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draft genome sequences of pseudomonas fluorescens bs2 and pusillimonas noertemannii bs8, soil bacteria that cooperate to degrade the poly-γ-d-glutamic acid anthrax capsule.a mixed culture of pseudomonas fluorescens bs2 and pusillimonas noertemannii bs8 degraded poly-γ-d-glutamic acid; when the 2 strains were cultured separately, no hydrolytic activity was apparent. here we report the draft genome sequences of both soil isolates.201323405351
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
development of a panel of recombinase polymerase amplification assays for detection of biothreat agents.syndromic panels for infectious disease have been suggested to be of value in point-of-care diagnostics for developing countries and for biodefense. to test the performance of isothermal recombinase polymerase amplification (rpa) assays, we developed a panel of 10 rpas for biothreat agents. the panel included rpas for francisella tularensis, yersinia pestis, bacillus anthracis, variola virus, and reverse transcriptase rpa (rt-rpa) assays for rift valley fever virus, ebola virus, sudan virus, and ...201323345286
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
mhc class ii and non-mhc class ii genes differentially influence humoral immunity to bacillus anthracis lethal factor and protective antigen.anthrax lethal toxin consists of protective antigen (pa) and lethal factor (lf), and current vaccination strategies focus on eliciting antibodies to pa. in human vaccination, the response to pa can vary greatly, and the response is often directed toward non-neutralizing epitopes. variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both mhc class ii and other genes playing roles. here, we investigated the relative contribution of mhc class ii v ...201223342680
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
the african buffalo: a villain for inter-species spread of infectious diseases in southern africa.the african buffalo (syncerus caffer) is a large wild bovid which until recently ranged across all but the driest parts of sub-saharan africa, and their local range being limited to about 20 km from surface water. they are of high ecological value due to their important role as bulk feeders in the grazing hierarchy. they also have high economic value, because they are one of the sought after 'big five' in the eco-tourism industry. in africa, buffaloes have been recognised for some time as an imp ...201223327373
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
new aspects of the infection mechanisms of bacillus anthracis.articles concerning new aspects of b. anthracis mechanisms of infection were reviewed. it was found, that the hair follicle plays an important role in the spore germination process. the hair follicle represent an important portal of entry in the course of the cutaneous form of disease infections. after mouse exposition to aerosol of spores prepared from b. anthracis strains, an increase in the level of tnf-α cytokines was observed. the tnf-α cytokines were produced after intrusion into the host ...201223311776
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
computational studies on molecular interactions of 6-thioguanosine analogs with anthrax toxin receptor 1.dormant endospores of bacillus anthracis are the causative agent of anthrax, which is an acute disease for both human and animals. anthrax has been practised as biological weapon because of two attributes: i) short duration of spore germination, and ii) lethal toxaemia of the vegetative stage. pathogenesis is caused by the activity of edema toxin and lethal toxin. protective antigen (pa), is an essential component of both complexes, binds to anthrax toxin receptor (atr) and mediates the lethalit ...201223292691
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
recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.we previously showed that a multiple antigenic peptide (map) vaccine displaying amino acids (aa) 304 to 319 from the 2β2-2β3 loop of protective antigen was capable of protecting rabbits from an aerosolized spore challenge with bacillus anthracis ames strain. antibodies to this sequence, referred to as the loop-neutralizing determinant (lnd), are highly potent at neutralizing lethal toxin yet are virtually absent in rabbit and human protective antigen (pa) antiserum. while the map vaccine was pro ...201323283638
evaluation of the filmarray® system for detection of bacillus anthracis, francisella tularensis and yersinia pestis.to evaluate the sensitivity and specificity of the biofire diagnostics filmarray(®) system in combination with their biothreat panel for the detection of bacillus anthracis (ba), francisella tularensis (ft) and yersinia pestis (yp) dna, and demonstrate the detection of ba spores.201323279070
development of a high throughput assay for indirectly measuring phage growth using the omnilog(tm) system.the conventional and most accepted method of measuring the lytic activity of a phage against its bacterial host is the plaque assay. this method is laborious, time consuming and expensive, especially in high throughput analyses where multiple phage-bacterial interactions are required to be monitored simultaneously. it can also vary considerably with the experimenter and by the growth and plating conditions. alternatively, the lytic activity can be measured indirectly by following the decrease in ...201223275867
the receptors that mediate the direct lethality of anthrax toxin.tumor endothelium marker-8 (tem8) and capillary morphogenesis protein-2 (cmg2) are the two well-characterized anthrax toxin receptors, each containing a von willebrand factor a (vwa) domain responsible for anthrax protective antigen (pa) binding. recently, a cell-based analysis was used to implicate another vwa domain-containing protein, integrin β1 as a third anthrax toxin receptor. to explore whether proteins other than tem8 and cmg2 function as anthrax toxin receptors in vivo, we challenged m ...201223271637
genetic populations of bacillus anthracis isolates from korea.bacillus (b.) anthracis is the pathogen that causes fatal anthrax. strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial population genetics. in the present study, we employed molecular approaches including multiple-locus variable-number tandem repeat analysis (mlva) and canonical single-nucleotide polymorphism (cansnp) analysis to perform molecular typing of b. anthracis strains isolated in korea. according to the mlva, 17 b. anthracis is ...201223271180
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
injection anthrax--a new outbreak in heroin users.injection anthrax is a rare disease that affects heroin users and is caused by bacillus anthracis. in 2012, there were four cases in germany, one of which was fatal, as well as a small number of cases in other european countries, including denmark, france, and the united kingdom. three cases among drug users occurred in germany in 2009/2010, in the setting of a larger outbreak centered on scotland, where there were 119 cases. case presentation and clinical course: we present three cases of injec ...201223267409
quantitative assessment of anthrax vaccine immunogenicity using the dried blood spot matrix.the collection, processing and transportation to a testing laboratory of large numbers of clinical samples during an emergency response situation present significant cost and logistical issues. blood and serum are common clinical samples for diagnosis of disease. serum preparation requires significant on-site equipment and facilities for immediate processing and cold storage, and significant costs for cold-chain transport to testing facilities. the dried blood spot (dbs) matrix offers an alterna ...201223266055
soft-x-ray-enhanced electrostatic precipitation for protection against inhalable allergens, ultrafine particles, and microbial infections.protection of the human lung from infectious agents, allergens, and ultrafine particles is difficult with current technologies. high-efficiency particulate air (hepa) filters remove airborne particles of >0.3 μm with 99.97% efficiency, but they are expensive to maintain. electrostatic precipitation has been used as an inexpensive approach to remove large particles from airflows, but it has a collection efficiency minimum in the submicrometer size range, allowing for a penetration window for some ...201223263945
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
recombinant groel enhances protective antigen-mediated protection against bacillus anthracis spore challenge.the fatal inhalation infection caused by bacillus anthracis results from a complex pathogenic cycle involving release of toxins by bacteria that germinate from spores. currently available vaccines against anthrax consist of protective antigen (pa), one of the anthrax toxin components. however, these pa-based vaccines are only partially protective against spore challenge in mice. this shows that exclusive elicitation of high anti-pa titer does not directly correlate with protection. here, we demo ...201223263010
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
effects of epidemic diseases on the distribution of bonobos.this study examined how outbreaks and the occurrence of anthrax, ebola, monkeypox and trypanosomiasis may differentially affect the distribution of bonobos (pan paniscus). using a combination of mapping, jaccard overlapping coefficients and binary regressions, the study determined how each disease correlated with the extent of occurrence of, and the areas occupied by, bonobos. anthrax has only been reported to occur outside the range of bonobos and so was not considered further. ebola, monkeypox ...201223251431
plasma bacterial and mitochondrial dna distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates.systemic inflammatory response syndrome (sirs) is a fundamental host response common to bacterial infection and sterile tissue injury. systemic inflammatory response syndrome can cause organ dysfunction and death, but its mechanisms are incompletely understood. moreover, sirs can progress to organ failure or death despite being sterile or after control of the inciting infection. biomarkers discriminating between sepsis, sterile sirs, and postinfective sirs would therefore help direct care. circu ...201323247122
public response to an anthrax attack: a multiethnic perspective.the 2001 anthrax attacks emphasized the need to develop outreach that would more effectively support racial/ethnic minority populations during a bioterrorism incident. given the importance of antibiotic prophylaxis in a future anthrax attack, it should be a priority to better support racial/ethnic minorities in mass dispensing programs. to examine the needs and perspectives of racial/ethnic minorities, this study used a nationally representative poll of 1,852 adults, including 1,240 whites, 261 ...201223244501
bacillus anthracis acetyltransferases pata1 and pata2 modify the secondary cell wall polysaccharide and affect the assembly of s-layer proteins.the envelope of bacillus anthracis encompasses a proteinaceous s-layer with two s-layer proteins (sap and ea1). protein assembly in the envelope of b. anthracis requires s-layer homology domains (slh) within s-layer proteins and s-layer-associated proteins (bsls), which associate with the secondary cell wall polysaccharide (scwp), an acetylated carbohydrate that is tethered to peptidoglycan. here, we investigated the contributions of two putative acetyltransferases, pata1 and pata2, on scwp acet ...201323243307
rapid deamidation of recombinant protective antigen when adsorbed on aluminum hydroxide gel correlates with reduced potency of vaccine.deamidation of the recombinant protective antigen (rpa) correlates with decreased effectiveness of the vaccine in protecting against infection by bacillus anthracis. we present data demonstrating dramatic deamidation of amino acid positions 713 and 719 of rpa adsorbed onto aluminum hydroxide gel, an adjuvant, relative to rpa stored in solution without adjuvant. although deamidation did not impact total levels of rpa-specific antibodies in a mouse model, it did correlate with a decrease in toxin- ...201323242822
analysing the spatial patterns of livestock anthrax in kazakhstan in relation to environmental factors: a comparison of local (gi*) and morphology cluster statistics.we compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle) and small (sheep and goats) domestic ruminants across kazakhstan. the getis-ord (gi*) statistic and a multidirectional optimal ecotope algorithm (amoeba) were compared using 1st, 2nd and 3rd order rook contiguity matrices. multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the amoeba and gi* tests. a logistic regression ...201223242686
critical challenges and impediments affecting rural physicians during a public health emergency.disaster preparedness has become a health policy priority for the united states in the aftermath of the anthrax attacks, 9/11, and other calamities. it is important for rural health care professionals to be prepared for a bioterrorist attack or other public health emergency. we sought to determine the barriers impeding rural physicians from being prepared for a human-induced disaster such as a bioterrorist attack.201223241464
the differential susceptibility of spores from virulent and attenuated bacillus anthracis strains to aldehyde- and hypochlorite-based disinfectants.this study compared the sensitivity of spores from virulent and attenuated bacillus anthracis strains in suspension to inactivation by various chemical disinfectants. spore suspensions from two virulent strains (a0256 and a0372) and two attenuated strains (sterne and a0141) of b. anthracis were tested against two aldehyde-based disinfectants and one hypochlorite-based disinfectant. a novel statistical model was used to estimate 4-log(10) reduction times for each disinfectant/strain combination. ...201223233190
coumarin-based inhibitors of bacillus anthracis and staphylococcus aureus replicative dna helicase: chemical optimization, biological evaluation, and antibacterial activities.the increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9-18-fold increased potency against staphylococcus aureus (sa) and bacillus anthracis (ba) helicases. compounds 20 and ...201223231076
[detection and identification of highly pathogenic bacteria within the framework of the eqadeba project--part ii: samples containing inactivated pathogens].the aim of the studies was analysis of methods applied and results of detection and identification of bacillus anthracis, yersinia pestis, francisella tularensis, brucella sp., bulkholderia mallei and b. pseudomallei in inactivated samples obtained within the framework of the third external quality assessment exercise (eqae) in the project ,,establishment of quality assurances for detection of highly pathogenic bacteria of potential bioterrorism risk (eqadeba)".201223230707
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
informed consent in the military: the anthrax vaccination case. 200723228579
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
[safe from biothreats? legislation protects you and society].the 9/11 terror attacks, followed by mailing of letters containing anthrax spores, changed our comprehension on threats towards modern society. finland is committed by international treaties to develop biosafety and biosecurity legislation, and general awareness of the legislation. however, the rapidly developing field of biosciences cannot be extensively regulated by legislation. awareness of the risks and challenges involved in handling of biological agents is an important tool in threat preve ...201223210284
dna sequence detection based on raman spectroscopy using single walled carbon nanotube.a biosensor for detection of dna sequence in bacterium bacillus anthracis has been developed using raman spectrum of single walled carbon nanotubes (swnts). we have utilized the fact that being hydrophobic in nature single strand of target dna (diseased dna) gets wrapped over swnt surface forming single stranded dna-swnt complex. the sensing ability of this sensor has been studied using the dependency of g peak intensity (in the raman spectrum of swnts) on the covered surface of swnts. when a dn ...201323207369
rapid detection of bacillus anthracis spores using a super-paramagnetic lateral-flow immunological detection system.there is an urgent need for convenient, sensitive, and specific methods to detect the spores of bacillus anthracis, the causative agent of anthrax, because of the bioterrorism threat posed by this bacterium. in this study, we firstly develop a super-paramagnetic lateral-flow immunological detection system for b. anthracis spores. this system involves the use of a portable magnetic assay reader, super-paramagnetic iron oxide particles, lateral-flow strips and two different monoclonal antibodies d ...201323206542
bacillus cereus g9241 s-layer assembly contributes to the pathogenesis of anthrax-like disease in mice.bacillus cereus g9241, the causative agent of anthrax-like disease, harbors virulence plasmids encoding anthrax toxins as well as hyaluronic acid (ha) and b. cereus exopolysaccharide (bps) capsules. b. cereus g9241 also harbors s-layer genes, including homologs of bacillus anthracis surface array protein (sap), extractable antigen 1 (ea1), and the s-layer-associated proteins (bsls). in b. anthracis, s-layer proteins and bsls attach via their s-layer homology domains (slh) to the secondary cell w ...201323204457
pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor.antibiotic treatment may fail to protect individuals, if not started early enough, after infection with bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. stable and easily stored inhibitors of the edema factor toxin (ef), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. the toxin's basic activity is to convert atp to camp, and it is thus in principle a simple phosphatase, which means that many ...201223202316
anthrax toxin receptor 2a controls mitotic spindle positioning.oriented mitosis is essential during tissue morphogenesis. the wnt/planar cell polarity (wnt/pcp) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (a-v) axis during zebrafish gastrulation. how wnt signalling orients the mitotic plane is, however, unknown. here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic a-v axi ...201323201782
monoclonal antibody against the poly-gamma-d-glutamic acid capsule of bacillus anthracis protects mice from enhanced lethal toxin activity due to capsule and anthrax spore challenge.the poly-gamma-d-glutamic acid (pga) capsule, a major virulence factor of bacillus anthracis, protects bacilli from immune surveillance and allows its unimpeded growth in the host. recently, the importance of the pga in the pathogenesis of anthrax infection has been reported. the pga capsule is associated with lethal toxin (lt) in the blood of experimentally infected animals and enhances the cytotoxicity of lt.201323201204
recombinant expression and purification of a tumor-targeted toxin in bacillus anthracis.many recombinant therapeutic proteins are purified from escherichia coli. while expression in e. coli is easily achieved, some disadvantages such as protein aggregation, formation of inclusion bodies, and contamination of purified proteins with the lipopolysaccharides arise. lipopolysaccharides have to be removed to prevent inflammatory responses in patients. use of the gram-positive bacillus anthracis as an expression host offers a solution to circumvent these problems. using the multiple prote ...201323200832
role of mechanical vs. chemical action in the removal of adherent bacillus spores during cip procedures.this study was designed to evaluate the respective roles of mechanical and chemical effects on the removal of bacillus spores during cleaning-in-place. this analysis was performed on 12 strains belonging to the bacillus cereus group (b. cereus, bacillus anthracis, bacillus thuringiensis) or to less related bacillus species (bacillus pumilus, bacillus licheniformis, bacillus sporothermodurans, bacillus subtilis). adherent spores were subjected to rinsing-in-place (mechanical action) and cleaning- ...201323200646
perhydrolase-nanotube paint composites with sporicidal and antiviral activity.act (perhydrolase) containing paint composites were prepared leading to broad-spectrum decontamination. act was immobilized onto multi-walled carbon nanotubes (mwnts) and then incorporated into latex-based paints to form catalytic coatings. these act-based paint composites showed a 6-log reduction in the viability of spores of bacillus cereus and bacillus anthracis (sterne) within 60 min. the paint composites also showed >4-log reduction in the titer of influenza virus (x-31) within 10 min (init ...201323188457
bacillus anthracis-derived nitric oxide induces protein s-nitrosylation contributing to macrophage death.bacillus anthracis, a causative agent of anthrax, is able to germinate and survive within macrophages. a recent study suggested that b. anthracis-derived nitric oxide (bno) is a key aspect of bacterial defense that protects bacterial dna from oxidative burst in the macrophages. however, the virulent effect of bno in host cells has not been investigated. here, we report that bno contributes macrophage killing by s-nitrosylation of bioenergetic-relating proteins within mitochondria. toxigenic ster ...201323178574
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
using a bacteriocin structure to engineer a phage lysin that targets yersinia pestis.purified phage lysins present an alternative to traditional antibiotics and work by hydrolysing peptidoglycan. phage lysins have been developed against gram-positive pathogens such as bacillus anthracis and streptococcus pneumoniae, where the peptidoglycan layer is exposed on the cell surface. addition of the lysin to a bacterial culture results in rapid death of the organism. gram-negative bacteria are resistant to phage lysins because they contain an outer membrane that protects the peptidogly ...201223176506
activated protein c ameliorates bacillus anthracis lethal toxin-induced lethal pathogenesis in rats.lethal toxin (lt) is a major virulence factor of bacillus anthracis. sprague dawley rats manifest pronounced lung edema and shock after lt treatments, resulting in high mortality. the heart failure that is induced by lt has been suggested to be a principal mechanism of lung edema and mortality in rodents. since lt-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of lt-induced p ...201223170801
clinical and forensic signs related to opioids abuse.for a good performance in clinical and forensic toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. this manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administ ...201223170787
anthrax cases in pregnant and postpartum women: a systematic review.to describe the worldwide experience of bacillus anthracis infection reported in pregnant, postpartum, and lactating women.201223168771
detection of multiple waterborne pathogens using microsequencing arrays.a microarray was developed to simultaneously detect cryptosporidium parvum, cryptosporidium hominis, enterococcus faecium, bacillus anthracis and francisella tularensis in water.201323167710
inactivation of bacillus anthracis spores by single-walled carbon nanotubes coupled with oxidizing antimicrobial chemicals.in this study, we investigated the sporicidal effects of single-walled carbon nanotubes (swcnts) and swcnts combined with oxidizing antimicrobial chemicals, h₂o₂ and naocl, on b. anthracis spores. the results indicated that treatment with swcnts alone exhibited little sporicidal effect on b. anthracis spores, while treatment with h₂o₂ or naocl alone showed moderate sporicidal effect. the combination treatment with swcnts (100 μg/ml) and h₂o₂ (1.5%) or naocl (0.25%) exhibited much stronger sporic ...201223167544
[analysis of outbreak of anthrax in omsk region in 2010].carrying out analysis of epizootologic-epidemiologic situation on anthrax that had emerged in omsk region in 2010 when horse meat from epizootic focus of anthrax was used in production of meat semi-finished products.201223163033
standoff detection of biological agents using laser induced fluorescence-a comparison of 294 nm and 355 nm excitation wavelengths.standoff detection measuring the fluorescence spectra of seven different biological agents excited by 294 nm as well as 355 nm wavelength laser pulses has been undertaken. the biological warfare agent simulants were released in a semi-closed aerosol chamber at 210 m standoff distance and excited by light at either of the two wavelengths using the same instrument. significant differences in several of the agents' fluorescence response were seen at the two wavelengths. the anthrax simulants' fluor ...201223162732
anthrax lethal toxin and the induction of cd4 t cell immunity.bacillus anthracis secretes exotoxins which act through several mechanisms including those that can subvert adaptive immunity with respect both to antigen presenting cell and t cell function. the combination of protective antigen (pa) and lethal factor (lf) forming lethal toxin (lt), acts within host cells to down-regulate the mitogen activated protein kinase (mapk) signaling cascade. until recently the mapk kinases were the only known substrate for lt; over the past few years it has become evid ...201223162703
anthrax lethal factor cleaves mouse nlrp1b in both toxin-sensitive and toxin-resistant macrophages.anthrax lethal factor (lf) is the protease component of anthrax lethal toxin (lt). lt induces pyroptosis in macrophages of certain inbred mouse and rat strains, while macrophages from other inbred strains are resistant to the toxin. in rats, the sensitivity of macrophages to toxin-induced cell death is determined by the presence of an lf cleavage sequence in the inflammasome sensor nlrp1. lf cleaves rat nlrp1 of toxin-sensitive macrophages, activating caspase-1 and inducing cell death. toxin-res ...201223152930
in vivo germination of bacillus anthracis spores during murine cutaneous infection.germination is a key step for successful bacillus anthracis colonization and systemic dissemination. few data are available on spore germination in vivo, and the necessity of spore and host cell interactions to initiate germination is unclear.201323148288
long genomic dna amplicons adsorption onto unmodified gold nanoparticles for colorimetric detection of bacillus anthracis.unmodified gold nanoparticles (gnps) can be wrapped with long genomic single- and double-stranded dna (ssdna and dsdna) molecules produced by asymmetric polymerase chain reaction (as-pcr). more importantly, the dna-au interaction can be utilized for colorimetric detection of a specific nucleic acid sequence in clinical samples.201323145437
estimated copy number of bacillus anthracis plasmids pxo1 and pxo2 using digital pcr.we evaluated digital pcr (dpcr) to directly enumerate plasmid and chromosome copies in three strains of bacillus anthracis. copy number estimates based on conventional quantitative pcr (qpcr) highlighted the variability of using qpcr to measure copy number whereas estimates based on direct sequencing are comparable to dpcr.201323142659
anthrax epizootic and migration: persistence or extinction.in this paper, we use an extension of the deterministic mathematical model of an anthrax epizootic of hahn and furniss to study the effects of anthrax transmission, carcass ingestion, carcass induced environmental contamination, and migration rates on the persistence or extinction of animal populations. we compute the basic reproduction number r(0) for the anthrax epizootic model with and without taking into account animal migration. we obtained conditions for an anthrax enzootic region. we demo ...201323137874
ability of elisa and a toxin neutralization assay to detect changes in immunogenicity of a recombinant bacillus anthracis protective antigen vaccine upon storage.we examined the capability of a mouse immunogenicity assay to detect improper storage of a recombinant protective antigen (rpa)-based anthrax vaccine formulated with an aluminum adjuvant, using elisa and a toxin neutralization assay (tna) to measure the antibody response to rpa. the vaccine was stored at 4 °c, room temperature (rt) or 37 °c for one, four and eight weeks and used for immunization, along with freshly prepared vaccine. results showed that, contrary to elisa, tna is suitable to dete ...201323137818
cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.lethal and edema toxins secreted by bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. however, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. this study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction.201223134810
a novel mode of regulation of the staphylococcus aureus catabolite control protein a (ccpa) mediated by stk1 protein phosphorylation.the staphylococcus aureus serine/threonine protein kinase stk1 (also known as pknb) affects different key pathways such as cell wall metabolism, antibiotic susceptibility, and regulation of virulence. here we report that the catabolite control protein a (ccpa), a highly conserved regulator of carbon catabolite repression and virulence in a number of gram-positive pathogens, was efficiently phosphorylated in vitro and in vivo by stk1 in s. aureus, whereas the ccpa homologues of bacillus subtilis ...201223132867
a new generation microarray for the simultaneous detection and identification of yersinia pestis and bacillus anthracis in food.the use of microarrays as a multiple analytic system has generated increased interest and provided a powerful analytical tool for the simultaneous detection of pathogens in a single experiment. a wide array of applications for this technology has been reported. a low density oligonucleotide microarray was generated from the genetic sequences of y. pestis and b. anthracis and used to fabricate a microarray chip. the new generation chip, consisting of 2,240 spots in 4 quadrants with the capability ...201223125935
poly-γ-(d)-glutamic acid capsule interferes with lytic infection of bacillus anthracis by b. anthracis-specific bacteriophages.the poly-γ-d-glutamic acid capsule of bacillus anthracis is a barrier to infection by b. anthracis-specific bacteriophages. capsule expression was found to completely inhibit lytic infection by γ phage, an observation supported by the demonstration that this phage does not elaborate a hydrolase that would facilitate penetration through the protective capsule outer layer.201323124233
cell-wall preparation containing poly-γ-d-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection.bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. many vaccine strategies were described to counteract anthrax infection. in contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent. however, in animal models this vaccine is less efficient than the live vaccine. in this study, we analyzed the protection afforded by a single extractable surface element. ...201223122993
[present status and prospects for the detection of bacillus anthracis--a review].anthrax, as a fulminating infectious disease, threatens human' s health seriously. bacillus anthracis, the agent of anthrax, was classified into the second kinds of pathogenic microorganisms (one kind of the highly pathogenic microorganism) in the list of human pathogenic microorganisms issued by the chinese government. the spores formed by b. anthracis are potential material for biological warfare agent and biological terror. therefore, it is very important and pressing to develop sensitive, ef ...201223115964
electrostatic ratchet in the protective antigen channel promotes anthrax toxin translocation.central to the power-stroke and brownian-ratchet mechanisms of protein translocation is the process through which nonequilibrium fluctuations are rectified or ratcheted by the molecular motor to transport substrate proteins along a specific axis. we investigated the ratchet mechanism using anthrax toxin as a model. anthrax toxin is a tripartite toxin comprised of the protective antigen (pa) component, a homooligomeric transmembrane translocase, which translocates two other enzyme components, let ...201223115233
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