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global metabolomic analysis of a mammalian host infected with bacillus anthracis.whereas dna provides the information to design life and proteins provide the materials to construct it, the metabolome can be viewed as the physiology that powers it. as such, metabolomics, the field charged with the study of the dynamic small-molecule fluctuations that occur in response to changing biology, is now being used to study the basis of disease. here, we describe a comprehensive metabolomic analysis of a systemic bacterial infection using bacillus anthracis, the etiological agent of a ...201526438791
human anthrax transmission at the urban-rural interface, georgia.human anthrax has increased dramatically in georgia and was recently linked to the sale of meat in an urban market. we assessed epidemiological trends and risk factors for human anthrax at the urban-rural interface. we reviewed epidemiologic records (2000-2012) that included the place of residence (classified as urban, peri-urban, or rural), age, gender, and self-reported source of infection (handling or processing animal by-products and slaughtering or butchering livestock). to estimate risk, w ...201526438026
enhanced immune response to dna vaccine encoding bacillus anthracis pa-d4 protects mice against anthrax spore challenge.anthrax has long been considered the most probable bioweapon-induced disease. the protective antigen (pa) of bacillus anthracis plays a crucial role in the pathogenesis of anthrax. in the current study, we evaluated the efficiency of a genetic vaccination with the fourth domain (d4) of pa, which is responsible for initial binding of the anthrax toxin to the cellular receptor. the eukaryotic expression vector was designed with the immunoglobulin m (igm) signal sequence encoding for pa-d4, which c ...201526430894
passive immunotherapy protects against enteric invasion and lethal sepsis in a murine model of gastrointestinal anthrax.the principal portal for anthrax infection in natural animal outbreaks is the digestive tract. enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. our group has developed a novel animal model of gastrointestinal (gi) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative bacillus anthracis (sterne strain) administered to a/j mice ( ...201526426050
potential role of autophagy in the bactericidal activity of human pmns for bacillus anthracis.bacillus anthracis, the causative agent of anthrax, is acquired by mammalian hosts from the environment, as quiescent endospores. these endospores must germinate inside host cells, forming vegetative bacilli, before they can express the virulence factors that enable them to evade host defenses and disseminate throughout the body. while the role of macrophages and dendritic cells in this initial interaction has been established, the role of polymorphonuclear leukocytes (pmns) has not been adequat ...201526424808
experimental validation of bacillus anthracis a16r proteogenomics.anthrax, caused by the pathogenic bacterium bacillus anthracis, is a zoonosis that causes serious disease and is of significant concern as a biological warfare agent. validating annotated genes and reannotating misannotated genes are important to understand its biology and mechanisms of pathogenicity. proteomics studies are, to date, the best method for verifying and improving current annotations. to this end, the proteome of b. anthracis a16r was analyzed via one-dimensional gel electrophoresis ...201526423727
a s-layer protein of bacillus anthracis as a building block for functional protein arrays by in vitro self-assembly.s-layer proteins create a cell-surface layer architecture in both bacteria and archaea. because s-layer proteins self-assemble into a native-like s-layer crystalline structure in vitro, they are attractive building blocks in nanotechnology. here, the potential use of the s-layer protein ea1 from bacillus anthracis in constructing a functional nanostructure is investigated, and apply this nanostructure in a proof-of-principle study for serological diagnosis of anthrax. ea1 is genetically fused wi ...201526422821
correction: bacillus anthracis diversity and geographic potential across nigeria, cameroon and chad: further support of a novel west african lineage. 201526417945
mass spectrometric detection of bacterial protein toxins and their enzymatic activity.mass spectrometry has recently become a powerful technique for bacterial identification. mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (maldi-tof) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. with some bacteria, such as bacillus anthracis and clostridium botulinum, the health threat posed by these organisms is not the organism its ...201526404376
contractile actin cables induced by bacillus anthracis lethal toxin depend on the histone acetylation machinery.it remains a challenge to decode the molecular basis of the long-term actin cytoskeleton rearrangements that are governed by the reprogramming of gene expression. bacillus anthracis lethal toxin (lt) inhibits mitogen-activated protein kinase (mapk) signaling, thereby modulating gene expression, with major consequences for actin cytoskeleton organization and the loss of endothelial barrier function. using a laser ablation approach, we characterized the contractile and tensile mechanical propertie ...201526403219
impact of gastrointestinal bacillus anthracis infection on hepatic b cells.ingestion of bacillus anthracis results in rapid gastrointestinal (gi) infection, known as gi anthrax. we previously showed that during gi anthrax, there is swift deterioration of intestinal barrier function leading to translocation of gut-associated bacteria into systemic circulation. additionally, we described dysfunction in colonic b cells. in concordance with our previous studies, here, we report early migration of the sterne strain of b. anthracis along with other gut-resident bacteria into ...201526402706
binding domains of bacillus anthracis phage endolysins recognize cell culture age-related features on the bacterial surface.bacteriolytic enzymes often possess a c-terminal binding domain that recognizes specific motifs on the bacterial surface and a catalytic domain that cleaves covalent linkages within the cell wall peptidoglycan. plyph, one such lytic enzyme of bacteriophage origin, has been reported to be highly effective against bacillus anthracis, and can kill up to 99.99% of the viable bacteria. the bactericidal activity of this enzyme, however, appears to be strongly dependent on the age of the bacterial cult ...201626399565
mechanisms of ricin toxin neutralization revealed through engineered homodimeric and heterodimeric camelid antibodies.novel antibody constructs consisting of two or more different camelid heavy-chain only antibodies (vhhs) joined via peptide linkers have proven to have potent toxin-neutralizing activity in vivo against shiga, botulinum, clostridium difficile, anthrax, and ricin toxins. however, the mechanisms by which these so-called bispecific vhh heterodimers promote toxin neutralization remain poorly understood. in the current study we produced a new collection of ricin-specific vhh heterodimers, as well as ...201526396190
decontamination efficacy and skin toxicity of two decontaminants against bacillus anthracis.decontamination of bacterial endospores such as bacillus anthracis has traditionally required the use of harsh or caustic chemicals. the aim of this study was to evaluate the efficacy of a chlorine dioxide decontaminant in killing bacillus anthracis spores in solution and on a human skin simulant (porcine cadaver skin), compared to that of commonly used sodium hypochlorite or soapy water decontamination procedures. in addition, the relative toxicities of these decontaminants were compared in hum ...201526394165
efficacy of single and combined antibiotic treatments of anthrax in rabbits.respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. rabbits are highly susceptible to infection with bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. this study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degre ...201526392505
targeting the membrane-anchored serine protease testisin with a novel engineered anthrax toxin prodrug to kill tumor cells and reduce tumor burden.the membrane-anchored serine proteases are a unique group of trypsin-like serine proteases that are tethered to the cell surface via transmembrane domains or glycosyl-phosphatidylinositol-anchors. overexpressed in tumors, with pro-tumorigenic properties, they are attractive targets for protease-activated prodrug-like anti-tumor therapies. here, we sought to engineer anthrax toxin protective antigen (prag), which is proteolytically activated on the cell surface by the proprotein convertase furin ...201526392335
microbiological laboratory diagnostics of neglected zoonotic diseases (nzds).this review reports on laboratory diagnostic approaches for selected, highly pathogenic neglected zoonotic diseases, i.e. anthrax, bovine tuberculosis, brucellosis, echinococcosis, leishmaniasis, rabies, taenia solium-associated diseases (neuro-/cysticercosis & taeniasis) and trypanosomiasis. diagnostic options, including microscopy, culture, matrix-assisted laser-desorption-ionisation time-of-flight mass spectrometry, molecular approaches and serology are introduced. these procedures are critic ...201726391646
bacillus anthracis lcp genes support vegetative growth, envelope assembly, and spore formation.bacillus anthracis, a spore-forming pathogen, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. surface (s)-layer proteins and b. anthracis s-layer-associated proteins (bsls) function as chain length determinants and are assembled in the envelope by binding to the secondary cell wall polysaccharide (scwp). b. anthracis expresses six different genes encoding lytr-cpsa-psr (lcp) enzymes (lcpb1 to -4, lcpc, and lcpd), which when expressed in staphylococc ...201526391207
nitric oxide as a regulator of b. anthracis pathogenicity.nitric oxide (no) is a key physiological regulator in eukaryotic and prokaryotic organisms. it can cause a variety of biological effects by reacting with its targets or/and indirectly inducing oxidative stress. no can also be produced by bacteria including the pathogenic bacillus anthracis; however, its role in the infectious process only begins to emerge. no incapacitates macrophages by s-nitrosylating the intracellular proteins and protects b. anthracis from oxidative stress. it is also implic ...201526388860
historical evolution of human anthrax from occupational disease to potentially global threat as bioweapon.anthrax is caused by bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. however, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, b. anthracis has been considered the most serious bioterrorism agent for a long time. during the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. several factors may mitigate the consequences ...201526386727
the role of practical advice in bioterrorism news coverage.this study examined the role of crisis advice appearing in us news coverage of the 2001 anthrax attacks. coverage of any crisis can spark public outrage, including fear, speculation, and contradictory or confusing evidence, especially when the stories do not contain practical advice. five coders analyzed 833 news stories from 272 major us newspapers, the associated press, national public radio, and 4 major us television networks. practical advice appeared in only a quarter of the stories, even t ...201526381372
environmental persistence of bacillus anthracis and bacillus subtilis spores.there is a lack of data for how the viability of biological agents may degrade over time in different environments. in this study, experiments were conducted to determine the persistence of bacillus anthracis and bacillus subtilis spores on outdoor materials with and without exposure to simulated sunlight, using ultraviolet (uv)-a/b radiation. spores were inoculated onto glass, wood, concrete, and topsoil and recovered after periods of 2, 14, 28, and 56 days. recovery and inactivation kinetics f ...201526372011
"phylogenetic and evolutionary analysis of functional divergence among gamma glutamyl transpeptidase (ggt) subfamilies".γ-glutamyltranspeptidase (ggt) is a bi-substrate enzyme conserved in all three domains of life. it catalyzes the cleavage and transfer of γ-glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). ggts exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. recently, ggt has been shown to be a virulence factor in microbes like helicobacter pylori and bacillus anthracis. in mammalian cells also, ggt in ...201526370226
investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.hybridomas were created using spleen of mice that were actively immunized with rlfn (recombinant n-terminal domain of lethal factor). later on, separate group of mice were immunized with rlfn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. this led to the identification of one cohort of rlfn-immnized mice that harboured disease-enhancing polyclonal antibodies. at the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. t ...201526364143
peptide probes reveal a hydrophobic steric ratchet in the anthrax toxin protective antigen translocase.anthrax toxin is a tripartite virulence factor produced by bacillus anthracis during infection. under acidic endosomal ph conditions, the toxin's protective antigen (pa) component forms a transmembrane channel in host cells. the pa channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps ...201526363343
development & validation of a quantitative anti-protective antigen igg enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax.anthrax caused by bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. elisa is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. the aims of this study were to develop and evaluate a quantitative elisa for determination of igg antibodies against b. anthracis protective antigen (pa) in human cutaneous anthrax cases.201526354217
a cluster of cns infections due to b. cereus in the setting of acute myeloid leukemia: neuropathology in 5 patients.bacillus cereus typically causes a self-limited foodborne gastrointestinal (gi) illness. severe invasive infection occurs rarely, mainly among immunocompromised hosts. we describe a cluster of b. cereus infections among 5 patients with acute myeloid leukemia and chemotherapy-induced neutropenia. the initial case presented with occipital lobe abscess and was found on biopsy to have organisms consistent with bacillus species. within 1 week, a second patient died of fulminant brain swelling and hem ...201526352989
the poly-γ-d-glutamic acid capsule surrogate of the bacillus anthracis capsule induces nitric oxide production via the platelet activating factor receptor signaling pathway.the poly-γ-d-glutamic acid (pga) capsule, a major virulence factor of bacillus anthracis, confers protection of the bacillus from phagocytosis and allows its unimpeded growth in the host. pga capsules released from b. anthracis are associated with lethal toxin in the blood of experimentally infected animals and enhance the cytotoxic effect of lethal toxin on macrophages. in addition, pga capsule itself activates macrophages and dendritic cells to produce proinflammatory cytokine such as il-1β, i ...201526350415
over-expression, purification, and confirmation of bacillus anthracis transcriptional regulator nprr.quorum sensing (qs) has been recognized as an important biological phenomenon in which bacterial cells communicate and coordinate their gene expression and cellular processes with respect to population density. bacillus anthracis is the etiological agent of fatal pulmonary anthrax infections, and the nprr/nprx qs system may be involved in its pathogenesis. nprr, renamed as aqsr for anthrax quorum sensing regulator, is a transcriptional regulator that may control the expression of genes required ...201626344899
role of the α clamp in the protein translocation mechanism of anthrax toxin.membrane-embedded molecular machines are utilized to move water-soluble proteins across these barriers. anthrax toxin forms one such machine through the self-assembly of its three component proteins--protective antigen (pa), lethal factor, and edema factor. upon endocytosis into host cells, acidification of the endosome induces pa to form a membrane-inserted channel, which unfolds lethal factor and edema factor and translocates them into the host cytosol. translocation is driven by the proton mo ...201526344833
lanthanide induced formation of novel luminescent alginate hydrogels and detection features.responsive photo-luminescent soft matters have led to the design of optical sensors and switches. in this research, two new organic-inorganic type hybrid hydrogels have been fabricated by the self-assembly of sodium alginate and lanthanide elements. the incorporation of europium ions (eu(3+)) (or terbium ions (tb(3+))) was required for the gelation of the dissolved alginate and thermally stable gels were formed. it has been found that red/green emissions derived from lanthanide ions were clearly ...201526344249
a case of cutaneous anthrax presenting with classical lesions. 201526340973
structure of the bacillus anthracis sortase a enzyme bound to its sorting signal: a flexible amino-terminal appendage modulates substrate access.the endospore forming bacterium bacillus anthracis causes lethal anthrax disease in humans and animals. the ability of this pathogen to replicate within macrophages is dependent upon the display of bacterial surface proteins attached to the cell wall by the b. anthracis sortase a ((ba)srta) enzyme. previously, we discovered that the class a (ba)srta sortase contains a unique n-terminal appendage that wraps around the body of the protein to contact the active site of the enzyme. to gain insight i ...201526324714
bacillus anthracis tago is required for vegetative growth and secondary cell wall polysaccharide synthesis.bacillus anthracis elaborates a linear secondary cell wall polysaccharide (scwp) that retains surface (s)-layer and associated proteins via their s-layer homology (slh) domains. the scwp is comprised of trisaccharide repeats [→4)-β-mannac-(1→4)-β-glcnac-(1→6)-α-glcnac-(1→] and tethered via acid-labile phosphodiester bonds to peptidoglycan. earlier work identified udp-glcnac 2-epimerases gney (bas5048) and gnez (bas5117), which act as catalysts of mannac synthesis, as well as a polysaccharide dea ...201526324447
whole genome protein microarrays for serum profiling of immunodominant antigens of bacillus anthracis.a commercial bacillus anthracis (anthrax) whole genome protein microarray has been used to identify immunogenic anthrax proteins (iap) using sera from groups of donors with (a) confirmed b. anthracis naturally acquired cutaneous infection, (b) confirmed b. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the uk anthrax protein vaccine and compared to naïve unexposed controls. anti-iap responses were obs ...201526322022
fighting ebola with novel spore decontamination technologies for the military.recently, global public health organizations such as doctors without borders (msf), the world health organization (who), public health canada, national institutes of health (nih), and the u.s. government developed and deployed field decontamination kits (fdks), a novel, lightweight, compact, reusable decontamination technology to sterilize ebola-contaminated medical devices at remote clinical sites lacking infra-structure in crisis-stricken regions of west africa (medical waste materials are pla ...201526322021
whole genome-sequencing and phylogenetic analysis of a historical collection of bacillus anthracis strains from danish cattle.bacillus anthracis, the causative agent of anthrax, is known as one of the most genetically monomorphic species. canonical single-nucleotide polymorphism (snp) typing and whole-genome sequencing were used to investigate the molecular diversity of eleven b. anthracis strains isolated from cattle in denmark between 1935 and 1988. danish strains were assigned into five cansnp groups or lineages, i.e. a.br.001/002 (n = 4), a.br.ames (n = 2), a.br.008/011 (n = 2), a.br.005/006 (n = 2) and a.br.aust94 ...201526317972
global gene expression by bacillus anthracis during growth in mammalian blood.during the late stages of systemic anthrax, bacillus anthracis grows rapidly in the host bloodstream. to identify potential genes necessary for this observed rapid growth, we defined the transcriptional profile of b. anthracis during in vitro growth in bovine blood. genome-wide transcriptome analysis indicated that b. anthracis undergoes significant changes in its transcriptome profile during growth in blood, including the differential regulation of genes associated both with metabolism and know ...201526316554
rapid detection of bacillus anthracis by γ phage amplification and lateral flow immunochromatography.new, rapid point-of-need diagnostic methods for bacillus anthracis detection can enhance civil and military responses to accidental or deliberate dispersal of anthrax as a biological weapon. current laboratory-based methods for clinical identification of b. anthracis require 12 to 120h, and are confirmed by plaque assay using the well-characterized γ typing phage, which requires an additional minimum of 24h for bacterial culture. to reduce testing time, the natural specificity of γ phage amplifi ...201526310605
investigation of anthrax cases in north-east china, 2010-2014.we determined the genotypes of seven bacillus anthracis strains that were recovered from nine anthrax outbreaks in north-east china from 2010 to 2014, and two approved vaccine strains that are currently in use in china. the causes of these cases were partly due to local farmers being unaware of the presence of anthrax, and butchers with open wounds having direct contact with anthrax-contaminated meat products. the genotype of five of the seven recovered strains was a.br.001/002 sub-lineage, whic ...201526308449
gastrointestinal problems in modern wars: clinical features and possible mechanisms.gastrointestinal problems are common during wars, and they have exerted significant adverse effects on the health of service members involved in warfare. the spectrum of digestive diseases has varied during wars of different eras. at the end of the 20th century, new frontiers of military medical research emerged due to the occurrence of high-tech wars such as the gulf war and the kosovo war, in which ground combat was no longer the primary method of field operations. the risk to the military per ...201526301101
background frequency of bacillus species at the canberra airport: a 12 month study.anthrax, caused by bacillus anthracis, is a naturally occurring disease in australia. whilst mainly limited to livestock in grazing regions of victoria and new south wales, movement of people, stock and vehicles means b. anthracis could be present outside this region. of particular interest is the "background" prevalence of b. anthracis at transport hubs including airports. the aim of this study was to determine the background frequency of b. anthracis and the commonly used hoax agent bacillus t ...201526298416
improved proteomic analysis following trichloroacetic acid extraction of bacillus anthracis spore proteins.proteomic analysis of bacterial samples provides valuable information about cellular responses and functions under different environmental pressures. analysis of cellular proteins is dependent upon efficient extraction from bacterial samples, which can be challenging with increasing complexity and refractory characteristics. while no single method can recover 100% of the bacterial proteins, selected protocols can improve overall protein isolation, peptide recovery, or enrichment for certain clas ...201526295278
cutaneous anthrax: evaluation of 28 cases in the eastern anatolian region of turkey.anthrax is an endemic disease in developing countries. human cases are usually associated with animal products. about 95% of naturally acquired cases are cutaneous anthrax.201626293781
bacillus anthracis diversity and geographic potential across nigeria, cameroon and chad: further support of a novel west african lineage.zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries. anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in nigeria. here we describe the genetic diversity of bacillus anthracis in nigeria and compare it to chad, cameroon and a broader global dataset based on the multiple locus variable number tandem repeat (mlva-25) genetic typing sys ...201526291625
insights into smad4 loss in pancreatic cancer from inducible restoration of tgf-β signaling.pancreatic ductal adenocarcinoma (pdac) is the fourth-leading cause of cancer death in the united states. the tgf-β signaling protein smad family member 4 is lost in 60% of pdac, and this has been associated with poorer prognosis. however, the mechanisms by which smad4 loss promotes pdac development are not fully understood. we expressed smad4 in human pdac cell lines bxpc3 and cfpac1 by selection of stable clones containing an inducible smad4 tetracycline inducible expression system construct. ...201526284758
intranasal immunization with protective antigen of bacillus anthracis induces a long-term immunological memory response.although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. here, we investigated whether intranasal immunization with recombinant protective antigen (rpa) of bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. intranasal immunization with rpa plus cholera toxin (ct) sustained pa-specific antibody responses for 6 months in lung, nasal was ...201526278659
pore-forming activity of clostridial binary toxins.clostridial binary toxins (clostridium perfringens iota toxin, clostridium difficile transferase, clostridium spiroforme toxin, clostridium botulinum c2 toxin) as bacillus binary toxins, including bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. clostridial binary toxins induce actin cytoskeleton disorganization through mono-adp-ribosylation of globular actin and ar ...201626278641
a method detection limit for bacillus anthracis spores in water using an automated waterborne pathogen concentrator.the method detection limit (mdl, 99% chance of detecting a positive result in a single replicate), as per the united states code of federal regulations, was determined for a protocol using an ultrafiltration based automated waterborne pathogen concentration device. bacillus anthracis sterne strain spores were seeded at low levels into 100 l reagent water samples. suspect colonies were confirmed through morphological, chemical, and genetic tests. samples of 100 l (n=14) of reagent water were seed ...201526268983
microevolution of anthrax from a young ancestor (m.a.y.a.) suggests a soil-borne life cycle of bacillus anthracis.during an anthrax outbreak at the pollino national park (basilicata, italy) in 2004, diseased cattle were buried and from these anthrax-foci bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. recent data suggest that b. anthracis multiplies in soil outside the animal-host body. this notion is supported by the frequent isolation of b. anthracis from soil lacking one or both virulence plasmids. such strains represent an evolutionary dead end, as they are l ...201526266934
reagent-free and portable detection of bacillus anthracis spores using a microfluidic incubator and smartphone microscope.bacillus anthracis is the causative agent of anthrax and can be contracted by humans and herbivorous mammals by inhalation, ingestion, or cutaneous exposure to bacterial spores. due to its stability and disease potential, b. anthracis is a recognized biothreat agent and robust detection and viability methods are needed to identify spores from unknown samples. here we report the use of smartphone-based microscopy (spm) in combination with a simple microfluidic incubation device (mid) to detect 50 ...201526266749
test methods and response surface models for hot, humid air decontamination of materials contaminated with dirty spores of bacillus anthracis ∆sterne and bacillus thuringiensis al hakam.to develop test methods and evaluate survival of bacillus anthracis ∆sterne or bacillus thuringiensis al hakam on materials contaminated with dirty spore preparations after exposure to hot, humid air using response surface modelling.201526258399
electrochemical dna sensor for anthrax toxin activator gene atxa-detection of pcr amplicons.we report the dna probe functionalized electrochemical genosensor for the detection of bacillus anthracis, specific towards the regulatory gene atxa. the dna sensor is fabricated on electrochemically deposited gold nanoparticle on self assembled layer of (3-mercaptopropyl) trimethoxysilane (mpts) on gc electrode. dna hybridization is monitored by differential pulse voltammogram (dpv). the modified gc electrode is characterized by atomic force microscopy (afm), cyclic voltammetry (cv), and electr ...201526257186
anti-infective immunoadhesins from plants.immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. all fda-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as etanercept (enbrel(®) ), which interferes with the binding of tumour necrosis factor (tnf) to the tnf-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. like antibodies, immunoadhesins h ...201526242703
dna persistence in a sink drain environment.biofilms are organized structures composed mainly of cells and extracellular polymeric substances produced by the constituent microorganisms. ubiquitous in nature, biofilms have an innate ability to capture and retain passing material and may therefore act as natural collectors of contaminants or signatures of upstream activities. to determine the persistence and detectability of dna passing through a sink drain environment, bacillus anthracis strain ames35 was cultured (6.35 x 107 cfu/ml), ster ...201526230525
toxins as weapons: a historical review.this review article summarizes the use of toxins as weapons dating from the first world war until today, when there is a high concern of possible terrorist attacks with weapons of mass destruction. all through modern history, military programs and terrorist groups have favored toxins because of their high toxicity. however, difficulties of extraction or synthesis, as well as effective dissemination to cause a large number of casualties, have been the most important drawbacks. special emphasis is ...201426227025
cutaneous anthrax: evaluation of 28 cases in the eastern anatolian region of turkey.anthrax is an endemic disease in developing countries. human cases are usually associated with animal products. about 95% of naturally acquired cases are cutaneous anthrax.201526225872
controlled release of an anthrax toxin-neutralizing antibody from hydrolytically degradable polyethylene glycol hydrogels.in this study, hydrophilic and hydrolytically degradable poly (ethylene glycol) (peg) hydrogels were formed via michael-type addition and employed for sustained delivery of a monoclonal antibody against the protective antigen of anthrax. taking advantage of the peg-induced precipitation of the antibody, burst release from the matrix was avoided. these hydrogels were able to release active antibodies in a controlled manner from 14 days to as long as 56 days in vitro by varying the polymer archite ...201626223817
anthrax toxin receptor 2 gene (antxr2) rs4333130 is associated with ankylosing spondylitis.results of recent published studies on the association between the antxr2 rs4333130 polymorphism and the risk of ankylosing spondylitis (as) have often been conflicting. to make a more precise estimation of the potential relationship, a meta-analysis was performed. we conducted a comprehensive search in the electronic database of pubmed and embase to retrieve relevant articles. nine studies including 14,523 cases and 34,421 controls were finally selected in this meta-analysis. antxr2 rs4333130 w ...201526221317
bacillus anthracis slaq promotes s-layer protein assembly.bacillus anthracis vegetative forms assemble an s-layer comprised of two s-layer proteins, sap and ea1. a hallmark of s-layer proteins are their c-terminal crystallization domains, which assemble into a crystalline lattice once these polypeptides are deposited on the bacterial surface via association between their n-terminal s-layer homology domains and the secondary cell wall polysaccharide. here we show that slaq, encoding a small cytoplasmic protein conserved among pathogenic bacilli elaborat ...201526216847
weissella oryzae dc6-facilitated green synthesis of silver nanoparticles and their antimicrobial potential.nanoparticles and nanomaterials are at the prominent edge of the rapidly developing field of nanotechnology. recently, nanoparticle synthesis using biological resources has been found to be a new area with considerable prospects for development. biological systems are the masters of ambient condition chemistry and are able to synthesize nanoparticles by utilizing metal salts. in the perspective of the current initiative to develop green technologies for the synthesis of nanoparticles, microorgan ...201626212222
structural basis of proline-proline peptide bond specificity of the metalloprotease zmp1 implicated in motility of clostridium difficile.clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. in common with other pathogenic bacteria, c. difficile secretes proteins involved in adhesion, colonization, and dissemination. the recently identified zmp1 is an extracellular metalloprotease showing a unique specificity for pro-pro peptide bonds. the endogenous substrates of zmp1 are two surface proteins implicated in adhesion of c. difficile to surface proteins of human cel ...201526211609
lab-on-a-chip-based pcr-rflp assay for the confirmed detection of short-length feline dna in food.wider availability but lack of legal market trades has given feline meat a high potential for use as an adulterant in common meat and meat products. however, mixing of feline meat or its derivatives in food is a sensitive issue, since it is a taboo in most countries and prohibited in certain religions such as islam and judaism. cat meat also has potential for contamination with of severe acute respiratory syndrome, anthrax and hepatitis, and its consumption might lead to an allergic reaction. we ...201526208950
anthrax pathogenesis.anthrax is caused by the spore-forming, gram-positive bacterium bacillus anthracis. the bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. these are encoded by two large plasmids, the former by pxo1 and the latter by pxo2. the expression of both is controlled by the bicarbonate-responsive transcriptional regulator, atxa. the anthrax toxins are three polypeptides-protective antigen (pa), lethal factor (lf), and edema factor (ef)-that com ...201526195305
acyl carrier protein is a bacterial cytoplasmic target of cationic antimicrobial peptide ll-37.in addition to membrane disruption, the cathelicidin antimicrobial peptide (amp) ll-37 translocates through the bacterial inner membrane to target intracellular molecules. the present study aims to identify an alternate mechanism and a cytoplasmic target of ll-37 in francisella. ll-37 binding proteins from francisella novicida u112 bacterial lysates were precipitated by using biotinylated ll-37 (b-ll-37) and neutravidin-agarose beads. bound proteins were identified by lc-ms/ms, validated and cha ...201526188040
the differential effects of heat-shocking on the viability of spores from bacillus anthracis, bacillus subtilis, and clostridium sporogenes after treatment with peracetic acid- and glutaraldehyde-based disinfectants.this study investigated (1) the susceptibility of bacillus anthracis (ames strain), bacillus subtilis (atcc 19659), and clostridium sporogenes (atcc 3584) spores to commercially available peracetic acid (paa)- and glutaraldehyde (ga)-based disinfectants, (2) the effects that heat-shocking spores after treatment with these disinfectants has on spore recovery, and (3) the timing of heat-shocking after disinfectant treatment that promotes the optimal recovery of spores deposited on carriers. suspen ...201526185111
unlocking the sporicidal potential of ethanol: induced sporicidal activity of ethanol against clostridium difficile and bacillus spores under altered physical and chemical conditions.due to their efficacy and convenience, alcohol-based hand sanitizers have been widely adopted as the primary method of hand hygiene in healthcare settings. however, alcohols lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we hypothesized that sporicidal activity could be induced in alcohols through alteration of physical or chemical conditions that have been shown to degrade or allow penetration of spore coats.201526177038
use of multicriteria risk ranking of zoonotic diseases in a developing country: case study of mongolia.many developing countries face significant health burdens associated with a high incidence of endemic zoonoses and difficulties in integrated control measures for both the human and animal populations. the objective of this study was to develop and apply a multicriteria ranking model for zoonoses in mongolia, a country highly affected by zoonotic disease, to inform optimal resource allocation at the national level. diseases were evaluated based on their impact on human health, livestock sector h ...201626177028
forensic dna analysis of wheat flour as commonly used in white powder cases.in the wake of terrorist attacks using anthrax and ricin, white powder is often encountered in cases of malicious mischief and terrorist threats. wheat flour is a common white powder encountered in such criminal investigations. we used dna analysis to investigate wheat flour samples for identification and discrimination as trace evidence. species identification of commercially available wheat flour was carried out by sequencing a partial region of the ribulose bisphosphate carboxylase large subu ...201526174661
ion selectivity of the anthrax toxin channel and its effect on protein translocation.anthrax toxin consists of three ∼ 85-kd proteins: lethal factor (lf), edema factor (ef), and protective antigen (pa). pa63 (the 63-kd, c-terminal portion of pa) forms heptameric channels ((pa63)7) in planar phospholipid bilayer membranes that enable the translocation of lf and ef across the membrane. these mushroom-shaped channels consist of a globular cap domain and a 14-stranded β-barrel stem domain, with six anionic residues lining the interior of the stem to form rings of negative charges. ( ...201526170174
metal iodate-based energetic composites and their combustion and biocidal performance.the biological agents that can be weaponized, such as bacillus anthracis, pose a considerable potential public threat. bacterial spores, in particular, are highly stress resistant and cannot be completely neutralized by common bactericides. this paper reports on synthesis of metal iodate-based aluminized electrospray-assembled nanocomposites which neutralize spores through a combined thermal and chemical mechanism. here metal iodates (bi(io3)3, cu(io3)2, and fe(io3)3) act as a strong oxidizer to ...201526161906
molecular characterization of the circulating bacillus anthracis in jordan.to understand the biomolecular charcteristics of bacillus anthracis in jordan, 20 blood smear slides from dead animals with suspected anthrax were analyzed using conventional and molecular approaches. all slides were positive for b. anthracis by conventional staining but no growth of the organism on selective media was detected. however, of the 20 samples, 16 were b. anthracis dna-positive using polymerase chain reaction (pcr). seven samples provided enough quantity and quality of dna, and their ...201526156620
electrochemical immunosensor based on bismuth nanocomposite film and cadmium ions functionalized titanium phosphates for the detection of anthrax protective antigen toxin.bacillus anthracis is a bioterrorism agent classified by the centers for disease control and prevention (cdc). herein, a novel electrochemical immunosensor for the sensitive, specific and easy detection of anthrax protective antigen (pa) toxin in picogram concentration was developed. the immunosensor consists of (i) a nafion-multiwall carbon nanotubes-bismuth nanocomposite film modified glassy carbon electrodes (binps/nafion-mwcnts/gce) as a sensing platform and (ii) titanium phosphate nanoparti ...201526148674
phosphate starvation enhances the pathogenesis of bacillus anthracis.identifying the factors responsible for survival and virulence of bacillus anthracis within the host is prerequisite for the development of therapeutics against anthrax. host provides several stresses as well as many advantages to the invading pathogen. inorganic phosphate (pi) starvation within the host has been considered as one of the major contributing factors in the establishment of infection by pathogenic microorganisms. here, we report for the first time that pi fluctuation encountered by ...201526143397
lessons to be learned from recent biosafety incidents in the united states.during recent months, the centers for disease control and prevention (cdc) announced the occurrence of three major biosafety incidents, raising serious concern about biosafety and biosecurity guideline implementation in the most prestigious agencies in the united states: the cdc, the national institutes of health (nih) and the federal drug administration (fda). these lapses included: a) the mishandling of bacillus anthracis spores potentially exposing dozens of employees to anthrax; b) the shipm ...201526137650
a novel chimeric anti-pa neutralizing antibody for postexposure prophylaxis and treatment of anthrax.anthrax is a highly lethal infectious disease caused by the bacterium bacillus anthracis, and the associated shock is closely related to the lethal toxin (letx) produced by the bacterium. the central role played by the 63 kda protective antigen (pa63) region of letx in the pathophysiology of anthrax makes it an excellent therapeutic target. in the present study, a human/murine chimeric igg mab, hmpa6, was developed by inserting murine antibody variable regions into human constant regions using a ...201526134518
identification and characterization of a novel geobacillus thermoglucosidasius bacteriophage, gve3.the study of extremophilic phages may reveal new phage families as well as different mechanisms of infection, propagation and lysis to those found in phages from temperate environments. we describe a novel siphovirus, gve3, which infects the thermophile geobacillus thermoglucosidasius. the genome size is 141,298 bp (g+c 29.6%), making it the largest geobacillus spp-infecting phage known. gve3 appears to be most closely related to the recently described bacillus anthracis phage vb_bans_tsamsa, ra ...201526123922
immunization of mice with anthrax protective antigen limits cardiotoxicity but not hepatotoxicity following lethal toxin challenge.protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. in animal models, in vivo challenges with toxin and/or spores can also be performed. however, neither of these approaches considers toxin-induced damage to specific organ systems. it is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. we therefore ...201526120785
differences in the purification and solution properties of purc gene products from streptococcus pneumoniae and bacillus anthracis.4-(n-succino)-5-aminoimidazole-4-carboxamide ribonucleotide synthetase (purc) is a key enzyme in the de novo purine biosynthetic pathway of bacteria and an ideal target pathway for the discovery of antimicrobials. bacillus anthracis (ba) and streptococcus pneumoniae (sp) are two of the bacteria shown to be severe detriments to public health. to be able to carry out the experimentation that leads to drug discovery, high yields of pure soluble recombinant protein must first be obtained. we studied ...201526118696
genome sequence of bacillus anthracis attenuated vaccine strain a16r used for human in china.an attenuated bacillus anthracis vaccine strain for human use, a16r, was obtained in china after ultraviolet radiation treatment and continuous subculture of the wild-type strain a16. a16r can synthesize the exotoxin, but without a capsule. we sequenced and annotated the a16r genome to encourage the use of this strain. the genome sequencing of the wild-type strain a16 is underway and the genomic comparison between the two strains will help to illustrate the attenuating mechanism of the a16r vacc ...201526116813
the effect of prolonged storage on the virulence of isolates of bacillus anthracis obtained from environmental and animal sources in the kars region of turkey.the stability of the plasmid-mediated virulence factors of bacillus anthracis, a tripartite toxin located on pxo1 and an antiphagocytic capsule encoded by genes located on pxo2, following long-term storage was investigated. a collection of 159 isolates of b. anthracis were collected from the kars region of turkey between 2000 and 2013 and stored at -20°c in brucella broth supplemented with 20% glycerine. a total of 142 isolates were recovered of which one failed to express a capsule upon primary ...201526109359
the disulfide bond cys255-cys279 in the immunoglobulin-like domain of anthrax toxin receptor 2 is required for membrane insertion of anthrax protective antigen pore.anthrax toxin receptors act as molecular clamps or switches that control anthrax toxin entry, ph-dependent pore formation, and translocation of enzymatic moieties across the endosomal membranes. we previously reported that reduction of the disulfide bonds in the immunoglobulin-like (ig) domain of the anthrax toxin receptor 2 (antxr2) inhibited the function of the protective antigen (pa) pore. in the present study, the disulfide linkage in the ig domain was identified as cys255-cys279 and cys230- ...201526107617
metal binding spectrum and model structure of the bacillus anthracis virulence determinant mnta.the potentially lethal human pathogen bacillus anthracis expresses a putative metal import system, mntbca, which belongs to the large family of abc transporters. mntbca is essential for virulence of bacillus anthracis: deletion of mnta, the system's substrate binding protein, yields a completely non-virulent strain. here we determined the metal binding spectrum of mnta. in contrast to what can be inferred from growth complementation studies we find no evidence that mnta binds fe(2+) or fe(3+). r ...201526106847
animal models for the pathogenesis, treatment, and prevention of infection by bacillus anthracis.this article reviews the characteristics of the major animal models utilized for studies on bacillus anthracis and highlights their contributions to understanding the pathogenesis and host responses to anthrax and its treatment and prevention. advantages and drawbacks associated with each model, to include the major models (murine, guinea pig, rabbit, nonhuman primate, and rat), and other less frequently utilized models, are discussed. although the three principal forms of anthrax are addressed, ...201526104551
virulence plasmids of spore-forming bacteria.plasmid-encoded virulence factors are important in the pathogenesis of diseases caused by spore-forming bacteria. unlike many other bacteria, the most common virulence factors encoded by plasmids in clostridium and bacillus species are protein toxins. clostridium perfringens causes several histotoxic and enterotoxin diseases in both humans and animals and produces a broad range of toxins, including many pore-forming toxins such as c. perfringens enterotoxin, epsilon-toxin, beta-toxin, and netb. ...201426104459
spore resistance properties.spores of various bacillus and clostridium species are among the most resistant life forms known. since the spores of some species are causative agents of much food spoilage, food poisoning, and human disease, and the spores of bacillus anthracis are a major bioweapon, there is much interest in the mechanisms of spore resistance and how these spores can be killed. this article will discuss the factors involved in spore resistance to agents such as wet and dry heat, desiccation, uv and γ-radiatio ...201426104355
application of pyrosequencing® in food biodefense.the perpetration of a bioterrorism attack poses a significant risk for public health with potential socioeconomic consequences. it is imperative that we possess reliable assays for the rapid and accurate identification of biothreat agents to make rapid risk-informed decisions on emergency response. the development of advanced methodologies for the detection of biothreat agents has been evolving rapidly since the release of the anthrax spores in the mail in 2001, and recent advances in detection ...201526103911
raxibacumab augments hemodynamic support and improves outcomes during shock with b. anthracis edema toxin alone or together with lethal toxin in canines.lethal and edema toxin contribute to shock and lethality with bacillus anthracis. we showed previously in a 96-h sedated canine model that raxibacumab, a monoclonal antibody against protective antigen, augmented hemodynamic support (hs) and improved survival with lethal toxin challenge. here we study raxibacumab further. using this model, we have now studied raxibacumab with 24 h edema toxin challenges (study 1), and lethal and edema toxin challenges together (study 2).201526097803
dormant bacillus spores protect their dna in crystalline nucleoids against environmental stress.bacterial spores of the genera bacillus and clostridium are extremely resistant against desiccation, heat and radiation and involved in the spread and pathogenicity of health relevant species such as bacillus anthracis (anthrax) or clostridium botulinum. while the resistance of spores is very well documented, underlying mechanisms are not fully understood. in this study we show, by cryo-electron microscopy of vitreous sections and particular resin thin section electron microscopy, that dormant b ...201526094877
bacillus anthracis infections--new possibilities of treatment.bacillus anthracis is one of biological agents which may be used in bioterrorism attacks. the aim of this study a review of the new treatment possibilities of anthrax, with particular emphasis on the treatment of pulmonary anthrax. abbreviated description of the state of knowledge. pulmonary anthrax, as the most dangerous clinical form of the disease, is also extremely difficult to treat. recently, considerable progress in finding new drugs and suitable therapy for anthrax has been achieved, for ...201526094508
reverse-phase microarray analysis reveals novel targets in lymph nodes of bacillus anthracis spore-challenged mice.anthrax is a frequently fatal infection of many animal species and men. the causative agent bacillus anthracis propagates through the lymphatic system of the infected host; however, the specific interactions of the host and microbe within the lymphatics are incompletely understood. we report the first description of the phosphoprotein signaling in the lymph nodes of dba/2 mice using a novel technique combining the reverse-phase microarray with the laser capture microdissection. mice were challen ...201526091359
draft genome sequences of bacillus anthracis strains stored for several decades in japan.we report the draft genome sequences of bacillus anthracis strains shikan-niid, 52-40-niah, and 44-niah stored in japan and belonging to the a3 cluster.201526089418
human anthrax outbreak associated with livestock exposure: georgia, 2012.human anthrax cases reported in the country of georgia increased 75% from 2011 (n = 81) to 2012 (n = 142). this increase prompted a case-control investigation using 67 culture- or pcr-confirmed cases and 134 controls matched by residence and gender to investigate risk factor(s) for infection during the month before case onset. independent predictors most strongly associated with disease in the multivariable modelling were slaughtering animals [odds ratio (or) 7·3, 95% confidence interval (ci) 2· ...201626088361
effect of particulate adjuvant on the anthrax protective antigen dose required for effective nasal vaccination.successful vaccine development is dependent on the development of effective adjuvants since the poor immunogenicity of modern subunit vaccines typically requires the use of potent adjuvants and high antigen doses. in recent years, adjuvant formulations combining both immunopotentiators and delivery systems have emerged as a promising strategy to develop effective and improved vaccines. in this study we investigate if the association of the mast cell activating adjuvant compound 48/80 (c48/80) wi ...201526087299
anthrax lethal toxin suppresses high glucose induced vegf over secretion through a post-translational mechanism.to prove anthrax lethal toxin (letx) blocks the mitogen activated protein kinases (mapks) activation by degrading the mapk/erk kinases (meks) to suppress vascular endothelial growth factor (vegf) secretion.201526085990
bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions.to better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems.201526075586
natural cutaneous anthrax infection, but not vaccination, induces a cd4(+) t cell response involving diverse cytokines.whilst there have been a number of insights into the subsets of cd4(+) t cells induced by pathogenic bacillus anthracis infections in animal models, how these findings relate to responses generated in naturally infected and vaccinated humans has yet to be fully established. we describe the cytokine profile produced in response to t cell stimulation with a previously defined immunodominant antigen of anthrax, lethal factor (lf), domain iv, in cohorts of individuals with a history of cutaneous ant ...201526075052
bridging non-human primate correlates of protection to reassess the anthrax vaccine adsorbed booster schedule in humans.anthrax vaccine adsorbed (ava, biothrax) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-im) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. a reduction in ava booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. because human inhalatio ...201526072016
anthrax lethal toxin-induced lung injury and treatment by activating mk2.anthrax is associated with severe vascular leak, which is caused by the bacterial lethal toxin (letx). pleural effusions and pulmonary edema that occur in anthrax are believed to reflect endothelial injury caused by the anthrax toxin. since vascular leak can also be observed consistently in rats injected intravenously with letx, the latter might present a simple physiologically relevant animal model of acute lung injury (ali). such a model could be utilized in evaluating and developing better tr ...201526066827
inhibitor bound crystal structures of bacterial nitric oxide synthase.nitric oxide generated by bacterial nitric oxide synthase (nos) increases the susceptibility of gram-positive pathogens staphylococcus aureus and bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. not surprisingly, nos inhibitors also improve the effectiveness of antimicrobials. development of potent and selective bacterial nos inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian nos isoforms. to expl ...201526062720
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