threat of ...200920052435
activity of dalbavancin against bacillus anthracis in vitro and in a mouse inhalation anthrax model.bacillus anthracis, the causative agent of anthrax, can produce fatal disease when it is inhaled or ingested by humans. dalbavancin, a novel, semisynthetic lipoglycopeptide, has potent activity, greater than that of vancomycin, against gram-positive bacteria and a half-life in humans that supports once-weekly dosing. dalbavancin demonstrated potent in vitro activity against b. anthracis (mic range, < or =0.03 to 0.5 mg/liter; mic(50) and mic(90), 0.06 and 0.25 mg/liter, respectively), which led ...201020047912
anthrax edema toxin inhibits nox1-mediated formation of reactive oxygen species by colon epithelial cells.one major route of intoxication by bacillus anthracis (anthrax) spores is via their ingestion and subsequent uptake by the intestinal epithelium. anthrax edema toxin (etx) is an adenylate cyclase that causes persistent elevation of camp in intoxicated cells. nadph oxidase enzymes (nox1-nox5, duox1 and 2) generate reactive oxygen species (ros) as components of the host innate immune response to bacteria, including nox1 in gastrointestinal epithelial tissues. we show that etx effectively inhibits ...200920046221
sequence motifs and proteolytic cleavage of the collagen-like glycoprotein bcla required for its attachment to the exosporium of bacillus anthracis.bacillus anthracis spores are enclosed by an exosporium comprised of a basal layer and an external hair-like nap. the filaments of the nap are composed of trimers of the collagen-like glycoprotein bcla. the attachment of essentially all bcla trimers to the exosporium requires the basal layer protein bxpb, and both proteins are included in stable high-molecular-mass exosporium complexes. bcla contains a proteolytically processed 38-residue amino-terminal domain (ntd) that is essential for basal-l ...201020038593
[recombinant antibodies against bioweapons].the threat posed by bioweapons (bw) could lead to the re-emergence of such deadly diseases as plague or smallpox, now eradicated from industrialized countries. the development of recombinant antibodies allows tackling this risk because these recombinant molecules are generally well tolerated in human medicine, may be utilized for prophylaxis and treatment, and because antibodies neutralize many bw. recombinant antibodies neutralizing the lethal toxin of anthrax, botulinum toxins and the smallpox ...200920035695
high-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.given their medical importance, proteases have been studied by diverse approaches and screened for small molecule protease inhibitors. here, we present a multiplexed microsphere-based protease assay that uses high-throughput flow cytometry to screen for inhibitors of the light chain protease of botulinum neurotoxin type a (bontalc). our assay uses a full-length substrate and several deletion mutants screened in parallel to identify small molecule inhibitors. the use of multiplex flow cytometry h ...201020035615
expression and regulation of antxr1 in the chick embryo.anthrax toxin receptor 1 (antxr1; also known as tumor endothelial marker 8, tem8) is one of several genes that was recently found to be up-regulated in tumor-associated endothelial cells. in vitro, the protein can link extracellular matrix components with the actin cytoskeleton to promote cell adhesion and cell spreading. both, antxr1 and the closely related antxr2 can bind anthrax toxin and interact with lipoprotein receptor-related protein 5 and 6, which also work as coreceptors in the wnt sig ...201020034073
antibacterial activity of radical scavengers against class ib ribonucleotide reductase from bacillus anthracis.bacillus anthracis is a severe mammalian pathogen. the deoxyribonucleotides necessary for dna replication and repair are provided via the ribonucleotide reductase (rnr) enzyme. rnr is also important for spore germination and cell proliferation upon infection. we show that the expression of b. anthracis class ib rnr responds to the environment that the pathogen encounters upon infection. we also show that several anti-proliferative agents (radical scavengers) specifically inhibit the b. anthracis ...201020030587
a new model of bioterrorism risk assessment.there has been an abundance of different bioterrorist attack scenarios and consequently an unclear biodefense strategy so far. we present a framework for bioterrorism risk assessment that we believe would be useful for policymakers and understandable without needing to be an expert in this field. we retrieved the medline database via pubmed (from january 1987 to january 2009) and cross-referenced and reviewed the terms biological weapons, biological attacks, bioterror, bio(defense), bio(strategy ...200920028253
source reduction in an anthrax-contaminated mail facility.following the 2001 bioterrorist attacks using letters containing bacillus anthracis spores, a number of sites had to be decontaminated. source reduction-the process of reducing biocontamination levels prior to the main decontamination treatment-is a critical step in decontaminating buildings. such activities include the removal of items from a facility either for off-site treatment and reuse or ultimate disposal, as well as the pretreatment of certain surfaces in the facility. in addition, waste ...200920028249
the four faces of microbial forensics.the emerging field of microbial forensics played a major role in the investigation of the 2001 anthrax mailings and has been closely associated with the process of attribution, or identifying the perpetrator of a biological attack for purposes of criminal prosecution or military retaliation. nevertheless, microbial forensics has other potential applications in intelligence, nonproliferation, and verification. this article describes the relevance of microbial forensics for a variety of law enforc ...200920028247
exposure to bioterrorism and mental health response among staff on capitol hill.the october 2001 anthrax attacks heralded a new era of bioterrorism threat in the u.s. at the time, little systematic data on mental health effects were available to guide authorities' response. for this study, which was conducted 7 months after the anthrax attacks, structured diagnostic interviews were conducted with 137 capitol hill staff workers, including 56 who had been directly exposed to areas independently determined to have been contaminated. postdisaster psychopathology was associated ...200920028246
a new prior for bayesian anomaly detection: application to biosurveillance.bayesian anomaly detection computes posterior probabilities of anomalous events by combining prior beliefs and evidence from data. however, the specification of prior probabilities can be challenging. this paper describes a bayesian prior in the context of disease outbreak detection. the goal is to provide a meaningful, easy-to-use prior that yields a posterior probability of an outbreak that performs at least as well as a standard frequentist approach. if this goal is achieved, the resulting po ...201020027381
sensitive and specific enzyme immunoassays for antigenic trisaccharide from bacillus anthracis spores.a straightforward synthesis of an anthrose-containing trisaccharide derived from bacillus anthracis was achieved. antibodies raised against this hapten provide a highly sensitive enzyme immunoassay with a detection limit of 8.5 pmol ml(-1). by investigating the specificity of the antibodies obtained using different mono-, di- and trisaccharide synthetic analogues, we demonstrated that the epitope was mainly made up of the methyl group at c-5, the butamido group at c-4 and the hydroxyl at c-3 of ...200920024115
pemk toxin of bacillus anthracis is a ribonuclease: an insight into its active site, structure, and function.bacillus anthracis genome harbors a toxin-antitoxin (ta) module encoding pemi (antitoxin) and pemk (toxin). this study describes the rpemk as a potent ribonuclease with a preference for pyrimidines (c/u), which is consistent with our previous study that demonstrated it as a translational attenuator. the in silico structural modeling of the pemk in conjunction with the site-directed mutagenesis confirmed the role of his-59 and glu-78 as an acid-base couple in mediating the ribonuclease activity. ...201020022964
bioterrorism - health emergency preparedness and response.health emergency planning for preparedness and response against acts of terrorism, including the malfeasant threat or actual release of biological agents designed to harm others, has assumed a higher level of concern for most western nations, including canada, following the explosive attacks in the united states on september 11, 2001. these terrorist attacks were followed by an outbreak of anthrax infections. the bacillus anthracis spores in these attacks were dispersed by using regular postal s ...200320019925
[genotyping of the bacillus anthracis vaccine strains using the multiloci vntr-analysis].the genotyping variety of 5 known anthracis vaccine strains using 18 variable loci of the chromosomal localization taken from a microbe culture collection of 48 research institute of ministry of defense was revealed in the research. the stability of the vntr-loci was shown to be inherited from the b. anthracis strains with common origin and an opportunity of their gene-identification application. the gene profile of each analyzed vaccine strain using every 18 polymorphic loci was determined and ...200920017359
dry thermal resistance of bacillus anthracis (sterne) spores and spores of other bacillus species: implications for biological agent destruction via waste incineration.to obtain needed data on the dry thermal resistance of bacillus anthracis spores and other bacillus species for waste incinerator applications.201020015207
primate study halted by us university. 200920010657
a slippery slope. 200920010640
lysogeny and sporulation in bacillus isolates from the gulf of mexico.eleven bacillus isolates from the surface and subsurface waters of the gulf of mexico were examined for their capacity to sporulate and harbor prophages. occurrence of sporulation in each isolate was assessed through decoyinine induction, and putative lysogens were identified by prophage induction by mitomycin c treatment. no obvious correlation between ability to sporulate and prophage induction was found. four strains that contained inducible virus-like particles (vlps) were shown to sporulate ...201020008174
animal research. rejection of anthrax study kicks up a dust storm in oklahoma. 200920007868
a rapid multiplex assay for nucleic acid-based diagnostics.we have developed a rapid (under 4 hours), multiplex, nucleic acid assay, adapted to a microsphere array detection platform. we call this assay multiplex oligonucleotide ligation-pcr (mol-pcr). unlike other ligation-based assays that require multiple steps, our protocol consists of a single tube reaction, followed by hybridization to a luminex microsphere array for detection. we demonstrate the ability of this assay to simultaneously detect diverse nucleic acid signatures (e.g., unique sequences ...201020006656
prediction of calcium-binding sites by combining loop-modeling with machine learning.protein ligand-binding sites in the apo state exhibit structural flexibility. this flexibility often frustrates methods for structure-based recognition of these sites because it leads to the absence of electron density for these critical regions, particularly when they are in surface loops. methods for recognizing functional sites in these missing loops would be useful for recovering additional functional information.200920003365
quantitative multiplex detection of pathogen biomarkers on multichannel waveguides.no single biomarker can accurately predict disease. an ideal biodetection technology should be capable of the quantitative, reproducible, and sensitive detection of a limited suite of such molecules. to this end, we have developed a multiplex biomarker assay for protective antigen and lethal factor of the bacillus anthracis lethal toxin using semiconductor quantum dots as the fluorescence reporters on our waveguide-based biosensor platform. the platform is extendable to a wide array of biomarker ...201020000585
detection of virulence-associated genes in clinical isolates of bacillus anthracis by multiplex pcr and dna probes.anthrax is a zoonotic disease caused by bacillus anthracis, and well recognized as a potential agent for bioterrorism. b. anthracis can be identified by detecting the virulence factors genes located on two plasmids, pxo1 and pxo2. the aim of the present study was to determine the presence of virulence genes in 27 isolates of b. anthracis isolated from clinical and environmental samples. for this purpose, multiplex pcr and dna probes were designed to detect protective antigen ( pag), edema factor ...200919996704
anthrax lethal toxin promotes dephosphorylation of ttp and formation of processing bodies.anthrax lethal toxin (letx) is composed of protective antigen (pa) and lethal factor (lf) - pa is the receptor-binding moiety and lf is a protease that cleaves mitogen-activated protein kinase kinases (mapkks). letx subverts the immune response to bacillus anthracis in several ways, such as downregulating interleukin-8 (il-8) by increasing the rate of il-8 mrna degradation. many transcripts are regulated through cis-acting elements that bind proteins that either impede or promote degradation. so ...201019995385
the influence of industry on public health.recognized specific risks of industry considered.under section 73, factory and workshop act, certain diseases contracted in a factory or workshop are notifiable by medical practitioners to the chief inspector of factories.lead poisoning, epitheliomatous and chrome ulceration and anthrax-considered in detail.effects of inhalation of dust in the causation of silicosis and asbestosis. relation of these diseases to tuberculosis. reason to believe that a large number of dusts of different characters ...193319989374
president's address: the old and the new of veterinary science and practice.the paper recalls how matters veterinary were regarded forty-six years ago, what has been achieved since, and future progress is reflected.the paper is divided into parts relating respectively to: (a) medicine; (b) surgery (c) teaching and research; (d) administration.formerly, glanders and farcy, and rabies, though acknowledged as contagious and specific, were also believed to be of spontaneous origin. experiences with regard to these two diseases, and the mallein test for glanders, are related ...192819986709
the eradication of glanders and anthrax in man and animals. 192319983044
case of shaving-brush anthrax of face; recovery. 192019980954
anthrax in the woollen industry, with special reference to bradford. 191319977235
contributions of four cortex lytic enzymes to germination of bacillus anthracis spores.bacterial spores remain dormant and highly resistant to environmental stress until they germinate. completion of germination requires the degradation of spore cortex peptidoglycan by germination-specific lytic enzymes (gsles). bacillus anthracis has four gsles: cwlj1, cwlj2, sleb, and slel. in this study, the cooperative action of all four gsles in vivo was investigated by combining in-frame deletion mutations to generate all possible double, triple, and quadruple gsle mutant strains. analyses o ...201019966006
haploid genetic screens in human cells identify host factors used by pathogens.loss-of-function genetic screens in model organisms have elucidated numerous biological processes, but the diploid genome of mammalian cells has precluded large-scale gene disruption. we used insertional mutagenesis to develop a screening method to generate null alleles in a human cell line haploid for all chromosomes except chromosome 8. using this approach, we identified host factors essential for infection with influenza and genes encoding important elements of the biosynthetic pathway of dip ...200919965467
integrated microfluidic enzyme reactor mass spectrometry platform for detection of anthrax lethal factor.in this work, we have developed a coupled microfluidic enzyme reactor mass spectrometry platform for the detection of protein toxins such as anthrax lethal factor. the lethal toxin produced during bacillus anthracis infection is a complex protective antigen, which localizes the toxin to the cell receptor and lethal factor (lf). we have demonstrated, in this work, the applicability of a microfluidic reactor for the capture and concentration of enzyme reaction solid-phase. the reaction solid-phase ...200919965140
quantum dots in molecular detection of disease.the unique photophysical properties of semiconductor quantum dots (qds) have made them ideal for use as spectral labels and luminescent probes. in this review, applications are presented in which qds function as active participants in nanoscale biosensor assemblies, where replacing traditional molecular fluorophores results in improved assay performance. specific focus is on disease detection with applications including multiplexed target detection, mutation detection by coincidence analysis and ...200919965019
anthrax lethal toxin down-regulates type-iia secreted phospholipase a(2) expression through mapk/nf-kappab inactivation.bacillus anthracis, the etiological agent of anthrax, produces lethal toxin (lt) that displays a metallo-proteolytic activity toward the n-terminus of the mapk-kinases. we have previously shown that secreted type-iia phospholipase a(2) (spla(2)-iia) exhibits potent anthracidal activity. in vitro expression of spla(2)-iia in guinea pig alveolar macrophages (ams), the major source of this enzyme in lung tissues, is inhibited by lt. here, we examined the mechanisms involved in spla(2)-iia inhibitio ...201019962969
anthrax toxin uptake by primary immune cells as determined with a lethal factor-beta-lactamase fusion protein.to initiate infection, bacillus anthracis needs to overcome the host innate immune system. anthrax toxin, a major virulence factor of b. anthracis, impairs both the innate and adaptive immune systems and is important in the establishment of anthrax infections.200919956758
characterization of a bacillus subtilis transporter for petrobactin, an anthrax stealth siderophore.iron deprivation activates the expression of components of the siderophore-mediated iron acquisition systems in bacillus subtilis, including not only the synthesis and uptake of its siderophore bacillibactin but also expression of multiple abc transporters for iron scavenging using xenosiderophores. the yclnopq operon is shown to encode the complete transporter for petrobactin (pb), a photoreactive 3,4-catecholate siderophore produced by many members of the b. cereus group, including b. anthraci ...200919955416
examination of anthrax lethal factor inhibition by siderophores, small hydroxamates, and protamine.based on their ability to chelate metals, hydroxamate molecules and siderophores have been successfully used as metalloenzyme inhibitors. as the anthrax toxin lethal factor (lf) is a zinc (zn)-metallopeptidase, an investigation of the ability of some small non-siderophore hydroxamate compounds, 5 hydroxamate-containing siderophores, and 1 catecholate siderophore was undertaken to determine whether these compounds would inhibit lf. in addition, salmon sperm protamine and ethylenediaminetetraaceti ...200919949750
cutting edge: resistance to bacillus anthracis infection mediated by a lethal toxin sensitive allele of nalp1b/nlrp1b.pathogenesis of bacillus anthracis is associated with the production of lethal toxin (lt), which activates the murine nalp1b/nlrp1b inflammasome and induces caspase-1-dependent pyroptotic death in macrophages and dendritic cells. in this study, we investigated the effect of allelic variation of nlrp1b on the outcome of lt challenge and infection by b. anthracis spores. nlrp1b allelic variation did not alter the kinetics or pathology of end-stage disease induced by purified lt, suggesting that, i ...201019949100
conjugative transfer of insecticidal plasmid pht73 from bacillus thuringiensis to b. anthracis and compatibility of this plasmid with pxo1 and pxo2.bacillus anthracis, the etiologic agent of anthrax, is genetically close to and commonly shares a giant gene pool with b. cereus and b. thuringiensis. in view of the human pathogenicity and the long persistence in the environment of b. anthracis, there is growing concern about the effects of genetic exchange with b. anthracis on public health. in this work, we demonstrate that an insecticidal plasmid, pht73, from b. thuringiensis strain kt0 could be efficiently transferred into two attenuated b. ...201019948871
substrate-mediated stabilization of a tetrameric drug target reveals achilles heel in anthrax.bacillus anthracis is a gram-positive spore-forming bacterium that causes anthrax. with the increased threat of anthrax in biowarfare, there is an urgent need to characterize new antimicrobial targets from b. anthracis. one such target is dihydrodipicolinate synthase (dhdps), which catalyzes the committed step in the pathway yielding meso-diaminopimelate and lysine. in this study, we employed cd spectroscopy to demonstrate that the thermostability of dhdps from b. anthracis (ba-dhdps) is signifi ...201019948665
crystal structure of prolyl 4-hydroxylase from bacillus anthracis.prolyl 4-hydroxylases (p4h) catalyze the post-translational hydroxylation of proline residues and play a role in collagen production, hypoxia response, and cell wall development. p4hs belong to the group of fe(ii)/alphakg oxygenases and require fe(ii), alpha-ketoglutarate (alphakg), and o(2) for activity. we report the 1.40 a structure of a p4h from bacillus anthracis, the causative agent of anthrax, whose immunodominant exosporium protein bcla contains collagen-like repeat sequences. the struct ...201019947658
the role of bacillus anthracis germinant receptors in germination and virulence.nutrient-dependent germination of bacillus anthracis spores is stimulated when receptors located in the inner membrane detect combinations of amino acid and purine nucleoside germinants. b. anthracis produces five distinct germinant receptors, gerh, gerk, gerl, gers and gerx. otherwise isogenic mutant strains expressing only one of these receptors were created and tested for germination and virulence. the gerh receptor was necessary and sufficient for wild-type levels of germination with inosine ...201019943909
dna vaccines for biodefense.an ideal biodefense vaccine platform would allow for the quick formulation of novel vaccines in response to emerging or engineered pathogens. the resultant vaccine should elicit protective immune responses in one to three doses and be unaffected by pre-existing immunity to vaccine components. in addition, it should be amenable to combination and multi-agent formulation, and should be safe for all populations and the environment. dna vaccines can potentially meet all of these requirements; thus, ...200919943766
discrimination and phylogenomic classification of bacillus anthracis-cereus-thuringiensis strains based on lc-ms/ms analysis of whole cell protein digests.modern taxonomy, diagnostics, and forensics of bacteria benefit from technologies that provide data for genome-based classification and identification of strains; however, full genome sequencing is still costly, lengthy, and labor intensive. therefore, other methods are needed to estimate genomic relatedness among strains in an economical and timely manner. although dna-dna hybridization and techniques based on genome fingerprinting or sequencing selected genes like 16s rdna, gyrb, or rpob are f ...201019938824
surface-enhanced raman spectroscopic detection of a bacteria biomarker using gold nanoparticle immobilized substrates.the development of ultrasensitive and rapid methods for the detection of dipicolinic acid (dpa), a biomarker for bacterial spores including bacillus anthracis, is increasingly important. this paper reports the results of an investigation of surface enhanced raman spectroscopy (sers) based ultrasensitive detection of dpa using a gold nanoparticle/polyvinylpyrrolidone/gold substrate (aunps/pvp/au). the strong sers effect of this substrate exploits the particle-particle and particle-substrate plasm ...200919928907
identification of novel non-hydroxamate anthrax toxin lethal factor inhibitors by topomeric searching, docking and scoring, and in vitro screening.anthrax is an infectious disease caused by bacillus anthracis, a gram-positive, rod-shaped, anaerobic bacterium. the lethal factor (lf) enzyme is secreted by b. anthracis as part of a tripartite exotoxin and is chiefly responsible for anthrax-related cytotoxicity. as lf can remain in the system long after antibiotics have eradicated b. anthracis from the body, the preferred therapeutic modality would be the administration of antibiotics together with an effective lf inhibitor. although lf has ga ...200919928768
diagnosis and management of palpebral anthrax.anthrax is an infectious disease that is not well known by ophthalmologists. in its cutaneous form, it may produce lesions of the eyelids. we report eight cases of palpebral anthrax. all patients presented with a black necrotic eschar and a tegumentary edema, with a history of contact with sick animals. the curative treatment was based on intravenous penicillin g in four cases and amoxicillin-clavulanic acid in the four other cases. the palpebral lesions resolved, leaving no clinical evidence of ...200919927487
lethal factor unfolding is the most force-dependent step of anthrax toxin translocation.cellular compartmentalization requires machinery capable of translocating polypeptides across membranes. in many cases, transported proteins must first be unfolded by means of the proton motive force and/or atp hydrolysis. anthrax toxin, which is composed of a channel-forming protein and two substrate proteins, is an attractive model system to study translocation-coupled unfolding, because the applied driving force can be externally controlled and translocation can be monitored directly by using ...200919926859
crystal structure of the transcriptional repressor pagr of bacillus anthracis.pagr is a transcriptional repressor in bacillus anthracis that controls the chromosomal s-layer genes eag and sap, and downregulates the protective antigen paga gene by direct binding to their promoter regions. the pagr protein sequence is similar to those of members of the arsr repressor family involved in the repression of arsenate-resistance genes in numerous bacteria. the crystal structure of pagr was solved using multi-wavelength anomalous diffraction (mad) techniques and was refined with 1 ...201019926656
anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is nlrp1b/nalp1b-dependent.nod-like receptors (nlrs) are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. activation of nlrs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. bacillus anthracis lethal toxin (lt), is recognized by a subset of alleles of the nlr protein nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. here we show that lt induces lysosomal membrane permeabilization ...200919924255
an anthrax lethal factor mutant that is defective at causing pyroptosis retains proapoptotic activity.anthrax lethal toxin triggers death in some cell types, such as macrophages, and causes a variety of cellular dysfunctions in others. collectively, these effects dampen the innate and adaptive immune systems to allow bacillus anthracis to survive and proliferate in the mammalian host. the diverse effects caused by the toxin have in part been attributed to its interference with signaling pathways in target cells. lethal factor (lf) is the proteolytic component of the toxin, and cleaves six member ...201019922472
anthrax letters: personal exposure, building contamination, and effectiveness of immediate mitigation measures.this report is the first detailed and quantitative study of potential mitigation procedures intended to deal with anthrax letters using a simulated anthrax letter release within an actual office building. spore aerosols were created by opening letters containing 0.1 g of dry powdered bacillus atrophaeus spores. culturable aerosol samples were collected using slit-to-agar and filter-based samplers. five test scenarios were designed to determine whether simple mitigation procedures or activities c ...201019916102
detection of b. anthracis spores and vegetative cells with the same monoclonal antibodies.bacillus anthracis, the causative agent of anthrax disease, could be used as a biothreat reagent. it is vital to develop a rapid, convenient method to detect b. anthracis. in the current study, three high affinity and specificity monoclonal antibodies (mabs, designated 8g3, 10c6 and 12f6) have been obtained using fully washed b. anthracis spores as an immunogen. these mabs, confirmed to direct against ea1 protein, can recognize the surface of b. anthracis spores and intact vegetative cells with ...200919915677
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