Publications

functional comparison of the two bacillus anthracis glutamate racemases.	glutamate racemase activity in bacillus anthracis is of significant interest with respect to chemotherapeutic drug design, because l-glutamate stereoisomerization to d-glutamate is predicted to be closely associated with peptidoglycan and capsule biosynthesis, which are important for growth and virulence, respectively. in contrast to most bacteria, which harbor a single glutamate racemase gene, the genomic sequence of b. anthracis predicts two genes encoding glutamate racemases, race1 and race2. ...	2007	17496086
a functional homing endonuclease in the bacillus anthracis nrde group i intron.	the essential bacillus anthracis nrde gene carries a self-splicing group i intron with a putative homing endonuclease belonging to the giy-yig family. here, we show that the nrde pre-mrna is spliced and that the homing endonuclease cleaves an intronless nrde gene 5 nucleotides (nt) upstream of the intron insertion site, producing 2-nt 3' extensions. we also show that the sequence required for efficient cleavage spans at least 4 bp upstream and 31 bp downstream of the cleaved coding strand. the p ...	2007	17496101
crystal structure of the bczbp, a zinc-binding protein from bacillus cereus.	bacillus cereus is an opportunistic pathogenic bacterium closely related to bacillus anthracis, the causative agent of anthrax in mammals. a significant portion of the b. cereus chromosomal genes are common to b. anthracis, including genes which in b. anthracis code for putative virulence and surface proteins. b. cereus thus provides a convenient model organism for studying proteins potentially associated with the pathogenicity of the highly infectious b. anthracis. the zinc-binding protein of b ...	2007	17501983
mucosal immunization with a novel nanoemulsion-based recombinant anthrax protective antigen vaccine protects against bacillus anthracis spore challenge.	the currently available commercial human anthrax vaccine requires multiple injections for efficacy and has side effects due to its alum adjuvant. these factors limit its utility when immunizing exposed populations in emergent situations. we evaluated a novel mucosal adjuvant that consists of a nontoxic, water-in-oil nanoemulsion (ne). this material does not contain a proinflammatory component but penetrates mucosal surfaces to load antigens into dendritic cells. mice and guinea pigs were intrana ...	2007	17502384
protective role of bacillus anthracis exosporium in macrophage-mediated killing by nitric oxide.	the ability of the endospore-forming, gram-positive bacterium bacillus anthracis to survive in activated macrophages is key to its germination and survival. in a previous publication, we discovered that exposure of primary murine macrophages to b. anthracis endospores upregulated nos 2 concomitant with an .no-dependent bactericidal response. since nos 2 also generates o(2).(-), experiments were designed to determine whether nos 2 formed peroxynitrite (onoo(-)) from the reaction of .no with o(2). ...	2007	17502390
cloning and molecular characterization of three arylamine n-acetyltransferase genes from bacillus anthracis: identification of unusual enzymatic properties and their contribution to sulfamethoxazole resistance.	the arylamine n-acetyltransferases (nats) are xenobiotic-metabolizing enzymes that catalyze the n-acetylation of arylamines and their n-hydroxylated metabolites. these enzymes play a key role in detoxication of numerous drugs and xenobiotics. we report here the cloning, functional expression, and characterization of three new nat genes (termed banata, banatb, and banatc) from the pathogen bacillus anthracis. the sequences of the corresponding proteins are approximately 30% identical with those o ...	2007	17511472
identification of high-stringency dna hairpin probes by partial gene folding.	hairpin dna sequences are widely used as probes for oligonucleotides in a broad range of assays, often as "molecular beacons". a potential disadvantage of the standard methodology for molecular beacon design is the need to add several self-complementary bases to each end of the probe, since these do not correspond to the target sequence. we describe a conceptually new method of hairpin dna probe identification, in which a secondary structure prediction algorithm is employed to identify oligonucl ...	2007	17512187
an automated front-end monitor for anthrax surveillance systems based on the rapid detection of airborne endospores.	a fully automated anthrax smoke detector (asd) has been developed and tested. the asd is intended to serve as a cost effective front-end monitor for anthrax surveillance systems. the principle of operation is based on measuring airborne endospore concentrations, where a sharp concentration increase signals an anthrax attack. the asd features an air sampler, a thermal lysis unit, a syringe pump, a time-gated spectrometer, and endospore detection chemistry comprised of dipicolinic acid (dpa)-trigg ...	2007	17514759
high-affinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (lf) of bacillus anthracis by inhibiting protective antigen-lf complex formation.	the anthrax lethal toxin (lt) consists of two subunits, the protective antigen (pa) and the lethal factor (lf), and is essential for anthrax pathogenesis. several recombinant antibodies directed against pa and intended for medical use have been obtained, but none against lf, despite the recommendations of anthrax experts. here we describe an anti-lf single-chain variable fragment (scfv) that originated from an immunized macaque (macaca fascicularis) and was obtained by phage display. panning of ...	2007	17517846
the large clostridial toxins from clostridium sordellii and c. difficile repress glucocorticoid receptor activity.	we have previously shown that bacillus anthracis lethal toxin represses glucocorticoid receptor (gr) transactivation. we now report that repression of gr activity also occurs with the large clostridial toxins produced by clostridium sordellii and c. difficile. this was demonstrated using a transient transfection assay system for gr transactivation. we also report that c. sordellii lethal toxin inhibited gr function in an ex vivo assay, where toxin reduced the dexamethasone suppression of the pro ...	2007	17517870
human lung innate immune response to bacillus anthracis spore infection.	bacillus anthracis, the causative agent of inhalational anthrax, enters a host through the pulmonary system before dissemination. we have previously shown that human alveolar macrophages participate in the initial innate immune response to b. anthracis spores through cell signal-mediated cytokine release. we proposed that the lung epithelia also participate in the innate immune response to this pathogen, and we have developed a human lung slice model to study this process. exposure of our model ...	2007	17517878
methyl bromide as a building disinfectant: interaction with indoor materials and resulting byproduct formation.	several buildings were contaminated with bacillus anthracis in the fall of 2001. these events required consideration of how to disinfect large indoor spaces for continued worker occupation. the interactions of gaseous disinfectants with indoor materials may inhibit the disinfection process, cause persistence of the disinfectant, and lead to possible byproduct formation and persistence. methyl bromide (ch3br) is a candidate for disinfection/deactivation of biological agents in buildings. in this ...	2007	17518223
density-equalizing euclidean minimum spanning trees for the detection of all disease cluster shapes.	existing disease cluster detection methods cannot detect clusters of all shapes and sizes or identify highly irregular sets that overestimate the true extent of the cluster. we introduce a graph-theoretical method for detecting arbitrarily shaped clusters based on the euclidean minimum spanning tree of cartogram-transformed case locations, which overcomes these shortcomings. the method is illustrated by using several clusters, including historical data sets from west nile virus and inhalational ...	2007	17519338
global genetic population structure of bacillus anthracis.	anthrax, caused by the bacterium bacillus anthracis, is a disease of historical and current importance that is found throughout the world. the basis of its historical transmission is anecdotal and its true global population structure has remained largely cryptic. seven diverse b. anthracis strains were whole-genome sequenced to identify rare single nucleotide polymorphisms (snps), followed by phylogenetic reconstruction of these characters onto an evolutionary model. this analysis identified snp ...	2007	17520020
anthrax toxins induce shock in rats by depressed cardiac ventricular function.	anthrax infections are frequently associated with severe and often irreversible hypotensive shock. the isolated toxic proteins of bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. these observations suggest the anthrax toxins have direct cardiovascular effects. here, we characterize these effects. as a first step, we administered systemically anthrax lethal toxin (letx) and edema toxin (edtx) to cohorts of three to twelve rats at different doses and de ...	2007	17520025
factors involved in the germination and inactivation of bacillus anthracis spores in murine primary macrophages.	since macrophages have been implicated in inhalation anthrax either for defense and/or as enablers for spore trafficking, their function has been further defined. spores were efficiently taken up by primary mouse bone marrow-derived macrophages even in the absence of serum but a minimal amount was required for spore germination and subsequent inactivation. with 10% fetal bovine serum (fbs) virtually all of the spores germinated but when the concentration of fbs was lowered to 1.0% or less, or wh ...	2007	17521404
optimizing the treatment of a new horseman of the apocalypse.		2007	17522542
[properties of live antibiotics-resistant anthrax vaccine sti-pr after long-term storage].	study showed that cultural, morphologic, genetic, immunologic characteristics, and resistance to antibiotics of sti-pr anthrax vaccine did not change after storage during 20 years in lyophilized condition. it has been shown that medium for lyophilization plays important role in preservation of vitality of anthrax spores. optimal preservative properties have been observed for thioureal and sucrose-gelatinous media for lyophilization. obtained results give reasons for prolongation of shelf live of ...	2007	17523426
optimization of high-resolution melting analysis for low-cost and rapid screening of allelic variants of bacillus anthracis by multiple-locus variable-number tandem repeat analysis.	molecular genotyping of bacillus anthracis, the etiologic agent of anthrax, is important for differentiating and identifying strains from different geographic areas and for tracing strains deliberately released in a bioterrorism attack. we previously described a multiple-locus variable-number tandem repeat (vntr) analysis (mlva) based on 25 marker loci. although the method has great differentiating power and reproducibility, faster genotyping at low cost may be requested to accurately identify b ...	2007	17525105
phenotypic and functional characterization of bacillus anthracis biofilms.	biofilms, communities of micro-organisms attached to a surface, are responsible for many chronic diseases and are often associated with environmental reservoirs or lifestyles. bacillus anthracis is a gram-positive, endospore-forming bacterium and is the aetiological agent of pulmonary, gastrointestinal and cutaneous anthrax. anthrax infections are part of the natural lifecycle of many ruminants in north america, including cattle and bison, and b. anthracis is thought to be a central part of this ...	2007	17526827
unfolding transitions of bacillus anthracis protective antigen.	protective antigen (pa) is an 83kda protein which, although essential for toxicity of bacillus anthracis, is harmless and an effective vaccine component. in vivo it undergoes receptor binding, proteolysis, heptamerisation and membrane insertion. here we probe the response of pa to denaturants, temperature and ph. we present analyses (including barycentric mean) of the unfolding and refolding behavior of pa and reveal the origin of two critical steps in the denaturant unfolding pathway in which t ...	2007	17531947
de novo asymmetric synthesis of the anthrax tetrasaccharide by a palladium-catalyzed glycosylation reaction.		2007	17534991
differentiation and characterization by molecular techniques of bacillus cereus group isolates from poto poto and dégué, two traditional cereal-based fermented foods of burkina faso and republic of congo.	poto poto (a maize sourdough) and dégué (a pearl millet-based food) are two traditional african fermented foods. the molecular biology of toxigenic and pathogenic bacteria found in those foods is largely unknown. the purpose of this study was to study the phylogenetic relatedness and toxigenic potential of 26 bacillus cereus group isolates from these traditional fermented foods. the relatedness of the isolates was evaluated with repetitive element sequence-based pcr (rep-pcr) and 16s rdna sequen ...	2007	17536675
the two-component system bacillus respiratory response a and b (brra-brrb) is a virulence factor regulator in bacillus anthracis.	bacillus anthracis, a bioterrorism threat as well as an agricultural concern, has complex mechanisms for regulation of its major virulence factors. genome searches identified the putative two-component system that we designated bacillus anthracis respiratory response (brr)a-brrb. a brra deletion strain was constructed, and real-time reverse transcriptase polymerase chain reaction and western blot analysis were used to assess the effect of brra-brrb on levels of virulence factors, the regulator a ...	2007	17536838
genetic basis for sulfonamide resistance in bacillus anthracis.	natural resistance of field strains of bacillus anthracis to drugs from the sulfonamide class of antimicrobials that act by inhibiting dihydropteroate synthase (dhps) has been reported. though the structure of b. anthracis dhps has been determined, its connection to the apparent intrinsic sulfonamide resistance of the bacterium has not been established. the aim of this study was to determine if a connection exists between dhps and the observed sulfonamide resistance of b. anthracis. microdilutio ...	2007	17536929
targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens.	pathogens or their toxins, including influenza virus, pseudomonas, and anthrax toxins, require processing by host proprotein convertases (pcs) to enter host cells and to cause disease. conversely, inhibiting pcs is likely to protect host cells from multiple furin-dependent, but otherwise unrelated, pathogens. to determine if this concept is correct, we designed specific nanomolar inhibitors of pcs modeled from the extended cleavage motif tpqrerrrkkr downward arrowgl of the avian influenza h5n1 h ...	2007	17537721
identification and analysis of novel amino-acid sequence repeats in bacillus anthracis str. ames proteome using computational tools.	we have identified four repeats and ten domains that are novel in proteins encoded by the bacillus anthracis str. ames proteome using automated in silico methods. a "repeat" corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. a "domain" corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. these correspond ...	2007	17538688
potential bio-terror agents.		2007	17540235
primary involvement of pharynx and peyer's patch in inhalational and intestinal anthrax.	bacillus anthracis causes three forms of anthrax: inhalational, gastrointestinal, and cutaneous. anthrax is characterized by both toxemia, which is caused by secretion of immunomodulating toxins (lethal toxin and edema toxin), and septicemia, which is associated with bacterial encapsulation. here we report that, contrary to the current view of b. anthracis pathogenesis, b. anthracis spores germinate and establish infections at the initial site of inoculation in both inhalational and cutaneous in ...	2007	17542645
a rare cause of preseptal cellulitis: anthrax.	infection of the eyelids confined to the preseptal space is relatively common but potentially serious. we report a child with cutaneous anthrax to remind that the interesting contagious cause be included in the differential diagnosis of the preseptal cellulitis.	2007	17542898
assembly of the small outer capsid protein, soc, on bacteriophage t4: a novel system for high density display of multiple large anthrax toxins and foreign proteins on phage capsid.	bacteriophage t4 capsid is a prolate icosahedron composed of the major capsid protein gp23, the vertex protein gp24, and the portal protein gp20. assembled on its surface are 810 molecules of the non-essential small outer capsid protein, soc (10 kda), and 155 molecules of the highly antigenic outer capsid protein, hoc (39 kda). in this study soc, a "triplex" protein that stabilizes t4 capsid, is targeted for molecular engineering of t4 particle surface. using a defined in vitro assembly system ...	2007	17544446
the contribution of gc1qr/p33 in infection and inflammation.	human gc1qr/p33 is a multi-compartmental and multi-functional cellular protein expressed on a wide range of tissues and cell types including lymphocytes, endothelial cells, dendritic cells, and platelets. although originally isolated as a receptor for c1q by virtue of its affinity (k(d)=15-50 nm), and specificity for the globular heads of this molecule, a large body of evidence has now been accumulated which shows that in addition to c1q, gc1qr can serve as a receptor for diverse proinflammatory ...	2007	17544818
activation of inhibitors by sortase triggers irreversible modification of the active site.	sortases anchor surface proteins to the cell wall of gram-positive pathogens through recognition of specific motif sequences. loss of sortase leads to large reductions in virulence, which identifies sortase as a target for the development of antibacterials. by screening 135,625 small molecules for inhibition, we report here that aryl (beta-amino)ethyl ketones inhibit sortase enzymes from staphylococci and bacilli. inhibition of sortases occurs through an irreversible, covalent modification of th ...	2007	17545669
lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route.	inhalational anthrax is a life-threatening infectious disease of considerable concern, especially because anthrax is an emerging bioterrorism agent. the exact mechanisms leading to a severe clinical form through the inhalational route are still unclear, particularly how immobile spores are captured in the alveoli and transported to the lymph nodes in the early steps of infection. we investigated the roles of alveolar macrophages and lung dendritic cells (ldc) in spore migration. we demonstrate t ...	2007	17548636
murine monoclonal antibodies against murine upa receptor produced in gene-deficient mice: inhibitory effects on receptor-mediated upa activity in vitro and in vivo.	binding of urokinase plasminogen activator (upa) to its cellular receptor, upar, potentiates plasminogen activation and localizes it to the cell surface. focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. the interaction between upa and upar therefore represents a potential target for anti-invasive cancer therapy. inhibitors of the human upa-upar interaction have no effect in the murine system. to enable in-vivo studies ...	2007	17549305
developing disaster management modules: a collaborative approach.	disasters, whether natural or human induced, can strike when least expected. the events of 9/11 in the us, the 7/7 bombings in the uk, and the anthrax incident in the us on 10th october 2001 indicate that there is a need to have a nursing workforce who is able to respond effectively to mass casualty events and incidents involving chemical, biological, radiological and nuclear substances. multi-agency collaboration is one of the fundamental principles of disaster preparedness and response. it was ...	2007	17551443
molecular analysis of the interaction of bordetella pertussis adenylyl cyclase with fluorescent nucleotides.	the calmodulin (cam)-dependent adenylyl cyclase (ac) toxin from bordetella pertussis (cyaa) substantially contributes to the pathogenesis of whooping cough. thus, potent and selective cyaa inhibitors may be valuable drugs for prophylaxis of this disease. we examined the interactions of fluorescent 2',3'-n-methylanthraniloyl (mant)-, anthraniloyl- and trinitrophenyl (tnp)-substituted nucleotides with cyaa. compared with mammalian ac isoforms and bacillus anthracis ac toxin edema factor, nucleotid ...	2007	17553924
new insights into the pathogenesis and treatment of anthrax toxin-induced shock.	inhalational bacillus anthracis infection is a leading bioterrorist health threat in the us today. lethal (letx) and edema toxin production are key to the virulent effects of this lethal bacteria. recent insights into the structure and function of these toxins have increased the understanding of both the pathogenesis and treatment of anthrax. these are binary type toxins comprised of protective antigen necessary for their cellular uptake and either lethal or edema factors, the toxigenic moieties ...	2007	17555370
characterization of a small plcr-regulated gene co-expressed with cereolysin o.	in the human pathogen bacillus cereus, the expression of most extracellular virulence factors is controlled by the transcriptional activator plcr. among these virulence factors, cereolysin o (clo) is an haemolysin belonging to the cholesterol-dependant cytolysins, a protein family extensively studied in gram-positive bacteria.	2007	17555563
evaluation of immune response to orally administered sterne strain 34f2 anthrax vaccine.	present animal vaccines against bacillus anthracis infection are capable of inducing protective immunity. however, due to the route of administration, the vaccine has limited or no use in wildlife especially in rural areas of the world. hence, an oral vaccine is needed for controlling this disease. for proof of concept we used the commercially available sterne strain 34f2 vaccine mixed with oral scarifying agents. although the immunological response as measured by elisa in this group was not equ ...	2007	17555849
colorimetric detection of anthrax dna with a peptide nucleic acid sandwich-hybridization assay.		2007	17569540
inhibition of s. aureus alpha-hemolysin and b. anthracis lethal toxin by beta-cyclodextrin derivatives.	many pathogens utilize the formation of transmembrane pores in target cells in the process of infection. a great number of pore-forming proteins, both bacterial and viral, are considered to be important virulence factors, which makes them attractive targets for the discovery of new therapeutic agents. our research is based on the idea that compounds designed to block the pores can inhibit the action of virulence factors, and that the chances to find high affinity blocking agents increase if they ...	2007	17572091
inhibitors of anthrax lethal factor.	an inhibitor of anthrax lethal toxin mediated cell death (1) was identified by a medium throughput cell-based screen. this compound was determined to specifically inhibit anthrax lethal factor (lf), and subsequent sar studies produced an even more potent inhibitor (4). mechanistic studies identified these agents as uncompetitive inhibitors of lf with ki values of 3.0 and 1.7 microm, respectively, with good cell potency and low cytotoxicity.	2007	17574849
a bacillus anthracis-based in vitro system supports replication of plasmid pxo2 as well as rolling-circle-replicating plasmids.	capsule-encoding virulence plasmid pxo2 of bacillus anthracis is predicted to replicate by a unidirectional theta-type mechanism. to gain a better understanding of the mechanism of replication of pxo2 and other plasmids in b. anthracis and related organisms, we have developed a cell-free system based on b. anthracis that can faithfully replicate plasmid dna in vitro. the newly developed system was shown to support the in vitro replication of plasmid pt181, which replicates by the rolling-circle ...	2007	17575005
flagellin (flic) protein sequence diversity among bacillus thuringiensis does not correlate with h serotype diversity.	in escherichia coli, the flic gene encodes flagellin, the protein responsible for eliciting the immunological reaction in h serotyping. here, the presence of the flagellin flic gene was studied in 86 bacillus thuringiensis strains encompassing 67 h serotypes. nineteen strains from four additional species in the b. cereus sensu lato group, b. cereus, b. anthracis, b. mycoides, and b. weihenstephanensis, were added for comparison purposes. the flic genes were amplified, cloned and their nucleotide ...	2007	17578675
enzymatic logic of anthrax stealth siderophore biosynthesis: asba catalyzes atp-dependent condensation of citric acid and spermidine.		2007	17579415
project bioshield: what it is, why it is needed, and its accomplishments so far.	project bioshield is a comprehensive effort involving the us department of health and human services (hhs), its component agencies, and other partner federal agencies to speed the research, development, acquisition, and availability of medical countermeasures to improve the government's preparedness for and ability to counter chemical, biological, radiological, and nuclear threat agents. the legislation authorizes use of the special reserve fund, which makes available $5.6 billion over 10 years ...	2007	17582574
development of a cell-based fluorescence resonance energy transfer reporter for bacillus anthracis lethal factor protease.	we report the construction of a cell-based fluorescent reporter for anthrax lethal factor (lf) protease activity using the principle of fluorescence resonance energy transfer (fret). this was accomplished by engineering an escherichia coli cell line to express a genetically encoded fret reporter and lf protease. both proteins were encoded in two different expression plasmids under the control of different tightly controlled inducible promoters. the fret-based reporter was designed to contain a l ...	2007	17586456
susceptibility of bacillus anthracis, bacillus cereus, bacillus mycoides, bacillus pseudomycoides and bacillus thuringiensis to 24 antimicrobials using sensititre automated microbroth dilution and etest agar gradient diffusion methods.	to examine susceptibilities of bacillus anthracis and related species to 24 antimicrobials using and concurrently comparing two methods.	2007	17586563
sortase c-mediated anchoring of basi to the cell wall envelope of bacillus anthracis.	vegetative forms of bacillus anthracis replicate in tissues of an infected host and precipitate lethal anthrax disease. upon host death, bacilli form dormant spores that contaminate the environment, thereby gaining entry into new hosts where spores germinate and once again replicate as vegetative forms. we show here that sortase c, an enzyme that is required for the formation of infectious spores, anchors basi polypeptide to the envelope of predivisional sporulating bacilli. basi anchoring to th ...	2007	17586639
autonomous microfluidic sample preparation system for protein profile-based detection of aerosolized bacterial cells and spores.	for domestic and military security, an autonomous system capable of continuously monitoring for airborne biothreat agents is necessary. at present, no system meets the requirements for size, speed, sensitivity, and selectivity to warn against and lead to the prevention of infection in field settings. we present a fully automated system for the detection of aerosolized bacterial biothreat agents such as bacillus subtilis (surrogate for bacillus anthracis) based on protein profiling by chip gel el ...	2007	17591754
detection of anti-protective antigen salivary igg antibodies in recipients of the us licensed anthrax vaccine.	the immune response of anthrax vaccine recipients is not routinely monitored. for field use, a noninvasive test would be beneficial to evaluate the antibody response of anthrax-vaccinated individuals working within a high-risk area of possible exposure. the aim of this cross-sectional study was to determine whether whole saliva can be used as a surrogate matrix for the detection of 83 kda protective antigen (pa)-specific immunoglobulin g (igg). an enzyme-linked immunosorbent assay was used for t ...	2007	17597265
activation of the nalp3 inflammasome is triggered by low intracellular potassium concentration.	inflammasomes are nod-like receptor(nlr)- and caspase-1-containing cytoplasmic multiprotein complexes, which upon their assembly, process and activate the proinflammatory cytokines interleukin (il)-1beta and il-18. the inflammasomes harboring the nlr members nalp1, nalp3 and ipaf have been best characterized. while the ipaf inflammasome is activated by bacterial flagellin, activation of the nalp3 inflammasome is triggered not only by several microbial components, but also by a plethora of danger ...	2007	17599094
nosocomial spread of bacillus anthracis.		2007	17602791
a model-based optimization framework for the inference of regulatory interactions using time-course dna microarray expression data.	proteins are the primary regulatory agents of transcription even though mrna expression data alone, from systems like dna microarrays, are widely used. in addition, the regulation process in genetic systems is inherently non-linear in nature, and most studies employ a time-course analysis of mrna expression. these considerations should be taken into account in the development of methods for the inference of regulatory interactions in genetic networks.	2007	17603872
immune response to two different dosing schedules of the anthrax vaccine precipitated (avp) vaccine.	a pilot study compared the immune response of regular (0, 3, 6, 32 weeks) and extended (0, 10, 13, 32 weeks) schedules of the uk anthrax vaccine (anthrax vaccine precipitated, avp). concentrations of antibodies to protective antigen (pa) were higher (p<0.05) among recipients of the extended (n=7) versus regular schedule (n=6) at week 32, and 2 weeks after the second and third vaccinations. toxin neutralisation assay levels and anti-lethal factor antibodies followed patterns similar to anti-pa an ...	2007	17604880
bacillus anthracis spores of the bcla mutant exhibit increased adherence to epithelial cells, fibroblasts, and endothelial cells but not to macrophages.	bacillus anthracis is the causative agent of anthrax, and the spore form of the bacterium represents the infectious particle introduced into a host. the spore is surrounded by an exosporium, a loose-fitting membrane composed of proteins and carbohydrates from which hair-like projections extend. these projections are composed mainly of bcla (bacillus-collagen-like protein of b. anthracis). to date, exact roles of the exosporium structure and bcla protein remain undetermined. we examined differenc ...	2007	17606596
evaluation of vacuum filter sock surface sample collection method for bacillus spores from porous and non-porous surfaces.	vacuum filter socks were evaluated for recovery efficiency of powdered bacillus atrophaeus spores from two non-porous surfaces, stainless steel and painted wallboard and two porous surfaces, carpet and bare concrete. two surface coupons were positioned side-by-side and seeded with aerosolized bacillus atrophaeus spores. one of the surfaces, a stainless steel reference coupon, was sized to fit into a sample vial for direct spore removal, while the other surface, a sample surface coupon, was sized ...	2007	17607386
novel semisynthetic derivative of antibiotic eremomycin active against drug-resistant gram-positive pathogens including bacillus anthracis.	five adamantyl-containing carboxamides of eremomycin or vancomycin were synthesized and their antibacterial activities against some gram-positive clinical isolates were investigated in vitro and in vivo. the adamantyl-2 amide of glycopeptide antibiotic eremomycin (1a in chart 1, an0900) was the most active compound and showed high activity against several gram-positive pathogens: vancomycin-susceptible staphylococci and enterococci, glycopeptide-intermediate-resistant staphylococcus aureus, and ...	2007	17608397
recent progress in biodefence countermeasure development.		2007	17608594
strengthening bioterrorism prevention: global biological materials management.	the anthrax attacks of 2001 demonstrated that bioterrorism poses a significant threat to u.s. national security. this threat is increasing as a result of the rapid expansion in scale and technical capabilities of the global biotechnology industry, which is broadening the availability of materials, technologies, and expertise needed to produce a biological weapon and is lowering the barriers to biological weapons terrorism and proliferation. at the same time, there has been a rise of sophisticate ...	2007	17608597
structural and functional analysis of two glutamate racemase isozymes from bacillus anthracis and implications for inhibitor design.	glutamate racemase (race) is responsible for converting l-glutamate to d-glutamate, which is an essential component of peptidoglycan biosynthesis, and the primary constituent of the poly-gamma-d-glutamate capsule of the pathogen bacillus anthracis. race enzymes are essential for bacterial growth and lack a human homolog, making them attractive targets for the design and development of antibacterial therapeutics. we have cloned, expressed and purified the two glutamate racemase isozymes, race1 an ...	2007	17610893
development of a competitive enzyme linked immunosorbent assay to identify epitope specific antibodies in recipients of the u.s. licensed anthrax vaccine.	vaccination with anthrax vaccine adsorbed (ava) results in the production of protective antigen (pa) specific antibodies, which play an important protective role against anthrax toxins. analyzing the specificity of serum antibodies generated in response to ava vaccination can provide insight into the mechanisms of protective immunity against this important pathogen. the goal of this study was to develop a competitive enzyme linked immunosorbent assay (celisa) to test human immune serum for antib ...	2007	17613668
comparative sporicidal effects of disinfectants after release of a biological agent.	because of spore formation, bacillus anthracis is considered the most resistant biological warfare agent known. the present study aimed to assess and compare well-known decontamination routes to inactivate the spores on daily-use environmental tools contaminated previously. to simulate the agent, bacillus atrophaeus was used. various environmental samples (such as tile, fabric clothing, wood, protective suit, glass, paper, soil, water, plastic, and metal) that may be contaminated after a biologi ...	2007	17615843
lethal factor of anthrax toxin binds monomeric form of protective antigen.	anthrax toxin consists of three components: the enzymatic moieties edema factor (ef) and the lethal factor (lf) and the receptor-binding moiety protective antigen (pa). these toxin components are released from bacillus anthracis as unassociated proteins and form complexes on the surface of host cells after proteolytic processing of pa into pa20 and pa63. the sequential order of pa heptamerization and ligand binding, as well as the exact mechanism of anthrax toxin entry into cells, are still uncl ...	2007	17617379
mitochondrial proteins bnip3 and bnip3l are involved in anthrax lethal toxin-induced macrophage cell death.	anthrax lethal toxin (letx) induces rapid cell death of raw246.7 macrophages. we recently found that a small population of these macrophages is spontaneously and temporally refractory to letx-induced cytotoxicity. analysis of genome-wide transcripts of a resistant clone before and after regaining letx sensitivity revealed that a reduction of two closely related mitochondrial proteins, bcl-2/adenovirus e1b 19-kda interacting protein 3 (bnip3) and bnip3-like (bnip3l), correlates with letx resistan ...	2007	17623653
cryo-electron microscopy study of bacteriophage t4 displaying anthrax toxin proteins.	the bacteriophage t4 capsid contains two accessory surface proteins, the small outer capsid protein (soc, 870 copies) and the highly antigenic outer capsid protein (hoc, 155 copies). as these are dispensable for capsid formation, they can be used for displaying proteins and macromolecular complexes on the t4 capsid surface. anthrax toxin components were attached to the t4 capsid as a fusion protein of the n-terminal domain of the anthrax lethal factor (lfn) with soc. the lfn-soc fusion protein w ...	2007	17624389
supercritical carbon dioxide and hydrogen peroxide cause mild changes in spore structures associated with high killing rate of bacillus anthracis.	the present work examines chemical and structural response in b. anthracis spores killed by a mixture of supercritical carbon dioxide (scco(2)) and hydrogen peroxide (h(2)o(2)). deactivation of 6-log of b. anthracis spores by scco(2)+h(2)o(2) was demonstrated, but changes in structure were observed in only a small portion of spores. results from phase contrast microscopy proved that this treatment is mild and does not trigger germination-like changes. tem imaging revealed mild damage in a portio ...	2007	17628729
a brief history of vaccines and vaccination.	human vaccinology, with its primary focus on the individual, seems far removed from veterinary medicine, with its concern for the health of the herd. yet several episodes in the past (smallpox, fowl cholera, anthrax, swine erysipelas, rabies, tuberculosis, etc.) serve to illustrate the proximity between research on veterinary and human vaccines. in some cases the human vaccine was developed first, while in other cases it was the animal vaccine. the history of vaccinology clearly demonstrates the ...	2007	17633292
in vitro screen of bioinformatically selected bacillus anthracis vaccine candidates by coupled transcription, translation, and immunoprecipitation analysis.	the availability of the bacillus anthracis genome sequence allowed for in silico selection of a few hundred open reading frames (orfs) as putative vaccine candidates. to screen such a vast number of candidate orfs, without resorting to laborious cloning and protein purification procedures, methods were developed for generation of pcr elements, compatible with in vitro transcription-translation and immunoprecipitation, as well as with their evaluation as dna vaccines. protocols will be provided f ...	2007	17634604
pharmacokinetics-pharmacodynamics of gatifloxacin in a lethal murine bacillus anthracis inhalation infection model.	we determined the pharmacokinetic-pharmacodynamic (pk-pd) measure most predictive of gatifloxacin efficacy and the magnitude of this measure necessary for survival in a murine bacillus anthracis inhalation infection model. we then used population pharmacokinetic models for gatifloxacin and simulation to identify dosing regimens with high probabilities of attaining exposures likely to be efficacious in adults and children. in this work, 6- to 8-week-old nonneutropenic female balb/c mice received ...	2007	17875992
in vitro efficacy of new antifolates against trimethoprim-resistant bacillus anthracis.	bacillus anthracis is innately resistant to trimethoprim (tmp), a synthetic antifolate that selectively inhibits several bacterial dihydrofolate reductases (dhfrs) but not human dhfr. previously, we were able to confirm that tmp resistance in b. anthracis (mic > 2,048 microg/ml) is due to the lack of selectivity of tmp for the b. anthracis dhfr (e. w. barrow, p. c. bourne, and w. w. barrow, antimicrob. agents chemother. 48:4643-4649, 2004). in this investigation, 24 2,4-diaminopyrimidine derivat ...	2007	17875993
proteasomes control caspase-1 activation in anthrax lethal toxin-mediated cell killing.	activation of caspase-1 through the inflammasome protein nalp1b controls anthrax lethal toxin (lt)-induced necrosis in murine macrophages. in this study we analyzed physiological changes controlled by caspase-1 in lt-treated murine macrophages. the caspase-1 inhibitor boc-d-cmk blocked caspase-1 activity and membrane impairment in lt-treated cells. to determine the relationship between caspase-1 activation and membrane integrity, we added boc-d-cmk to j774a.1 macrophages at different time points ...	2007	17878154
differential analysis of bacillus anthracis after px01 plasmid curing and comprehensive data on bacillus anthracis infection in macrophages and glial cells.	bacillus anthracis is a gram-positive bacterial organism responsible for anthrax. this organism has two pathogenic plasmids: px01 and px02. the genetic function of px01, which comprises about 198 kb, is not known, except for a region called the pathogenic island, which contains three genes-pag, lef, and cya-that code for three toxic proteins. a 2-d difference gel electrophoresis (2-d dige) system was used to verify the existence of proteins controlled by the px01 plasmid, and protein regulation ...	2007	17880004
protein dynamics and monomer-monomer interactions in antr activation by electron paramagnetic resonance and double electron-electron resonance.	the anthracis repressor (antr) is a mn(ii)-activated dna binding protein that is involved in the regulation of mn(ii) homeostasis in bacillus anthracis. antr is structurally and functionally homologous to mn(ii)-activated repressor from bacillus subtillis (mntr). our studies on antr focus on metal-regulated activation of the protein. line shape analysis of continuous wave electron paramagnetic resonance (epr) spectra showed that metal binding resulted in a general reduction of backbone dynamics ...	2007	17880108
safety, reactogenicity and immunogenicity of a recombinant protective antigen anthrax vaccine given to healthy adults.	bacillus anthracis causes anthrax, a vaccine-preventable zoonotic disease that may follow intentional or unintentional exposure to its spores. although an anthrax vaccine is currently licensed in the usa, better vaccines are desirable for both pre- and post-exposure prophylaxis.	2007	17881903
[immunogenicity of the recombinant bacillus strains with cloned gene of biosynthesis of protective antigen against bacillus anthracis].	microbe russian anti-plague research institute, saratov a hybrid plasmid pub110pa-1 demonstrating stable functioning in the cells of bacillus strains and containing the gene of biosynthesis of bacillus anthracis protective antigen was constructed. the recombinant strains surpassing the anthrax vaccinal cultures in the secreted synthesis of the protective antigen were obtained and their immunological efficacy was assessed. a single inoculation of guinea pigs with the dose of 5 x 107 spores of the ...	2007	17886469
identification of the amino acid residues critical for specific binding of the bacteriolytic enzyme of gamma-phage, plyg, to bacillus anthracis.	bacillus anthracis causes anthrax, a lethal disease affecting humans, which has attracted attention due to its bioterrorism potential. gamma-phage specifically infects b. anthracis, and is used for its detection. gamma-phage lysin, plyg, specifically lyses b. anthracis. mutational analysis of plygb (plyg binding domain; residues 156-233) indicated that positions 190-199 are necessary for binding to b. anthracis. this region is the central part of plygb and is predicted to form a beta-sheet. the ...	2007	17888883
the opinion of the production sector on the role of vaccines in the control and eradication of livestock diseases in argentina.	research by a number of international organisations indicates that world demand for red meat protein is set to increase significantly in the coming years. however, faced with the risk of infectious animal diseases and zoonoses--factors that could limit the growth of this production sector--the fight against livestock diseases must continue, especially against those that affect food safety or pose a threat to human life. the use of vaccination to prevent infectious animal diseases is of key impor ...	2007	17892168
hydrogen/deuterium exchange mass spectrometry: potential for investigating innate immunity proteins.		2007	17892227
establishing a high level of knowledge regarding bioterrorist threats in emergency department physicians: methodology and the results of a national bio-preparedness project.	medical systems worldwide are facing the new threat of morbidity associated with the deliberate dispersal of microbiological agents by terrorists. rapid diagnosis and containment of this type of unannounced attack is based on the knowledge and capabilities of medical staff. in 2004, the knowledge of emergency department physicians of anthrax was tested. the average test score was 58%. consequently, a national project on bioterrorism preparedness was developed. the aim of this article is to prese ...	2007	17894214
formaldehyde gas inactivation of bacillus anthracis, bacillus subtilis, and geobacillus stearothermophilus spores on indoor surface materials.	to evaluate the decontamination of bacillus anthracis, bacillus subtilis, and geobacillus stearothermophilus spores on indoor surface materials using formaldehyde gas.	2007	17897215
assembly of pili on the surface of bacillus cereus vegetative cells.	vegetative forms of bacillus cereus are reported to form pili, thin protein filaments that protrude up to 1 mum from the bacterial surface. pili are assembled from two precursor proteins, bcpa and bcpb, in a manner requiring a pilus-associated sortase enzyme (srtd). pili are also formed on the surface of bacillus anthracis expressing bcpa-srtd-bcpb. bcpa is distributed throughout the entire pilus, whereas bcpb appears positioned at its tip. in agreement with the hypothesis for pilus assembly in ...	2007	17897374
anthrax vaccine and public health policy.	the centers for disease control and prevention has classified bacillus anthracis, the causative organism of anthrax, as a category a potential bioterrorism agent. there are critical shortcomings in the us anthrax vaccine program. rather than depending on the private sector, the government must assume direct production of anthrax vaccine. the development of a capacity capable of preemptive immunization of the public against anthrax should be considered.	2007	17901434
field testing a head-of-household method to dispense antibiotics.	using a simulated anthrax exposure scenario, the philadelphia department of public health tested how rapidly and accurately a head-of-household (hoh) point of dispensing (pod) site with an express dispensing line could provide medication to heads of households collecting antibiotics for all household members.	2007	17903094
anthrax lethal toxin inhibits growth of and vascular endothelial growth factor release from endothelial cells expressing the human herpes virus 8 viral g protein coupled receptor.	in this study, we tested the hypothesis that inhibition of mitogen-activated protein kinase kinases (mkk) inhibits tumor growth by acting on angiogenic signaling and by extension may form the basis of an effective strategy for treatment of kaposi's sarcoma.	2007	17908989
crystallization and preliminary x-ray characterization of arylamine n-acetyltransferase c (banatc) from bacillus anthracis.	the arylamine n-acetyltransferase (nat) enzymes are xenobiotic metabolizing enzymes that have been found in a large range of eukaryotes and prokaryotes. these enzymes catalyse the acetylation of arylamine drugs and/or pollutants. recently, a bacillus anthracis nat isoform (banatc) has been cloned and shown to acetylate the sulfonamide antimicrobial sulfamethoxazole (smx). subsequently, it was shown that banatc contributes to the resistance of this bacterium to smx. here, the crystallization and ...	2007	17909290
anthrax vaccination in a military population before the war in iraq: side effects and informed choice.	to assess any health consequences of the anthrax vaccination programme in uk armed forces deployed to iraq.	2007	17913313
systemic but not mucosal immunity induced by ava prevents inhalational anthrax.	improved vaccines and adjuvants are being developed to reduce the threat posed by a terrorist attack involving aerosolized anthrax spores. nevertheless, uncertainty persists concerning the relative benefits of inducing mucosal vs systemic immunity to host survival following inhalational exposure to anthrax spores. this work examines the effect of delivering the licensed human vaccine (anthrax vaccine adsorbed, ava) combined with a cpg oligodeoxynucleotide (odn) adjuvant intraperitoneally or intr ...	2007	17913545
potential use of inhibitors of bacteria spore germination in the prophylactic treatment of anthrax and clostridium difficile-associated disease.	spore germination is the first step in establishing bacillus and clostridium infections. germination is triggered by the binding of small molecules by the resting spore. subsequently, the activated spore secretes dipicolinic acid and calcium, the spore core is rehydrated and spore structures are degraded. inhibition of any of the germination-related events will prevent development to the vegetative stage. inhibition of spore germination has been studied intensively in the prevention of food spoi ...	2007	17914913
quantitative inhibitor fingerprinting of metalloproteases using small molecule microarrays.	current methods to identify interactions on small molecule microarrays (smms) introduce false positives that are difficult to dissect from the "real" binding events without tedious downstream re-evaluation. to specifically elucidate only activity-dependent ligand binding interactions, we have developed a technique that can be universally applied to present smm systems. our method makes use of a dual-color application strategy and is based on the simultaneous application of differentially treated ...	2007	17915867
modeling and detection of respiratory-related outbreak signatures.	time series methods are commonly used to detect disease outbreak signatures (e.g., signals due to influenza outbreaks and anthrax attacks) from varying respiratory-related diagnostic or syndromic data sources. typically this involves two components: (i) using time series methods to model the baseline background distribution (the time series process that is assumed to contain no outbreak signatures), (ii) detecting outbreak signatures using filter-based time series methods.	2007	17919318
a viral nanoparticle with dual function as an anthrax antitoxin and vaccine.	the recent use of bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. b. anthracis produces an ab-type toxin composed of the receptor-binding moiety protective antigen (pa) and the enzymatic moieties edema factor and lethal factor. pa is a key target for both antitoxin and vaccine development. we used the icosahedral insect virus flock house virus as a platform to display 180 copies of the high affinity, ...	2007	17922572
effects of endogenous d-alanine synthesis and autoinhibition of bacillus anthracis germination on in vitro and in vivo infections.	bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. the timing of germination is important during early steps in infection and may determine if b. anthracis survives or succumbs to responsive macrophages. in the current study experiments determined the contribution of endogenous d-alanine production to the efficiency and timing of b. anthracis spore germination under in vitro ...	2007	17923523
antitumor activities of tem8-fc: an engineered antibody-like molecule targeting tumor endothelial marker 8.	tumor endothelial marker 8 (tem8) was discovered as a cell membrane protein that is predominantly expressed in tumor endothelium and identified as a receptor for anthrax toxin. we developed an antibody-like molecule that consists of the protective antigen (pa)-binding domain of human tem8 linked to the fc portion of human immunoglobulin g1 (tem8-fc). this engineered protein bound to pa in a divalent cation-dependent manner and efficiently protected j774a.1 macrophage-like cells against anthrax t ...	2007	17925540
detection and quantification of anthrax lethal factor in serum by mass spectrometry.	the lethal toxin produced during bacillus anthracis infection is a complex of protective antigen, which localizes the toxin to the cell receptor, and lethal factor (lf), a zinc-dependent endoproteinase whose known targets include five members of the mitogen-activated protein kinase kinase (mapkk) family of response regulators. we have developed a method for detecting functional lf in serum. anti-lf murine monoclonal antibodies immobilized on magnetic protein g beads were used to capture and conc ...	2007	17929949
new transposon delivery plasmids for insertional mutagenesis in bacillus anthracis.	two new transposon delivery vector systems utilizing mariner and mini-tn10 transposons have been developed for in vivo insertional mutagenesis in bacillus anthracis and other compatible gram-positive species. the utility of both systems was directly demonstrated through the mutagenesis of a widely used b. anthracis strain.	2007	17931726
tentacle probes: differentiation of difficult single-nucleotide polymorphisms and deletions by presence or absence of a signal in real-time pcr.	false-positive results are a common problem in real-time pcr identification of dna sequences that differ from near neighbors by a single-nucleotide polymorphism (snp) or deletion. because of a lack of sufficient probe specificity, post-pcr analysis, such as a melting curve, is often required for mutation differentiation.	2007	17932130
interprosurf: a web server for predicting interacting sites on protein surfaces.	a new web server, interprosurf, predicts interacting amino acid residues in proteins that are most likely to interact with other proteins, given the 3d structures of subunits of a protein complex. the prediction method is based on solvent accessible surface area of residues in the isolated subunits, a propensity scale for interface residues and a clustering algorithm to identify surface regions with residues of high interface propensities. here we illustrate the application of interprosurf to de ...	2007	17933856
strain-specific single-nucleotide polymorphism assays for the bacillus anthracis ames strain.	highly precise diagnostics and forensic assays can be developed through a combination of evolutionary analysis and the exhaustive examination of genomic sequences. in bacillus anthracis, whole-genome sequencing efforts revealed ca. 3,500 single-nucleotide polymorphisms (snps) among eight different strains and evolutionary analysis provides the identification of canonical snps. we have previously shown that snps are highly evolutionarily stable, and the clonal nature of b. anthracis makes them id ...	2007	17093023