| hydroxylamine-amplified gold nanoparticles for the naked eye and chemiluminescent detection of sequence-specific dna with notable potential for single-nucleotide polymorphism discrimination. | herein, we report a hydroxylamine-amplified gold nanoparticle-based assay with naked eye and chemiluminescent (cl) detection of sequence-specific dna. for the naked eye detection assay, the signal can be observed by naked eye directly, which provides a general way for other biological assays. in contrast, the cl detection method can improve the detection limit by two orders of magnitude as compared to the naked eye detection, and a limit as low as 10 amol of target dna can be sensitively detecte ... | 2009 | 19238286 |
| cutaneous anthrax, west bengal, india, 2007. | | 2009 | 19239777 |
| crystal structure of the bacillus anthracis nucleoside diphosphate kinase and its characterization reveals an enzyme adapted to perform under stress conditions. | nucleoside diphosphate kinases (ndks) play an important role in a plethora of regulatory and metabolic functions. inhibition of the b. anthracis ndk mrna results in the formation of nonviable aberrant spores. we report the characterization and crystal structure of the enzyme from b. anthracis nucleoside diphosphate kinase (bandk), the first from sporulating bacteria. the enzyme, although from a mesophilic source, is active at extremes of ph (3.5-10.5), temperature (10-95 degrees c) and ionic str ... | 2009 | 19241473 |
| norepinephrine increases blood pressure but not survival with anthrax lethal toxin in rats. | the response of anthrax lethal toxin (letx) induced shock and lethality to conventional therapies has received little study. previously, fluids worsened outcome in letx-challenged rats in contrast to its benefit with lipopolysaccharide (lps) or escherichia coli. the current study investigated norepinephrine treatment. | 2009 | 19242337 |
| dendritic cell targeting of bacillus anthracis protective antigen expressed by lactobacillus acidophilus protects mice from lethal challenge. | efficient vaccines potentiate antibody avidity and increase t cell longevity, which confer protection against microbial lethal challenge. a vaccine strategy was established by using lactobacillus acidophilus to deliver bacillus anthracis protective antigen (pa) via specific dendritic cell-targeting peptides to dendritic cells (dcs), which reside in the periphery and mucosal surfaces, thus directing and regulating acquired immunity. the efficiency of oral delivery of l. acidophilus expressing a p ... | 2009 | 19246373 |
| the danger of lime use in agricultural anthrax disinfection procedures: the potential role of calcium in the preservation of anthrax spores. | previously, lime (calcium oxide) was recommended by the canadian food inspection agency (cfia) as an anthrax disinfectant. however, a recent scientific review of the subject has found evidence to suggest that exposure of anthrax spores to calcium may aid in their survival and viability. for this reason, the cfia no longer recommends the use of lime for agricultural anthrax disinfection. | 2008 | 19252713 |
| isolation of full-length igg antibodies from combinatorial libraries expressed in escherichia coli. | we have developed a technology for the facile isolation of full-length igg antibodies with desired specificity from combinatorial libraries expressed in escherichia coli. full-length heavy and light chains are expressed from a bicistronic operon and are secreted into the periplasm where they assemble into aglycosylated iggs that are fully functional for antigen binding. expression of an inner membrane-tethered fc-binding protein is used to capture the igg molecules and anchor them to the cell. f ... | 2009 | 19252859 |
| self-assembled peptide monolayers as a toxin sensing mechanism within arrayed microchannels. | a sensor for the lethal bacterial enzyme, botulinum neurotoxin type a (bont/a), was developed using self-assembled monolayers (sams). sams consisting of an immobilized synthetic peptide that mimicked the toxin's in vivo snap-25 protein substrate were formed on au and interfaced with arrayed microfluidic channels. efforts to optimize sam composition and assay conditions for greatest reaction efficiency and sensitivity are described in detail. channel design provided facile fluid manipulation, sam ... | 2009 | 19253949 |
| siderophore-mediated iron acquisition systems in bacillus cereus: identification of receptors for anthrax virulence-associated petrobactin . | during growth under iron limitation, bacillus cereus and bacillus anthracis, two human pathogens from the bacillus cereus group of gram-positive bacteria, secrete two siderophores, bacillibactin (bb) and petrobactin (pb), for iron acquisition via membrane-associated substrate-binding proteins (sbps) and other abc transporter components. since pb is associated with virulence traits in b. anthracis, the pb-mediated iron uptake system presents a potential target for antimicrobial therapies; its cha ... | 2009 | 19254027 |
| anthrax, toxins and vaccines: a 125-year journey targeting bacillus anthracis. | bacillus anthracis is the causative agent of anthrax, a disease that plagues both humans and various animal species. effective vaccines are available, but those approved for human use are crude culture supernatants that require multiple injections and a yearly boost. many experts agree that it is now time for the next generation of human vaccines against anthrax. accordingly, this review will succinctly focus upon: pathogenesis of b. anthracis, with particular emphasis upon the immune system; th ... | 2009 | 19254170 |
| statistical scales of order in dna. | in the present paper we examine the statistics of occurrence of a-t and c-g base pairs in dna. we focus on the net base composition in blocks of base pairs of various sizes. this paper extends our previous work on randomness and order in dna sequences and examines order on various scales. for structure on the local scale (10(0)-10(1) bp) we have seen that the net base composition in given block sizes is fitted very accurately by the discrete binomial distribution for a random system. if the stat ... | 2009 | 19254822 |
| enantioselective desymmetrisation of citric acid catalysed by the substrate-tolerant petrobactin biosynthetic enzyme asba. | asba catalyses the highly enantioselective desymmetrisation of citric acid via atp-dependent condensation with spermidine, as well as the condensation of citric acid with several spermidine analogues and the condensation of the citric acid analogue tricarballylic acid with spermidine, suggesting that it may be a useful biocatalyst for asymmetric synthesis. | 2009 | 19259597 |
| the adenylate cyclase toxins of bacillus anthracis and bordetella pertussis promote th2 cell development by shaping t cell antigen receptor signaling. | the adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by camp, to modulate apc activation, resulting in the expression of th2-driving cytokines. on the other hand, camp has been demonstrated to induce a th2 bias when present during t cell priming, suggesting that bacterial camp elevating toxins may directly affect the th1/th2 balance. here we have investigated the effects on human cd4(+) t cell differentiation of two adenylate cyclase toxin ... | 2009 | 19266022 |
| reduced expression of cd45 protein-tyrosine phosphatase provides protection against anthrax pathogenesis. | the modulation of cellular processes by small molecule inhibitors, gene inactivation, or targeted knockdown strategies combined with phenotypic screens are powerful approaches to delineate complex cellular pathways and to identify key players involved in disease pathogenesis. using chemical genetic screening, we tested a library of known phosphatase inhibitors and identified several compounds that protected bacillus anthracis infected macrophages from cell death. the most potent compound was ass ... | 2009 | 19269962 |
| sortase d forms the covalent bond that links bcpb to the tip of bacillus cereus pili. | bacillus cereus and other gram-positive bacteria elaborate pili via a sortase d-catalyzed transpeptidation mechanism from major and minor pilin precursor substrates. after cleavage of the lpxtg sorting signal of the major pilin, bcpa, sortase d forms an amide bond between the c-terminal threonine and the amino group of lysine within the ypkn motif of another bcpa subunit. pilus assembly terminates upon sortase a cleavage of the bcpa sorting signal, resulting in a covalent bond between bcpa and t ... | 2009 | 19269972 |
| secondary cell wall polysaccharides of bacillus anthracis are antigens that contain specific epitopes which cross-react with three pathogenic bacillus cereus strains that caused severe disease, and other epitopes common to all the bacillus cereus strains tested. | the immunoreactivities of hydrogen fluoride (hf)-released cell wall polysaccharides (hf-pss) from selected bacillus anthracis and bacillus cereus strains were compared using antisera against live and killed b. anthracis spores. these antisera bound to the hf-pss from b. anthracis and from three clinical b. cereus isolates (g9241, 03bb87, and 03bb102) obtained from cases of severe or fatal human pneumonia but did not bind to the hf-pss from the closely related b. cereus atcc 10987 or from b. cere ... | 2009 | 19270075 |
| the anthrax vaccine: no new tricks for an old dog. | the original license for production of the anthrax vaccine, anthrax vaccine adsorbed (ava), was issued in 1970. since that time, over 8 million ava immunizations have been administered to 2+ million individuals. in 2002, the national academy of sciences, institute of medicine, reviewed the safety and efficacy of ava. they concluded that the vaccine is acceptably safe and effective in protecting humans against anthrax. the vaccine should protect people against all known strains of anthrax bacteri ... | 2009 | 19270504 |
| lung epithelial injury by b. anthracis lethal toxin is caused by mkk-dependent loss of cytoskeletal integrity. | bacillus anthracis lethal toxin (lt) is a key virulence factor of anthrax and contributes significantly to the in vivo pathology. the enzymatically active component is a zn(2+)-dependent metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (mkks). using ex vivo differentiated human lung epithelium we report that lt destroys lung epithelial barrier function and wound healing responses by immobilizing the actin and microtubule network. long-term exposure to the to ... | 2009 | 19270742 |
| anthrax toxin: pathologic effects on the cardiovascular system. | anthrax is a disease caused by infection with spores from the bacteria bacillus anthracis. after entering the body, the spores germinate into bacteria and secrete a toxin that causes local edema and, in systemic infections, cardiovascular collapse and death. the toxin is a tripartite polypeptide, consisting of protective antigen (pa), lethal factor (lf) and edema factor (ef), which have key roles in the bacterial pathogenesis and disease progression. pa facilitates transfer of lf and ef to the c ... | 2009 | 19273204 |
| pathophysiology of anthrax. | infection by bacillus anthracis in animals and humans results from accidental or intentional exposure, by oral, cutaneous or pulmonary routes, to spores, which are normally present in the soil. treatment includes administration of antibiotics, vaccination or treatment with antibody to the toxin. a better understanding of the molecular basis of the processes involved in the pathogenesis of anthrax namely, spore germination in macrophages and biological effects of the secreted toxins on heart and ... | 2009 | 19273366 |
| anthrax edema toxin induces maturation of dendritic cells and enhances chemotaxis towards macrophage inflammatory protein 3beta. | bacillus anthracis secretes two bipartite toxins, edema toxin (et) and lethal toxin (lt), which impair immune responses and contribute directly to the pathology associated with the disease anthrax. edema factor, the catalytic subunit of et, is an adenylate cyclase that impairs host defenses by raising cellular cyclic amp (camp) levels. synthetic camp analogues and compounds that raise intracellular camp levels lead to phenotypic and functional changes in dendritic cells (dcs). here, we demonstra ... | 2009 | 19273556 |
| bryan krantz: from folding to unfolding proteins. interview by liz savage. | | 2009 | 19273611 |
| [fluoroquinolones: antimicrobial activity and chemotherapeutic efficacy with respect to various pathogens in highly dangerous diseases]. | comparative in vitro and in vivo efficacy of new fluoroquinolones with respect to pathogens of tularemia, glanders, melioidosis and anthrax was estimated. it was shown that the strains of the tularemia, glanders, melioidosis and anthrax pathogens were in vitro highly susceptible to the new agents. the experiments on laboratory animals demonstrated that pefloxacin and sparfloxacin had extremely broad spectra and were of special value in emergency prophylaxis of tularemia, glanders, melioidosis an ... | 2007 | 19275053 |
| pre-columbian origins for north american anthrax. | disease introduction into the new world during colonial expansion is well documented and had a major impact on indigenous populations; however, few diseases have been associated with early human migrations into north america. during the late pleistocene epoch, asia and north america were joined by the beringian steppe ecosystem which allowed animals and humans to freely cross what would become a water barrier in the holocene. anthrax has clearly been shown to be dispersed by human commerce and t ... | 2009 | 19283072 |
| biosecurity. paul keim on his life with the fbi during the anthrax investigation. interview by yudhijit bhattacharjee. | | 2009 | 19286527 |
| comparative transcriptional profiling of bacillus cereus sensu lato strains during growth in co2-bicarbonate and aerobic atmospheres. | bacillus species are spore-forming bacteria that are ubiquitous in the environment and display a range of virulent and avirulent phenotypes. this range is particularly evident in the bacillus cereus sensu lato group; where closely related strains cause anthrax, food-borne illnesses, and pneumonia, but can also be non-pathogenic. although much of this phenotypic range can be attributed to the presence or absence of a few key virulence factors, there are other virulence-associated loci that are co ... | 2009 | 19295911 |
| efficacy of recombinant anthrax vaccine against bacillus anthracis aerosol spore challenge: preclinical evaluation in rabbits and rhesus monkeys. | this report describes the immunogenicity and protective efficacy of escherichia coli-expressed recombinant protective antigen (rpa) in new zealand white rabbits and rhesus macaques against an aerosol challenge with bacillus anthracis spores (ivri strain, tox+cap+). a dose-ranging study was performed in which it became evident that the level of anti-pa igg and toxin-neutralizing antibody titer was directly proportional to the dose of rpa administered. however, the onset time of primary and second ... | 2009 | 19296443 |
| anthrax meningoencephalitis--declining trends in an uncommon but catastrophic cns infection in rural tamil nadu, south india. | anthrax, a cattle-born zoonosis has been a serious infectious disease and its meningoencephalitic form remains a rapidly fatal illness even now. | 2009 | 19304297 |
| distribution, diversity, and potential mobility of extrachromosomal elements related to the bacillus anthracis pxo1 and pxo2 virulence plasmids. | the presence of a pxo1- and/or pxo2-like plasmid(s) in clinical isolates of bacillus cereus sensu stricto and in strains of the biopesticide bacillus thuringiensis has been reported recently, and the pxo2-like plasmid pbt9727 and another pxo2-like plasmid, paw63, were found to be conjugative. in this study, a total of 1,000 b. cereus group isolates were analyzed for the presence of pxo1- and pxo2-like replicons and for the presence of pxo2-related conjugative modules. pxo1- and pxo2-like replico ... | 2009 | 19304837 |
| structure and complexity of a bacterial transcriptome. | although gene expression has been studied in bacteria for decades, many aspects of the bacterial transcriptome remain poorly understood. transcript structure, operon linkages, and information on absolute abundance all provide valuable insights into gene function and regulation, but none has ever been determined on a genome-wide scale for any bacterium. indeed, these aspects of the prokaryotic transcriptome have been explored on a large scale in only a few instances, and consequently little is kn ... | 2009 | 19304856 |
| label-free detection of b. anthracis spores using a surface plasmon resonance biosensor. | this study demonstrates the first use of surface plasmon resonance (spr) technology for the rapid, sensitive and label-free detection of whole b. anthracis spores. the approach involves the use of an spr biosensor (biacore 3000), and a monoclonal antibody which was raised against the b. anthracis spore (mab 8g3). by means of subtractive inhibition assays, whole b. anthracis spores with concentrations as low as 10(4) colony-forming units (cfu) ml(-1) can be detected within 40 min, and other relat ... | 2009 | 19305924 |
| cellular functions and x-ray structure of anthrolysin o, a cholesterol-dependent cytolysin secreted by bacillus anthracis. | anthrolysin o (alo) is a pore-forming, cholesterol-dependent cytolysin (cdc) secreted by bacillus anthracis, the etiologic agent for anthrax. growing evidence suggests the involvement of alo in anthrax pathogenesis. here, we show that the apical application of alo decreases the barrier function of human polarized epithelial cells as well as increases intracellular calcium and the internalization of the tight junction protein occludin. using pharmacological agents, we also found that barrier func ... | 2009 | 19307185 |
| bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase a and exchange protein activated by cyclic amp pathways. | bacillus anthracis, the etiological agent of anthrax, is a gram-positive spore-forming bacterium. it produces edema toxin (edtx), a powerful adenylate cyclase that increases cyclic amp (camp) levels in host cells. because other camp-increasing agents inhibit key macrophage (mphi) functions, such as phagocytosis, it was hypothesized that edtx would exhibit similar suppressive activities. our previous genechip data showed that edtx downregulated mphi genes involved in actin cytoskeleton remodeling ... | 2009 | 19307216 |
| structure of the diaminopimelate epimerase dapf from mycobacterium tuberculosis. | the meso (or d,l) isomer of diaminopimelic acid (dap), a precursor of l-lysine, is a key component of the pentapeptide linker in bacterial peptidoglycan. while the peptidoglycan incorporated in the highly complex cell wall of the pathogen mycobacterium tuberculosis structurally resembles that of escherichia coli, it is unique in that it can contain penicillin-resistant meso-dap-->meso-dap linkages. the interconversion of l,l-dap and meso-dap is catalysed by the dap epimerase dapf, a gene product ... | 2009 | 19307721 |
| norepinephrine in anthrax-associated shock: even worse than figs? | | 2009 | 19318844 |
| the solution structure of bacillus anthracis dihydrofolate reductase yields insight into the analysis of structure-activity relationships for novel inhibitors. | there is a significant need for new therapeutics to treat infections caused by the biodefense agent bacillus anthracis. in pursuit of drug discovery against this organism, we have developed novel propargyl-linked inhibitors that target the essential enzyme dihydrofolate reductase (dhfr) from b. anthracis. previously, we reported an initial series of these inhibitors and a high-resolution crystal structure of the ternary complex of the enzyme bound to its cofactor and one of the most potent inhib ... | 2009 | 19323450 |
| complement protein c3 binding to bacillus anthracis spores enhances phagocytosis by human macrophages. | alveolar macrophages are thought to play a central role in the pathogenesis of inhalational anthrax. receptors present on macrophages that mediate phagocytosis of bacillus anthracis spores have yet to be completely defined. to begin to determine if soluble factors that are present in the lung such as immunoglobulin and complement are involved, we characterized the binding of human igg and c3 to the surface of b. anthracis spores at different concentrations of nonimmune human serum. furthermore w ... | 2009 | 19328844 |
| molecular modification of t4 bacteriophage proteins and its potential application - review. | bacteriophage t4 is a virus with well-known genetics, structure, and biology. such techniques as x-ray crystallography, cryo-em, and three-dimensional (3d) image reconstruction allowed describing its structure very precisely. the genome of this bacteriophage was completely sequenced, which opens the way for the use of many molecular techniques, such as site-specific mutagenesis, which was widely applied, e.g., in investigating the functions of some essential t4 proteins. the phage-display method ... | 2009 | 19330539 |
| fusion protein of delta 27lfn and efn has the potential as a novel anthrax toxin inhibitor. | pa-binding domain of lf (lfn) or pa-binding domain of ef (efn) is the anthrax protective antigen (pa) binding domain of anthrax lethal factor (lf) or edema factor (ef). here we show the development of a novel anthrax toxin inhibitor, fusion protein of n-terminal 27 amino acids deletion of lfn (delta27lfn) and efn. in a cell model of intoxication, fusion protein of delta27lfn and efn (delta27lfn-efn) was a 62-fold more potent toxin inhibitor than lfn or efn, and this increased activity correspond ... | 2009 | 19332063 |
| idf's anthrax vaccine trial "violated helsinki convention". | | 2009 | 19332445 |
| inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small molecules. | furin is a ubiquitously expressed proprotein convertase (pc) that plays a vital role in numerous disease processes including cancer metastasis, bacterial toxin activation (e.g. anthrax and pseudomonas), and viral propagation (e.g. avian influenza and human immunodeficiency virus). to identify small molecule inhibitors of furin and related processing enzymes, we performed high-throughput screens of chemical diversity libraries utilizing both enzyme-based and cell-based assays. the screens identif ... | 2009 | 19332539 |
| localization and assembly of proteins comprising the outer structures of the bacillus anthracis spore. | bacterial spores possess a series of concentrically arranged protective structures that contribute to dormancy, survival and, ultimately, germination. one of these structures, the coat, is present in all spores. in bacillus anthracis, however, the spore is surrounded by an additional, poorly understood, morphologically complex structure called the exosporium. here, we characterize three previously discovered exosporium proteins called exsfa (also known as bxpb), exsfb (a highly related paralogue ... | 2009 | 19332815 |
| 27th annual jpmorgan healthcare conference--biocryst and emergent biosolutions. | | 2009 | 19333891 |
| existing antibacterial vaccines. | there are countless bacterial pathogens that cause disease in humans. many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. vaccines allow for reduction and potential eradication of such diseases. this article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, haemophilus influenza, cholera, ty ... | 2009 | 19335724 |
| extraordinary pleiotropy of protein kinase ck2 revealed by weblogo phosphoproteome analysis. | a weblogo has been generated from the sequences surrounding 433 ser/thr protein residues whose phosphorylation by protein kinase ck2 had been previously validated ("bona fide" ck2 phosphosites). this has been compared to the weblogo extracted from 2275 putative ck2 phosphosites displaying the motif ps/pt-x1-x2-d/e/ps (where x1 not=p) present in the human phosphoelm database including 10899 naturally occurring phosphosites. the two weblogos are strikingly similar supporting the notion that indeed ... | 2009 | 19339213 |
| anthrax lethal toxin impairs il-8 expression in epithelial cells through inhibition of histone h3 modification. | lethal toxin (lt) is a critical virulence factor of bacillus anthracis, the etiological agent of anthrax, whose pulmonary form is fatal in the absence of treatment. inflammatory response is a key process of host defense against invading pathogens. we report here that intranasal instillation of a b. anthracis strain bearing inactive lt stimulates cytokine production and polymorphonuclear (pmn) neutrophils recruitment in lungs. these responses are repressed by a prior instillation of an lt prepara ... | 2009 | 19343203 |
| lysozyme catalyzes the formation of antimicrobial silver nanoparticles. | hen egg white lysozyme acted as the sole reducing agent and catalyzed the formation of silver nanoparticles in the presence of light. stable silver colloids formed after mixing lysozyme and silver acetate in methanol and the resulting nanoparticles were concentrated and transferred to aqueous solution without any significant changes in physical properties. activity and antimicrobial assays demonstrated lysozyme-silver nanoparticles retained the hydrolase function of the enzyme and were effective ... | 2009 | 19344124 |
| rapid detection of the poly-gamma-d-glutamic acid capsular antigen of bacillus anthracis by latex agglutination. | latex agglutination has been used to detect capsular polysaccharides from a variety of bacteria in body fluids. a latex agglutination assay was constructed for detection of the poly-gamma-d-glutamic acid (gammadpga) capsular polypeptide of bacillus anthracis in serum from animal models of pulmonary anthrax. the assay was able to detect gammadpga in serum from infected animals at concentrations of 100 to 200 ng/ml. | 2009 | 19345041 |
| quantitative method to determine sporicidal decontamination of building surfaces by gaseous fumigants, and issues related to laboratory-scale studies. | chlorine dioxide gas and vaporous hydrogen peroxide sterilant have been used in the cleanup of building interiors contaminated with spores of bacillus anthracis. a systematic study, in collaboration with the u.s. environmental protection agency, was jointly undertaken by the u.s. army-edgewood chemical biological center to determine the sporicidal efficacies of these two fumigants on six building structural materials: carpet, ceiling tile, unpainted cinder block, painted i-beam steel, painted wa ... | 2009 | 19346341 |
| bacillus anthracis edema toxin impairs neutrophil actin-based motility. | inhalation anthrax results in high-grade bacteremia and is accompanied by a delay in the rise of the peripheral polymorphonuclear neutrophil (pmn) count and a paucity of pmns in the infected pleural fluid and mediastinum. edema toxin (et) is one of the major bacillus anthracis virulence factors and consists of the adenylate cyclase edema factor (ef) and protective antigen (pa). relatively low concentrations of et (100 to 500 ng/ml of pa and ef) significantly impair human pmn chemokinesis, chemot ... | 2009 | 19349425 |
| health concerns in uk armed forces personnel. | | 2009 | 19349506 |
| chlorine dioxide reactions with indoor materials during building disinfection: surface uptake. | chlorine dioxide received attention as a building disinfectant in the wake of bacillus anthracis contamination of several large buildings in the fall of 2001. it is increasingly used for the disinfection of homes and other indoor environments afflicted by mold. however, little is known regarding the interaction of chlorine dioxide and indoor materials, particularly as related to the removal of chlorine dioxide from air. such removal may be undesirable with respect to the subsequent formation of ... | 2009 | 19350899 |
| susceptibilities of bacillus subtilis, bacillus cereus, and avirulent bacillus anthracis spores to liquid biocides. | the susceptibility of spores of bacillus subtilis, bacillus cereus, and avirulent bacillus anthracis to treatment with hydrogen peroxide, peroxyacetic acid, a peroxy-fatty acid mixture, sodium hypochlorite, and acidified sodium chlorite was investigated. results indicated that b. cereus spores may be reasonable predictors of b. anthracis spore inactivation by peroxyacetic acid-based biocides. however, b. cereus was not a reliable predictor of b. anthracis inactivation by the other biocides. in s ... | 2009 | 19350981 |
| identification and characterization of immunodominant b-cell epitope of the c-terminus of protective antigen of bacillus anthracis. | bacillus anthracis is the etiological agent of anthrax. protective antigen (pa) has been established as the key protective immunogen and is the major component of anthrax vaccine. prior studies have indicated that c-terminus host cell receptor binding region contains dominant protective epitopes of pa. in the present study, we focused our attention on determining b-cell epitopes from this region, which could be employed as a vaccine. using b-cell epitope prediction systems, three regions were id ... | 2009 | 19356802 |
| structure-activity relationship studies of a novel series of anthrax lethal factor inhibitors. | we report on the identification of a novel small molecule inhibitor of anthrax lethal factor using a high-throughput screening approach. guided by molecular docking studies, we carried out structure-activity relationship (sar) studies and evaluated activity and selectivity of most promising compounds in in vitro enzyme inhibition assays and cellular assays. selected compounds were further analyzed for their in vitro adme properties, which allowed us to select two compounds for further preliminar ... | 2009 | 19359184 |
| substrate recognition of anthrax lethal factor examined by combinatorial and pre-steady-state kinetic approaches. | lethal factor (lf), a zinc-dependent protease of high specificity produced by bacillus anthracis, is the effector component of the binary toxin that causes death in anthrax. new therapeutics targeting the toxin are required to reduce systemic anthrax-related fatalities. in particular, new insights into the lf catalytic mechanism will be useful for the development of lf inhibitors. we evaluated the minimal length required for formation of bona fide lf substrates using substrate phage display. pha ... | 2009 | 19359249 |
| estimating the location and spatial extent of a covert anthrax release. | rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. we extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. a back-calculation method is developed allowing the cha ... | 2009 | 19360099 |
| crystal structure of the engineered neutralizing antibody m18 complexed to domain 4 of the anthrax protective antigen. | the virulence of bacillus anthracis is critically dependent on the cytotoxic components of the anthrax toxin, lethal factor (lf) and edema factor (ef). lf and ef gain entry into host cells through interactions with the protective antigen (pa), which binds to host cellular receptors such as cmg2. antibodies that neutralize pa have been shown to confer protection in animal models and are undergoing intense clinical development. a murine monoclonal antibody, 14b7, has been reported to interact with ... | 2009 | 19361425 |
| crystal structure of bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative rab1 provides a structural explanation of potency and selectivity. | bacillus anthracis possesses an innate resistance to the antibiotic trimethoprim due to poor binding to dihydrofolate reductase (dhfr); currently, there are no commercial antibacterials that target this enzyme in b. anthracis. we have previously reported a series of dihydrophthalazine-based trimethoprim derivatives that are inhibitors for this target. in the present work, we have synthesized one compound (rab1) displaying favorable 50% inhibitory concentration (54 nm) and mic (< or =12.8 microg/ ... | 2009 | 19364848 |
| framework for evaluating anthrax risk in buildings. | if bacillus anthracis (ba), the organism that causes anthrax, is known or suspected to have contaminated a building, a critical decision is what level of contamination is unacceptable. this decision has two components: (1) what is the relationship between the degree of contamination and the risk to occupants, (2) and what is an acceptable risk to occupants? these lead to a further decision: (3) how many samples must be taken to determine whether a building is unacceptably contaminated? we discus ... | 2009 | 19368172 |
| bacillus anthracis in china and its relationship to worldwide lineages. | the global pattern of distribution of 1033 b. anthracis isolates has previously been defined by a set of 12 conserved canonical single nucleotide polymorphisms (cansnp). these studies reinforced the presence of three major lineages and 12 sub-lineages and sub-groups of this anthrax-causing pathogen. isolates that form the a lineage (unlike the b and c lineages) have become widely dispersed throughout the world and form the basis for the geographical disposition of "modern" anthrax. an archival c ... | 2009 | 19368722 |
| vaccines for preventing anthrax. | anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine. | 2009 | 19370633 |
| antimicrobial ambiguine isonitriles from the cyanobacterium fischerella ambigua. | five new antibacterial ambiguine k-o isonitriles (1-5) and eight previously described indole alkaloids were isolated from the cultured cyanobacterium fischerella ambigua (utex 1903) by bioassay-guided fractionation. the planar structures of the new compounds were determined by spectroscopic analysis including ms and 1d and 2d nmr. x-ray crystallography was used to determine the absolute stereoconfiguration of ambiguine k isonitrile. the isolates were evaluated for their antibacterial activities ... | 2009 | 19371071 |
| matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis. | solid tumor growth is dependent on angiogenesis, the formation of neovasculature from existing vessels. endothelial activation of the extracellular signal-regulated kinase 1/2, c-jun nh(2)-terminal kinase, and p38 mitogen-activated protein kinase pathways is central to this process, and thus presents an attractive target for the development of angiogenesis inhibitors. anthrax lethal toxin (letx) has potent catalytic mitogen-activated protein kinase inhibition activity. preclinical studies showed ... | 2009 | 19372576 |
| x-ray structure of the ternary mtx.nadph complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design. | for reasons of bioterrorism and drug resistance, it is imperative to identify and develop new molecular points of intervention against anthrax. dihydrofolate reductase (dhfr) is a highly conserved enzyme and an established target in a number of species for a variety of chemotherapeutic programs. recently, the crystal structure of bacillus anthracis dhfr (badhfr) in complex with methotrexate (mtx) was determined and, based on the structure, proposals were made for drug design strategies directed ... | 2009 | 19374017 |
| sex differences in injection site reactions with human vaccines. | adverse events following immunization (aefi) are not uncommon, with injection site reactions (isrs) being the most common. predictors of injection site reactions are vaccine factors (antigen characteristics, antigen dose, dose number of antigen, antigen adjuvanting and type of diluent), vaccine administration factors (site and route of administration) and vaccinee factors (age and sex, the latter the subject of this review). 1,074 studies which reported isrs were retrieved by searching of on lin ... | 2009 | 19377279 |
| imaging specific cell surface protease activity in living cells using reengineered bacterial cytotoxins. | the scarcity of methods to visualize the activity of individual cell surface proteases in situ has hampered basic research and drug development efforts. in this chapter, we describe a simple, sensitive, and noninvasive assay that uses nontoxic reengineered bacterial cytotoxins with altered protease cleavage specificity to visualize specific cell surface proteolytic activity in single living cells. the assay takes advantage of the absolute requirement for site-specific endoproteolytic cleavage of ... | 2009 | 19377967 |
| dissecting the urokinase activation pathway using urokinase-activated anthrax toxin. | anthrax toxin is a three-part toxin secreted by bacillus anthracis, consisting of protective antigen (prag), edema factor (ef), and lethal factor (lf). to intoxicate host mammalian cells, prag, the cell-binding moiety of the toxin, binds to cells and is then proteolytically activated by furin on the cell surface, resulting in the active heptameric form of prag. this heptamer serves as a protein-conducting channel that translocates ef and lf, the two enzymatic moieties of the toxin, into the cyto ... | 2009 | 19377974 |
| a decision framework for coordinating bioterrorism planning: lessons from the bionet program. | effective disaster preparedness requires coordination across multiple organizations. this article describes a detailed framework developed through the bionet program to facilitate coordination of bioterrorism preparedness planning among military and civilian decision makers. | 2009 | 19378669 |
| animal carcass and eyelid anthrax: a case report. | anthrax is a worldwide zoonosis of herbivores, which is caused by the spore-forming bacteria bacillus anthracis, and humans become infected when they are exposed to infected animals and their tissues or the organism directly. in this report, we present a 13-year-old boy who developed eyelid anthrax after contact with a sheep carcass during his summer holiday that resulted in eyelid anthrax and cicatricial ectropion. | 2009 | 19378894 |
| use of molecular beacons and multi-allelic real-time pcr for detection of and discrimination between virulent bacillus anthracis and other bacillus isolates. | the awareness of the threat of bacillus anthracis, the causative agent of the disease anthrax, as a biowarfare and bioterrorism weapon has revived the development of new technologies for rapid and accurate detection of virulent isolates in environmental and clinical samples. here we explore the utility of molecular beacon real-time pcr technology for detection of virulent bacillus anthracis strains. molecular beacons are nucleic acid probes with high specificity, that act as switches by emitting ... | 2009 | 19379778 |
| antibodies to squalene in us navy persian gulf war veterans with chronic multisymptom illness. | since the end of the 1991 gulf war, there have been reports of unexplained, multisymptom illnesses afflicting veterans who consistently report more symptoms than do nondeployed veterans. one of the many possible exposures suspected of causing chronic multisymptom illnesses gulf war veterans is squalene, thought to be present in anthrax vaccine. we examined the relationship between squalene antibodies and chronic symptoms reported by navy construction workers (seabees), n=579. 30.2% were deployer ... | 2009 | 19379786 |
| geographical distribution of genotypic and phenotypic markers among bacillus anthracis isolates and related species by historical movement and horizontal transfer. | the geographical distribution of bacillus anthracis strains and isolates bearing some of the same genetic markers as the amerithrax ames isolate was examined and evaluated. at least one mechanism for the horizontal movement of genetic markers was shown amongst isolates and closely related species and the effect of such mixing was demonstrated on phenotype. the results provided potential mechanisms by which attempts to attribute isolates of bacillus anthracis to certain geographical and isolate s ... | 2009 | 19381470 |
| a strain-variable bacteriocin in bacillus anthracis and bacillus cereus with repeated cys-xaa-xaa motifs. | bacteriocins are peptide antibiotics from ribosomally translated precursors, produced by bacteria often through extensive post-translational modification. minimal sequence conservation, short gene lengths, and low complexity sequence can hinder bacteriocin identification, even during gene calling, so they are often discovered by proximity to accessory genes encoding maturation, immunity, and export functions. this work reports a new subfamily of putative thiazole-containing heterocyclic bacterio ... | 2009 | 19383135 |
| [construction of eag deletion mutant of bacillus anthracis vaccine strain a16r]. | construction of eag deletion mutant of bacillus anthracis vaccine strain a16r. | 2009 | 19388260 |
| bacillus anthracis lethal toxin represses mmtv promoter activity through transcription factors. | we have recently shown that the anthrax lethal toxin (letx) selectively represses nuclear hormone receptors. in this study, we found that letx repressed the activation of the mouse mammary tumor virus promoter related to overexpression of the transcription factors hepatocyte nuclear factor 3, octamer-binding protein 1, and c-jun. letx transcriptional repression was associated with a decrease in the protein levels of these transcription factors in a lethal factor protease activity-dependent manne ... | 2009 | 19389405 |
| swraa activates poly-gamma-glutamate synthesis in addition to swarming in bacillus subtilis. | poly-gamma-glutamic acid (gamma-pga) is an extracellular polymer produced by various strains of bacillus. iotat was first described as the component of the capsule in bacillus anthracis, where it plays a relevant role in virulence. gamma-pga is also a distinctive component of 'natto', a traditional japanese food consisting of soybean fermented by bacillus subtilis (natto). domesticated b. subtilis strains do not synthesize gamma-pga although they possess the functional biosynthetic pgs operon. i ... | 2009 | 19389763 |
| implications of autophagy in anthrax pathogenicity. | the etiological agent for anthrax is bacillus anthracis, which produces lethal toxin (lt) that exerts a myriad of effects on many immune cells. in our previous study, it was demonstrated that lt and protective antigen (pa) induce autophagy in mammalian cells. preliminary results suggest that autophagy may function as a cellular defense mechanism against lt-mediated toxemia. this degradation pathway may also be relevant to other aspects of the immune response in both innate and adaptive immunity. ... | 2009 | 19395870 |
| sporulation and germination gene expression analysis of bacillus anthracis sterne spores in skim milk under heat and different intervention techniques. | to investigate how b. anthracis sterne spores survive in milk under heat (80 degrees c, 10 min), pasteurization (72 degrees c, 15 s), microfiltration, and pasteurization and microfiltration, the expression levels of genes related to sporulation and germination were tested using real-time pcr assays. twenty-seven sporulation- and germination-related genes were selected for the target genes. our results demonstrated that gene expression levels were altered by heat and microfiltration whereas the p ... | 2009 | 19397727 |
| evaluation of gram-positive rod surveillance for early anthrax detection. | since 2003, connecticut laboratories have reported gram-positive rod (gpr) isolates detected within 32 h of inoculation from blood or cerebrospinal fluid. the objectives were to rapidly identify inhalational anthrax and unusual clostridium spp. infections, and to establish round-the-clock laboratory reporting of potential indicators of bioterrorism. from 2003 to 2006, connecticut's gpr surveillance system identified 1134 isolates, including 657 bacillus spp. (none b. anthracis) and 241 clostridi ... | 2009 | 19397835 |
| simultaneous expression of homologous and heterologous antigens in rough, attenuated brucella melitensis. | the possibility of expressing a homologous antigen and a heterologous antigen simultaneously in an attenuated brucella melitensis strain was investigated. the brucella wboa gene encoding a mannosyltransferase involved in biosynthesis of lipopolysaccharide o-antigen, and the bacillus anthracis pag gene encoding the protective antigen (pa) were cloned into plasmid pbbr4mcs. the resulting plasmid was introduced into o-antigen deficient b. melitensis strain wrrp1 to produce strain wrspa. strain wrsp ... | 2009 | 19397881 |
| biocidal activity of partially purified fractions from methanolic extract of garcinia kola (heckel) seeds on bacterial isolates. | the in vitro antibacterial activity of crude methanolic extract of the seeds of garcinia kola was investigated. the extracts exhibited antibacterial activities with zones of inhibition ranging from 10 mm to 25 mm. the minimum inhibitory concentration of the diethyl ether fraction was between 0.313 and 5.0 mg/ml, while that of butanol fraction varied from 0.157 to 5.0 mg/ml. the butanol fraction killed about 77% of bacillus anthracis and 79% of escherichia coli cells within 120 min at a concentra ... | 2009 | 19399341 |
| protective antigen detection using horizontally stacked hexagonal zno platelets. | anthrax toxin detection before bacteremia, when toxin concentration is low, improves the chances of efficient treatment and cure. we present a novel technique for ultrasensitive detection of a protective antigen (pa(83)) of anthrax using an array of zinc oxide nanorods in conjunction with a fitc-labeled pa affinity peptide. the nanorods are composed of horizontally stacked hexagonal platelets which are uniformly spaced and grown unidirectionally upon a glass substrate via a new and simple techni ... | 2009 | 19400578 |
| photoclinic: anthrax. | | 2009 | 19400615 |
| bacillus anthracis hssrs signalling to hrtab regulates haem resistance during infection. | bacillus anthracis proliferates to high levels within vertebrate tissues during the pathogenesis of anthrax. this growth is facilitated by the acquisition of nutrient iron from host haem. however, haem acquisition can lead to the accumulation of toxic amounts of haem within b. anthracis. here, we show that b. anthracis resists haem toxicity by sensing haem through the hssrs two-component system, which regulates expression of the haem-detoxifying transporter hrtab. in addition, we demonstrate tha ... | 2009 | 19400785 |
| chloroplast-derived vaccine antigens and biopharmaceuticals: expression, folding, assembly and functionality. | chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance, and multi-gene expression in a single transformation event. oral delivery is facilitated by hyperexpression of vaccine antigens against cholera, tetanus, anthrax, plague, or canine parvovirus (4%-31% of total soluble protein, tsp) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato) as well as the availability of antibiot ... | 2009 | 19401820 |
| a single-dose combination therapy that both prevents and treats anthrax infection. | exposure to anthrax leaves susceptible hosts at prolonged risk of infection since spores can persist in vivo for months before germinating to cause life-threatening disease. anthrax vaccine adsorbed (ava, the licensed us vaccine) induces immunity too slowly to protect susceptible individuals post-exposure. antibiotics prevent the proliferation of vegetative bacilli but do not block latent spores from germinating. thus, anthrax-exposed individuals must remain on antibiotic therapy for months to e ... | 2009 | 19402202 |
| epidemiologic questions from anthrax outbreak, hunter valley, australia. | | 2009 | 19402992 |
| sar studies for a new class of antibacterial nad biosynthesis inhibitors. | a new lead class of antibacterial drug-like nad synthetase (nads) inhibitors was previously identified from a virtual screening study. here a solution-phase synthetic library of 76 compounds, analogs of the urea-sulfonamide 5838, was synthesized in parallel to explore sar on the sulfonamide aryl group. all library members were tested for enzyme inhibition against nads and nicotinic acid mononucleotide adenylyltransferase (namnat), the last two enzymes in the biosynthesis of nad, and for growth i ... | 2009 | 19408950 |
| an overlap between the control of programmed cell death in bacillus anthracis and sporulation. | the staphylococcus aureus cid and lrg operons have been shown to control cell death and lysis in a manner thought to be analogous to programmed cell death (apoptosis) in eukaryotic organisms. although orthologous operons are present in a wide variety of bacterial species, members of the bacillus cereus group are unique in that they have a total of four cid-/lrg-like operons. two of these operons are similar to the s. aureus cid and lrg operons, while the other two (designated clhab(1) and clhab( ... | 2009 | 19411321 |
| anthrax in free-ranging bison in the prince albert national park area of saskatchewan in 2008. | | 2009 | 19412394 |
| decreased time for detection and quantification of virulent bacillus anthracis and yersinia pestis using a bionanopore (bnp) membrane technology. | many aspects of biodefense research require quantitative growth assessments of the test agent. this study evaluated the bionanopore (bnp) technology to quantitate bacillus anthracis and yersinia pestis faster than traditional plate counting methods. the bnp technology enabled quantification of b. anthracis and y. pestis in phosphate-buffered saline and naïve rabbit blood at 6 and 24 h, respectively. after 6 h of growth, counts for b. anthracis ranged from 6.19-6.45 log(10) cfu ml(-1) on bnp, whi ... | 2009 | 19413803 |
| anthrax infection inhibits the akt signaling involved in the e-cadherin-mediated adhesion of lung epithelial cells. | the effect of anthrax infection on phosphoprotein signaling was studied in human small airway lung epithelial cells exposed to b. anthracis spores of the plasmidless dsterne strain in comparison with the sterne strain containing the toxigenic plasmid (pxo1). the differential regulation of phosphorylation was found in the mitogen-activated protein kinase cascade (erk, p38, and p90rsk), the pi3k cascade (akt, gsk-3alpha/beta), and downstream in the case of the proapoptotic bad and the transcriptio ... | 2009 | 19416348 |
| the structure of a cytolytic alpha-helical toxin pore reveals its assembly mechanism. | pore-forming toxins (pfts) are a class of potent virulence factors that convert from a soluble form to a membrane-integrated pore. they exhibit their toxic effect either by destruction of the membrane permeability barrier or by delivery of toxic components through the pores. among the group of bacterial pfts are some of the most dangerous toxins, such as diphtheria and anthrax toxin. examples of eukaryotic pfts are perforin and the membrane-attack complex, proteins of the immune system. pfts can ... | 2009 | 19421192 |
| phage-mediated bioluminescent detection of bacillus anthracis. | bacillus anthracis, the causative agent of anthrax, is a serious human pathogen. the aim of this study was to provide the proof of principle results for the development of a 'bioluminescent' reporter bacteriophage that was capable of specifically detecting b. anthracis. | 2009 | 19426264 |
| comparison of traditional and molecular analytical methods for detecting biological agents in raw and drinking water following ultrafiltration. | to compare the performance of traditional methods to quantitative polymerase chain reaction (qpcr) for detecting five biological agents in large-volume drinking-water samples concentrated by ultrafiltration (uf). | 2009 | 19426268 |
| recovery efficiency and limit of detection of aerosolized bacillus anthracis sterne from environmental surface samples. | after the 2001 anthrax incidents, surface sampling techniques for biological agents were found to be inadequately validated, especially at low surface loadings. we aerosolized bacillus anthracis sterne spores within a chamber to achieve very low surface loading (ca. 3, 30, and 200 cfu per 100 cm(2)). steel and carpet coupons seeded in the chamber were sampled with swab (103 cm(2)) or wipe or vacuum (929 cm(2)) surface sampling methods and analyzed at three laboratories. agar settle plates (60 cm ... | 2009 | 19429546 |
| activation of plasminogen activator inhibitor implicates protease inha in the acute-phase response to bacillus anthracis infection. | anthrax is a zoonotic disease caused by bacillus anthracis. the infection is associated with inflammation and sepsis, but little is known about the acute-phase response during disease and the nature of the bacterial factors causing it. in this study, we examined the levels of the acute-phase proteins (apps) in comparative experiments using mice challenged with spores and a purified b. anthracis protease inha as a possible factor mediating the response. a strong increase in the plasma levels of a ... | 2009 | 19429749 |
| effects of altering the germination potential of bacillus anthracis spores by exogenous means in a mouse model. | inhalational anthrax is the most severe form of anthrax. it has been shown in small-animal and non-human primate models that relatively large pools of ungerminated bacillus anthracis spores can remain within the alveolar spaces for days to weeks post-inhalation or until transported to areas more favourable for germination and bacillary outgrowth. in this study, spores of the ames strain that were exposed to germination-inducing media prior to intranasal delivery were significantly less infectiou ... | 2009 | 19429760 |
| validation of molecular docking programs for virtual screening against dihydropteroate synthase. | dihydropteroate synthase (dhps) is the target of the sulfonamide class of antibiotics and has been a validated antibacterial drug target for nearly 70 years. the sulfonamides target the p-aminobenzoic acid (paba) binding site of dhps and interfere with folate biosynthesis and ultimately prevent bacterial replication. however, widespread bacterial resistance to these drugs has severely limited their effectiveness. this study explores the second and more highly conserved pterin binding site of dhp ... | 2009 | 19434845 |