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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
htra is a major virulence determinant of bacillus anthracis.we demonstrate that disruption of the htra (high temperature requirement a) gene in either the virulent bacillus anthracis vollum (pxo1(+) , pxo2(+) ), or in the δvollum (pxo1(-) , pxo2(-) , nontoxinogenic and noncapsular) strains, affect significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress. the δhtra mutants manifest altered secretion of several proteins, as well as complete silencing of the abundant extracellular starvation-associated neut ...201121801240
grp78(bip) facilitates the cytosolic delivery of anthrax lethal factor (lf) in vivo and functions as an unfoldase in vitro.anthrax toxin is an a/b bacterial protein toxin which is composed of the enzymatically active lethal factor (lf) and/or oedema factor (ef) bound to protective antigen 63 (pa63) which functions as both the receptor binding and transmembrane domains. once the toxin binds to its cell surface receptors it is internalized into the cell and traffics through rab5- and rab7-associated endosomal vesicles. following acidification of the vesicle lumen, pa63 undergoes a dynamic change forming a beta-barrel ...201121797942
fluorescent detection of an anthrax biomarker based on pva film.due to the dangerous nature of anthrax, the development of a cost-effective, sensitive and field-portable sensor for the anthrax biomarker-calcium dipicolinate (cadpa)-is of exceptional significance for both military and civilian use. herein, a flexible polymer-film-based ratiometric sensor for detecting cadpa was demonstrated. a reference dye and a probe ligand were covalently immobilized onto the film surface through a highly selective and efficient "click chemistry" reaction. the reference dy ...201121796290
lethal factor is not required for bacillus anthracis virulence in guinea pigs and rabbits.the major virulence factor of bacillus anthracis is the tripartite anthrax toxin, comprising the protective antigen (pa), lethal factor (lf) and edema factor (ef). the lf of b. anthracis is a metalloprotease that has been shown to play an important role in pathogenicity. deletion of this gene (lef) in the sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was reported to be as dramatic as the deletion of pa. we evaluated the effect on pathogenicity of ...201121791242
the development of a silica nanoparticle-based label-free dna biosensor.a silica nanoparticle-based dna biosensor capable of detecting bacillus anthracis bacteria through the use of unlabelled ss-oligonucleotides has been developed. the biosensor makes use of the optical changes that accompany a nanoparticle-immobilized cationic conjugated polymer (polythiophene) interacting with single-stranded vs. hybridized oligonucleotides, where a fluorescence signal appears only when hybridized dna is present (i.e. only when the ss-oligonucleotide interacting with the polymer ...201121789325
molecular epidemiological study of bacillus anthracis isolated in mongolia by multiple-locus variable-number tandem-repeat analysis for 8 loci (mlva-8).the incidence of anthrax, which is caused by bacillus anthracis, in the human and animal population of mongolia has increased recently, and control of this infection is a nationwide concern. in this study, 29 isolates obtained from animals and various regions in mongolia from 2001 to 2007 were analyzed by performing multiple-locus variable-number tandem-repeat analysis for 8 loci (mlva-8) to understand the genetic relationship between the mongolian b. anthracis isolates. we found that all the mo ...201121788715
environmental and biofilm-dependent changes in a bacillus cereus secondary cell wall polysaccharide.bacterial species from the bacillus genus, including bacillus cereus and bacillus anthracis, synthesize secondary cell wall polymers (scwp) covalently associated to the peptidoglycan through a phospho-diester linkage. although such components were observed in a wide panel of b. cereus and b. anthracis strains, the effect of culture conditions or of bacterial growth state on their synthesis has never been addressed. herein we show that b. cereus atcc 14579 can synthesize not only one, as previous ...201121784857
new inhibitors of colony spreading in bacillus subtilis and bacillus anthracis.we have recently characterized sliding motility in bacillus subtilis strains that lack functional flagella, and here describe the discovery of inhibitors of colony spreading in these strains as well as the aflagellate pathogen, bacillus anthracis. aflagellate b. subtilis strains were used to screen for new types of antibacterials that might inhibit colony spreading on semi-solid media. from a diverse set of organic structures, p-nitrophenylglycerol (npg), an agent used primarily in clinical labo ...201121784632
biological terrorism and the allergist's office practice.during the anthrax outbreak and threat in trenton (2001), our allergy practice experienced increased visits from approximately 50 of our regular patients with symptoms they believed resulted from anthrax exposure. in all cases, their symptoms were caused by a combination of an exacerbation of their underlying allergic disease and anxiety because of possible exposure to anthrax. our objective is to present an orderly approach to the allergist's outpatients presenting with possible exposure to a b ...201121781403
bacillus anthracis tubulin-related protein ba-tubz assembles force-generating polymers.pathogenecity of bacillus anthracis depends on the faithful inheritance of plasmid pxo1, in a process that requires the plasmid encoded tubulin-related protein ba-tubz. here we show, using heterologous expression in schizosaccharomyces pombe, that ba-tubz assembles into a dynamic polymer in the absence of other b. anthracis proteins and can generate force capable of deforming the fission yeast nuclear envelope. the polymer bundles contain 27 ± 15 protofilaments / µm assuming that each protofilam ...201121780309
ultra-rapid flow-through polymerase chain reaction microfluidics using vapor pressure.a novel flow-through polymerase chain reaction (pcr) microfluidic system using vapor pressure was developed that can achieve ultra-rapid, small-volume dna amplification on a chip. the 40-cycle amplification can be completed in as little as 120s, making this device the fastest pcr system in the world. the chip device is made of a pressure-sensitive polyolefin (psp) film and cyclo-olefin polymer (cop) substrate which was processed by cutting-work to fabricate the microchannel. the enclosed structu ...201121778045
cutaneous manifestations of category a bioweapons.the 2001 anthrax attacks on the united states brought bioterrorism to the forefront of the medical community. because many bioterrorist agents produce cutaneous disease, dermatologists will likely be first responders during a future attack. despite this, many dermatologists are not adequately prepared to deal with a bioterrorism attack. it is critical that all first responders be able to recognize symptoms of bioterrorism-related disease and prepared to respond to a bioterrorist attack to minimi ...201121777993
'bioluminescent' reporter phage for the detection of category a bacterial pathogens.yersinia pestis and bacillus anthracis are category a bacterial pathogens that are the causative agents of the plague and anthrax, respectively (1). although the natural occurrence of both diseases' is now relatively rare, the possibility of terrorist groups using these pathogens as a bioweapon is real. because of the disease's inherent communicability, rapid clinical course, and high mortality rate, it is critical that an outbreak be detected quickly. therefore methodologies that provide rapid ...201121775956
analysis of the binding forces driving the tight interactions between {beta}-lactamase inhibitory protein-ii (blip-ii) and class a {beta}-lactamases.ß-lactamases hydrolyze ß-lactam antibiotics to provide drug resistance to bacteria. blip-ii is a potent proteinaceous inhibitor that exhibits low picomolar affinity for class a ß-lactamases. this study examines the driving forces for binding between blip-ii and ß-lactamases using a combination of pre-steady state kinetics, isothermal titration calorimetry and x-ray crystallography. the measured dissociation rate constants for blip-ii and various ß-lactamases ranged from 10-4-10-7 s-1 and are com ...201121775426
glms riboswitch binding to the glucosamine-6-phosphate a-anomer shifts the pk(a) toward neutrality.the glms riboswitch regulates gene expression through a self-cleavage activity. the reaction is catalyzed with the assistance of the metabolite cofactor glucosamine-6-phosphate (glcn6p), whose amino group is proposed to serve as the general acid during the reaction. this reaction is ph-dependent with a pk(a) that is lower than the observed pk(a) for the amine of glcn6p in solution. glcn6p, like other pyranose sugars, undergoes spontaneous and rapid interconversion between the a and ß anomers at ...201121770472
humanized {theta}-defensins (retrocyclins) enhance macrophage performance and protect mice from experimental anthrax infections.retrocyclins are humanized versions of the -defensin peptides expressed by the leukocytes of several nonhuman primates. previous studies, performed in serum-free media, determined that retrocyclins 1 and 2 could prevent successful germination of bacillus anthracis (ba) spores, kill vegetative ba cells, and inactivate anthrax lethal factor. we now report that retrocyclins are extensively bound by components of native mouse, human and fetal calf sera, that heat-inactivated sera show greatly enhanc ...201121768520
improvement of a potential anthrax therapeutic by computational protein design.past anthrax attacks in the united states have highlighted the need for improved measures against bioweapons. the virulence of anthrax stems from the shielding properties of the bacillus anthracis poly-?-d-glutamate capsule. in the presence of excess capd, a b. anthracis ?-glutamyl transpeptidase, the protective capsule is degraded and the immune system can successfully combat the infection. while capd shows promise as a next generation protein therapeutic against anthrax, improvements in produc ...201121768086
quaternary structure, conformational variability, and global motions of phosphoglucosamine mutase.phosphoglucosamine mutase (pngm) is a bacterial enzyme that participates in the peptidoglycan biosynthetic pathway. recent crystal structures of pngm from two bacterial pathogens, bacillus anthracis and francisella tularensis, revealed key structural features of this enzyme for the first time. here, we follow up on several novel findings from the crystallographic studies, including the observation of a structurally conserved interface between polypeptide chains and conformational variability of ...201121767345
rapid viability polymerase chain reaction method for detection of virulent bacillus anthracis from environmental samples.in the event of a biothreat agent release, hundreds of samples would need to be rapidly processed to characterize the extent of contamination and determine the efficacy of remediation activities. current biological agent identification and viability determination methods are both labor- and time-intensive such that turnaround time for confirmed results is typically several days. in order to alleviate this issue, automated, high throughput sample processing methods were developed in which real-ti ...201121764960
primary cutaneous infection with bacillus megaterium mimicking cutaneous anthrax. 201121763557
sensitive fluorescence assay of anthrax protective antigen with two new dna aptamers and their binding properties.a homogeneous assay of the protective antigen in anthrax toxin is reported using two new pa-specific aptamers for selective and sensitive detection, based on reduction in the fluorescence emission according to the formation of the aptamer-pa ternary complex. pa at 1 nm was readily detected using oligreen as a fluorophore in hepes buffer. we also demonstrated that the pa detection could be performed in blood serum. the binding interaction between the aptamer and pa was strong enough to dehybridiz ...201121743920
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
allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to bacillus anthracis.anthrax is a potentially fatal disease resulting from infection with bacillus anthracis. the outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (lt), as well as by genetic variation within the host. to identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the lt-responsive cast/ei strain introgressed on a lt-resistant c57bl/6 (b6) background was screened for ...201122241984
An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics.An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990.201121962024
Antibodies against anthrax: mechanisms of action and clinical applications.B. anthracis is a bioweapon of primary importance and its pathogenicity depends on its lethal and edema toxins, which belong to the A-B model of bacterial toxins, and on its capsule. These toxins are secreted early in the course of the anthrax disease and for this reason antibiotics must be administered early, in addition to other limitations. Antibodies (Abs) may however neutralize those toxins and target this capsule to improve anthrax treatment, and many Abs have been developed in that perspe ...201122174979
a longitudinal study of uk military personnel offered anthrax vaccination: informed choice, symptom reporting, uptake and pre-vaccination health.aim: to determine longer term health outcome in a cohort of uk service personnel who received the anthrax vaccination. method: we conducted a three year follow up of uk service personnel all of whom were in the armed forces at the start of the iraq war. 3206 had been offered the anthrax vaccination as part of preparations for the 2003 invasion of iraq. a further 1190 individuals who did not deploy to iraq in 2003 were subsequently offered the vaccination as part of later deployments, and in whom ...201122178523
the role of bacillus anthracis recd2 helicase in dna mismatch repair.dna mismatch repair (mmr) systems can be classified as either muth-dependent or muth-independent. in bacteria, extensive studies have been conducted with the muth-dependent mmr in escherichia coli and its close relatives. the picture of muth-independent mmr in other bacteria is less clear, as mmr components other than muts and mutl have not been identified in the majority of bacteria. bacillus anthracis is one of the muth-less gram(+) bacteria in the phylum of firmicutes. we used papillation as ...201121940221
challenges in disposing of anthrax waste.disasters often create large amounts of waste that must be managed as part of both immediate response and long-term recovery. while many federal, state, and local agencies have debris management plans, these plans often do not address chemical, biological, and radiological contamination. the interagency biological restoration demonstration's (ibrd) purpose was to holistically assess all aspects of an anthrax incident and assist in the development of a plan for long-term recovery. in the case of ...201121882972
risk factors associated with anthrax in cattle on smallholdings.summaryunprecedented high rates of anthrax outbreaks have been observed recently in cattle and humans in bangladesh, with 607 human cases in 2010. by enrolling 15 case and 15 control cattle smallholdings in the spatial zone in july-september 2010, we conducted a case-control study, data of which were analysed by matched-pair analysis and multivariable conditional logistic regression. feeding animals with uprooted and unwashed grass [odds ratio (or) 41·2, 95% confidence interval (ci) 3·7-458·8, p ...201122123521
the effects of anthrax lethal toxin on host barrier function.the pathological actions of anthrax toxin require the activities of its edema factor (ef) and lethal factor (lf) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (pa). lf is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (mkks), but its activity is not directly lethal to many types of primary and transformed cells in vitro. nevertheless, in vivo treatment of several animal species with the combin ...201122069727
the bacillus anthracis arylamine n-acetyltransferase ((bacan)nat1) that inactivates sulfamethoxazole, reveals unusual structural features compared with the other nat isoenzymes.arylamine n-acetyltransferases (nats) are xenobiotic-metabolizing enzymes that biotransform arylamine drugs. the bacillus anthracis (bacan)nat1 enzyme affords increased resistance to the antibiotic sulfamethoxazole through its acetylation. we report the structure of (bacan)nat1. unexpectedly, endogenous coenzymea was present in the active site. the structure suggests that, contrary to the other prokaryotic nats, (bacan)nat1 possesses a 14-residue insertion equivalent to the "mammalian insertion" ...201122062153
anthrax and the inflammasome.anthrax lethal toxin (lt), a major virulence determinant of anthrax disease, induces vascular collapse in mice and rats. lt activates the nlrp1 inflammasome in macrophages and dendritic cells, resulting in caspase-1 activation, il-1β and il-18 maturation and a rapid cell death (pyroptosis). this review presents the current understanding of lt-induced activation of nlrp1 in cells and its consequences for toxin-mediated effects in rodent toxin and spore challenge models.201122207185
Fluorescent europium-modified polymer nanoparticles for rapid and sensitive anthrax sensors.Novel fluorescent polyacrylonitrile nanoparticles were synthesized by microemulsion polymerization and Schiff base modification. By further modification with europium, the polyacrylonitrile nanoparticles could be used as a highly sensitive and rapid sensor for Bacillus anthracis spore detection in aqueous solution. The europium-modified polyacrylonitrile nanoparticles were readily combined with dipicolinic acid as a unique biomarker of B. anthracis, leading to high fluorescence emission. These n ...201121893406
A Decade of Spore-Forming Bacterial Infections Among European Injecting Drug Users: Pronounced Regional Variation.The recent anthrax outbreak among injecting drug users (IDUs) in Europe has highlighted an ongoing problem with severe illness resulting from spore-forming bacteria in IDUs. We collated the numbers of cases of 4 bacterial illnesses (botulism, tetanus, Clostridium novyi, and anthrax) in European IDUs for 2000 to 2009 and calculated population rates. Six countries reported 367 cases; rates varied from 0.03 to 7.54 per million people.Most cases (92%) were reported from 3 neighboring countries: Irel ...201122095355
Optical and electrochemical responses of an anthrax biomarker based on single-walled carbon nanotubes covalently loaded with terbium complexes.An effective single-walled carbon nanotube (SWNT) covalently loaded with unsaturated terbium emissive material was designed for specific and rapid (2-3 s) detection of calcium dipicolinate (CaDPA) (detection limit 1 µM). The nanoprobe was successfully assembled onto electrodes and its sensing abilities were investigated through electrochemical measurement. Cyclic voltammetry curves were selectively responsive to calcium dipicolinate compared with benzoic acid, o-phthalic acid and m-phthalic acid ...201122027893
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