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efficient methods for large-area surface sampling of sites contaminated with pathogenic microorganisms and other hazardous agents: current state, needs, and perspectives.the recovery operations following the 2001 attacks with bacillus anthracis spores were complicated due to the unprecedented need for large-area surface sampling and decontamination protocols. since this event, multiple reports have been published describing recovery efficiencies of several surface sampling materials. these materials include fibrous swabs of various compositions, cloth wipes, vacuum socks, and adhesive tapes. these materials have reported recovery efficiencies ranging from approx ...200919644689
implications of limits of detection of various methods for bacillus anthracis in computing risks to human health.used for decades for biological warfare, bacillus anthracis (category a agent) has proven to be highly stable and lethal. quantitative risk assessment modeling requires descriptive statistics of the limit of detection to assist in defining the exposure. furthermore, the sensitivities of various detection methods in environmental matrices are vital information for first responders. a literature review of peer-reviewed journal articles related to methods for detection of b. anthracis was undertake ...200919648357
novel and unique diagnostic biomarkers for bacillus anthracis infection.a search for bacterium-specific biomarkers in peripheral blood following infection with bacillus anthracis was carried out with rabbits, using a battery of specific antibodies generated by dna vaccination against 10 preselected highly immunogenic bacterial antigens which were identified previously by a genomic/proteomic/serologic screen of the b. anthracis secretome. detection of infection biomarkers in the circulation of infected rabbits could be achieved only after removal of highly abundant s ...200919648366
biofilm formation and cell surface properties among pathogenic and nonpathogenic strains of the bacillus cereus group.biofilm formation by 102 bacillus cereus and b. thuringiensis strains was determined. strains isolated from soil or involved in digestive tract infections were efficient biofilm formers, whereas strains isolated from other diseases were poor biofilm formers. cell surface hydrophobicity, the presence of an s layer, and adhesion to epithelial cells were also examined.200919648377
potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding.this study describes the isolation and characterization of a neutralizing monoclonal antibody (mab) against anthrax edema factor, ef13d. ef13d neutralized edema toxin (et)-mediated cyclic amp (camp) responses in cells and protected mice from both et-induced footpad edema and systemic et-mediated lethality. the antibody epitope was mapped to domain iv of ef. the mab was able to compete with calmodulin (cam) for ef binding and displaced cam from ef-cam complexes. ef-mab binding affinity (0.05-0.12 ...200919651602
the case for developing consensus standards for research in microbial pathogenesis: bacillus anthracis toxins as an example. 200919651858
the global regulator cody regulates toxin gene expression in bacillus anthracis and is required for full virulence.in gram-positive bacteria, cody is an important regulator of genes whose expression changes upon nutrient limitation and acts as a repressor of virulence gene expression in some pathogenic species. here, we report the role of cody in bacillus anthracis, the etiologic agent of anthrax. disruption of cody completely abolished virulence in a toxinogenic, noncapsulated strain, indicating that the activity of cody is required for full virulence of b. anthracis. global transcriptome analysis of a cody ...200919651859
expression of nlrp1b inflammasome components in human fibroblasts confers susceptibility to anthrax lethal toxin.anthrax lethal toxin causes macrophages and dendritic cells from some mouse strains to undergo caspase-1-dependent cell death. central to this process is the nod-like receptor nlrp1b (nalp1b), which detects intoxication and then self-associates to form a complex, termed an inflammasome, that is capable of activating the procaspase-1 zymogen. the nature of the signal detected directly by nlrp1b is not known, and the mechanisms of inflammasome assembly are poorly understood. here, we demonstrate t ...200919651869
bacillus anthracis physiology and genetics.bacillus anthracis is a member of the bacillus cereus group species (also known as the "group 1 bacilli"), a collection of gram-positive spore-forming soil bacteria that are non-fastidious facultative anaerobes with very similar growth characteristics and natural genetic exchange systems. despite their close physiology and genetics, the b. cereus group species exhibit certain species-specific phenotypes, some of which are related to pathogenicity. b. anthracis is the etiologic agent of anthrax. ...200919654018
complete sequence of three plasmids from bacillus thuringiensis inta-fr7-4 environmental isolate and comparison with related plasmids from the bacillus cereus group.bacillus thuringiensis is an insect pathogen used worldwide as a bioinsecticide. it belongs to the bacillus cereus sensu lato group as well as bacillus anthracis and b. cereus. plasmids from this group of organisms have been implicated in pathogenicity as they carry the genes responsible for different types of diseases that affect mammals and insects. some plasmids, like paw63 and pbt9727, encode a functional conjugation machinery allowing them to be transferred to a recipient cell. they also sh ...200919654019
analysis of the fc gamma receptor-dependent component of neutralization measured by anthrax toxin neutralization assays.anthrax toxin neutralization assays are used to measure functional antibody levels elicited by anthrax vaccines in both preclinical and clinical studies. in this study, we investigated the magnitude and molecular nature of fc gamma (fcgamma) receptor-dependent toxin neutralization observed in commonly used forms of the anthrax toxin neutralization assay. significantly more fcgamma receptor-dependent neutralization was observed in the j774a.1 cell-based assay than in the raw 264.7 cell-based assa ...200919656993
bacterial inactivation by solar ultraviolet radiation compared with sensitivity to 254 nm radiation.our goal was to derive a quantitative factor that would allow us to predict the solar sensitivity of vegetative bacterial cells to natural solar radiation from the wealth of data collected for cells exposed to uvc (254 nm) radiation. we constructed a solar effectiveness spectrum for inactivation of vegetative bacterial cells by combining the available action spectra for vegetative cell killing in the solar range with the natural sunlight spectrum that reaches the ground. we then analyzed previou ...200919659922
the anthrax lethal factor and its mapk kinase-specific metalloprotease activity.the anthrax lethal factor is a multi-domain protein toxin released by bacillus anthracis which enters cells in a process mediated by the protective antigen and specific cell receptors. in the cytosol, the lethal factor cleaves the n-terminal tail of many mapk kinases, thus deranging a major cell signaling pathway. the structural features at the basis of these activities of lf are reviewed here with particular attention to the proteolytic activity and to the identification of specific inhibitors. ...200919665472
animal models of human anthrax: the quest for the holy grail.anthrax is rare among humans, few data can be collected from infected individuals and they provide a fragmentary view of the dynamics of infection and human host-pathogen interactions. therefore, the development of animal models is necessary. anthrax has the particularity of being a toxi-infection, a combination of infection and toxemia. the ideal animal model would explore these two different facets and mimic human disease as much as possible. in the past decades, the main effort has been focus ...200919665473
cd14-mac-1 interactions in bacillus anthracis spore internalization by macrophages.anthrax, a potentially lethal disease of animals and humans, is caused by the gram-positive spore-forming bacterium bacillus anthracis. the outermost exosporium layer of b. anthracis spores contains an external hair-like nap formed by the glycoprotein bcla. recognition of bcla by the integrin mac-1 promotes spore uptake by professional phagocytes, resulting in the carriage of spores to sites of spore germination and bacterial growth in distant lymphoid organs. we show that cd14 binds to rhamnose ...200919666536
the secret life of the anthrax agent bacillus anthracis: bacteriophage-mediated ecological adaptations.ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. a central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alteratio ...200919672290
insights into the mode of action of the two-peptide lantibiotic haloduracin.haloduracin, a recently discovered two-peptide lantibiotic composed of the post-translationally modified peptides halalpha and halbeta, is shown to have high potency against a range of gram-positive bacteria and to inhibit spore outgrowth of bacillus anthracis. the two peptides display optimal activity in a 1:1 stoichiometry and have efficacy similar to that of the commercially used lantibiotic nisin. however, haloduracin is more stable at ph 7 than nisin. despite significant structural differen ...200919678697
the bacillus anthracis spore.in response to starvation, bacillus anthracis can form a specialized cell type called the spore, which is the infectious particle for the disease anthrax. the spore is largely metabolically inactive and can resist a wide range of stresses found in nature. in spite of its dormancy, the spore can sense the presence of nutrient and rapidly return to vegetative growth. these properties help the spore to persist for long periods of time in the environment, survive host defenses after entering the bod ...200919683018
galactoxylomannan-mediated immunological paralysis results from specific b cell depletion in the context of widespread immune system damage.the mechanisms responsible for polysaccharide-induced immunological paralysis have remained unexplained almost a century after this phenomenon was first described. cryptococcus neoformans capsular polysaccharides glucuronoxylomannan and galactoxylomannan (galxm) elicit little or no ab responses. this study investigates the immunological and biological effects of galxm in mice. galxm immunization elicits a state of immunological paralysis in mice characterized by the disappearance of ab-producing ...200919684080
impact of spore biology on the rate of kill and suppression of resistance in bacillus anthracis.bacillus anthracis is complex because of its spore form. the spore is invulnerable to antibiotic action. it also has an impact on the emergence of resistance. we employed the hollow-fiber infection model to study the impacts of different doses and schedules of moxifloxacin on the total-organism population, the spore population, and the subpopulations of vegetative- and spore-phase organisms that were resistant to moxifloxacin. we then generated a mathematical model of the impact of moxifloxacin, ...200919687233
identification and quantitation of bacillus globigii using metal enhanced electrochemical detection and capillary biosensor.presented herein are two detection strategies for the identification and quantification of bacillus globigii, a spore forming nonpathogenic simulant of bacillus anthracis. the first strategy involves a label-free, metal-enhanced electrochemical immunosensor for the quantitative detection of bacillus globigii (atrophaeus). the immunosensor comprises of antibacillus globigii (bg) antibody self-assembled onto a gold quartz crystal electrode via cystamine bond. a solid-phase monolayer of silver unde ...200919689112
biochemical and structural characterization of alanine racemase from bacillus anthracis (ames).bacillus anthracis is the causative agent of anthrax and a potential bioterrorism threat. here we report the biochemical and structural characterization of b. anthracis (ames) alanine racemase (alrbax), an essential enzyme in prokaryotes and a target for antimicrobial drug development. we also compare the native alrbax structure to a recently reported structure of the same enzyme obtained through reductive lysine methylation.200919695097
construction of bifunctional phage display for biological analysis and immunoassay.a phage display-based bifunctional display system was developed for simple and sensitive immunoassay. the resulting bifunctional phage could simultaneously display a few single-chain variable fragment (scfv) and many copies of the gold-binding peptide on its surface, thereby mediating antigen recognition and signal amplification. as a demonstration study, it was possible for bifunctional phage-based immunoassay to identify bacillus anthracis spores from other bacillus strains with detection sens ...201019699710
neutralizing monoclonal antibodies directed against defined linear epitopes on domain 4 of anthrax protective antigen.the anthrax protective antigen (pa) is the receptor-binding subunit common to lethal toxin (lt) and edema toxin (et), which are responsible for the high mortality rates associated with inhalational bacillus anthracis infection. although recombinant pa (rpa) is likely to be an important constituent of any future anthrax vaccine, evaluation of the efficacies of the various candidate rpa vaccines is currently difficult, because the specific b-cell epitopes involved in toxin neutralization have not ...200919703971
radiolabeled antibodies to bacillus anthracis toxins are bactericidal and partially therapeutic in experimental murine anthrax.bacillus anthracis is a powerful agent for use in biological warfare, and infection with the organism is associated with a high rate of mortality, underscoring the need for additional effective therapies for anthrax. radioimmunotherapy (rit) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver a microbicidal radioactive nuclide to a site of infection. rit has proven therapeutic in experimental models of viral, bacterial, and fungal infections; but it is ...200919704133
the potential anti-herbivory role of microorganisms on plant thorns.thorns, spines and prickles are some of the anti-herbivore defenses that plants have evolved. they were recently found to be commonly aposematic (warning coloration). however, the physical anti-herbivore defense executed by these sharp structures seems to be only the tip of the iceberg. we show that thorns of various plant species commonly harbor an array of aerobic and anaerobic pathogenic bacteria including clostridium perfringens the causative agent of the life-threatening gas gangrene, bacil ...200719704540
atp conformations and ion binding modes in the active site of anthrax edema factor: a computational analysis.the edema factor (ef), one of the virulence factors of anthrax, is an adenylyl cyclase that promotes the overproduction of cyclic-amp (camp) from atp, and therefore perturbs cell signaling. crystallographic structures of ef bound to atp analogs and reaction products, cyclic-amp, and pyrophosphate (ppi), revealed different substrate conformations and catalytic-cation binding modes, one or two cations being observed in the active site. to shed light into the biological significance of these crysta ...200919705488
[methodic approaches to testing bacillus anthracis susceptibility to antibacterials].susceptibility of 50 isolates of bacillus anthracis to 24 antibiotics was tested by the disk-diffusion method and the method of serial dilutions in solid media. the tests allowed to determine the boundary values of the growth inhibition zones and the minimum inhibitory concentrations of the antibiotics for susceptible and resistant strains of b. anthracis. nutrient media and reference strains for testing antibiotic susceptibility of b. anthracis are recommended.200919711841
adverse events after anthrax vaccination reported to the vaccine adverse event reporting system (vaers), 1990-2007 [vaccine 2009;27:290-297]. 200919716457
targeting nad biosynthesis in bacterial pathogens: structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase nadd.the emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. nicotinate mononucleotide adenylyltransferase of the nadd family, an essential enzyme of nad biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. using iterative in silico and in vitro screens, we identified small molecule compounds that efficiently inhibited target enzymes from escherichia coli (ecnadd) and bacillus ant ...200919716475
an extracytoplasmic function sigma factor controls beta-lactamase gene expression in bacillus anthracis and other bacillus cereus group species.the susceptibility of most bacillus anthracis strains to beta-lactam antibiotics is intriguing considering that the closely related species bacillus cereus and bacillus thuringiensis typically produce beta-lactamases and the b. anthracis genome harbors two beta-lactamase genes, bla1 and bla2. we show that beta-lactamase activity associated with b. anthracis is affected by two genes, sigp (ba2502) and rsip (ba2503), predicted to encode an extracytoplasmic function sigma factor and an anti-sigma f ...200919717606
reproductive toxicity of biothrax in rabbits.an increasing number of women are being vaccinated during child-bearing years, including vaccination with biothrax (anthrax vaccine adsorbed, or ava). as only a limited number of studies exist in humans that have examined the effects of ava on reproductive health, this study was conducted in order to evaluate the impact ava vaccination may have on pregnant female rabbits and their offspring.200919718687
the ecology of bacillus anthracis.the global distribution of anthrax is largely determined by soils with high calcium levels and a ph above 6.1, which foster spore survival. it is speculated that the spore exosporium probably plays a key part by restricting dispersal and thereby increasing the probability of a grazing animal acquiring a lethal dose. 'anthrax seasons' are characterized by hot-dry weather which stresses animals and reduces their innate resistance to infection allowing low doses of spores to be infective. necrophag ...200919720074
bacillus anthracis lethal toxin attenuates lipoteichoic acid-induced maturation and activation of dendritic cells through a unique mechanism.lethal toxin (lt), produced by the gram-positive bacterium bacillus anthracis, was identified as a major etiologic agent causing anthrax due to its strong immunotoxicity. gram-positive bacteria express lipoteichoic acid (lta), which is considered as a counterpart to lipopolysaccharide (lps) of gram-negative bacteria, but differs from lps in the structure and function. since dendritic cells (dcs) are essential for the appropriate initiation of immune response, we investigated the effect of lt on ...200919720398
the major neutralizing antibody responses to recombinant anthrax lethal and edema factors are directed to non-cross-reactive epitopes.anthrax lethal and edema toxins (letx and edtx, respectively) form by binding of lethal factor (lf) or edema factor (ef) to the pore-forming moiety protective antigen (pa). immunity to lf and ef protects animals from anthrax spore challenge and neutralizes anthrax toxins. the goal of the present study is to identify linear b-cell epitopes of ef and to determine the relative contributions of cross-reactive antibodies of ef and lf to letx and edtx neutralization. a/j mice were immunized with recom ...200919720758
domain 4 of the anthrax protective antigen maintains structure and binding to the host receptor cmg2 at low ph.domain 4 of the anthrax protective antigen (pa) plays a key role in cellular receptor recognition as well as in ph-dependent pore formation. we present here the 1.95 a crystal structure of domain 4, which adopts a fold that is identical to that observed in the full-length protein. we have also investigated the structural properties of the isolated domain 4 as a function of ph, as well as the ph-dependence on binding to the von willebrand factor a domain of capillary morphogenesis protein 2 (cmg2 ...200919722284
anthrax in animals.anthrax is the archetype zoonosis; no other infectious disease affects such a wide range of species, including humans, although most susceptible are herbivorous mammals. although the disease appears to have been recognized for centuries, it has yet to be established scientifically how animals contract it. while primarily a disease of warmer regions, it has long been spread to cooler zones through the trade of infected animals or contaminated animal products. today it is still endemic in many cou ...200919723532
crystal structure and catalytic properties of bacillus anthracis coadr-rhd: implications for flavin-linked sulfur trafficking.rhodanese homology domains (rhds) play important roles in sulfur trafficking mechanisms essential to the biosynthesis of sulfur-containing cofactors and nucleosides. we have now determined the crystal structure at 2.10 a resolution for the bacillus anthracis coenzyme a-disulfide reductase isoform (bacoadr-rhd) containing a c-terminal rhd domain; this is the first structural representative of the multidomain proteins class of the rhodanese superfamily. the catalytic cys44 of the coadr module is s ...200919725515
the genome and variation of bacillus anthracis.the bacillus anthracis genome reflects its close genetic ties to bacillus cereus and bacillus thuringiensis but has been shaped by its own unique biology and evolutionary forces. the genome is comprised of a chromosome and two large virulence plasmids, pxo1 and pxo2. the chromosome is mostly co-linear among b. anthracis strains and even with the closest near neighbor strains. an exception to this pattern has been observed in a large inversion in an attenuated strain suggesting that chromosome co ...200919729033
anthrax vaccination strategies.the biological attack conducted through the us postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. the expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against bacillus anthracis. the currently-licensed anthrax vaccine, adsorbed (ava) and anthrax vaccine, precipitated (avp) are capable of generating a protective immune response ...200919729034
strong antibody responses induced by protein antigens conjugated onto the surface of lecithin-based nanoparticles.an accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. the nanoparticles were spheres of around 200nm. model protein antigens, bovine serum albumin (bsa) or bacillus anthracis protective antigen (pa) protein, were covalently conjugated onto the nanoparticles. mice immunized with the bsa-conjugated nanoparticles develop ...201019729045
square wave voltammetric detection of anthrax utilizing a peptide for selective recognition of a protein biomarker.a short chain peptide (16mer) has been successfully utilized for the selective electrochemical detection of the protein biomarker, protective antigen (pa), for the diagnosis of anthrax. the major motivation of using a peptide instead of an antibody for the development of a biosensor is that there are advantages associated with the smaller size, better biological stability and easy synthesizability of a peptide. pa-selective peptide was synthesized and conjugated on a binding layer previously imm ...200919729294
poly-gamma-d-glutamic acid and protective antigen conjugate vaccines induce functional antibodies against the protective antigen and capsule of bacillus anthracis in guinea-pigs and rabbits.anthrax is a lethal infectious disease caused by the spore-forming bacillus anthracis. the two major virulence factors of b. anthracis are exotoxin and the poly-gamma-d-glutamic acid (pga) capsule. the three components of the exotoxin, protective antigen (pa), lethal factor and edema factor act in a binary combination, which results in massive edema and organ failure in the progress of anthrax disease. the antiphagocytic pga capsule disguises the bacilli from immune surveillance and allows unimp ...200919732139
receptors of anthrax toxin and cell entry.anthrax toxin-receptor interactions are critical for toxin delivery to the host cell cytoplasm. this review summarizes what is known about the molecular details of the protective antigen (pa) toxin subunit interaction with either the antxr1 and antxr2 cellular receptors, and how receptor-type can dictate the low ph threshold of pa pore formation. the roles played by cellular factors in regulating the endocytosis of toxin-receptor complexes is also discussed.200919732789
editorial. 200919733583
innate immune response during yersinia infection: critical modulation of cell death mechanisms through phagocyte activation.yersinia pestis, the etiological agent of plague, is one of the most deadly pathogens on our planet. this organism shares important attributes with its ancestral progenitor, yersinia pseudotuberculosis, including a 70-kb virulence plasmid, lymphotropism during growth in the mammalian host, and killing of host macrophages. infections with both organisms are biphasic, where bacterial replication occurs initially with little inflammation, followed by phagocyte influx, inflammatory cytokine producti ...200919734471
bacillus anthracis capsule activates caspase-1 and induces interleukin-1beta release from differentiated thp-1 and human monocyte-derived dendritic cells.the poly-gamma-d-glutamic acid (pga) capsule is one of the major virulence factors of bacillus anthracis, which causes a highly lethal infection. the antiphagocytic pga capsule disguises the bacilli from immune surveillance and allows unimpeded growth of bacilli in the host. recently, efforts have been made to include pga as a component of anthrax vaccine; however, the innate immune response of pga itself has been poorly investigated. in this study, we characterized the innate immune response el ...201019737897
web-based training on weapons of mass destruction response for emergency medical services personnel.to develop, implement, and assess a web-based simulation training program for emergency medical services (ems) personnel on recognition and treatment of ocular injuries resulting from weapons of mass destruction (wmd) attacks.200919739458
aluminum hydroxide injections lead to motor deficits and motor neuron degeneration.gulf war syndrome is a multi-system disorder afflicting many veterans of western armies in the 1990-1991 gulf war. a number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (als) except for the age of onset. this als "cluster" represents the second such als cluster described in the literature to date. possible causes of gws include sev ...200919740540
g-rich sequence-functionalized polystyrene microsphere-based instantaneous derivatization for the chemiluminescent amplified detection of dna.herein, we develop a novel chemiluminescence (cl) approach with high sensitivity and excellent selectivity, by taking advantage of magnetic beads as preconcentration carriers and polystyrene microspheres as an amplification platform. briefly, a 'sandwich-type' detection strategy is employed in our design, which involves capture probe dna immobilized on the surface of carboxyl-terminated magnetic beads and multiple biotinylated reporter dna self-assembled on the surface of streptavidin-modified p ...201019743522
gene expression profiling of human alveolar macrophages infected by b. anthracis spores demonstrates tnf-alpha and nf-kappab are key components of the innate immune response to the pathogen.bacillus anthracis, the etiologic agent of anthrax, has recently been used as an agent of bioterrorism. the innate immune system initially appears to contain the pathogen at the site of entry. because the human alveolar macrophage (ham) plays a key role in lung innate immune responses, studying the ham response to b. anthracis is important in understanding the pathogenesis of the pulmonary form of this disease.200919744333
endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics.bacterial nitric oxide synthases (bnos) are present in many gram-positive species and have been demonstrated to synthesize no from arginine in vitro and in vivo. however, the physiological role of bnos remains largely unknown. we show that no generated by bnos increases the resistance of bacteria to a broad spectrum of antibiotics, enabling the bacteria to survive and share habitats with antibiotic-producing microorganisms. no-mediated resistance is achieved through both the chemical modificatio ...200919745150
anthrax undervalued zoonosis.anthrax is a non-contagious disease, known since ancient times. however, it became a matter of global public interest after the bioterrorist attacks in the u.s.a. during the autumn of 2001. the concern of politicians and civil authorities everywhere towards this emergency necessitated a significant research effort and the prevention of new bioterrorist acts. anthrax is primarily a disease that affects livestock and wildlife; its distribution is worldwide; and it can represent a danger to humans ...201019747785
identification of the udp-n-acetylglucosamine 4-epimerase involved in exosporium protein glycosylation in bacillus anthracis.spores of bacillus anthracis, the causative agent of anthrax, are enclosed by a loosely fitting exosporium composed of a basal layer and an external hair-like nap. the filaments of the nap are formed by trimers of the collagen-like glycoprotein bcla. the side chains of bcla include multiple copies of two linear rhamnose-containing oligosaccharides, a trisaccharide and a pentasaccharide. the pentasaccharide terminates with the unusual deoxyamino sugar anthrose. both oligosaccharide side chains ar ...200919749053
perturbation of mouse retinal vascular morphogenesis by anthrax lethal toxin.lethal factor, the enzymatic moiety of anthrax lethal toxin (letx) is a protease that inactivates mitogen activated protein kinase kinases (mek or mkk). in vitro and in vivo studies demonstrate letx targets endothelial cells. however, the effects of letx on endothelial cells are incompletely characterized. to gain insight into this process we used a developmental model of vascularization in the murine retina. we hypothesized that application of letx would disrupt normal retinal vascularization, ...200919750016
bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model.the in vivo inflammatory effects of the bacillus anthracis cell wall are unknown. we therefore investigated these effects in rats and, for comparison, those of known inflammatory stimulants, staphylococcus aureus cell wall or lipopolysaccharide (lps).201019756496
heme transfer to the bacterial cell envelope occurs via a secreted hemophore in the gram-positive pathogen bacillus anthracis.to initiate and sustain an infection in mammals, bacterial pathogens must acquire host iron. however, the host's compartmentalization of large amounts of iron in heme, which is bound primarily by hemoglobin in red blood cells, acts as a barrier to bacterial iron assimilation. bacillus anthracis, the causative agent of the disease anthrax, secretes two neat (near iron transporter) proteins, isdx1 and isdx2, which scavenge heme from host hemoglobin and promote growth under low iron conditions. the ...200919759022
recombinant sindbis virus vectors designed to express protective antigen of bacillus anthracis protect animals from anthrax and display synergy with ciprofloxacin.recombinant sindbis viruses were engineered to express alternative forms of the protective antigen (pa) of bacillus anthracis. the recombinant viruses induced pa-specific immunoglobulin g and neutralizing antibodies in swiss webster mice. vaccination with the recombinant viruses induced immunity that offered some protection from a lethal ames strain spore challenge and synergized the protective effects of ciprofloxacin.200919759250
high temperature unfolding of bacillus anthracis amidase-03 by molecular dynamics simulations.the stability of amidase-03 structure (a cell wall hydrolase protein) from bacillus anthracis was studied using classical molecular dynamics (md) simulation. this protein (genbank accession number: np_844822) contains an amidase-03 domain which is known to exhibit the catalytic activity of n-acetylmuramoyl-l-alanine amidase (digesting murnac-lalanine linkage of bacterial cell wall). the amidase-03 enzyme has stability at high temperature due to the core formed by the combination of several secon ...200919759865
nucleoside triphosphate mimicry: a sugar triazolyl nucleoside as an atp-competitive inhibitor of b. anthracis pantothenate kinase.the synthesis of a library of nucleoside triphosphate mimetics is described where the mg(2+) chelated triphosphate sidechain is replaced by an uncharged methylene-triazole linked monosaccharide sidechain. the compounds have been evaluated as inhibitors of bacillus anthracis pantothenate kinase and a competitive inhibitor has been identified with a k(i) that is 3-fold lower than the k(m) value of atp.200919763307
identification and classification of bcl genes and proteins of bacillus cereus group organisms and their application in bacillus anthracis detection and fingerprinting.the bacillus cereus group includes three closely related species, b. anthracis, b. cereus, and b. thuringiensis, which form a highly homogeneous subdivision of the genus bacillus. one of these species, b. anthracis, has been identified as one of the most probable bacterial biowarfare agents. here, we evaluate the sequence and length polymorphisms of the bacillus collagen-like protein bcl genes as a basis for b. anthracis detection and fingerprinting. five genes, designated bcla to bcle, are pres ...200919767469
identification of bacillus anthracis by using matrix-assisted laser desorption ionization-time of flight mass spectrometry and artificial neural networks.this report demonstrates the applicability of a combination of matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry (ms) and chemometrics for rapid and reliable identification of vegetative cells of the causative agent of anthrax, bacillus anthracis. bacillus cultures were prepared under standardized conditions and inactivated according to a recently developed ms-compatible inactivation protocol for highly pathogenic microorganisms. maldi-tof ms was then emplo ...200919767470
transcriptional profiling of bacillus anthracis sterne (34f2) during iron starvation.lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. here we define the transcriptional response of b. anthracis sterne (34f(2)) to iron depleted conditions. genome-wide transcript analysis showed that b. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known an ...200919768119
microneedle-based vaccines.the threat of pandemic influenza and other public health needs motivate the development of better vaccine delivery systems. to address this need, microneedles have been developed as micron-scale needles fabricated using low-cost manufacturing methods that administer vaccine into the skin using a simple device that may be suitable for self-administration. delivery using solid or hollow microneedles can be accomplished by (1) piercing the skin and then applying a vaccine formulation or patch onto ...200919768415
anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.the intentional release of anthrax spores in 2001 confirmed this pathogen's ability to cause widespread panic, morbidity and mortality. while individuals exposed to anthrax can be successfully treated with antibiotics, pre-exposure vaccination can reduce susceptibility to infection-induced illness. concern over the safety and immunogenicity of the licensed us vaccine (anthrax vaccine adsorbed (ava)) has fueled research into alternatives. second-generation anthrax vaccines based on purified recom ...200919769541
identification of a polymorphic collagen-like protein in the crustacean bacteria pasteuria ramosa.pasteuria ramosa is a spore-forming bacterium that infects daphnia species. previous results demonstrated a high specificity of host clone/parasite genotype interactions. surface proteins of bacteria often play an important role in attachment to host cells prior to infection. we analyzed surface proteins of p. ramosa spores by two-dimensional gel electrophoresis. for the first time, we prove that two isolates selected for their differences in infectivity reveal few but clear-cut differences in p ...200919770039
bacillus anthracis lethal toxin disrupts tcr signaling in cd1d-restricted nkt cells leading to functional anergy.exogenous cd1d-binding glycolipid (alpha-galactosylceramide, alpha-gc) stimulates tcr signaling and activation of type-1 natural killer-like t (nkt) cells. activated nkt cells play a central role in the regulation of adaptive and protective immune responses against pathogens and tumors. in the present study, we tested the effect of bacillus anthracis lethal toxin (lt) on nkt cells both in vivo and in vitro. lt is a binary toxin known to suppress host immune responses during anthrax disease and i ...200919779559
systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.the niaid (national institute for allergy and infectious diseases) biodefense proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. the program includes seven proteomics research centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagen ...200919779614
sympatric soil communities of bacillus cereus sensu lato: population structure and potential plasmid dynamics of pxo1- and pxo2-like elements.eighty soil-borne bacillus cereus group isolates were collected from two neighbouring geographical sites in belgium. their genetic relationships and population structure were assessed using multilocus sequence typing analysis of five chromosomal genes, while the contribution of extrachromosomal elements to the population dynamics was gauged by the presence, diversity and transfer capacity of pxo1- and pxo2-like plasmids. globally, the bacterial population displayed a broad diversity, including a ...200919780824
medical countermeasures to protect humans from anthrax bioterrorism.the deliberate dissemination of bacillus anthracis spores via the us mail system in 2001 confirmed their potential use as a biological weapon for mass human casualties. this dramatically highlighted the need for specific medical countermeasures to enable the authorities to protect individuals from a future bioterrorism attack. although vaccination appears to be the most effective and economical form of mass protection, current vaccines have significant drawbacks that justify the immense research ...200919781945
discovery and structure-activity relationship analysis of staphylococcus aureus sortase a inhibitors.methicillin resistant staphylococcus aureus (mrsa) is a major health problem that has created a pressing need for new antibiotics. compounds that inhibit the s. aureus srta sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. using high-throughput screening, we have identified several compounds that inhibit the enzymatic activity of the srta. a structure-activity relationship (sar) analysis led to the identification of several pyridazin ...200919781950
natural product leads for drug discovery: isolation, synthesis and biological evaluation of 6-cyano-5-methoxyindolo[2,3-a]carbazole based ligands as antibacterial agents.indolo[2,3-a]carbazole based inhibitors were synthesized from readily available indigo via a seven-step linear synthetic sequence with a moderate overall yield. the inhibitors were selectively and readily functionalized at the nitrogen on the indole portion of the carbazole unit. the synthesized analogs displayed moderate inhibitory activities toward bacillus anthracis and mycobacterium tuberculosis, indicating that indolo[2,3-a]carbazoles could serve as promising leads in the development of new ...200919783449
encapsulated bacillus anthracis interacts closely with liver endothelium.the bacillus anthracis poly-gamma-d-glutamate capsule is essential for virulence. it impedes phagocytosis and protects bacilli from the immune system, thus promoting systemic dissemination.200919785525
is new always better than old?: the development of human vaccines for anthrax.anthrax is caused by a gram-positive aerobic spore-forming bacillus called bacillus anthracis. although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. as a result of concerns over the illicit use of this organism, considerable effort is focused on the development of therapies capable of conferring protection against anthrax. while effective concerns over the toxicity of the current vaccines have driven the development of second-generation products. rec ...200919786839
correlation of nosocomial bloodstream infection incidences: an ecological study.this study aimed to correlate nosocomial bloodstream infections (nbis) across time against the ecological effect of infection control activities. all patients hospitalised >or=48h in the haematology and intensive care departments of a university hospital and discharged between 1 january 2004 and 30 june 2006 were prospectively included. the case definition of nbi infection was: (1) at least one positive blood culture justified by clinical signs, or (2) at least two positive blood cultures when t ...200919788948
detection of known mutations for medical diagnostics by fret spectroscopy.a rapid, simple and low-cost method for the detection of known mutations in dna oligonucleotide in a biothreat agent, bacillus anthracis, has been reported. the technique is based on fluorescence resonance energy transfer (fret), that utilizes a cationic conjugated polymer and a pna probe labeled with fluorescein dye (pnac*). when the pna probe is hybridized with a complementary target ssdna and its mutated sequences separately, the energy transfer from polymer to pnac*/ssdna complex decreases w ...200919793441
clinical and pathologic features of cynomolgus macaques (macaca fascicularis) infected with aerosolized yersinia pestis.since the anthrax attacks of 2001, the emphasis on developing animal models of aerosolized select agent pathogens has increased. many scientists believe that nonhuman primate models are the most appropriate to evaluate pulmonary response to, vaccines for, and treatments for select agents such as yersinia pestis (y. pestis), the causative agent of plague. a recent symposium concluded that the cynomolgus macaque (macaca fascicularis) plague model should be characterized more fully. to date, a well ...200819793459
development of antibodies against anthrose tetrasaccharide for specific detection of bacillus anthracis spores.methods for the immunological detection of bacillus anthracis in various environmental samples and the discrimination of b. anthracis from other members of the b. cereus group are not yet well established. to generate specific discriminating antibodies, we immunized rabbits, mice, and chickens with inactivated b. anthracis spores and, additionally, immunized rabbits and mice with the tetrasaccharide beta-ant-(1-->3)-alpha-l-rhap-(1-->3)-alpha-l-rhap-(1-->2)-l-rhap. it is a constituent of the exo ...200919793896
unanswered questions and ethical issues concerning us biodefence research.unanswered questions and ethical issues associated with us biodefence medical research over the past five decades are discussed. objective scientific standards are essential for making policy decisions that can stand the test of time. for decades, scholars have reported that the human anthrax vaccine field trials conducted in the 1950s by brachman and his colleagues were single-blind rather than double-blind. nevertheless, in march 2005, dr philip s brachman reported in a letter to the us food a ...200919793937
booming biosafety labs probed. 200919794463
production of recombinant anthrax toxin receptor (atr/cmg2) fused with human fc in planta.mass vaccination against anthrax with existing vaccines is costly and unsafe due to potential side effects. for post-infection treatment, passive immunotherapy measures are currently available, most based on anthrax protective antigen (pa)-specific therapeutic antibodies. efficient against wild-type strains, these treatment(s) might fail to protect against infections caused by genetically engineered bacillus anthracis strains. a recent discovery revealed that the von willebrand factor a (vwa) do ...201019796689
uncertainty and operational considerations in mass prophylaxis workforce planning.the public health response to an influenza pandemic or other large-scale health emergency may include mass prophylaxis using multiple points of dispensing (pods) to deliver countermeasures rapidly to affected populations. computer models created to date to determine "optimal" staffing levels at pods typically assume stable patient demand for service. the authors investigated pod function under dynamic and uncertain operational environments.200919797960
comparative analysis of the virulence of invertebrate and mammalian pathogenic bacteria in the oral insect infection model galleria mellonella.infection of galleria mellonella by feeding a mixture of bacillus thuringiensis spores or vegetative bacteria in association with the toxin cry1c results in high levels of larval mortality. under these conditions the toxin or bacteria have minimal effects on the larva when inoculated separately. in order to evaluate whether g. mellonella can function as an oral infection model for human and entomo-bacterial pathogens, we tested strains of bacillus cereus, bacillus anthracis, enterococcus faecali ...201019800349
characteristics of cutaneous anthrax in turkey.incidence of anthrax is diminishing in developed countries; however, it remains a public health problem in developing countries, especially those whose main source of income is farming.200919801802
a heterologous helper t-cell epitope enhances the immunogenicity of a multiple-antigenic-peptide vaccine targeting the cryptic loop-neutralizing determinant of bacillus anthracis protective antigen.we previously showed that a multiple antigenic peptide (map) displaying amino acids (aa) 305 to 319 from the 2beta2-2beta3 loop of protective antigen (pa) can elicit high-titered antibody that neutralizes lethal toxin (letx) in vitro and that this loop-neutralizing determinant (lnd) specificity is absent in pa-immune rabbits. some immune rabbits were, however, nonresponders to the map. we hypothesized that the immunogen elicited suboptimal major histocompatibility complex (mhc) class ii-restrict ...200919805525
improvement of a selective media for the isolation of b. anthracis from soils.to prove linkage between an environmental sample and an anthrax case, there must be isolates obtained from both that can be compared. although bacillus anthracis is easily isolated from powder samples, isolating it from soil is difficult because of the high bacterial count in it. formulations of plet were prepared, inoculated with b. anthracis, b. cereus and b. thuringiensis and examined for growth. two hundred eighty-three isolates including 23 b. anthracis were placed onto one formulation whil ...200919808058
staphylococcus aureus synthesizes adenosine to escape host immune responses.staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant s. aureus. we examined the ability of s. aureus to escape phagocytic clearance in blood and identified adenosine synthase a (adsa), a cell wall-anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. staphylococcal synthesis of adenosine in blood, escape from ...200919808256
resistance of human alveolar macrophages to bacillus anthracis lethal toxin.the etiologic agent of inhalational anthrax, bacillus anthracis, produces virulence toxins that are important in the disease pathogenesis. current studies suggest that mouse and human macrophages are susceptible to immunosuppressive effects of one of the virulence toxins, lethal toxin (lt). thus a paradigm has emerged that holds that the alveolar macrophage (am) does not play a significant role in the innate immune response to b. anthracis or defend against the pathogen as it is disabled by lt. ...200919812208
hospital staff goes into overdrive during anthrax scare. 200919813584
temporal production of the two bacillus anthracis siderophores, petrobactin and bacillibactin.bacillus anthracis secretes two siderophores, petrobactin (pb) and bacillibactin (bb). these siderophores were temporally produced during germination and outgrowth of spores (the usual infectious form of b. anthracis) in low-iron medium. the siderophore pb was made first while bb secretion began several hours later. spore outgrowth early in an infection may require pb, whereas delayed bb production suggests a role for bb in the later stages of the infection. incubation of cultures (inoculated as ...201019816776
direct interaction between anthrax toxin receptor 1 and the actin cytoskeleton.the protective antigen component of anthrax toxin binds the i domain of the anthrax toxin receptors, antxr1 and antxr2, in a manner akin to how integrins bind their ligands. the i domains of integrins and antxr1 both have high- and low-affinity conformations, and the cytosolic tails of these receptors associate with the actin cytoskeleton. the association of antxr1 with the cytoskeleton correlates with weakened binding to pa, although a mechanistic explanation for this observation is lacking. he ...200919817382
penetration of the blood-brain barrier by bacillus anthracis requires the pxo1-encoded bsla protein.anthrax is a zoonotic disease caused by the gram-positive spore-forming bacterium bacillus anthracis. human infection occurs after the ingestion, inhalation, or cutaneous inoculation of b. anthracis spores. the subsequent progression of the disease is largely mediated by two native virulence plasmids, pxo1 and pxo2, and is characterized by septicemia, toxemia, and meningitis. in order to produce meningitis, blood-borne bacteria must interact with and breach the blood-brain barrier (bbb) that is ...200919820089
humans and evolutionary and ecological forces shaped the phylogeography of recently emerged diseases.the development of human civilizations and global commerce has led to the emergence and worldwide circulation of many infectious diseases. anthrax, plague and tularaemia are three zoonotic diseases that have been intensely studied through genome characterization of the causative species and phylogeographical analyses. a few highly fit genotypes in each species represent the causative agents for most of the observed disease cases. together, mutational and selective forces create highly adapted pa ...200919820723
proteomic studies of bacillus anthracis.bacillus anthracis is a gram-positive, spore-forming bacterium representing the etiological cause of anthrax, a rare lethal disease of animals and humans. development of anthrax countermeasures has gained increasing attention owing to the potential use of b. anthracis spores as a bioterror weapon. the various forms of infection by b. anthracis are characterized both by toxemia and septicemia, both of which are the result of spore entry into the host followed by their germination into rapidly mul ...200919824790
bacillus anthracis, francisella tularensis and yersinia pestis. the most important bacterial warfare agents - review.there are three most important bacterial causative agents of serious infections that could be misused for warfare purposes: bacillus anthracis (the causative agent of anthrax) is the most frequently mentioned one; however, fracisella tularensis (causing tularemia) and yersinia pestis (the causative agent of plague) are further bacterial agents enlisted by centers for disease control and prevention into the category a of potential biological weapons. this review intends to summarize basic informa ...200919826916
[the time course of changes in cell immunological parameters during administration of live dry plague vaccine].the study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all t lymphocyte subpopulations on day 14 after vaccination. these changes are most typical of a primary vaccinated cohort. the increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines ...200919827193
cross-sectional survey of anthrax vaccine coverage and kap among deployed us military.the recently refocused effort on anthrax (ava) vaccination has been the source of much ethical and legal deliberation. however, the factors affecting one's decision to receive any or all of the vaccine doses are poorly understood. using a self-administered questionnaire, we sought to evaluate ava coverage among a cross-section of deployed active duty us military personnel and identify factors associated with receipt of the vaccine. a questionnaire was distributed to u.s. military personnel deplo ...200919829070
a continuous-flow polymerase chain reaction microchip with regional velocity control.this paper presents a continuous-flow polymerase chain reaction (pcr) microchip with a serpentine microchannel of varying width for "regional velocity control." varying the channel width by incorporating expanding and contracting conduits made it possible to control dna sample velocities for the optimization of the exposure times of the sample to each temperature phase while minimizing the transitional periods during temperature transitions. a finite element analysis (fea) and semi-analytical he ...200619829760
processing, assembly and localization of a bacillus anthracis spore protein.all bacillus spores are encased in macromolecular shells. one of these is a proteinacious shell called the coat that, in bacillus subtilis, provides critical protective functions. the bacillus anthracis spore is the infectious particle for the disease anthrax. therefore, the coat is of particular interest because it may provide essential protective functions required for the appearance of anthrax. here, we analyse a protein component of the spore outer layers that was previously designated bxpa. ...201019833771
identification of the channel-forming domain of clostridium perfringens epsilon-toxin (etx).epsilon-toxin (etx) is a potent toxin produced by clostridium perfringens strains b and d. the bacteria are important pathogens in domestic animals and cause edema mediated by etx. this toxin acts most likely by heptamer formation and rapid permeabilization of target cell membranes for monovalent anions and cations followed by a later entry of calcium. in this study, we compared the primary structure of etx with that of the channel-forming stretches of a variety of binding components of a-b-type ...200919835840
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