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phenotypic changes in spores and vegetative cells of bacillus anthracis associated with benk.a transposon insertional mutagenesis spore library of the pathogen bacillus anthracis was screened to identify mutants altered in germination kinetics. one mutant exhibited an accelerated rate of germination in association with disruption of benk. this gene encodes a putative protein with high homology to membrane transporters that facilitate benzoate transport. we hypothesized that benk may not be only spore associated, but also have a vegetative cell role. a reporter strain with a translationa ...201323178382
activation of the nlrp1b inflammasome by reduction of cytosolic atp.the efficacy of the innate immune system depends on its ability to mount an appropriate response to diverse infections and damaging agents. key components of this system are pattern recognition receptors that detect pathogen-associated and damage-associated molecular patterns (pamps and damps). nlrp1b is a pattern recognition receptor that forms a caspase-1 activation platform, known as an inflammasome, upon sensing the proteolytic activity of anthrax lethal toxin. the activation of caspase-1 le ...201323230290
anthrax infection in an intravenous drug user. 201323229347
cyclopentane-peptide nucleic acids for qualitative, quantitative, and repetitive detection of nucleic acids.we report the development of chemically modified peptide nucleic acids (pnas) as probes for qualitative and quantitative detection of dna. the remarkable stability of pnas toward enzymatic degradation makes this class of molecules ideal to develop as part of a diagnostic device that can be used outside of a laboratory setting. using an enzyme-linked reporter assay, we demonstrate that excellent levels of detection and accuracy for anthrax dna can be achieved using pna probes with suitable chemic ...201323214925
recovery balance: a method for estimating losses in a bacillus anthracis spore sampling protocol.the aim of this study was to develop a method to calculate the performance, and isolate error contributions occurring in a microbial surface sampling protocol.201323210624
anthrax receptors position the spindle.spindle orientation plays a pivotal role in tissue morphogenesis. an asymmetric anthrax receptor cap is revealed to promote activation of a formin to orient the spindle along the planar cell polarity (pcp) axis in zebrafish dorsal epiblast cells.201323263369
use of medical simulation to teach bioterrorism preparedness: the anthrax example.the 2001 anthrax bioterrorism attacks demonstrated vulnerability for future similar attacks. this article describes mechanisms that can be used to prepare the medical community and healthcare facilities for the diagnosis and management of a subsequent bioterrorism attack should such an event occur and the fundamentals of medical simulation and its use in teaching learners about the diagnosis of management of anthrax exposure.201323263314
preparedness of rural physicians for bioterrorist events in florida.human-induced public health emergencies such as the anthrax bioterrorism event and the terrorism events of september 11, 2001 in the united states have increased awareness of the nation's vulnerability to large-scale emergencies. scant attention has been given to preparing physicians in sparsely populated areas for public health emergencies. this study introduces a conceptual model developed from participants' responses that can be used to improve our understanding of rural physicians' preparedn ...201323263309
comparison of single domain antibody immobilization strategies evaluated by surface plasmon resonance.the use of single domain antibodies (sdabs) in place of conventional antibodies for both therapeutic and diagnostic applications continues to grow. sdabs offer a number of advantages when compared to conventional antibodies such as their small size and low structural complexity which allows them to readily be produced as fusions in a variety formats. in this work we compared the utility of various c-terminal fusions and immobilization strategies for two sdabs; one which recognizes ricin and the ...201323261918
infections with spore-forming bacteria in persons who inject drugs, 2000-2009.since 2000 in the united kingdom, infections caused by spore-forming bacteria have been associated with increasing illness and death among persons who inject drugs (pwid). to assess temporal and geographic trends in these illnesses (botulism, tetanus, clostridium novyi infection, and anthrax), we compared rates across england and scotland for 2000-2009. overall, 295 infections were reported: 1.45 per 1,000 pwid in england and 4.01 per 1,000 pwid in scotland. the higher rate in scotland was mainl ...201323260795
a field usable qualitative anti-protective antigen enzyme-linked immunosorbent assay for serodiagnosis of human anthrax.although all mammals, including humans, are vulnerable when they come into direct contact with infected animals, anthrax is primarily a disease of herbivorous animals. in countries like india, cutaneous anthrax is a public health problem in several regions. hence, a simple and efficacious serodiagnostic assay for large scale surveillance of endemic populations is required. in the present study, a field-usable, qualitative elisa was developed for serodiagnosis of human anthrax. results are assess ...201323252995
serodiagnosis of human cutaneous anthrax in india using an indirect anti-lethal factor igg enzyme-linked immunosorbent assay.anthrax, caused by bacillus anthracis, is primarily a zoonotic disease. being a public health problem also in several developing countries, its early diagnosis is very important in human cases. in this study, we describe the use of an indirect enzyme-linked immunosorbent assay (elisa) for detection of anti-lethal factor (anti-lf) igg in human serum samples. a panel of 203 human serum samples consisting of 50 samples from patients with confirmed cutaneous anthrax, 93 samples from healthy controls ...201323269414
an investigation of a cluster of parapoxvirus cases in missouri, feb-may 2006: epidemiologic, clinical and molecular aspects.in the spring of 2006, four human cases of parapoxvirus infections in missouri residents were reported to the centers for disease control and prevention (cdc), two of which were initially diagnosed as cutaneous anthrax. this investigation was conducted to determine the level of recognition of zoonotic parapoxvirus infections and prevention measures, the degree to which veterinarians may be consulted on human infections and what forces were behind this perceived increase in reported infections. i ...201326487314
fast identification of yersinia pestis, bacillus anthracis and francisella tularensis based on conventional pcr.rapid and accurate diagnostic tools for detection and identification of y pestis, b. anthracis and f. tularensis are essential for timely initial appropriate treatment of exposed individuals, which will be critical to their survival, as well as for reduction of the public health impact and the spread of the disease. the paper presents application of fast polymerases and fast dry electrophoresis in conventional pcr as an alternative for real-time pcr application for detection and identification o ...201324730142
targeting her2-positive cancer cells with receptor-redirected anthrax protective antigen.targeted therapeutics have emerged in recent years as an attractive approach to treating various types of cancer. one approach is to modify a cytocidal protein toxin to direct its action to a specific population of cancer cells. we created a targeted toxin in which the receptor-binding and pore-forming moiety of anthrax toxin, termed protective antigen (pa), was modified to redirect its receptor specificity to her2, a marker expressed at the surface of a significant fraction of breast and ovaria ...201323290417
characterization of amiba2446, a novel bacteriolytic enzyme active against bacillus species.there continues to be a need for developing efficient and environmentally friendly treatments for bacillus anthracis, the causative agent of anthrax. one emerging approach for inactivation of vegetative b. anthracis is the use of bacteriophage endolysins or lytic enzymes encoded by bacterial genomes (autolysins) with highly evolved specificity toward bacterium-specific peptidoglycan cell walls. in this work, we performed in silico analysis of the genome of bacillus anthracis strain ames, using a ...201323872558
optimizing snp microarray probe design for high accuracy microbial genotyping.microarrays to characterize single nucleotide polymorphisms (snps) provide a cost-effective and rapid method (under 24h) to genotype microbes as an alternative to sequencing. we developed a pipeline for snp discovery and microarray design that scales to 100's of microbial genomes. here we tested various snp probe design strategies against 8 sequenced isolates of bacillus anthracis to compare sequence and microarray data. the best strategy allowed probe length to vary within 32-40 bp to equalize ...201323871857
anthrax drug first antibacterial mab to win approval. 201323302914
study of charge distribution on the surface of biocolloids.potentiometric titration and zeta potential measurements are crucial techniques for the characterization of the surface properties of bacterial cells. in this study, we investigated the effects of two commonly used electrolytes, nano(3) and naclo(4), on the viability and acid-base properties of gram-positive bacteria bacillus subtilis. b. subtilis are non-pathogenic bacteria which are often used to model the surface properties of pathogenic microorganisms of the same genus, including bacillus an ...201323298596
identification of cody targets in bacillus anthracis by genome-wide in vitro binding analysis.in gram-positive bacteria, cody is an important regulator of genes whose expression changes under conditions of nutrient limitation. bacillus anthracis cody represses or activates directly or indirectly approximately 500 genes. affinity purification of cody-dna complexes was used to identify the direct targets of cody. of the 389 dna binding sites that were copurified with cody, 132 sites were in or near the regulatory regions governing the expression of 197 cody-controlled genes, indicating tha ...201323292769
a plant-produced protective antigen vaccine confers protection in rabbits against a lethal aerosolized challenge with bacillus anthracis ames spores.the potential use of bacillus anthracis as a bioterrorism weapon threatens the security of populations globally, requiring the immediate availability of safe, efficient and easily delivered anthrax vaccine for mass vaccination. extensive research efforts have been directed toward the development of recombinant subunit vaccines based on protective antigen (pa), the principal virulence factor of b. anthracis. among the emerging technologies for the production of these vaccine antigens is our launc ...201323324615
vaccine protection against bacillus cereus-mediated respiratory anthrax-like disease in mice.bacillus cereus strains harboring a pxo1-like virulence plasmid cause respiratory anthrax-like disease in humans, particularly in welders. we developed mouse models for intraperitoneal as well as aerosol challenge with spores of b. cereus g9241, harboring pbcxo1 and pbc218 virulence plasmids. compared to wild-type b. cereus g9241, spores with a deletion of the pbcxo1-carried protective antigen gene (paga1) were severely attenuated, whereas spores with a deletion of the pbc218-carried protective ...201323319564
effect of ph on the catalytic function and zinc content of native and immobilized anthrax lethal factor.translocation of the zinc-dependent metalloendopeptidase anthrax lethal factor (lf) from the endosome to the cytosol requires an acidic endosomal milieu. in the current study, we utilized immobilized (to prevent protein aggregation below ph 5.5) and native lf to assess the effect of ph on the function and metal content of lf. our results reveal the diminution of lf's catalytic competence under moderately acidic conditions (ph ∼6) to be uncorrelated to the metal content of the protein. however, a ...201323313942
fusion of laboratory and textual data for investigative bioforensics.chemical and biological forensic programs focus on the identification of a threat and acquisition of laboratory measurements to determine how a threat agent may have been produced. however, to generate investigative leads, it might also be useful to identify institutions where the same agent has been produced by the same or a very similar process, since the producer of the agent may have learned methods at a university or similar institution. we have developed a bayesian network framework that f ...201323313599
ground anthrax bacillus refined isolation (gabri) method for analyzing environmental samples with low levels of bacillus anthracis contamination.in this work are reported the results of a qualitative analytical method capable of detecting bacillus anthracis spores when they are present in very low concentration in the soil. the ground anthrax bacillus refined isolation (gabri) method, assessed in our laboratory, was compared with the classic method. the comparison involved artificially anthrax-contaminated soil samples (500 spores/7.5 grams soil) and naturally contaminated soil samples collected in bangladesh during a field investigation ...201323865983
constant domains influence binding of mouse-human chimeric antibodies to the capsular polypeptide of bacillus anthracis.our laboratory previously described the binding characteristics of the murine igg3 monoclonal antibody (muab) f26g3. this antibody binds the poly-glutamic acid capsule (pga) of bacillus anthracis, an essential virulence factor in the progression of anthrax. f26g3 igg3 muab binds pga with a relatively high functional affinity (10 nm), produces a distinct "rim" quellung reaction, and is protective in a murine model of pulmonary anthrax. this study engineered an igg subclass family of f26g3 mouse-h ...201323863605
a human/murine chimeric fab antibody neutralizes anthrax lethal toxin in vitro.human anthrax infection caused by exposure to bacillus anthracis cannot always be treated by antibiotics. this is mostly because of the effect of the remaining anthrax toxin in the body. lethal factor (lf) is a component of lethal toxin (letx), which is the major virulence of anthrax toxin. a murine igg monoclonal antibody (mab) against lf with blocking activity (coded lf8) was produced in a previous study. in this report, a human/murine chimeric fab mab (coded lf8-fab) was developed from lf8 by ...201323861692
inhibitors of bacillus anthracis edema factor.edema factor (ef) is a calmodulin (cam)-activated adenylyl cyclase (ac) toxin from bacillus anthracis that contributes to anthrax pathogenesis. anthrax is an important medical problem, but treatment of b. anthracis infections is still unsatisfying. thus, selective ef inhibitors could be valuable drugs in the treatment of anthrax infection, most importantly shock. the catalytic site of ef, the ef/cam interaction site and allosteric sites constitute potential drug targets. to this end, most effort ...201323850654
designed azolopyridinium salts block protective antigen pores in vitro and protect cells from anthrax toxin.several intracellular acting bacterial protein toxins of the ab-type, which are known to enter cells by endocytosis, are shown to produce channels. this holds true for protective antigen (pa), the binding component of the tripartite anthrax-toxin of bacillus anthracis. evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric pa63 binding/translocation component are r ...201323840407
high temperature unfolding of a truncated hemoglobin by molecular dynamics simulation.heme containing proteins are associated with peroxidase activity. the proteins like hemoglobin, myoglobins, cytochrome c and micro-peroxidase other than peroxidases have been shown to exhibit weak peroxidase-like activity. this weak peroxidase-like activity in hemoglobin-like molecules is due to heme moiety. we conducted molecular dynamics (md) studies to decipher the unfolding path of ba-glb (a truncated hemoglobin from bacillus anthracis) and the role of heme moiety to its unfolding path. the ...201323839248
[a severe cutaneous anthrax case complicated with sepsis in bursa, turkey].anthrax is a zoonotic infection caused by bacillus anthracis. although the incidence of disease has been decreasing in turkey, it is still endemic in some regions of the country. the cutaneous form of disease is the most common clinical form, usually benign and rarely causes bacteriemia and sepsis. in this report, a case of cutaneous anthrax complicated with sepsis where b.anthracis was isolated from blood and wound cultures, was presented. a 53-years-old male living in bursa province (northwest ...201323971931
decontamination of a hospital room using gaseous chlorine dioxide: bacillus anthracis, francisella tularensis, and yersinia pestis.this study assessed the efficacy of gaseous chlorine dioxide for inactivation of bacillus anthracis, francisella tularensis, and yersinia pestis in a hospital patient care suite. spore and vegetative cells of bacillus anthracis sterne 34f2, spores of bacillus atrophaeus atcc 9372 and vegetative cells of both francisella tularensis atcc 6223 and yersinia pestis a1122 were exposed to gaseous chlorine dioxide in a patient care suite. organism inactivation was then assessed by log reduction in viabl ...201323971883
thermally modulated porous silica multispectral filters and their application in remote imaging.we report a thermally tunable multispectral imaging filter based on reversible condensation of volatile organic fluids within a nanoporous one-dimensional photonic crystal. the photonic crystal (optical rugate filter) comprises oxidized porous silicon, prepared by electrochemical etch of silicon and subsequent air oxidation (porous silica rugate filter, psif). the reflectance spectrum of the psif is designed and constructed to match two of the red emission bands of the luminescent complex europi ...201323968219
dual effects of single-walled carbon nanotubes coupled with near-infrared radiation on bacillus anthracis spores: inactivates spores and stimulates the germination of surviving spores.bacillus anthracis is a pathogen that causes life-threatening disease--anthrax. b. anthracis spores are highly resistant to extreme temperatures and harsh chemicals. inactivation of b. anthracis spores is important to ensure the environmental safety and public health. the 2001 bioterrorism attack involving anthrax spores has brought acute public attention and triggered extensive research on inactivation of b. anthracis spores. single-walled carbon nanotubes (swcnts) as a class of emerging nanoma ...201323965258
high throughput detection of human neutrophil peptides from serum, saliva, and tear by anthrax lethal factor-modified nanoparticles.human α defensins human neutrophil peptide 1-3 (hnp 1-3) are potential prognostic cancer biomarkers. metalloprotein anthrax lethal factor (alf) binds to hnp 1-3 in a zn2+-dependent manner. we conjugated alf to the surface of magnetic nanoparticles (mnp) to magnetically isolate the hnps, and used zn2+ to control the capture and release hnps.201323965149
monitoring the kinetics of the ph-driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance.domain 2 of the anthrax protective antigen (pa) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 å β barrel pore that inserts into the endosomal membrane. the pa pore facilitates the ph-dependent unfolding and translocation of bound toxin enzymic components, lethal factor (lf) and/or edema factor, from the endosome to the cytoplasm. we constructed immobilized complexes of the prepore with the pa-binding domain of lf (lfn) to monitor the real-time pre ...201323964683
equivalent t cell epitope promiscuity in ecologically diverse human pathogens.the hla (human leukocyte antigen) molecules that present pathogen-derived epitopes to t cells are highly diverse. correspondingly, many pathogens such as hiv evolve epitope variants in order to evade immune recognition. in contrast, another persistent human pathogen, mycobacterium tuberculosis, has highly conserved epitope sequences. this raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse hla alleles, referred to as an epitope's bin ...201323951341
anthrax toxin-induced rupture of artificial lipid bilayer membranes.we demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. when the solution ph is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. the results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm.201323947891
receptor-directed chimeric toxins created by sortase-mediated protein fusion.chimeric protein toxins that act selectively on cells expressing a designated receptor may serve as investigational probes and/or antitumor agents. here, we report use of the enzyme sortase a (srta) to create four chimeric toxins designed to selectively kill cells bearing the tumor marker her2. we first expressed and purified: (i) a receptor recognition-deficient form of diphtheria toxin that lacks its receptor-binding domain and (ii) a mutated, receptor-binding-deficient form of anthrax-protect ...201323945077
co-infection of an animal with more than one genotype can occur in anthrax.during the routine fingerprinting of outbreak strains of bacillus anthracis of european and african origin by means of a 31-marker multi-locus variable number of tandem repeats analysis (mlva), four cultures, two from the etosha national park (enp), namibia, and two from an outbreak in the pyrenees in 1997, were found to harbour different genotypes (gts). to investigate this further, isolates from 10 samples of blood-soaked soil from beneath anthrax carcasses and 18 clinical swabs taken from car ...201323937393
field-based pcr for rapid diagnosis of cutaneous anthrax in the deployed setting using the joint biological agent identification and diagnostic system.anthrax is occasionally encountered by u.s. military physicians in the deployed setting, where limited resources make it difficult to obtain laboratory confirmation. we present a case of cutaneous anthrax diagnosed using a ruggedized polymerase chain reaction device in austere combat conditions.201323929060
d-cycloserine or similar physiochemical compounds may be uniquely suited for use in bacillus anthracis spore decontamination strategies.as observed in the aftermath of the anthrax attacks of 2001, decontamination and remediation of a site contaminated by the accidental or intentional release of bacillus anthracis spores is difficult, costly and potentially damaging to the environment. the identification of novel strategies that neutralize the threat of spores while minimizing environmental damage remains a high priority. we investigated the efficacy of d-cycloserine (dcs), an antibiotic and inhibitor of the spore-associated enzy ...201323927578
biophysical characterization and immunization studies of dominant negative inhibitor (dni), a candidate anthrax toxin subunit vaccine.dominant negative inhibitor (dni) is a translocation-deficient homolog of recombinant protective antigen of bacillus anthracis that is a candidate for a next generation anthrax vaccine. this study demonstrates that the biophysical characteristics of the dni protein stored in lyophilized form at 4°c for 8 y were similar to recombinant protective antigen (rpa). to provide information on the accelerated stability of dni, samples in the lyophilized form were subjected to thermal stress (40°c and 70° ...201323925275
periocular cutaneous anthrax in jimma zone, southwest ethiopia: a case series.anthrax is a zoonotic disease caused by bacillus anthracis. naturally occurring human infection is rare and is generally the result of contact with anthrax-infected animals or animal products.201323924443
anthrax lethal toxin induces acute diastolic dysfunction in rats through disruption of the phospholamban signaling network.anthrax lethal toxin (lt), secreted by bacillus anthracis, causes severe cardiac dysfunction by unknown mechanisms. lt specifically cleaves the docking domains of mapkk (meks); thus, we hypothesized that lt directly impairs cardiac function through dysregulation of mapk signaling mechanisms.201323907041
assessing agreement of repeated binary measurements with an application to the cdc's anthrax vaccine clinical trial.cohen's kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. however, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. this study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions ...201323898025
regulation of bacillus subtilis bacillithiol biosynthesis operons by spx.bacillithiol is the major low molecular mass thiol produced by many firmicutes bacteria, including the model organism bacillus subtilis and pathogens such as bacillus anthracis and staphylococcus aureus. we have previously shown that four genes (bsha, bshb1, bshb2 and bshc) are involved in bacillithiol biosynthesis. here, we report that these four genes are encoded within three, unlinked operons all expressed from canonical σ(a)-dependent promoters as determined by 5'race (rapid amplification of ...201323894131
differentiation of strains from the bacillus cereus group by rflp-pfge genomic fingerprinting.bacillus mycoides, bacillus pseudomycoides, bacillus weihenstephanensis, bacillus anthracis, bacillus thuringiensis, and bacillus cereus belong to the b. cereus group. the last three species are characterized by different phenotype features and pathogenicity spectrum, but it has been shown that these species are genetically closely related. the macrorestriction analysis of the genomic dna with the noti enzyme was used to generate polymorphism of restriction profiles for 39 food-borne isolates (b ...201323893780
identification of a ligand on the wip1 bacteriophage highly specific for a receptor on bacillus anthracis.tectiviridae is a family of tailless bacteriophages with gram-negative and gram-positive hosts. the family model prd1 and its close relatives all infect a broad range of enterobacteria by recognizing a plasmid-encoded conjugal transfer complex as a receptor. in contrast, tectiviruses with gram-positive hosts are highly specific to only a few hosts within the same bacterial species. the cellular determinants that account for the observed specificity remain unknown. here we present the genome sequ ...201323893110
present-day conservative treatment retinopathy of prematurity.retinopathy of prematurity occurs in prematurely born babies. etiology of disease is multifactorial and frequency of retinopathy of prematurity diagnosis increases. retinopathy is one of causes for major loss of vision and amaurosis in newborns around the world. low efficacy of treatment leads to necessity for looking for new solutions and modern therapy use in treatment of this disease. so far, therapies used are: laser and cryotherapy and cases of retina detachment, the course is combined with ...201323882745
in vitro and in vivo activities of recombinant anthrax protective antigen co-expressed with thioredoxin in escherichia coli.because of the central role it plays in the formation of lethal toxin and edema toxin, protective antigen (pa) is the principal target for the development of vaccines against anthrax. in the present study, we explored and compared the in vitro and in vivo activities of recombinant anthrax protective antigen (rpa) and receptor binding domain of protective antigen (pa4). as a result, the fully soluble rpa and pa4 proteins were successfully expressed in escherichia coli by co-expression with thiore ...201323880942
toxin inhibition of antimicrobial factors induced by bacillus anthracis peptidoglycan in human blood.here, we describe the capacity of bacillus anthracis peptidoglycan (bapgn) to trigger an antimicrobial response in human white blood cells (wbcs). analysis of freshly isolated human blood cells found that monocytes and neutrophils, but not b and t cells, were highly responsive to bapgn and produced a variety of cytokines and chemokines. this bapgn-induced response was suppressed by anthrax lethal toxin (lt) and edema toxin (et), with the most pronounced effect on human monocytes, and this corres ...201323876807
engineering biomaterial-associated complement activation to improve vaccine efficacy.the complement system plays an important role in innate and adaptive immunity, which suggests that complement activation could be exploited as a potential strategy for vaccine adjuvants. here we explored the potential of chitosan-based microparticles (cs-nh2 mps) as a vaccine adjuvant with an active surface for complement activation due to the abundance of amino groups. in vaccination studies, using recombinant anthrax protective antigen as a model antigen, compared with the control microparticl ...201323875970
transcriptomic and phenotypic analysis of paralogous spx gene function in bacillus anthracis sterne.spx of bacillus subtilis is a redox-sensitive protein, which, under disulfide stress, interacts with rna polymerase to activate genes required for maintaining thiol homeostasis. spx orthologs are highly conserved among low %gc gram-positive bacteria, and often exist in multiple paralogous forms. in this study, we used b. anthracis sterne, which harbors two paralogous spx genes, spxa1 and spxa2, to examine the phenotypes of spx null mutations and to identify the genes regulated by each spx paralo ...201323873705
poly(acrylic acid)-grafted fluoropolymer films for highly sensitive fluorescent bioassays.in this study, a facile and effective method for the surface functionalization of inert fluoropolymer substrates using surface grafting was demonstrated for the preparation of a new platform for fluorescence-based bioassays. the surface of perfluorinated poly(ethylene-co-propylene) (fep) films was functionalized using a 150 kev ion implantation, followed by the graft polymerization of acrylic acid, to generate a high density of carboxylic acid groups on the implanted surface. the resulting funct ...201323452270
biosurveillance in outbreak investigations.following the terrorist attacks of september 11 and the anthrax attacks in 2001, public health entities implemented automated surveillance systems based on disease syndromes for early detection of bioterror events and to increase timeliness of responses. despite widespread adoption, syndromic surveillance systems' ability to provide early notification of outbreaks is unproven, and there is little documentation on their role in outbreak response. we hypothesized that biosurveillance is used in pr ...201323448272
increased long-term immunity to bacillus anthracis protective antigen in mice immunized with a cia06b-adjuvanted anthrax vaccine.anthrax is an acute infectious disease caused by bacillus anthracis. we previously reported that the adjuvant cia06b, which consists of tlr4 agonist cia05 and aluminum hydroxide (alum), enhanced the immune response to anthrax protective antigen (pa) in mice. this study was carried out to determine whether cia06b can enhance long-term immune responses to pa in mice. balb/c mice were immunized intramuscularly three times at 2-week intervals with recombinant pa alone or pa combined with alum or cia ...201323440578
evaluation of peracetic acid fog for the inactivation of bacillus anthracis spore surrogates in a large decontamination chamber.the purpose of this study was to evaluate the sporicidal (inactivation of bacterial spores) effectiveness and operation of a fogging device utilizing peracetic acid/hydrogen peroxide (paa). experiments were conducted in a pilot-scale 24 m(3) stainless steel chamber using either biological indicators (bis) or bacterial spores deposited onto surfaces via aerosolization. wipe sampling was used to recover aerosol-deposited spores from chamber surfaces and coupon materials before and after fogging to ...201323434480
cutaneous anthrax resulting in renal failure with generalized tissue damage.anthrax is a zoonotic infection caused by bacillus anthracis which can be clinically present in a cutaneous, gastrointestinal or inhalational form depending on the entry site of the agent. the most frequent clinical type with the mildest clinical course is cutaneous anthrax. in this report, a patient with cutaneous anthrax which begins at the dorsal hand and progresses up to the proximal forearm resulting in massive tissue damage is presented. prerenal azotemia developed due to massive tissue da ...201323431997
current biodefense vaccine programs and challenges.the defense threat reduction agency's joint science and technology office manages the chemical and biological defense program's science and technology portfolio. the joint science and technology office's mission is to invest in transformational ideas, innovative people and actionable technology development for chemical and biological defense solutions, with the primary goal to deliver science and technology products and capabilities to the warfighter and civilian population that outpace the thre ...201323428906
vector-mediated selective expression of lethal factor, a toxic element of bacillus anthracis, damages a549 cells via inhibition of mapk and akt pathways.lethal factor (lf), a major toxic element of bacillus anthracis combined with its protective antigen (pa), enters the cells through the cytomembrane receptors and causes damage to the host cells, thereby leading to septicemia, toxemia, and meningitis with high mortality. lf has been identified as a potential biotech-weapon, which can impede cancer growth in vascular endothelial cells because of its cytotoxicity. however, the feasibility of lf application and further investigations has been limit ...201323423542
awareness and attitude toward zoonoses with particular reference to anthrax among cattle owners in selected rural communities of zimbabwe.we conducted a cross-sectional study to assess cattle owners' awareness, perceptions, and attitudes toward zoonoses, with particular emphasis regarding anthrax. data on awareness of zoonoses, clinical signs of anthrax in animals and human, its routes of transmission and methods of prevention, the families' consumption habits of anthrax-infected carcasses, and other family activities that increase exposure to anthrax were collected using an interviewer-administered questionnaire. a total of 41.4% ...201323421887
cytotoxicity of anthrax lethal toxin to human acute myeloid leukemia cells is nonapoptotic and dependent on extracellular signal-regulated kinase 1/2 activity.in this study, we attempt to target the mitogen-activated protein kinase (mapk) pathway in acute myeloid leukemia (aml) cells using a recombinant anthrax lethal toxin (letx). letx consists of protective antigen (prag) and lethal factor (lf). prag binds cells, is cleaved by furin, oligomerizes, binds three to four molecules of lf, and undergoes endocytosis, releasing lf into the cytosol. lf cleaves mapk kinases, inhibiting the mapk pathway. we tested potency of letx on a panel of 11 human aml cel ...201323418614
bacillus weihenstephanensis characteristics are present in bacillus cereus and bacillus mycoides strains.the bacillus cereus group comprises seven bacterial species: bacillus cereus, bacillus anthracis, bacillus thuringiensis, bacillus mycoides, bacillus pseudomycoides, bacillus cytotoxicus, and bacillus weihenstephanensis. bacillus weihenstephanensis is distinguished based on its capability to grow at 7 °c but not at 43 °c, and the presence of specific signature sequences in the 16s rrna and cspa genes and in several housekeeping genes: glpf, gmk, purh, and tpi. bacillus weihenstephanensis-specifi ...201323413955
a genetic approach for the identification of exosporium assembly determinants of bacillus anthracis.the exosporium is the outermost layer of spores of the zoonotic pathogen bacillus anthracis. the composition of the exosporium and its functions are only partly understood. because this outer spore layer is refractive to traditional biochemical analysis, a genetic approach is needed in order to define the proteins which comprise this important spore layer and its assembly pathway. we have created a novel genetic screening system for the identification and isolation of mutants with defects in exo ...201323411372
portable, quantitative detection of bacillus bacterial spores using surface-enhanced raman scattering.portable rapid detection of pathogenic bacteria such as bacillus is highly desirable for safety in food manufacture and under the current heightened risk of biological terrorism. surface-enhanced raman scattering (sers) is becoming the preferred analytical technique for bacterial detection, due to its speed of analysis and high sensitivity. however in seeking methods offering the lowest limits of detection, the current research has tended toward highly confocal, microscopy-based analysis, which ...201323409961
genome sequence of the attenuated carbosap vaccine strain of bacillus anthracis.the bacillus anthracis carbosap genome, which includes the pxo1 and pxo2 plasmids, has been shown to encode the major b. anthracis virulence factors, yet this strain's attenuation has not yet been explained. here we report the draft genome sequence of this strain, and a comparison to fully virulent b. anthracis.201323405332
1,2,3,4,6-penta-o-galloyl-β-d-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2.capillary morphogenesis gene 2 (cmg2) is a transmembrane extracellular matrix binding protein that is also an anthrax toxin receptor. we have shown that high-affinity cmg2 binders can inhibit angiogenesis and tumor growth. we recently described a high-throughput fret assay to identify cmg2 inhibitors. we now report the serendipitous discovery that pgg (1,2,3,4,6-penta-o-galloyl-β-d-glucopyranose) is a cmg2 inhibitor with antiangiogenic activity. pgg is a gallotannin produced by a variety of medi ...201323394144
engineering anthrax toxin variants that exclusively form octamers and their application to targeting tumors.anthrax toxin protective antigen (pa) delivers its effector proteins into the host cell cytosol through formation of an oligomeric pore, which can assume heptameric or octameric states. by screening a highly directed library of pa mutants, we identified variants that complement each other to exclusively form octamers. these pa variants were individually nontoxic and demonstrated toxicity only when combined with their complementary partner. we then engineered requirements for activation by matrix ...201323393143
assembly of anthrax toxin pore: lethal-factor complexes into lipid nanodiscs.we have devised a procedure to incorporate the anthrax protective antigen (pa) pore complexed with the n-terminal domain of anthrax lethal factor (lfn ) into lipid nanodiscs and analyzed the resulting complexes by negative-stain electron microscopy. insertion into nanodiscs was performed without relying on primary and secondary detergent screens. the preparations were relatively pure, and the percentage of pa pore inserted into nanodiscs on em grids was high (∼43%). three-dimensional analysis of ...201323389868
studies in mice reveal a role for anthrax toxin receptors in matrix metalloproteinase function and extracellular matrix homeostasis.the genes encoding anthrax toxin receptors (antxrs) were originally identified based on expression in endothelial cells suggesting a role in angiogenesis. the focus of this review is to discuss what has been learned about the physiological roles of these receptors through evaluation of the antxr knockout mouse phenotypes. mice mutant in antxr genes have defects in extracellular matrix homeostasis. we discuss how knowledge of physiological antxr function relates to what is already known about ant ...201323389402
a novel homogeneous immunoassay for anthrax detection based on the alphalisa method: detection of b. anthracis spores and protective antigen (pa) in complex samples.amplified luminescent proximity homogeneous assay (alphalisa) technology is an energy-transfer-based assay, utilizing singlet oxygen as an energy donor to a fluorescent acceptor. the long singlet oxygen migration distance allows the energy transfer mechanism to go up to ~200 nm, facilitating flexible and sensitive homogeneous immunoassays. while soluble protein detection using alphalisa was previously described, the detection of particles such as bacteria and viruses was not reported. in this wo ...201323388689
concentration, detection and discrimination of bacillus anthracis spores in orange juice using aptamer based surface enhanced raman spectroscopy.herein, we developed an innovative label free platform for concentration, detection and discrimination of bacillus anthracis spores. based on aptamer capture and surface enhanced raman scattering detection, we were able to detect 10(4) cfu spores spiked in orange juice and discriminate between spores b. anthracis and b. mycoides within 40 min.201323386216
elastic and inelastic diffraction changes upon variation of the relative humidity environment of pure crystals.the different changes observed in the diffraction patterns of three different crystal forms (hexagonal, trigonal and monoclinic) of pure (ec 4.1.1.21), an enzyme from the purine-biosynthesis pathway of bacillus anthracis, upon a wide range of changes in the relative humidity environment of the crystals are documented. in addition, the changes in the unit-cell parameters, volume and bulk solvent in the three different crystal forms were systematically followed. in an attempt to explain the elasti ...201323385456
colonic immune stimulation by targeted oral vaccine.currently, sufficient data exist to support the use of lactobacilli as candidates for the development of new oral targeted vaccines. to this end, we have previously shown that lactobacillus gasseri expressing the protective antigen (pa) component of anthrax toxin genetically fused to a dendritic cell (dc)-binding peptide (dcpep) induced efficacious humoral and t cell-mediated immune responses against bacillus anthracis sterne challenge.201323383086
fatal cutaneous anthrax in a heroin user.cutaneous anthrax usually has a mortality rate of less than 1 per cent. however, since december 2009 there have been more than 13 deaths in the uk due to anthrax-contaminated heroin. we therefore wish to raise clinical awareness of this treatable disease.201323374534
the near-iron transporter (neat) domains of the anthrax hemophore isdx2 require a critical glutamine to extract heme from methemoglobin.several gram-positive pathogenic bacteria employ near-iron transporter (neat) domains to acquire heme from hemoglobin during infection. however, the structural requirements and mechanism of action for neat-mediated heme extraction remains unknown. bacillus anthracis exhibits a rapid growth rate during systemic infection, suggesting that the bacterium expresses efficient iron acquisition systems. to understand how b. anthracis acquires iron from heme sources, which account for 80% of mammalian ir ...201323364793
pathology and pathophysiology of inhalational anthrax in a guinea pig model.nonhuman primates (nhps) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the fda's "animal rule." however, a need for an alternative animal model may arise in certain cases. the development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. the guinea p ...201323357384
a simple, reliable m'fadyean stain for visualizing the bacillus anthracis capsule.the simple polychrome methylene blue (pmb) staining procedure for blood or tissue smears from dead animals (m'fadyean reaction) established in 1903 remained accepted as a highly reliable, rapid diagnostic test for anthrax for six decades while that disease was still common in livestock throughout the world. improvements in disease control led to anthrax becoming rare in industrialized countries and less frequent in developing countries with the result that quality controlled, commercially produc ...201323357124
rapid vaccination using an acetalated dextran microparticulate subunit vaccine confers protection against triplicate challenge by bacillus anthracis.a rapid immune response is required to prevent death from anthrax, caused by bacillus anthracis.201323354770
genetic tools to enhance the study of gene function and regulation in staphylococcus aureus.the bursa aurealis transposon has been used to create transposon insertion libraries of bacillus anthracis and staphylococcus aureus. to provide a set of genetic tools to enhance the utility of these libraries, we generated an allelic-exchange system that allows for the replacement of the transposon with useful genetic markers and fluorescent reporter genes. these tools were tested in the nebraska transposon mutant library (ntml), containing defined transposon insertions in 1,952 nonessential s. ...201323354696
a comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen.development of nasal immunization for human use is hindered by the lack of acceptable adjuvants. although ct is an effective adjuvant, its toxicity will likely prevent its use in nasal vaccines. this study compared non-toxin adjuvants to ct for their ability to induce protective antibody responses with nasal immunization. c3h/hen and c57bl/6 mice were immunized with rpa formulated with the following adjuvants: ct, il-1α, lps, cpg, pam3csk4, 3m-019, resiquimod/r848 or c48/80. serum and nasal wash ...201323352329
carbon microarrays for the direct impedimetric detection of bacillus anthracis using gamma phages as probes.a direct and efficient impedimetric method is presented for the detection of bacillus anthracis sterne vegetative cells, using gamma phages as probes attached to screen-printed carbon electrode microarrays. the carbon electrodes were initially functionalized through cyclic-voltammetric reduction of a nitro-aryl diazonium moiety, followed by further reduction of nitro groups to amino groups, and finally by treatment with glutaraldehyde. functionalization (probe immobilization) using gamma phages ...201323348920
bacillus anthracis protective antigen kinetics in inhalation spore-challenged untreated or levofloxacin/ raxibacumab-treated new zealand white rabbits.inhaled bacillus anthracis spores germinate and the subsequent vegetative growth results in bacteremia and toxin production. anthrax toxin is tripartite: the lethal factor and edema factor are enzymatic moieties, while the protective antigen (pa) binds to cell receptors and the enzymatic moieties. antibiotics can control b. anthracis bacteremia, whereas raxibacumab binds pa and blocks lethal toxin effects. this study assessed plasma pa kinetics in rabbits following an inhaled b. anthracis spore ...201323344456
identification of novel host-targeted compounds that protect from anthrax lethal toxin-induced cell death.studying how pathogens subvert the host to cause disease has contributed to the understanding of fundamental cell biology. bacillus anthracis, the causative agent of anthrax, produces the virulence factor lethal toxin to disarm host immunity and cause pathology. we conducted a phenotypic small molecule screen to identify inhibitors of lethal toxin-induced macrophage cell death and used an ordered series of secondary assays to characterize the hits and determine their effects on cellular function ...201323343607
medical aspects of bio-terrorism.bioterrorism is a terrorist action involving the intentional release or dissemination of a biological warfare agent (bwa), which includes some bacteria, viruses, rickettsiae, fungi or biological toxins. bwa is a naturally occurring or human-modified form that may kill or incapacitate humans, animals or plants as an act of war or terrorism. bwa is a weapon of choice for mass destruction and terrorism, because of the incubation period, less effective amount than chemical warfare agents, easily dis ...201323339855
distinct functions of polysaccharide deacetylases in cell shape, neutral polysaccharide synthesis and virulence of bacillus anthracis.peptidoglycan deacetylases (pgng-dacs) belong to the carbohydrate esterase family 4 (ce4) and have been described as required for bacterial evasion to lysozyme and innate immune responses. interestingly, there is an unusual occurrence of 10 putative polysaccharide deacetylases, including five pgng-dacs, in the bacillus sp. genomes, especially b. cereus and b. anthracis. to elucidate the physiological role of these multiple deacetylases, we employed genetic analysis and protein localization studi ...201323336745
new generation of oral mucosal vaccines targeting dendritic cells.as most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. both local mucosal immunity and robust systemic ...201323835515
antxr1, a stem cell-enriched functional biomarker, connects collagen signaling to cancer stem-like cells and metastasis in breast cancer.cancer stem-like cells are thought to contribute to tumor recurrence. the anthrax toxin receptor 1 (antxr1) has been identified as a functional biomarker of normal stem cells and breast cancer stem-like cells. primary stem cell-enriched basal cells (cd49f(+)/epcam(-)/lin(-)) expressed higher levels of antxr1 compared with mature luminal cells. cd49f(+)/epcam(-), cd44(+)/epcam(-), cd44(+)/cd24(-), or aldefluor-positive subpopulations of breast cancer cells were enriched for antxr1 expression. cd4 ...201323832666
biowarfare and bioterrorism.bioterrorism is not only a reality of the times in which we live but bioweapons have been used for centuries. critical care physicians play a major role in the recognition of and response to a bioterrorism attack. critical care clinicians must be familiar with the diagnosis and management of the most likely bioterrorism agents, and also be adequately prepared to manage a mass casualty situation. this article reviews the epidemiology, diagnosis, and treatment of the most likely agents of biowarfa ...201323830660
a new murine model for gastrointestinal anthrax infection.the scientific community has been restricted by the lack of a practical and informative animal model of gastrointestinal infection with vegetative bacillus anthracis. we herein report the development of a murine model of gastrointestinal anthrax infection by gavage of vegetative sterne strain of bacillus anthracis into the complement-deficient a/j mouse strain. mice infected in this manner developed lethal infections in a dose-dependent manner and died 30 h-5 d following gavage. histological fin ...201323825096
engineering unnatural variants of plantazolicin through codon reprogramming.plantazolicin (pzn) is a polyheterocyclic natural product derived from a ribosomal peptide that harbors remarkable antibiotic selectivity for the causative agent of anthrax, bacillus anthracis. to simultaneously establish the structure-activity relationship of pzn and the substrate tolerance of the biosynthetic pathway, an escherichia coli expression strain was engineered to heterologously produce pzn analogues. variant pzn precursor genes were produced by site-directed mutagenesis and later scr ...201323823732
genetic diversity of korean bacillus anthracis isolates from soil evaluated with a single nucleotide repeat analysis.bacillus (b.) anthracis, the etiological agent of anthrax, is one of the most genetically monomorphic bacteria species in the world. due to the very limited genetic diversity of this species, classification of isolates of this bacterium requires methods with high discriminatory power. single nucleotide repeat (snr) analysis is a type of variable-number tandem repeat assay that evaluates regions with very high mutation rates. to subtype a collection of 21 isolates that were obtained during a b. a ...201323820210
cbrne tc3: a hybrid approach to casualty care in the cbrne environment.the implementation of tactical combat casualty care (tccc) guidelines for the operation enduring freedom and operation iraqi freedom contingency operations has dramatically reduced preventable combat deaths. a study of these principles and their application to medical treatment in the chemical, biological, radiological, nuclear, and high-yield explosives (cbrne), weapons of mass destruction (wmd) environment is presented as a potential readiness and force multiplier for units engaged in this are ...201323817878
3-substituted indole inhibitors against francisella tularensis fabi identified by structure-based virtual screening.in this study, we describe novel inhibitors against francisella tularensis schus4 fabi identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. two 3-substituted indoles, 54 and 57, preferentially bound the nad(+) form of the enzyme and inhibited growth of f. tularensis schus4 at concentrations near that of their measured ki. while 57 was species-specific, 54 showed a broader sp ...201323815100
analysis of the errors in the electrostatically embedded many-body expansion of the energy and the correlation energy for zn and cd coordination complexes with five and six ligands and use of the analysis to develop a generally successful fragmentation strategy.in the present paper, we apply the electrostatically embedded many-body expansion of the correlation energy (ee-mb-ce) to the calculation of zinc-ligand and cadmium-ligand bond dissociation energies, and we analyze the errors due to various fragmentation schemes in a variety of neutral, positively charged, and negatively charged zn(2+) and cd(2+) coordination complexes. as a result of the analysis, we are able to present a new, simple, and unambiguous fragmentation strategy. following this strat ...201323814509
inhalational anthrax in a vaccinated soldier. 201323813313
rapid detection and identification of bacillus anthracis in food using pyrosequencing technology.the development of advanced methodologies for the detection of bacillus anthracis has been evolving rapidly since the release of the anthrax spores in the mail in 2001. recent advances in detection and identification techniques could prove to be an essential component in the defense against biological attacks. sequence based such as pyrosequencing, which has the capability to determine short dna stretches in real-time using biotinylated pcr amplicons, has potential biodefense applications. using ...201323810955
suspect vector transmission of human cutaneous anthrax during an animal outbreak in southern italy.during an outbreak of sheep anthrax in basilicata, southern italy, the owner of a flock located about 3 km away from the affected farm developed skin lesions attributable to cutaneous anthrax. the dna extracted from the human scabs confirmed the diagnosis, and a 15-loci multiple locus variable number tandem repeat (vntr) analysis (mlva) following single-nucleotide repeat (snr) analysis yielded the same genotype as that found in the dead sheep. the breeder, who had not had contact with infected o ...201323808978
de novo asymmetric synthesis of oligo-rhamno di- and tri-saccharides related to the anthrax tetrasaccharide.an asymmetric synthesis of the di- and trisaccharide portion of the naturally occurring anthrax tetrasaccharide from acetylfuran has been developed. the construction of the di- and trisaccharide subunits is based upon our previously disclosed route to anthrax tetrasaccharide. the approach uses iterative diastereoselective palladium-catalyzed glycosylations, luche reductions, diastereoselective dihydroxylations, and regioselective protections for the assembly of the rhamno- di- and tri-saccharide ...201323794755
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