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discovery of mouse spleen signaling responses to anthrax using label-free quantitative phosphoproteomics via mass spectrometry.inhalational anthrax is caused by spores of the bacterium bacillus anthracis (b. anthracis), and is an extremely dangerous disease that can kill unvaccinated victims within 2 weeks. modern antibiotic-based therapy can increase the survival rate to ∼50%, but only if administered presymptomatically (within 24-48 h of exposure). to discover host signaling responses to presymptomatic anthrax, label-free quantitative phosphoproteomics via liquid chromatography coupled to mass spectrometry was used to ...201021189417
the effect of cationic liposomes encapsulating pcdna3.1+pa plasmids on humoral immune response in mice.dna vaccines are third generation vaccines which have made promises to combat infectious diseases. cationic liposomes are used as effective delivery systems for dna vaccines to generate stronger immunity.201021189443
you cannot b. cereus.this month's genome watch looks at the different bacillus species that can cause anthrax.201021189478
adulterants in illicit drugs: a review of empirical evidence.widespread public perception is that illicit drugs contain substances that are a serious risk to health, even though adulterants are often not considered in clinical or forensic toxicology. this review attempts to present an evidence-based overview of adulterants in illicit drugs, and their associated toxicity. adulterants are deliberately added to increase bulk, enhance or mimic a pharmacological effect, or to facilitate drug delivery. those present unintentionally are as a result of poor manuf ...201021191909
development of an aerosol surface inoculation method for bacillus spores.a method was developed to deposit bacillus subtilis spores via aerosolization onto various surface materials for biological agent decontamination and detection studies. this new method uses an apparatus coupled with a metered dose inhaler to reproducibly deposit spores onto various surfaces. a metered dose inhaler was loaded with bacillus subtilis spores, a surrogate for bacillus anthracis. five different material surfaces (aluminum, galvanized steel, wood, carpet, and painted wallboard paper) w ...201021193670
viability of bacillus licheniformis and bacillus thuringiensis spores as a model for predicting the fate of bacillus anthracis spores during composting of dead livestock.safe disposal of dead livestock and contaminated manure is essential for the effective control of infectious disease outbreaks. composting has been shown to be an effective method of disposal, but no information exists on its ability to contain diseases caused by spore-forming bacteria, such as bacillus anthracis. duplicate composters (east and west), each containing 16 dead cattle, were constructed (final capacity, 85,000 kg). spores (10(7) cfu/g manure) of bacillus licheniformis and bacillus t ...201021193674
multivariate bayesian modeling of known and unknown causes of events-an application to biosurveillance.this paper investigates bayesian modeling of known and unknown causes of events in the context of disease-outbreak detection. we introduce a multivariate bayesian approach that models multiple evidential features of every person in the population. this approach models and detects (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively n ...201021195503
adulterants in illicit drugs: a review of empirical evidence.widespread public perception is that illicit drugs contain substances that are a serious risk to health, even though adulterants are often not considered in clinical or forensic toxicology. this review attempts to present an evidence-based overview of adulterants in illicit drugs, and their associated toxicity. adulterants are deliberately added to increase bulk, enhance or mimic a pharmacological effect, or to facilitate drug delivery. those present unintentionally are as a result of poor manuf ...201021322119
a tracing tool portfolio to detect bacillus anthracis, clostridium botulinum and noroviruses: bioterrorism is a food safety and security issue. 201021324542
risk factors for contracting anthrax in kuwirirana ward, gokwe north, zimbabwe.a report of an anthrax outbreak was received at gokwe district hospital from the veterinary department on the 23(rd) january 2007. this study was therefore conducted to determine risk factors for contracting anthrax amongst residents of kuwirirana ward.201021326969
receptor mimicry as novel therapeutic treatment for biothreat agents.the specter of intentional release of pathogenic microbes and their toxins is a real threat. this article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. the minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the galβ1-4glcnac structure. the botulinum toxin serotypes a ...201021327124
mysterious mortality in camels (camelus dromedarius) in borana, ethiopia: evidence of its association with reproductive age groups.in may and june of 2007, sudden death was observed in camels in southern pastoral areas of oromia, ethiopia. it significantly (p < 0.001) affected reproductive age groups of both male and female camels (in females and males, 63.9% and 10.8% of those in reproductive age groups were affected, respectively). pregnant females (37.6%) were affected significantly more often (p < 0.001) than non-pregnant females. absence of rigor mortis and absence of blood clotting, together with the death of pregnant ...201021309459
extended and global phylogenetic view of the bacillus cereus group population by combination of mlst, aflp, and mlee genotyping data.the bacillus cereus group of bacteria includes species that can cause food-poisoning or spoilage, such as b. cereus, as well as bacillus anthracis, the cause of anthrax. in the present report we have conducted a multi-datatype analysis using tools from the hypercat database (http://mlstoslo.uio.no/) that we recently developed, combining data from multilocus sequence typing (tourasse et al., 2010), amplified fragment length polymorphism, and multilocus enzyme electrophoresis typing techniques. we ...201021315979
re-assessment of mitigation strategies for deliberate releases of anthrax using a real-time outbreak characterization tool.responding rapidly and appropriately to a covert anthrax release is an important public health challenge. a methodology to assist the geographical targeting of such a response has recently been published; as have a number of independent studies that investigate mitigation strategies. here, we review and combine some of these published techniques to more realistically assess how key aspects of the public health response might impact on the outcomes of a bioterrorist attack. we combine a within-ho ...201021352789
[tobacco--a highly efficient producer of vaccines].along with the depreciation of tobacco as a source of nicotine-containing commercial products, the increase of its appreciation as a potential producer of recombinant therapeutical proteins can be observed. two species of tobacco--nicotiana tabacum l. and n. benthamiana are easily grown by well established methods of field or green-house cultivation or cell culture, yield high biomass and soluble protein content, can be easily transformed by several methods and are not food for humans or feed fo ...201021360963
passive vaccination with a human monoclonal antibody: generation of antibodies and studies for efficacy in bacillus anthracis infections.a major difficulty in creating human monoclonal antibodies is the lack of a suitable myeloma cell line to be used for fusion experiments. in order to create fully human monoclonal antibodies for passive immunization, the human mouse heteromyeloma cell line cb-f7 was evaluated. using this cell line, we generated human monoclonal antibodies against bacillus anthracis toxin components. antibodies against protective antigen (pa) and against lethal factor (lf) were obtained using peripheral blood lym ...201021397977
defense and death responses to pore forming toxins.pore forming toxins (pft) are important virulence factors produced by bacteria to kill eukaryotic cells by forming holes in the cellular membrane. they represent a diverse group of proteins with a wide range of target cells. although the amino acid sequence is not conserved among the different pft, many of them share some aspects of their mechanism of action. in general, the mode of action of pft involves receptor recognition, activation by proteases, and aggregation into oligomeric-structures t ...201021415876
the forgotten giants behind louis pasteur: contributions by the veterinarians toussaint and galtier. 201021466009
emergence of anthrax edema toxin as a master manipulator of macrophage and b cell functions.anthrax edema toxin (et), a powerful adenylyl cyclase, is an important virulence factor of bacillus anthracis. until recently, only a modest amount of research was performed to understand the role this toxin plays in the organism's immune evasion strategy. a new wave of studies have begun to elucidate the effects this toxin has on a variety of host cells. while efforts have been made to illuminate the effect et has on cells of the adaptive immune system, such as t cells, the greatest focus has b ...201022069663
consequences and utility of the zinc-dependent metalloprotease activity of anthrax lethal toxin.anthrax is caused by the gram-positive bacterium bacillus anthracis. the pathogenesis of this disease is dependent on the presence of two binary toxins, edema toxin (edtx) and lethal toxin (letx). letx, the major virulence factor contributing to anthrax, contains the effector moiety lethal factor (lf), a zinc-dependent metalloprotease specific for targeting mitogen-activated protein kinase kinases. this review will focus on the protease-specific activity and function of lf, and will include a di ...201022069624
[species-specific sera against surface antigens of bacillus anthracis strains].the species-related specificity of sera against 94-kd proteins isolated from culture filtrates of b. anthracis strains with different levels of virulence plasmids was studied to determine whether they might be used to identify the pathogen of anthrax. sera against fractions 1 of culture filtrates of b. anthracis strains cti (pxo1+ pxo2-), 81/1tr (pxo1- pxo2-), davies (pxo1- pxo) separated by gel chromatography on sephacryl s-300 were examined. in the gel immunodiffusion test with growing culture ...201021319392
[current situation of the most frequent zoonosis in the world].zoonoses are at the present time more important than ever due to their magnitude and impact. the international trade in animals, products and sub products, as well as the intense travel of people around the world, represent risks of dissemination of infectious diseases, and are the reason for a new age of emerging and reemerging zoonotic diseases. under these conditions, public health and animal health authorities are obliged to work together in order to get more efficient control programs. in t ...201021384639
antimicrobial activity of copper and silver nanofilms on nosocomial bacterial species.contaminated surfaces are possible vehicles in infection transmission. it is known that both copper (cu) and silver (ag) efficiently inactivate microbes by direct contact. aiming at using these metals for benefitting from their antimicrobial effect, but to avoid subsequent toxic effects, we evaluated the antimicrobial activity of nanometric thin silver and copper films covering less expensive materials. using a modified version of the japan industrial standard jis z 2801:2000, we demonstrated th ...201021462835
the glucocorticoid receptor: a revisited target for toxins.the hypothalamic-pituitary-adrenal (hpa) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the hpa axis or gr blockade enhances mortality rates. replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. much research has focused on th ...201022069642
biological warfare agents.the recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. there has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern ...201021829313
knowledge and attitude towards zoonoses among animal health workers and livestock keepers in arusha and tanga, tanzania.zoonoses are infections naturally transmitted between vertebrate animals and humans. an exploratory questionnaire-based survey of animal health workers(n=36) and livestock keepers(n=43) was carried out from april 2001 to march 2002 in tanga and arusha regions, northern tanzania, to assess local knowledge, attitudes and public awareness for animal zoonoses. a combination of closed and open-ended questions, focus group discussions and ranking techniques were employed to gather information on perce ...201024409636
multiplex pcr assay for the detection of enterotoxic bacillus cereus group strains and its application in food matrices.bacillus cereus, bacillus thuringiensis and bacillus anthracis are the major concerns for the food safety in terms of frequency and/or seriousness of the disease. being members of the same group and sharing dna homology to a larger extent, they do create problems when their specific detection/identification is attempted from different food and environmental sources. numerous individual polymerase chain reaction (pcr) and few multiplex pcr (mpcr) methods have been employed to detect these organis ...201023100823
multiplexed electrochemical detection of yersinia pestis and staphylococcal enterotoxin b using an antibody microarray.the combimatrix antibody microarray is a versatile, sensitive detection platform based on the generation and transduction of electrochemical signals following antigen binding to surface antibodies. the sensor chip described herein is comprised of microelectrodes coupled to an adjacent bio-friendly matrix coated with antibodies to the biological pathogens yersinia pestis and bacillus anthracis, and the bacterial toxin staphylococcal enterotoxin b (seb). using this system, we were able to detect s ...201022319302
binary fingerprints at fluctuation-enhanced sensing.we have developed a simple way to generate binary patterns based on spectral slopes in different frequency ranges at fluctuation-enhanced sensing. such patterns can be considered as binary "fingerprints" of odors. the method has experimentally been demonstrated with a commercial semiconducting metal oxide (taguchi) sensor exposed to bacterial odors (escherichia coli and anthrax-surrogate bacillus subtilis) and processing their stochastic signals. with a single taguchi sensor, the situations of e ...201022315545
ampd3 is involved in anthrax letx-induced macrophage cell death.the responses of macrophages to bacillus anthracis infection are important for the survival of the host, since macrophages are required for the germination of b. anthracis spores in lymph nodes, and macrophage death exacerbates anthrax lethal toxin (letx)-induced organ collapse. to elucidate the mechanism of macrophage cell death induced by letx, we performed a genetic screen to search for genes associated with letx-induced macrophage cell death. raw264.7 cells, a macrophage-like cell line sensi ...201121822801
dnaj sequences of bacillus cereus strains isolated from outbreaks of hospital infection are highly similar to bacillus anthracis.bacillus cereus is becoming an important nomosomial pathogen because of frequent isolation from blood cultures and from severe systemic infections. to differentiate highly pathogenic outbreak strain of b. cereus from other sources of the bacillus cereus, we attempted to analyze their dnaj sequences. assays indicated that dnaj sequence similarity of all of 52 blood culture isolates of b. cereus ranged from 92.8% to 100%. the distance between b. anthracis and b. cereus except six outbreak isolates ...201121683265
bovine bacillus anthracis in cameroon.bovine bacillus anthracis isolates from cameroon were genetically characterized. they showed a strong homogeneity, and they belong, together with strains from chad, to cluster a+¦, which appears to be predominant in western africa. however, one strain that belongs to a newly defined clade (d) and cluster (d1) is penicillin resistant and shows certain phenotypes typical of bacillus cereus.201121705535
the poly-{gamma}-d-glutamic acid capsule of bacillus anthracis enhances lethal toxin activity.the poly-+¦-d-glutamic acid (pga) capsule is one of the major virulence factors of bacillus anthracis, which causes a highly lethal infectious disease. the pga capsule disguises b. anthracis from immune surveillance and allows its unimpeded growth in the host. the pga capsule recently was reported to be associated with lethal toxin (lt) in the blood of experimentally infected animals (m. h. cho, et al., infect. immun. 78:387-392, 2010). the effect of pga, either alone or in combination with lt, ...201121690241
anthrax toxin induces macrophage death by p38 mapk inhibition but leads to inflammasome activation via atp leakage.detection of microbial constituents by membrane associated and cytoplasmic pattern recognition receptors is the essence of innate immunity, leading to activation of protective host responses. however, it is still unclear how immune cells specifically respond to pathogenic bacteria. using virulent and nonvirulent strains of bacillus anthracis, we have shown that secretion of atp by infected macrophages and the sequential activation of the p2x7 purinergic receptor and nucleotide binding oligomeriz ...201121683629
b. anthracis in a wool-processing factory: seroprevalence and occupational risk.summaryin a belgian wool-processing factory, living anthrax spores were found in raw goat hair and air dust, but confirmed anthrax cases had never been reported. anthrax vaccines are not licensed nor recommended in belgium. we conducted a b. anthracis seroprevalence study to investigate risk factors associated with positive serology and advise on protective measures. overall 12…1% (8/66) employees were seropositive; 30% of persons processing raw goat hair and 20% of persons sorting raw goat hai ...201121835070
inhibition of anthrax toxins with a bispecific monoclonal antibody that cross reacts with edema factor as well as lethal factor of bacillus anthracis.bacillus anthracis overwhelms its victims by way of two toxins, namely edema toxin and lethal toxin. lethal toxin is formed by the combination of protective antigen with lethal factor while edema toxin is formed by the combination of protective antigen with edema factor. overlapping regions between edema factor and lethal factor have been reported in past. for the first time, this study reports characterization of a bispecific monoclonal antibody (mab), h10, which showed high affinity interactio ...201121704379
access to antigens related to anthrose using pivotal cyclic sulfite/sulfate intermediates.anthrose is the upstream terminal unit of the tetrasaccharide side chain from a major glycoprotein of bacillus anthracis exosporium and is part of important antigenic determinants. a novel entry to anthrose-containing antigens and precursors is described. the synthetic route, starting from d(+)-fucose, makes use of intermediates featuring a cyclic sulfite or sulfate function which serves successively as a protecting and a leaving group.201121678952
macrophage responses to bacterial toxins: a balance between activation and suppression.toxins secreted by bacteria can impact the host in a number of different ways. in some infections, toxins play a crucial and central role in pathogenesis (i.e., anthrax), while in other bacterial infections, the role of toxins is less understood. the cholesterol-dependent cytolysins (cdcs), of which streptolysin o is a prototype, are a class of pore-forming toxins produced by many gram-positive bacteria and have only been studied in a few experimental infection models. our laboratory has demonst ...201121717083
a systematic methodology for selecting decontamination strategies following a biocontamination event.decontamination and recovery of a facility or outdoor area after a wide-area biological incident involving a highly persistent agent (eg, bacillus anthracis spores) is a complex process that requires extensive information and significant resources, which are likely to be limited, particularly if multiple facilities or areas are affected. this article proposes a systematic methodology for evaluating information to select the decontamination or alternative treatments that optimize use of resources ...201121823924
risk of disability for us army personnel vaccinated against anthrax, 1998-2005.to evaluate the potential for long-term or delayed onset health effects, we extended a previous cohort study of disability separation from the army associated with vaccination against anthrax. analyses included stratified cox proportional hazards and multiple logistic regression models. forty-one percent of 1,001,546 soldiers received at least one anthrax vaccination; 5.21% were evaluated for disability. no consistent patterns or statistically significant differences in risk of disability evalua ...201121704102
temporal and spatial distribution of cattle anthrax outbreaks in zimbabwe between 1967 and 2006.this retrospective study aimed to assess the spatial and temporal distribution of anthrax and to identify risk areas in zimbabwe. the data were extracted from the monthly and annual reports of the division of livestock production and veterinary services for the period 1967 to 2006. the data were analyzed in relation to temporal and spatial factors. the hot-dry season was found to be significantly (x (2)ôçë=ôçë847.8, pôçë<ôçë0.001) associated with the occurrence of anthrax in cattle, and the dise ...201121701924
tumor endothelial marker 8 amplifies canonical wnt signaling in blood vessels.tumor endothelial marker 8/anthrax toxin receptor 1 (tem8/antxr1) expression is induced in the vascular compartment of multiple tumors and therefore, is a candidate molecule to target tumor therapies. this cell surface molecule mediates anthrax toxin internalization, however, its physiological function in blood vessels remains largely unknown. we identified the chicken chorioallantoic membrane (cam) as a model system to study the endogenous function of tem8 in blood vessels as we found that tem8 ...201121829615
an unusual case of peritonitis in an intravenous drug user. 201121712037
cooperativity and interference of germination pathways in bacillus anthracis spores.spore germination is the first step to bacillus anthracis pathogenicity. previous work has shown that b. anthracis spores use germination (ger) receptors to recognize amino acids and nucleosides as germinants. genetic analysis has putatively paired each individual ger receptor with a specific germinant. however, ger receptors seem to be able to partially compensate for each other and recognize alternative germinants. using kinetic analysis of b. anthracis spores germinated with inosine and l-ala ...201121685276
potent antimicrobial peptides with selectivity for bacillus anthracis over human erythrocytes.in this study, 39 antimicrobial peptides, most with documented low haemolytic activity and potent efficacy against gram-negative and gram-positive bacteria, were evaluated for their haemolytic activity against human red blood cells as well as their antimicrobial activity against escherichia coli, burkholderia thailandensis, bacillus globigii and bacillus anthracis. the majority of the peptides had a minimum inhibitory concentration (mic) of <10++m against b. globigii. however, only eight of thes ...201121741801
combined proteomic and transcriptomic analysis of the response of bacillus anthracis to oxidative stress.the endospore-forming gram-positive pathogen bacillus anthracis is responsible for the usually fatal disease, inhalational anthrax. the success of this pathogen is dependent on its ability to subvert elements of the innate immune system of its animal hosts. b. anthracis spores, which are the main infective agent, are engulfed and germinate in patrolling alveolar macrophages. in order for the infection to progress, the resulting vegetative cells must resist the antimicrobial oxidative burst mount ...201121726052
public response to an anthrax attack: reactions to mass prophylaxis in a scenario involving inhalation anthrax from an unidentified source.an attack with bacillus anthracis ("anthrax") is a known threat to the united states. when weaponized, it can cause inhalation anthrax, the deadliest form of the disease. due to the rapid course of inhalation anthrax, delays in initiation of antibiotics may decrease survival chances. because a rapid response would require cooperation from the public, there is a need to understand the public's response to possible mass dispensing programs. to examine the public's response to a mass prophylaxis pr ...201121819225
(1)h, (13)c, and (15)n resonance assignments and secondary structure prediction of the full-length transition state regulator abrb from bacillus anthracis.the abrb protein is a transcription factor that regulates the expression of numerous essential genes during the cells transition phase state. abrb from bacillus anthracis is, nototriously, the principal protein responsible for anthrax toxin gene expression and is highly homologous to the much-studied abrb protein from bacillus subtilis having 85% sequence identity and the ability to regulate the same target promoters. here we report backbone and sidechain resonance assignments and secondary stru ...201121845362
enzymatic characterization of catalase from bacillus anthracis and prediction of critical residues using information theoretic measure of relative entropy.in order to cope up with the reactive oxygen species (ros) generated by host innate immune response, most of the intracellular organisms express catalase for the enzymatic destruction/detoxification of hydrogen peroxide, to combat its deleterious effects. catalase thus, scavenges ros thereby playing a pivotal role in facilitating the survival of the pathogen within the host, and thus contributes to its pathogenesis. bacillus anthracis harbors five isoforms of catalase, but none of them has been ...201121723851
an integrated system for disaster preparedness and response.kaiser permanente, the usa's largest not-for-profit integrated healthcare provider, has developed a hybrid emergency preparedness and response system. it consists of a tiered structure of national 'workgroups' and traditional physical command centre operations. the workgroups provide integration and coordination across a large organisation while allowing for necessary regional operational flexibility. workgroup membership taps the best available expertise in a functional area, drawn from all lev ...201121835750
molecular phylogenetic diversity of bacillus community and its temporal-spatial distribution during the swine manure of composting.in order to obtain the diversity and temporal-spatial distribution of bacillus community during the swine manure composting, we utilized traditional culture methods and the modern molecular biology techniques of polymerase chain reaction-restriction fragment length polymorphism (pcr-rflp) and -denaturing gradient gel electrophoresis (pcr-dgge). bacillus species were firstly isolated from the composting. based on temperature changes, the temporal-spatial characteristics of total culturable bacill ...201121701982
efficient immobilization and patterning of biomolecules on poly(ethylene terephthalate) films functionalized by ion irradiation for biosensor applications.the surface of a poly(ethylene terephthalate) (pet) film was selectively irradiated with proton beams at various fluences to generate carboxylic acid groups on the surface; the resulting functionalized pet surface was then characterized in terms of its wettability, chemical structure, and chemical composition. the results revealed that (i) carboxylic acid groups were successfully generated in the irradiated regions of the pet surface, and (ii) their relative amounts were dependent on the fluence ...201121699214
a bacillus anthracis strain deleted for six proteases serves as an effective host for production of recombinant proteins.bacillus anthracis produces a number of extracellular proteases that impact the integrity and yield of other proteins in the b. anthracis secretome. in this study we show that anthrolysin o (alo) and the three anthrax toxin proteins, protective antigen (pa), lethal factor (lf), and edema factor (ef), produced from the b. anthracis ames 35 strain (pxo1(+), pxo2(-)), are completely degraded at the onset of stationary phase due to the action of proteases. an improved cre-loxp gene knockout system w ...201121827967
decontamination of a hard surface contaminated with bacillus anthracis+österne and b.-áanthracis ames spores using electrochemically generated liquid-phase chlorine dioxide (eclo(2) ).aims:ôçé to evaluate the inactivation of bacillus anthracis+österne and ames spores using electrochemically generated liquid-phase chlorine dioxide (eclo(2) ) and compare two sporulation and decontamination methods with regard to cost, safety and technical constraints. methods and results:ôçé spores were prepared via agar and broth methods and subsequently inoculated and dried onto clean, autoclave-sterilized glass coupons. bacillus anthracis spore inactivation efficacy was evaluated using the m ...201121824240
localization and assembly of the novel exosporium protein beta of bacillus anthracis.the exosporium of bacillus anthracis is comprised of two distinct layers: a basal layer and a hair-like nap that covers the basal layer. the hair-like nap contains the glycoproteins bcla and most likely bclb. bcla and bclb are directed to assemble into the exosporium by motifs in their n-terminal domains. here, we identify a previously uncharacterized putative gene encoding this motif, which we have named beta (bacillus exosporium targeted protein of anthracis). like bcla, beta encodes a putativ ...201121821770
extending the aerolysin family: from bacteria to vertebrates.a number of bacterial virulence factors have been observed to adopt structures similar to that of aerolysin, the principal toxin of aeromonas species. however, a comprehensive description of architecture and structure of the aerolysin-like superfamily has not been determined. in this study, we define a more compact aerolysin-like domain--or aerolysin fold--and show that this domain is far more widely spread than anticipated since it can be found throughout kingdoms. the aerolysin-fold could be f ...201121687664
the role of net charge on the catalytic domain and the influence of the cell-wall binding domain on the bactericidal activity, specificity and host-range of phage lysins.the recombinant lysins of lytic phages, when applied externally to gram-positive bacteria, can be efficient bactericidal agents, typically retaining high specificity. their development as novel antibacterial agents offer many potential advantages over conventional antibiotics. protein engineering could exploit this potential further by generating novel lysins fit for distinct target populations and environments. however, access to the peptidoglycan (pg) layer is controlled by a variety of second ...201121816821
a review of exotic animal disease in great britain and in scotland specifically between 1938 and 2007.incursions of contagious diseases of livestock into disease-free zones are inevitable as long as the diseases persist elsewhere in the world. knowledge of where, when and how incursions have occurred helps assess the risks, and regionalize preventative and reactive measures.201121818292
disease control during the colonial period in australia.the first permanent european settlers of australia arrived in 1788 to establish a penal colony at sydney, new south wales (nsw). as the colony grew and wool production increased, more free settlers and emancipists developed farming in inland australia. during the 1840s veterinarians commenced arriving in small numbers but they were not closely associated with the development and execution of disease control programs, which was left to lay inspectors of stock. the arrival of william tyson kendall ...201121696369
nrdh-redoxin mediates high enzyme activity in manganese-reconstituted ribonucleotide reductase from bacillus anthracis.bacillus anthracis is a severe mammalian pathogen encoding a class ib ribonucleotide reductase (rnr). rnr is a universal enzyme that provides the four essential deoxyribonucleotides needed for dna replication and repair. almost all bacillus spp. encode both class ib and class iii rnr operons, but the b. anthracis class iii operon was reported to encode a pseudogene and conceivably class ib rnr is necessary for spore germination and proliferation of b. anthracis upon infection. the class ib rnr o ...201121832039
Crystal Structure of Bacillus anthracis Phosphoglucosamine Mutase, an Enzyme in the Peptidoglycan Biosynthetic Pathway.Phosphoglucosamine mutase (PNGM) is an evolutionarily conserved bacterial enzyme that participates in the cytoplasmic steps of peptidoglycan biosynthesis. As peptidoglycan is essential for bacterial survival and is absent in humans, enzymes in this pathway have been the focus of intensive inhibitor design efforts. Many aspects of the structural biology of the peptidoglycan pathway have been elucidated, with the exception of the PNGM structure. We present here the crystal structure of PNGM from t ...201121685296
Key aspects of the molecular and cellular basis of inhalational anthrax.Bacillus anthracis is the etiologic agent of the disease inhalational anthrax, an acute systemic infection initiated by inhaling spores, which if not rapidly detected and treated, results in death. Decades of research have elucidated novel aspects of anthrax pathogenesis but there are many issues left unresolved.201121816231
Rapidly Progressive, Fatal, Inhalation Anthraxlike Infection in a Human: Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response.Context.-Ten years ago a bioterrorism event involving Bacillus anthracis spores captured the nation's interest, stimulated extensive new research on this pathogen, and heightened concern about illegitimate release of infectious agents. Sporadic reports have described rare, fulminant, and sometimes fatal cases of pneumonia in humans and nonhuman primates caused by strains of Bacillus cereus , a species closely related to Bacillus anthracis . Objectives.-To describe and investigate a case of rapid ...201121827220
pilot-scale crossflow-microfiltration and pasteurization to remove spores of bacillus anthracis (sterne) from milk.high-temperature, short-time pasteurization of milk is ineffective against spore-forming bacteria such as bacillus anthracis (ba), but is lethal to its vegetative cells. crossflow microfiltration (mf) using ceramic membranes with a pore size of 1.4 μm has been shown to reject most microorganisms from skim milk; and, in combination with pasteurization, has been shown to extend its shelf life. the objectives of this study were to evaluate mf for its efficiency in removing spores of the attenuated ...201121854901
stable dry powder formulation for nasal delivery of anthrax vaccine.there is a current biodefense interest in protection against anthrax. here, we developed a new generation of stable and effective anthrax vaccine. we studied the immune response elicited by recombinant protective antigen (rpa) delivered intranasally with a novel mucosal adjuvant, a mast cell activator compound 48/80 (c48/80). the vaccine formulation was prepared in a powder form by spray-freeze-drying (sfd) under optimized conditions to produce particles with a target size of d(50) = 25 μm, suit ...201121905034
establishing the detection threshold for bacillus subtilis in a complex matrix using an inorganic fingerprint approach.methods for the detection and characterization of airborne biological warfare agents, such as bacteria, using their dna or organic composition are fairly well developed. this approach is useful for identifying the type of bacterial strain once the organism has been isolated from the matrix sampled (e.g., dust particles) and can identify genetically related organisms, which might be helpful during a forensic investigation. however, this genetic signature will not reveal information related to the ...201121872011
national validation study of a cellulose sponge wipe-processing method for use after sampling bacillus anthracis spores from surfaces.this work was initiated to address the gaps identified by congress regarding validated biothreat environmental sampling and processing methods. nine laboratory response network-affiliated laboratories participated in a validation study of a cellulose sponge wipe-processing protocol for the recovery, detection, and quantification of viable bacillus anthracis sterne spores from steel surfaces. steel coupons (645.16 cm(2)) were inoculated with 1 to 4 log(10) spores and then sampled with cellulose s ...201121965403
aoac smpr 2010.003. standard method performance requirements for polymerase chain reaction (pcr) methods for detection of bacillus anthracis in aerosol collection filters and/or liquids. 201121919367
determination of post-culture processing with carbohydrates by maldi-ms and tms derivatization gc-ms.biological materials generally require stabilization to retain activity or viability in a dry form. a number of industrial products, such as vaccines, probiotics and biopesticides have been produced as dry preparations. the same methods and materials used for stabilizing commercial microbial products may be applicable to preserving biothreat pathogens in a dry form. this is a likely step that may be encountered when looking at samples from terrorism attempts since only spores, such as those from ...201121962653
Screening of Peptide Libraries against Protective Antigen of Bacillus anthracis in a Disposable Microfluidic Cartridge.Bacterial surface peptide display has gained popularity as a method of affinity reagent generation for a wide variety of applications ranging from drug discovery to pathogen detection. In order to isolate the bacterial clones that express peptides with high affinities to the target molecule, multiple rounds of manual magnetic activated cell sorting (MACS) followed by multiple rounds of fluorescence activated cell sorting (FACS) are conventionally used. Although such manual methods are effective, ...201122140433
anthrax infection.bacillus anthracis infection is rare in developed countries. however, recent outbreaks in the united states and europe and the potential use of the bacteria for bioterrorism have focused interest on it. furthermore, although anthrax was known to typically occur as one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection in injectional drug users is emerging. although shock has been described wit ...201121852539
ultrasensitive diagnosis for an anthrax-protective antigen based on a polyvalent directed peptide polymer coupled to zinc oxide nanorods.a flexible poly-d-lysine polymer conjugated with different target-binding peptides is demonstrated with an ultralow concentration detection limit compared to those of other conventional detection systems. this polyvalent directed peptide polymer (pdpp) exhibits increased binding affinity and detects anthrax protective antigen at low levels using a well-known zinc oxide nanorod detection system.201121997757
validation and long term performance characteristics of a quantitative enzyme linked immunosorbent assay (elisa) for human anti-pa igg.accurate, reliable and standardized quantification of anti-protective antigen (pa) igg antibody levels is essential for comparative analyses of anti-toxin immune responses in anthrax cases, recipients of pa-based anthrax vaccines and for evaluation of anti-pa based immunotherapies. we have previously reported the early performance characteristics and application of a quantitative anti-pa igg enzyme linked immunosorbent assay. the principal application of this assay was in a phase 4 human clinica ...201122197974
anthrax lethal toxin-mediated disruption of endothelial ve-cadherin is attenuated by inhibition of the rho-associated kinase pathway.systemic anthrax disease is characterized by vascular leakage pathologies. we previously reported that anthrax lethal toxin (lt) induces human endothelial barrier dysfunction in a cell death-independent manner with actin stress fiber formation and disruption of adherens junctions (ajs). in the present study, we further characterize the molecular changes in the aj complex and investigate whether aj structure and barrier function can be preserved by modulating key cytoskeletal signaling pathways. ...201122069696
a supramolecular sensing platform for phosphate anions and an anthrax biomarker in a microfluidic device.a supramolecular platform based on self-assembled monolayers (sams) has been implemented in a microfluidic device. the system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. a eu(iii)-edta complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. the self-assembly of the eu(iii)-edta conjugate and naphthalene β-diketone as a ...201122174602
Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case report, pathogen genome sequencing, pathology, and coordinated response.Ten years ago a bioterrorism event involving Bacillus anthracis spores captured the nation's interest, stimulated extensive new research on this pathogen, and heightened concern about illegitimate release of infectious agents. Sporadic reports have described rare, fulminant, and sometimes fatal cases of pneumonia in humans and nonhuman primates caused by strains of Bacillus cereus , a species closely related to Bacillus anthracis.201121882964
comparison of the efficiency of antibody selection from semi-synthetic scfv and non-immune fab phage display libraries against protein targets for rapid development of diagnostic immunoassays.rapid development of diagnostic immunoassays against novel emerging or genetically modified pathogens in an emergency situation is dependent on the timely isolation of specific antibodies. non-immune antibody phage display libraries are an efficient in vitro method for selecting monoclonal antibodies and hence ideal in these circumstances. such libraries can be constructed from a variety of sources e.g. b cell cdna or synthetically generated, and use a variety of antibody formats, typically scfv ...201121856306
chlorine dioxide inactivation of bacterial threat agents.aims:  to evaluate the efficacy of chlorine dioxide (clo(2) ) against seven species of bacterial threat (bt) agents in water. methods and results:  two strains of bacillus anthracis spores, yersinia pestis, francisella tularensis, burkholderia pseudomallei, burkholderia mallei, and brucella species were each inoculated into a clo(2) solution with an initial concentration of 2·0 mg l(-1) (spores only) and 0·25 mg l(-1) (all other bacteria) at ph 7 or 8, 5°c or 25°c. at 0·25 mg l(-1) in potable wa ...201121623848
marked enhancement of the immune response to biothrax(®) (anthrax vaccine adsorbed) by the tlr9 agonist cpg 7909 in healthy volunteers.immunization with biothrax(®) (anthrax vaccine adsorbed) is a safe and effective means of preventing anthrax. animal studies have demonstrated that the addition of cpg dna adjuvants to biothrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (pa) antibody and anthrax toxin-neutralizing antibody (tna) concentrations. the immune response to cpg-adjuvanted biothrax in animals was not only stronger, but was also more rapid and led to higher leve ...201121624418
a kinetic analysis of protein transport through the anthrax toxin channel.anthrax toxin is composed of three proteins: a translocase heptameric channel, (pa(63))(7), formed from protective antigen (pa), which allows the other two proteins, lethal factor (lf) and edema factor (ef), to translocate across a host cell's endosomal membrane, disrupting cellular homeostasis. (pa(63))(7) incorporated into planar phospholipid bilayer membranes forms a channel capable of transporting lf and ef. protein translocation through the channel can be driven by voltage on a timescale of ...201121624946
colorimetric and dynamic light scattering detection of dna sequences by using positively charged gold nanospheres: a comparative study with gold nanorods.we introduce a new genosensing approach employing ctab (cetyltrimethylammonium bromide)-coated positively charged colloidal gold nanoparticles (gnps) to detect target dna sequences by using absorption spectroscopy and dynamic light scattering. the approach is compared with a previously reported method employing unmodified ctab-coated gold nanorods (gnrs). both approaches are based on the observation that whereas the addition of probe and target ssdna to ctab-coated particles results in particle ...201121625041
an unusual mechanism of isopeptide bond formation attaches the collagenlike glycoprotein bcla to the exosporium of bacillus anthracis.abstract the outermost exosporium layer of spores of bacillus anthracis, the causative agent of anthrax, is comprised of a basal layer and an external hairlike nap. the nap includes filaments composed of trimers of the collagenlike glycoprotein bcla. essentially all bcla trimers are tightly attached to the spore in a process requiring the basal layer protein bxpb (also called exsfa). both bcla and bxpb are incorporated into stable, high-molecular-mass complexes, suggesting that bcla is attached ...201121628501
multigenic control and sex-bias in host susceptibility to spore-induced pulmonary anthrax in mice.mechanisms underlying susceptibility to anthrax infection are unknown. using a phylogenetically diverse panel of inbred mice and spores of bacillus anthracis ames, we investigated host susceptibility to pulmonary anthrax. susceptibility profiles for survival time and organ pathogen load differed across strains, indicating distinct genetic controls. tissue infection kinetics analysis showed greater systemic dissemination in susceptible dba/2j (d) mice, but higher terminal bacterial load in resist ...201121628518
bacillus anthracis: molecular taxonomy, population genetics, phylogeny and patho-evolution.bacillus anthracis, the etiological agent of anthrax, manifests a particular bimodal lifestyle. this bacterial species alternates between short replication phases of 20-40 generations that strictly require infection of the host, normally causing death, interrupted by relatively long, mostly dormant phases as spores in the environment. hence, the b. anthracis genome is highly homogeneous. this feature and the fact that strains from nearly all parts of the world have been analysed for canonical si ...201121640849
noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. we visualized the interactions between wild-type bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. we show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. edema toxin (et), but not lethal toxin (lt), markedly modified the pat ...201121641378
lysozyme as a barrier to growth of bacillus anthracis strain sterne in liquid egg white, milk and beef.in this study, we investigated the role of lysozyme on the viability of bacillus cereus, bacillus subtilis, bacillus pumilus and bacillus anthracis (sterne) in egg white (ew), ground beef and milk. at 35 °c in ew, growth rates (gr) for b. cereus, b. subtilis, b. pumilus and b. anthracis were 0.005, -0.018, -0.028 and -0.029 od(600)/h, respectively. heat-treating ew at 55 and 60 °c reduced the inactivating effect of ew by 3.1 and 10.5-fold, respectively. addition of lysozyme (2 mg/ml) to 60 °c-tr ...201121645824
yersinia pestis yope contains a dominant cd8 t cell epitope that confers protection in a mouse model of pneumonic plague.septic bacterial pneumonias are a major cause of death worldwide. several of the highest priority bioterror concerns, including anthrax, tularemia, and plague, are caused by bacteria that acutely infect the lung. bacterial resistance to multiple antibiotics is increasingly common. although vaccines may be our best defense against antibiotic-resistant bacteria, there has been little progress in the development of safe and effective vaccines for pulmonary bacterial pathogens. the gram-negative bac ...201121653834
efficient targeting of head and neck squamous cell carcinoma by systemic administration of a dual upa and mmp-activated engineered anthrax toxin.head and neck squamous cell carcinoma (hnscc) is the sixth most common cancer worldwide. although considerable progress has been made in elucidating the etiology of the disease, the prognosis for individuals diagnosed with hnscc remains poor, underscoring the need for development of additional treatment modalities. hnscc is characterized by the upregulation of a large number of proteolytic enzymes, including urokinase plasminogen activator (upa) and an assortment of matrix metalloproteinases (mm ...201121655226
carbohydrate molecules: an expanding horizon in drug delivery and biomedicine.this review presents successful applications of carbohydrate molecules in drug delivery, vaccine development, cancer, hiv and various other diseases based on advances in glycobiology and glycochemistry. carbohydrate-mediated delivery could be site specific/cell specific. carbohydrate-based delivery system has been successfully utilized for the delivery of macromolecular drugs, antigen, and potential therapeutic drug candidates. lectin, the high affinity carbohydrate-binding nonimmune glycoprotei ...201121663577
feasibility of the use of elisa in an immunogenicity-based potency test of anthrax vaccines.complexities of lethal challenge animal models have prompted the investigation of immunogenicity assays as potency tests of anthrax vaccines. an elisa was used to measure the antibody response to protective antigen (pa) in mice immunized once with a commercially available (ava) or a recombinant pa vaccine (rpav) formulated in-house with aluminum hydroxide. results from the anti-pa elisa were used to select a single dose appropriate for the development of a potency test. immunization with 0.2ml o ...201121664832
targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax.to establish whether activation of adenosine type-3 receptors (a3rs) and inhibition of interleukin-1+¦-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores.201121666812
neutral metallated and meso-substituted porphyrins as antimicrobial agents against gram-positive pathogens.staphylococcus aureus is a bacterial pathogen that causes severe infections among humans. the increasing emergence of antibiotic resistance necessitates the development of new strategies to combat the spread of disease. one approach is photodynamic inactivation using porphyrin photosensitizers, which generate superoxide and other radicals in the presence of light, causing cell death via the oxidation of proteins and lipids. in this study, we analyzed a novel library of meso-substituted and metal ...201121667268
a model for in-vivo delivered dose estimation for inhaled bacillus anthracis spores in humans with interspecies extrapolation.the quantitative yardstick for quantitative microbial risk assessment (qmra) is the dose response assessment phase. in this phase of the qmra paradigm a mathematical model is used to describe the relationship between host response (infection, disease, etc.) and pathogen dose. there are, however, key uncertainties which if addressed can expand our understanding of the dose response relationship and improve its accuracy. the dose response models most frequently used in this phase of qmra are based ...201121667964
a tetrameric structure is not essential for activity in dihydrodipicolinate synthase (dhdps) from mycobacterium tuberculosis.dihydrodipicolinate synthase (dhdps) is a validated antibiotic target for which a new approach to inhibitor design has been proposed: disrupting native tetramer formation by targeting the dimer-dimer interface. in this study, rational design afforded a variant of mycobacterium tuberculosis, mtb-dhdps-a204r, with disrupted quaternary structure. x-ray crystallography (at a resolution of 2.1Å) revealed a dimeric protein with an identical fold and active-site structure to the tetrameric wild-type e ...201121672512
regulation of petrobactin and bacillibactin biosynthesis in bacillus anthracis under iron and oxygen variation.bacillus anthracis produces two catecholate siderophores, petrobactin and bacillibactin, under iron-limited conditions. here, we investigate how variable iron and oxygen concentrations influence the biosynthetic output of both siderophores in b. anthracis. in addition, we describe the differential levels of transcription of select genes within the b. anthracis siderophore biosynthetic operons that are responsible for synthesis of petrobactin and bacillibactin, during variable growth conditions.201121673962
tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.anthrax toxin is the major virulence factor produced by bacillus anthracis. the toxin consists of three protein subunits: protective antigen (pa), lethal factor, and edema factor. inhibition of pa binding to its receptors, tumor endothelium marker-8 (tem8) and capillary morphogenesis protein-2 (cmg2) can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual ...201121674060
imaging tumor endothelial marker 8 using an (18)f-labeled peptide.purpose: tumor endothelial marker 8 (tem8) has been reported to be upregulated in both tumor cells and tumor-associated endothelial cells in several cancer types. tem8 antagonists and tem8-targeted delivery of toxins have been developed as effective cancer therapeutics. the ability to image tem8 expression would be of use in evaluating tem8-targeted cancer therapy. methods: a 13-meric peptide, kyndrlplyisnp (qqm), identified from the small loop in domain iv of protective antigen of anthrax toxin ...201121814853
the five near-iron transporter (neat) domain anthrax hemophore, isdx2, scavenges heme from hemoglobin and transfers heme to the surface protein isdc.pathogenic bacteria require iron to replicate inside mammalian hosts. recent studies indicate that heme acquisition in gram-positive bacteria is mediated by proteins containing one or more near-iron transporter (neat) domains. b. anthracis is a spore-forming, gram-positive pathogen and the causative agent of anthrax disease. the rapid, extensive and efficient replication of b. anthracis in host tissues makes this pathogen an excellent model organism for the study of bacterial heme acquisition. b ...201121808055
disinfection methods for spores of bacillus atrophaeus, b. anthracis, clostridium tetani, c. botulinum and c. difficile.to evaluate disinfection methods for environments contaminated with bioterrorism-associated microorganism (bacillus anthracis), we performed the following experiments. first, the sporicidal effects of sodium hypochlorite on spores of five bacterial species were evaluated. bacillus atrophaeus was the most resistant to hypochlorite, followed in order by b. anthracis, clostridium botulinum and clostridium tetani, and clostridium difficile. subsequently, using b. atrophaeus spores that were the most ...201121804226
anthrax phylogenetic structure in northern italy.abstract: background: anthrax has almost disappeared from mainland europe, except for the mediterranean region where cases are still reported. in central and south italy, anthrax is enzootic, but in the north there are currently no high risk areas, with only sporadic cases having been registered in the last few decades. regional genetic and molecular characterizations of anthrax in these regions are still lacking. to investigate the potential molecular diversity of bacillus anthracis in northern ...201121801397
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