Publications

the impact of incomplete vaccination schedules on the magnitude and duration of protective antigen-specific igg responses in recipients of the us licensed anthrax vaccine.	using a cross-sectional analysis design, we measured serum anti-protective antigen (pa) concentrations in individuals receiving six or fewer us licensed anthrax vaccinations. samples were collected from 363 individuals with a mean of 29.6+/-8.42 months after their last vaccination (range 3-57 months). an enzyme-linked immunosorbent assay (elisa) developed and validated by the centers for disease control and prevention (cdc) was used to evaluate the range and status of anthrax vaccine-induced ser ...	2007	17150286
discontinued drugs in 2005: anti-infectives.	this perspective is the fifth in a series discussing drugs dropped from development in 2005, of which 11 were being developed for infectious diseases. of these, eight were antivirals and were dropped in phase ii or iii: medivir's alovudine, ono pharmaceuticals' aplaviroc hydrochloride and excite's immunotherapeutic xcellerate for hiv; boehringer ingelheim's ciluprevir, viropharma's hcv-086, isis pharmaceuticals' antisense oligonucleotide isis-14803, japan tobacco's jtk-003 and rigel's r803 for h ...	2007	17155849
raman chemical imaging spectroscopy reagentless detection and identification of pathogens: signature development and evaluation.	an optical detection method, raman chemical imaging spectroscopy (rcis), is reported, which combines raman spectroscopy, fluorescence spectroscopy, and digital imaging. using this method, trace levels of biothreat organisms are detected in the presence of complex environmental backgrounds without the use of amplification or enhancement techniques. rcis is reliant upon the use of raman signatures and automated recognition algorithms to perform species-level identification. the rationale and steps ...	2007	17338507
anthrax edema toxin sensitizes dba/2j mice to lethal toxin.	anthrax toxin is made up of three separate protein components: the receptor-binding protective antigen (pa), the adenylyl cyclase edema factor (ef), and the metalloproteinase lethal factor (lf). ef and pa constitute edema toxin (et), which causes edema when injected subcutaneously. at higher doses, et causes severe pathologies and death in balb/cj mice (a. m. firoved et al., am. j. pathol. 167:1309-1320, 2005). a striking effect of et at lethal doses is adrenal necrosis. here we show that low do ...	2007	17339348
role of bacillus anthracis spore structures in macrophage cytokine responses.	the innate immune response of macrophages (mphi) to spores, the environmentally acquired form of bacillus anthracis, is poorly characterized. we therefore examined the early mphi cytokine response to b. anthracis spores, before germination. mphi were exposed to bacilli and spores of sterne strain 34f2 and its congenic nongerminating mutant (deltagerh), and cytokine expression was measured by real-time pcr and an enzyme-linked immunosorbent assay. the exosporium spore layer was retained (exo+) or ...	2007	17339355
evaluation of the mets and murb loci for antibiotic discovery using targeted antisense rna expression analysis in bacillus anthracis.	the biowarfare-relevant bacterial pathogen bacillus anthracis contains two paralogs each of the mets and murb genes, which encode the important antibiotic target functions methionyl-trna synthetase and udp-n-acetylenolpyruvoylglucosamine reductase, respectively. empirical screens were conducted to detect and characterize gene fragments of each of these four genes that could cause growth reduction of b. anthracis when inducibly expressed from a plasmid-borne promoter. numerous such gene fragments ...	2007	17339372
a case of naturally acquired inhalation anthrax: clinical care and analyses of anti-protective antigen immunoglobulin g and lethal factor.	this report describes the first case of naturally acquired inhalation anthrax in the united states since 1976. the patient's clinical course included adjunctive treatment with human anthrax immunoglobulin. clinical correlation of serologic assays for the lethal factor component of lethal toxin and anti-protective antigen immunoglobulin g are also presented.	2007	17342650
lrp5 and lrp6 are not required for protective antigen-mediated internalization or lethality of anthrax lethal toxin.	anthrax toxin (antx) plays a key role in the pathogenesis of anthrax. antx is composed of three proteins: protective antigen (pa), edema factor, and lethal factor (lf). pa is not toxic but serves to bind cells and translocate the toxic edema factor or lf moieties to the cytosol. recently, the low-density lipoprotein receptor-related protein lrp6 has been reported to mediate internalization and lethality of antx. based on its similarity to lrp6, we hypothesized that lrp5 may also play a role in c ...	2007	17335347
anthrax toxin: receptor binding, internalization, pore formation, and translocation.	anthrax toxin consists of three nontoxic proteins that self-assemble at the surface of receptor-bearing mammalian cells or in solution, yielding a series of toxic complexes. two of the proteins, called lethal factor (lf) and edema factor (ef), are enzymes that act on cytosolic substrates. the third, termed protective antigen (pa), is a multifunctional protein that binds to receptors, orchestrates the assembly and internalization of the complexes, and delivers them to the endosome. there, the pa ...	2007	17335404
[biodefense: a new challenge for microbiology and public health].	bioterrorism and the potential use of biological weapons has become an important concern of governments and responsible authorities. an example of this threat occurred in 2001 in the usa, when letters were sent containing spores of the agent that produces anthrax; this resulted in some deaths, and caused panic and negative effects on the world economy. if this small-scale event was able to cause such a huge impact, the repercussions of a massive attack could be catastrophic. in many countries, t ...	2007	17335699
structure of 5-formyltetrahydrofolate cyclo-ligase from bacillus anthracis (ba4489).	bacillus anthracis is a spore-forming bacterium and the causative agent of the disease anthrax. the oxford protein production facility has been targeting proteins from b. anthracis in order to develop high-throughput technologies within the structural proteomics in europe project. as part of this work, the structure of 5-formyltetrahydrofolate cyclo-ligase (ba4489) has been determined by x-ray crystallography to 1.6 a resolution. the structure, solved in complex with magnesium-ion-bound adp and ...	2007	17329806
amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies.	amoxicillin is recommended for anthrax prevention in pregnancy. the objective of this study was to evaluate the pharmacokinetics of amoxicillin during pregnancy and postpartum (pp). sixteen women received amoxicillin during gestation (18-22 weeks (t2) and 30-34 weeks (t3)) as well as 3 months postpartum (pp) to evaluate single-dose pharmacokinetics. amoxicillin compartmental pharmacokinetic parameters were used to simulate amoxicillin concentration-time profiles following different dosage strate ...	2007	17329990
collision-activated dissociation, infrared multiphoton dissociation, and electron capture dissociation of the bacillus anthracis siderophore petrobactin and its metal ion complexes.	siderophores are high-affinity iron-chelating ligands produced by microorganisms to scavenge vital fe(3+) from the environment. thus, siderophores constitute potential therapeutic targets and their structural determination is important for exploiting their therapeutic value. here, the virulence-associated siderophore petrobactin from bacillus anthracis was characterized with electron capture dissociation (ecd). fragmentation of doubly protonated petrobactin was investigated and compared to susta ...	2007	17331739
effect of aluminum hydroxide adjuvant and formaldehyde in the formulation of rpa anthrax vaccine.	the serological response and efficacy of bacillus anthracis recombinant protective antigen (rpa) vaccines formulated with aluminum hydroxide adjuvant, either with or without formaldehyde, were evaluated in rabbits. rabbits that had been injected with a single dose of 25 microg of rpa adsorbed to 500 microg of aluminum in aluminum hydroxide gel (alhydrogel) had a significantly higher quantitative anti-rpa igg elisa titers (p<0.0001) and toxin neutralizing antibody (tna) assay titers (p<0.0001) th ...	2007	17240008
the 1.6 a crystal structure of the catalytic domain of plyb, a bacteriophage lysin active against bacillus anthracis.	lysins are peptidoglycan hydrolases that are produced by bacteriophage and act to lyse the bacterial host cell wall during progeny phage release. here, we describe the structure and function of a novel bacteriophage-derived lysin, plyb, which displays potent lytic activity against the bacillus anthracis-like strain atcc 4342. this molecule comprises an n-terminal catalytic domain (plyb(cat)) and a c-terminal bacterial sh3-like domain, sh3b. it is shown that both domains are required for effectiv ...	2007	17182056
identification of inhibitors using a cell-based assay for monitoring golgi-resident protease activity.	noninvasive real-time quantification of cellular protease activity allows monitoring of enzymatic activity and identification of activity modulators within the protease's natural milieu. we developed a protease activity assay based on differential localization of a recombinant reporter consisting of a golgi retention signal and a protease cleavage sequence fused to alkaline phosphatase (ap). when expressed in mammalian cells, this protein localizes to golgi bodies and, on protease-mediated cleav ...	2007	17316541
microresonator mass sensors for detection of bacillus anthracis sterne spores in air and water.	towards the goal of developing a real-time monitoring device for microorganisms, we demonstrate the use of microcantilevers as resonant mass sensors for detection of bacillus anthracis sterne spores in air and liquid. the detection scheme was based on measuring resonant frequency decrease driven by thermally induced oscillations, as a result of the added mass of the spores with the use of a laser doppler vibrometer (ldv). viscous effects were investigated by comparing measurements in air and dei ...	2007	17317142
a high-throughput screening approach to anthrax lethal factor inhibition.	a high-throughput screening approach was used to identify new inhibitors of the metallo-protease lethal factor from bacillus anthracis. a library of approximately 14,000 compounds was screened using a fluorescence-based in vitro assay and hits were further characterized enzymatically via measurements of ic50 and ki values against a small panel of metallo-proteases. this study led to the identification of new scaffolds that inhibit lf and the botulinum neurotoxin type a in the low micromolar rang ...	2007	17320146
nanowire labeled direct-charge transfer biosensor for detecting bacillus species.	a direct-charge transfer (dct) biosensor was developed for the detection of the foodborne pathogen, bacillus cereus. the biosensor was fabricated using antibodies as the sensing element and polyaniline nanowire as the molecular electrical transducer. the sensor design consisted of four membrane pads, namely, sample application, conjugate, capture and absorption pads. two sets of polyclonal antibodies, secondary antibodies conjugated with polyaniline nanowires and capture antibodies were applied ...	2007	17320373
mkk signaling and vascularization.	in 1998, george vande woude's lab discovered that anthrax lethal factor (lf), the principal virulence component of anthrax toxin, was a zinc-metalloprotease that cleaved and inactivated mitogen-activated protein kinase kinases (mkk). it was perhaps not surprising, given the known roles of mkk1 and 2 in cell proliferation, that lf was subsequently found to dramatically inhibit tumor growth in vivo. what was not anticipated, however, was that the tumors treated with lf would have a substantially r ...	2007	17322914
structure of the type iii pantothenate kinase from bacillus anthracis at 2.0 a resolution: implications for coenzyme a-dependent redox biology.	coenzyme a (coash) is the major low-molecular weight thiol in staphylococcus aureus and a number of other bacteria; the crystal structure of the s. aureus coenzyme a-disulfide reductase (coadr), which maintains the reduced intracellular state of coash, has recently been reported [mallett, t.c., wallen, j.r., karplus, p.a., sakai, h., tsukihara, t., and claiborne, a. (2006) biochemistry 45, 11278-89]. in this report we demonstrate that coash is the major thiol in bacillus anthracis; a bioinformat ...	2007	17323930
cethromycin: a-195773, a-195773-0, a-1957730, abbott-195773, abt 773.	cethromycin [abt 773, a-195773, abbott-195773, a-1957730, a-195773-0] is a once-daily ketolide antibiotic that originated from abbott laboratories' research into next-generation compounds to the macrolide antibacterial, clarithromycin. the aim of the research programme was to maintain the positive attributes of clarithromycin and to add the property of efficacy against macrolide-resistant organisms. cethromycin acts by binding to the 23s molecule of the 50s ribosomal subunit. advanced life scien ...	2007	17324007
technological advancements for the detection of and protection against biological and chemical warfare agents.	there is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. in this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. in particular ...	2007	17325785
regulation of virulence in bacillus anthracis: the phosphotransferase system transmits the signals.	bacillus anthracis causes host damage by producing two toxins, the lethal factor and the oedema factor. their production and that of other virulence factors depend on the activity of the atxa transcription factor. the mechanisms that control atxa activity are reported in this issue of molecular microbiology. the protein can be phosphorylated at two distinct sites by components of the phosphotransferase system (pts). one phosphorylation event stimulates transcription activation by atxa, whereas t ...	2007	17302796
opposing effects of histidine phosphorylation regulate the atxa virulence transcription factor in bacillus anthracis.	expression of genes for bacillus anthracis toxin and capsule virulence factors are dependent upon the atxa transcription factor. the mechanism by which atxa regulates the transcription of its target genes is unknown. here we report that bioinformatic analyses suggested the presence in atxa of two pts (phosphenolpyruvate : sugar phosphotransferase system) regulation domains (prd) generally regulated by phosphorylation/dephosphorylation at conserved histidine residues. by means of amino acid subst ...	2007	17302798
ligand binding and gene control characteristics of tandem riboswitches in bacillus anthracis.	most riboswitches are composed of a single metabolite-binding aptamer and a single expression platform that function together to regulate genes in response to changing metabolite concentrations. in rare instances, two aptamers or sometimes two complete riboswitches reside adjacent to each other in untranslated regions (utrs) of mrnas. we have examined an example of a tandem riboswitch in the gram-positive bacterium bacillus anthracis that includes two complete riboswitches for thiamine pyrophosp ...	2007	17307816
suitability of partial 16s ribosomal rna gene sequence analysis for the identification of dangerous bacterial pathogens.	in a bioterrorism event a rapid tool is needed to identify relevant dangerous bacteria. the aim of the study was to assess the usefulness of partial 16s rrna gene sequence analysis and the suitability of diverse databases for identifying dangerous bacterial pathogens.	2007	17309636
sensitive detection of bacillus anthracis using a binding protein originating from gamma-phage.	detection of biological weapons is a primary concern in force protection, treaty verification, and safeguarding civilian populations against domestic terrorism. one great concern is the detection of bacillus anthracis, the causative agent of anthrax. therefore, there is a pressing need to develop novel methods for rapid, simple, and precise detection of b. anthracis. here, we report that the c-terminal region of gamma-phage lysin protein (plyg) binds specifically to the cell wall of b. anthracis ...	2007	17310083
raftlike polyvalent inhibitors of the anthrax toxin: modulating inhibitory potency by formation of lipid microdomains.		2007	17310484
northwest territories. an outbreak of anthrax (bacillus anthracis) in free-roaming bison in the northwest territories, june-july 2006.		2007	17310621
accounting for ligand-bound metal ions in docking small molecules on adenylyl cyclase toxins.	the adenylyl cyclase toxins produced by bacteria (such as the edema factor (ef) of bacillus anthracis and cyaa of bordetella pertussis) are important virulence factors in anthrax and whooping cough. co-crystal structures of these proteins differ in the number and positioning of metal ions in the active site. metal ions bound only to the ligands in the crystal structures are not included during the docking. to determine what effect these "missing" metals have on docking results, the autodock, lig ...	2007	17311351
communicable disease and health protection quarterly review: july to september 2006. from the health protection agency.		2007	17311831
cutting edge: ifn-gamma-producing cd4 t lymphocytes mediate spore-induced immunity to capsulated bacillus anthracis.	virulent strains of bacillus anthracis produce immunomodulating toxins and an antiphagocytic capsule. the toxin component-protective ag is a key target of the antianthrax immune response that induces production of toxin-neutralizing abs. coimmunization with spores enhances the antitoxin vaccine, and inactivated spores alone confer measurable protection. we aimed to identify the mechanisms of protection induced in inactivated-spore immunized mice that function independently of the toxin/antitoxin ...	2007	17312104
manipulation of host signalling pathways by anthrax toxins.	infectious microbes face an unwelcoming environment in their mammalian hosts, which have evolved elaborate multicelluar systems for recognition and elimination of invading pathogens. a common strategy used by pathogenic bacteria to establish infection is to secrete protein factors that block intracellular signalling pathways essential for host defence. some of these proteins also act as toxins, directly causing pathology associated with disease. bacillus anthracis, the bacterium that causes anth ...	2007	17313374
characterization and analysis of early enzymes for petrobactin biosynthesis in bacillus anthracis.	recently, iron acquisition and, more specifically, enzymes involved in siderophore biosynthesis have become attractive targets for discovery of new antibiotics. accordingly, targeted inhibition of the biosynthesis of petrobactin, a virulence-associated siderophore encoded by the asb locus in bacillus anthracis, may hold promise as a potential therapy against anthrax. this study describes the biochemical characterization of asbc, the first reported 3,4-dihydroxybenzoic acid-amp ligase, and a key ...	2007	17346033
first detection of bacillus anthracis in feces of free-ranging raptors from central argentina.	prevalence of anthrax spores in feces of raptors was determined from samples collected in november-december 2000 and april-may 2001 in an agricultural region of santa fé province, argentina. feces were tested from 48 birds of six raptor species. one of 14 chimango caracaras (milvago chimango) and one of eight road-side hawks (buteo magnirostris) tested positive. the prevalence of bacillus anthracis spores in feces for the six species was 4% (n=48). the prevalence was 7% (n=14) for chimango carac ...	2007	17347404
pathobiology and management of laboratory rodents administered cdc category a agents.	the centers for disease control and prevention category a infectious agents include bacillus anthracis (anthrax), clostridium botulinum toxin (botulism), yersinia pestis (plague), variola major virus (smallpox), francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers. these agents are regarded as having the greatest potential for adverse impact on public health and therefore are a focus of renewed attention in infectious disease research. fre ...	2007	17348288
identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the bacillus anthracis secretome.	in a previous comparative proteomic study of bacillus anthracis examining the influence of the virulence plasmids and of various growth conditions on the composition of the bacterial secretome, we identified 64 abundantly expressed proteins (t. chitlaru, o. gat, y. gozlan, n. ariel, and a. shafferman, j. bacteriol. 188:3551-3571, 2006). using a battery of sera from b. anthracis-infected animals, in the present study we demonstrated that 49 of these proteins are immunogenic. thirty-eight b. anthr ...	2007	17353282
murine aerosol challenge model of anthrax.	the availability of relevant and useful animal models is critical for progress in the development of effective vaccines and therapeutics. the infection of rabbits and non-human primates with fully virulent bacillus anthracis spores provides two excellent models of anthrax disease. however, the high cost of procuring and housing these animals and the specialized facilities required to deliver fully virulent spores limit their practical use in early stages of product development. conversely, the s ...	2007	17353290
adverse reactions to anthrax vaccine (eg, optic neuritis) may be more complex or delayed than reported initially by payne et al (2006).		2007	17353397
isolation of engineered, full-length antibodies from libraries expressed in escherichia coli.	we describe facile isolation of full-length igg antibodies from combinatorial libraries expressed in e. coli. full-length heavy and light chains are secreted into the periplasm, where they assemble into aglycosylated iggs that are captured by an fc-binding protein that is tethered to the inner membrane. after permeabilizing the outer membrane, spheroplast clones expressing so-called e-clonal antibodies, which specifically recognize fluorescently labeled antigen, are selected using flow cytometry ...	2007	17435747
assessment of anthrax vaccination data in the defense medical surveillance system, 1998-2004.	understanding the completeness and accuracy of u.s. military anthrax vaccination data is important to the design and interpretation of studies to assess the safety of anthrax vaccine. we estimated the agreement between electronically recorded anthrax vaccination data in the defense medical surveillance system (dmss) versus anthrax vaccination data abstracted from hardcopy medical charts in a representative sample of the u.s. military from 1998 to 2004.	2007	17437247
public health response to an anthrax attack: an evaluation of vaccination policy options.	a discrete-time, deterministic, compartmental model was developed and analyzed to provide insight into how the use of anthrax vaccine before or after a large-scale attack can reduce casualties. the model accounts for important response and protection factors such as antibiotic and vaccine efficacy, the protective effects of buildings, the timing of emergency response, and antibiotic adherence and vaccine coverage in the population prior to the attack. the relative benefit of pre- versus post-exp ...	2007	17437349
bioterrorism-related inhalational anthrax: can extrapolated adult guidelines be applied to a pediatric population?	since the 2001 anthrax attacks, an extensive body of literature has evolved, but there has been a limited focus on the management of pediatric-specific issues. we looked at the symptom complexes of all pediatric patients presenting to the emergency department of our hospital during this period and examined whether their presentations would likely allow current guidelines to be used as potential screening criteria to identify children infected with anthrax.	2007	17437350
regulating biorisks: developing a coherent policy logic (part ii).	this is the second of two articles that empirically details the working practices of regulators charged with overseeing biological research. the first article considered how regulators from the biological agents unit of the uk health and safety executive went about implementing the british legislation controlling work with biological agents and genetically modified organisms prior to the terrorist attacks of 11 september 2001 and the ensuing anthrax letters in the u.s. this second article contin ...	2007	17437352
multiplexed identification of blood-borne bacterial pathogens by use of a novel 16s rrna gene pcr-ligase detection reaction-capillary electrophoresis assay.	we have developed a novel high-throughput pcr-ligase detection reaction-capillary electrophoresis (pcr-ldr-ce) assay for the multiplexed identification of 20 blood-borne pathogens (staphylococcus epidermidis, staphylococcus aureus, bacillus cereus, enterococcus faecalis, enterococcus faecium, listeria monocytogenes, streptococcus pneumoniae, streptococcus pyogenes, streptococcus agalactiae, escherichia coli, klebsiella pneumoniae, haemophilus influenzae, pseudomonas aeruginosa, acinetobacter bau ...	2007	17428930
pathogenesis and sepsis caused by organisms potentially utilized as biologic weapons: opportunities for targeted intervention.	the microorganisms potentially utilized as biologic weapons have a variety of pathogenic mechanisms that lead to overwhelming infection, septic shock and death. although many of these organisms have unique pathogenic attributes, the development of generic therapies for common pathways would be exceedingly useful as countermeasures. this review will examine the features of pathogenesis leading to sepsis for key biologic threat agents (causative agents of anthrax, plague, tularemia, smallpox and v ...	2007	17430123
targeting the methyl erythritol phosphate (mep) pathway for novel antimalarial, antibacterial and herbicidal drug discovery: inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (dxr) enzyme.	the 2-c-methyl-d-erythritol-4-phosphate (mep) pathway for isoprenoid biosynthesis has come under increased scrutiny as a target for novel antimalarial, antibacterial and herbicidal agents. 1-deoxy-d-xylulose 5-phosphate reductoisomerase (dxr) is a key enzyme of the pathway that catalyzes the rearrangement and nicotinamide adenine dinucleotide phosphate (nadph)-dependent reduction of 1-deoxy-d-xylulose 5-phosphate (dxp) to mep. the unique properties of dxr make it a remarkable and rational target ...	2007	17430177
optimizing the laser-pulse configuration for coherent raman spectroscopy.	we introduce a hybrid technique that combines the robustness of frequency-resolved coherent anti-stokes raman scattering (cars) with the advantages of time-resolved cars spectroscopy. instantaneous coherent broadband excitation of several characteristic molecular vibrations and the subsequent probing of these vibrations by an optimally shaped time-delayed narrowband laser pulse help to suppress the nonresonant background and to retrieve the species-specific signal. we used this technique for coh ...	2007	17431177
immunotherapeutic activity of a conjugate of a toll-like receptor 7 ligand.	the immunotherapeutic activity of toll-like receptor (tlr) activators has been difficult to exploit because of side effects related to the release and systemic dispersion of proinflammatory cytokines. to overcome this barrier, we have synthesized a versatile tlr7 agonist, 4-[6-amino-8-hydroxy-2-(2-methoxyethoxy)purin-9-ylmethyl]benzaldehyde (uc-1v150), bearing a free aldehyde that could be coupled to many different auxiliary chemical entities through a linker molecule with a hydrazine or amino g ...	2007	17360465
standard practice for bulk sample collection and swab sample collection of visible powders suspected of being biological agents from nonporous surfaces: collaborative study.	the draft astm standard, "standard practice for bulk sample collection and swab sample collection of visible powders suspected of being biological agents from nonporous surfaces," was validated in a collaborative study consisting of 6 teams comprised of civil support personnel and first responders, 2 levels of bacillus anthracis sterne and bacillus thuringiensis kurstaki spores, and 7 nonporous surfaces. the sample collection standard includes collection of the bulk sample (method a) using a dry ...	2007	17373464
anthrax lethal toxin kills macrophages in a strain-specific manner by apoptosis or caspase-1-mediated necrosis.	murine macrophages have been classified as either susceptible or nonsusceptible to killing by anthrax lethal toxin (lt) depending upon genetic background. while considered resistant to lt killing, we found that bone marrow-derived macrophages (bmms) from dba/2, akr, and c57bl/6 mice were slowly killed by apoptosis following lt exposure. lt killing was not restricted to in vitro assays, as splenic macrophages were also depleted in lt-injected c57bl/6 mice. human macrophages, also considered lt re ...	2007	17374996
intranasal administration of dry powder anthrax vaccine provides protection against lethal aerosol spore challenge.	the use of an aerosolizable form of anthrax as a biological weapon is considered to be among the most serious bioterror threats. intranasal (in) delivery of a dry powder anthrax vaccine could provide an effective and non-invasive administration alternative to traditional intramuscular (im) or subcutaneous (sc) injection. we evaluated a dry powder vaccine based on the recombinant protective antigen (rpa) of bacillus anthracis for vaccination against anthrax via in immunization in a rabbit model. ...	2007	17375001
chemical genetic screening identifies critical pathways in anthrax lethal toxin-induced pathogenesis.	anthrax lethal toxin (lt)-induced cell death via mitogen-activated protein kinase kinase (mapkk) cleavage remains questionable. here, a chemical genetics approach was used to investigate what pathways mediate lt-induced cell death. several small molecules were found to protect macrophages from anthrax lt cytotoxicity and mapkk from cleavage by lethal factor (lf), without inhibiting lf enzymatic activity or cellular proteasome activity. interestingly, the compounds activated mapk-signaling molecu ...	2007	17379140
characterization of the interaction between anthrax toxin and its cellular receptors.	mutations in capillary morphogenesis gene 2 (cmg2), one of the two closely related proteins that act as anthrax toxin receptors, cause two rare human autosomal recessive conditions, juvenile hyaline fibromatosis (jhf) and infantile systemic hyalinosis (ish). here we demonstrate that cmg2 proteins with certain jhf- and ish-associated single amino acid substitutions in their von willebrand factor a domain or transmembrane region do not function as anthrax toxin receptors. however, an ish-associate ...	2007	17381430
anthrax vaccination in the millennium cohort: validation and measures of health.	in 1998, the united states department of defense initiated the anthrax vaccine immunization program. concerns about vaccine-related adverse health effects followed, prompting several studies. although some studies used self-reported vaccination data, the reliability of such data has not been established. the purpose of this study was to compare self-reported anthrax vaccination to electronic vaccine records among a large military cohort and to evaluate the relationship between vaccine history an ...	2007	17383567
the global transcriptional responses of bacillus anthracis sterne (34f2) and a delta soda1 mutant to paraquat reveal metal ion homeostasis imbalances during endogenous superoxide stress.	microarray analyses were conducted to evaluate the paraquat-induced global transcriptional response of bacillus anthracis sterne (34f(2)) to varying levels of endogenous superoxide stress. data revealed that the transcription of genes putatively involved in metal/ion transport, bacillibactin siderophore biosynthesis, the glyoxalase pathway, and oxidoreductase activity was perturbed most significantly. a b. anthracis mutant lacking the superoxide dismutase gene soda1 (delta soda1) had transcripti ...	2007	17384197
putative type iv secretion genes in bacillus anthracis.	although the physiology of bacillus anthracis, the causative agent of anthrax, has been studied extensively, we still do not know how toxins are dispatched from the bacterial cell. here, by means of distant homology and genome context analyses, we identify genes encoding putative type iv secretion system-related elements on the b. anthracis plasmids pxo1 and pxo2 and in the chromosome. we argue that this type iv secretion system-like system could be responsible for anthrax toxin secretion, altho ...	2007	17387016
agroterrorism: where are we in the ongoing war on terrorism?	the u.s. agricultural infrastructure is one of the most productive and efficient food-producing systems in the world. many of the characteristics that contribute to its high productivity and efficiency also make this infrastructure extremely vulnerable to a terrorist attack by a biological weapon. several experts have repeatedly stated that taking advantage of these vulnerabilities would not require a significant undertaking and that the nation's agricultural infrastructure remains highly vulner ...	2007	17388078
anthrax toxin receptor 2 determinants that dictate the ph threshold of toxin pore formation.	the anthrax toxin receptors, antxr1 and antxr2, act as molecular clamps to prevent the protective antigen (pa) toxin subunit from forming pores until exposure to low ph. pa forms pores at ph approximately 6.0 or below when it is bound to antxr1, but only at ph approximately 5.0 or below when it is bound to antxr2. here, structure-based mutagenesis was used to identify non-conserved antxr2 residues responsible for this striking 1.0 ph unit difference in ph threshold. residues conserved between an ...	2007	17389920
a detailed analysis of 16s ribosomal rna gene segments for the diagnosis of pathogenic bacteria.	bacterial 16s ribosomal rna (rrna) genes contain nine "hypervariable regions" (v1-v9) that demonstrate considerable sequence diversity among different bacteria. species-specific sequences within a given hypervariable region constitute useful targets for diagnostic assays and other scientific investigations. no single region can differentiate among all bacteria; therefore, systematic studies that compare the relative advantage of each region for specific diagnostic goals are needed. we characteri ...	2007	17391789
genetic diversity in a bacillus anthracis historical collection (1954 to 1988).	bacillus anthracis, the etiologic agent of anthrax, has been widely described as a genetically monomorphic species. we used both multiple-locus variable-number tandem-repeat analysis (mlva) and paga gene sequencing to determine the genetic diversity of a historical collection of b. anthracis isolates collected from the 1950s to the 1980s from various geographic locations and sources. we sequenced the paga gene of 124 diverse b. anthracis isolates and found all previously identified b. anthracis ...	2007	17392445
antimicrobial activity and brine shrimp toxicity of extracts of terminalia brownii roots and stem.	ternimalia brownii fresen (combretaceae) is widely used in traditional medicine to treat bacterial, fungal and viral infections. there is a need to evaluate extracts of this plant in order to provide scientific proof for it's wide application in traditional medicine system.	2007	17394672
inhibition of cftr cl- channel function caused by enzymatic hydrolysis of sphingomyelin.	numerous mutations in the cystic fibrosis (cf) transmembrane conductance regulator (cftr, a cl(-) channel) disrupt salt and fluid transport and lead to the formation of thick mucus in patients' airways. obstruction by mucus predisposes cf patients to chronic infections and inflammation, which become gradually harder to control and eventually fatal. aggressive antibiotic therapy and supportive measures have dramatically lengthened cf patients' lives. here, we report that sphingomyelinases (smase) ...	2007	17400751
differentiation of bacillus anthracis, b. cereus, and b. thuringiensis by using pulsed-field gel electrophoresis.	a pulsed-field gel electrophoresis (pfge) method was developed for discriminating bacillus anthracis from b. cereus and b. thuringiensis. a worldwide collection of 25 b. anthracis isolates showed high-profile homology, and these isolates were unambiguously distinguished from b. cereus and b. thuringiensis isolates by cluster analysis of the whole-genome macrorestriction enzyme digestion patterns generated by noti.	2007	17400781
monochloramine inactivation of bacterial select agents.	seven species of bacterial select agents were tested for susceptibility to monochloramine. under test conditions, the monochloramine routinely maintained in potable water would reduce six of the species by 2 orders of magnitude within 4.2 h. bacillus anthracis spores would require up to 3.5 days for the same inactivation with monochloramine.	2007	17400782
systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice.	the novel recombinant anthrax toxin, pragu2/fp59, composed of the urokinase-activated protective antigen and a fusion protein of pseudomonas exotoxin and lethal factor was tested for anti-lung cancer efficacy in an in vivo human tumor model. male athymic nude mice (age 4-6 weeks) were inoculated s.c. with 10 million h1299 non-small cell lung cancer (nsclc) cells in the left flank. when tumor volumes reached 200 mm(3) (6-8 days), i.p. injection of 100 mul saline or different ratios and doses of p ...	2007	17409442
immunogens related to the synthetic tetrasaccharide side chain of the bacillus anthracis exosporium.	the known methyl 2-o-acetyl-3,4-di-o-benzyl-1-thio-alpha-l-rhamnopyranoside (3) was converted to the corresponding 5-methoxycarbonylpentyl glycoside 4 which was deacetylated. the product 5 was used as the initial glycosyl acceptor to construct two trirhamnoside glycosyl acceptors having ho-3(iii) flanked by either benzoyl or benzyl groups, compounds 10 and 29, respectively [fully protected, except ho-3(iii), alpha-l-rha-(1-->3)-alpha-l-rha-(1-->2)-alpha-l-rha-1-o-(ch2)5cooch3]. when these were g ...	2007	17412599
induction of cytotoxic t lymphocyte response against mycobacterial antigen using domain i of anthrax edema factor as antigen delivery system.	we have investigated the efficiency of n-terminal 1-260 residues of edema factor (efn) as a delivery system for esat-6, an antigenic protein of mycobacterium tuberculosis h(37)r(v), into the cytosol of mammalian cells. the efn.esat-6 recombinant protein was obtained by genetic fusion of efn and esat-6 dna. our data shows that in the presence of pa, efn.esat-6 fusion protein is internalized into the cytosol of antigen presenting cells, and the splenocytes produced both th1 and th2 cytokines in vi ...	2007	17416345
identification and characterization of a novel toxin-antitoxin module from bacillus anthracis.	comparative genome analysis of bacillus anthracis revealed a pair of linked genes encoding pemk (k, killer protein) and pemi (i, inhibitory protein) homologous to pem loci of other organisms. expression of pemk in escherichia coli and bacillus anthracis was bacteriostatic whereas the concomitant expression of pemi reversed the growth arrest. pemk expression effectively inhibited protein synthesis with no significant effect on dna replication. coexpression and interaction of these proteins confir ...	2007	17416361
the multiple mechanisms of ca2+ signalling by listeriolysin o, the cholesterol-dependent cytolysin of listeria monocytogenes.	cholesterol-dependent cytolysins (cdcs) represent a large family of conserved pore-forming toxins produced by several gram-positive bacteria such as listeria monocytogenes, streptococcus pyrogenes and bacillus anthracis. these toxins trigger a broad range of cellular responses that greatly influence pathogenesis. using mast cells, we demonstrate that listeriolysin o (llo), a prototype of cdcs produced by l. monocytogenes, triggers cellular responses such as degranulation and cytokine synthesis i ...	2007	17419718
bacillus anthracis anthrolysin o and three phospholipases c are functionally redundant in a murine model of inhalation anthrax.	although traditionally considered to be an extracellular pathogen, bacillus anthracis has a brief intracellular step to initiate anthrax. at the onset of infection, b. anthracis must withstand the bactericidal activities of the macrophage. recently, three phospholipases c (plcs) were shown to contribute to macrophage-associated growth of b. anthracis by presumably aiding in the escape of the bacterium from phagocytic vacuoles following phagocytosis. however, in the absence of all three plcs, veg ...	2007	17419764
genome-wide identification of francisella tularensis virulence determinants.	francisella tularensis is a gram-negative pathogen that causes life-threatening infections in humans and has potential for use as a biological weapon. the genetic basis of the f. tularensis virulence is poorly understood. this study screened a total of 3,936 transposon mutants of the live vaccine strain for infection in a mouse model of respiratory tularemia by signature-tagged mutagenesis. we identified 341 mutants attenuated for infection in the lungs. the transposon disruptions were mapped to ...	2007	17420240
responding to a small-scale bioterrorist anthrax attack: cost-effectiveness analysis comparing preattack vaccination with postattack antibiotic treatment and vaccination.	in 2001, a small-scale bioterrorism-related anthrax attack was perpetrated via the us mail. the optimal future response may require strategies different from those required in a large-scale attack.	2007	17420423
proteomic analysis of the response of the human neutrophil-like cell line nb-4 after exposure to anthrax lethal toxin.	we used 2-d dige to analyze the early response of nb-4 cells, a human promyelotic leukemia cell line, exposed to lethal toxin from bacillus anthracis at the proteome level. after a 2 h exposure, cells were still viable and 43% of spots (n = 1042) showed a significant change in protein level. we identified 59 spots whose expression had changed significantly, and these reflected cytoskeleton damage, mitochondrial lysis and endoplasmic reticulum stress. actin filament assembly was disrupted as evid ...	2007	21136624
the potential anti-herbivory role of microorganisms on plant thorns.	thorns, spines and prickles are some of the anti-herbivore defenses that plants have evolved. they were recently found to be commonly aposematic (warning coloration). however, the physical anti-herbivore defense executed by these sharp structures seems to be only the tip of the iceberg. we show that thorns of various plant species commonly harbor an array of aerobic and anaerobic pathogenic bacteria including clostridium perfringens the causative agent of the life-threatening gas gangrene, bacil ...	2007	19704540
sample concentration using optical chromatography.	optical chromatography is a technique for the separation of particles that capitalizes on the balance between optic and fluidic forces. when microscopic particles in a fluid flow encounter a laser beam propagating in the opposite direction, they are trapped axially along the beam. they are then optically pushed upstream from the laser focal point to rest at a point where the optic and fluidic forces on the particle balance. because optical and fluid forces are sensitive to differences in the phy ...	2007	19532509
[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
[treatment of late stages of anthracic infection].	ways for increasing the anthrax treatment efficacy by combined use of antibiotics, toxin neutralizing, immunomodulating, symptomatic and pathogenetic agents are considered. the dynamics of the infection development was studied on rabbits by the microbiological, cytochemical, biochemical and cytomorphologic criteria. the efficacy of monoantibacterial and complex schemes of the etiopathogenetic therapy of the disease at the early and late stages (phases) of the infection generalization was estimat ...	2007	20583468
a personal history of veterinary public health in the pan american health organization.	the introduction of disease into the new world changed both flora and fauna. the need for coordinated veterinary public health activities was highlighted when anthrax and encephalitis were reported in native populations. the pan american health organization has been a proponent of public health and animal health since its inception. neither discipline can be successful without the other.	2007	20422557
planning the bioterrorism response supply chain: learn and live.	responses to bioterrorism require rapid procurement and distribution of medical and pharmaceutical supplies, trained personnel, and information. thus, they present significant logistical challenges. on the basis of a review of the manufacturing and service supply chain literature, the authors identified five supply chain strategies that can potentially increase the speed of response to a bioterrorism attack, reduce inventories, and save money: effective supply chain network design; effective inv ...	2007	18491839
[indication of extremely dangerous infectious pathogens using immunochromatography and digital video analysis].	the use of immunochromatographic indicatory elements based on antibody conjugates and colloidal gold was suggested to detect cells and the antigens of extremely dangerous infectious pathogens. the specificity and specific activity (sensitivity) of the mentioned elements were studied on vaccinal strains of plague, anthrax, and tularemia pathogens. the researchers studied a possibility to increase the sensitivity of immunochromatographic analysis using computed scanning and reflecom, a specialized ...	2007	18225501
[the development of peroxosolvate-based composites and the evaluation of their effectiveness against extremely dangerous infective pathogens].	the article contains the results of the test of pfk-m composition bactericidal activity against a range of extremely dangerous infective pathogens. the preparation proved to be highly effective for the disinfection of surfaces, sanitary and technical equipment, linen, dishes, and medical utensils contaminated by plague, cholera, and anthrax pathogens. the study found that the antimicrobial activity of the preparation increased after heating and lowered when the object to be disinfected was conta ...	2007	18225504
[a research into the possibility of the application of new peroxosolvate-based compounds as chemical disinfectants].	a newly synthesized peroxosolvate, ammonium sulphate peroxosolvate, can be used in disinfectology and other areas along with other hard forms of hydrogen. optimal conditions for ammonium sulphate peroxosolvate synthesis were determined by this study. it was established that (nh4)2so4 . h2o2 stabilized with carboxylic acids did not lose active oxygen when stored in dry atmosphere. the sporocidal activity of the compound against the suspension of b. cereus var. anthracoides 250 was studied. the re ...	2007	18225505
[important issues of biological safety].	the problem of biological security raises alarm due to the real growth of biological threats. biological security includes a wide scope of problems, the solution of which becomes a part of national security as a necessary condition for the constant development of the country. a number of pathogens, such as human immunodeficiency virus, exotic ebola and lassa viruses causing hemorrhagic fever,rotaviruses causing acute intestinal diseases, etc. were first discovered in the last century. terrorist ...	2007	18225506
[occupational infectious respiratory diseases].	occupational infectious respiratory diseases are underestimate pathology because of an asymptomatic infection or the general, unspecific symptoms.	2007	18216753
[healthcare response to bioterrorism].	bioterrorists seek to use highly virulent pathogens to cause social and economic disruption. historical agents such as anthrax, yersinia pestis and botulinum toxin can easily be produced, whereas others such as hemorragic fever virus require much more sophisticated infrastructure and government-scale resources. in the near future, with the spread of new biotechnologies, bioterrorists may produce new transgenic pathogens. epidemiological surveillance and diagnostic capacities should thus be more ...	2007	18402160
anthrax in animals and humans in mongolia.	anthrax is endemic throughout mongolia, except in the semi-desert and desert areas of the south. the prevalence of anthrax in mongolia had drastically decreased since the 1950s due to the use of anthrax antiserum and vaccines, but the privatisation of the animal husbandry sector and changes in the structures of the veterinary and medical delivery systems in mongolia over the last decade have resulted in challenges for disease control. animal and human anthrax has become an increasing problem sin ...	2007	18293618
a human antibody against anthrax protective antigen protects rabbits from lethal infection with aerosolized spores.	alxn4100, a fully human antibody that binds to the protective antigen of anthrax toxin, was generated from a fab isolated from a phage display library and was analyzed for its pharmacokinetic properties in rabbits and then used to protect rabbits from challenge with a lethal aerosol dose of bacillus anthracis spores (approximately 322x ld(50)). all rabbits receiving 15 or 40 mg/kg of antibody 24 hours before challenge survived; survival of rabbits receiving 4 mg/kg either subcutaneously or intra ...	2007	18334745
casting a wider net for countermeasure r&d funding decisions.	among potential bioweapons attacks, endemic infectious diseases (that is, those naturally occurring diseases that afflict us every year), and a potential influenza pandemic, how should we apportion funding and resources for basic research and countermeasure development? to address this question, i argue for a "combined risk assessment" that considers bioweapons attacks with natural pandemics and endemic infectious disease. at present, risk assessments for bioweapons attacks are carried out separ ...	2007	18081491
purification, crystallization and preliminary structural analysis of nucleoside diphosphate kinase from bacillus anthracis.	bacillus anthracis nucleoside diphosphate kinase (bandk) is an enzyme whose primary function is to maintain deoxynucleotide triphosphate (dntp) pools by converting deoxynucleotide diphosphates to triphosphates using atp as the major phosphate donor. although the structures of ndks from a variety of organisms have been elucidated, the enzyme from sporulating bacteria has not been structurally characterized to date. crystals of the b. anthracis enzyme were grown using the vapour-diffusion method f ...	2007	18084101
the changing world of biocontainment and biosecurity.	since the 1980s, a number of key events have significantly altered our ideas on biosecurity and the role of biocontainment laboratories, such as the bovine spongiform encephalopathy (bse) and severe acute respiratory syndrome (sars) outbreaks and the anthrax episode of 2001 in the usa. this has resulted in the development of plans to build "high containment" facilities around the world and an array of new regulations at both national and international levels regarding the management of pathogens ...	2007	18084927
biothreat agents and pathology laboratories.	pathologists and laboratory staff are likely to be among the first health care workers to be aware that a potential bioterrorism attack has occurred. to prepare for such an event, it is necessary to be familiar with 1) the characteristics of bioterrorism attacks versus natural disease outbreaks, 2) which pathogens are potential bioterrorism agents; 3) the types of lesions that each causes; 4) the microbiological characteristics of each agent; 5) the laboratory response network and reporting requ ...	2007	18085061
[assessment of immunity and allergy after vaccination with dry combined anthrax vaccine].	study of humoral immune response and allergy in recipients of dry combined anthrax vaccine was performed. immune response was assessed by antibody titers to protective antigen and by index of preventive properties of blood serum (pps) of recipients. relation of index of pps and antibody titers in blood serum of the donors was established. distribution of erythrocyte antigens in recipients of live dry and combined anthraxvaccines depending on blood group, rh-factor, and age was studied. it has be ...	2007	18038547
effect of 2-fluorohistidine labeling of the anthrax protective antigen on stability, pore formation, and translocation.	the action of anthrax toxin relies in part upon the ability of the protective antigen (pa) moiety to form a heptameric pore in the endosomal membrane, providing a portal for entry of the enzymic moieties of the toxin into the cytosol. pore formation is dependent on a conformational change in the heptameric prepore that occurs in the neutral to mildly acidic ph range, and it has been hypothesized that protonation of one or more histidine residues triggers this transition. to test this hypothesis, ...	2007	18044973
the stringent response of bacillus anthracis contributes to sporulation but not to virulence.	the gram-positive, spore-forming pathogen bacillus anthracis is the aetiological agent of anthrax. its main virulence factors are two toxins and an anti-phagocytic capsule. when b. anthracis is grown in laboratory culture, the highest expression of the anthrax toxin genes occurs during entry into stationary phase, suggesting that nutrient limitation is an environmental cue which induces toxin production. a common bacterial response to starvation is the so-called stringent response, in which the ...	2007	18048936
generation of a specific marker to discriminate gacillus anthracis from other bacteria of the bacillus cereus group.	bacillus anthracis is a soil pathogen capable of causing anthrax that is closely related to several environmental species, including b. cereus, b. mycoides, and b. thuringiensis. dna homology studies showed that b. anthracis, b. cereus, b. mycoides, and b. thuringiensis are closely related, with a high sequence homology. to establish a method to specifically detect b. anthracis in situations such as environmental contamination, we initially performed rapd-pcr with a 10-mer random primer and conf ...	2007	18051303
simultaneous detection and identification of bacillus cereus group bacteria using multiplex pcr.	bacillus cereus group bacteria share a significant degree of genetic similarity. thus, to differentiate and identify the bacillus cereus group efficiently, a multiplex pcr method using the gyrb and groel genes as diagnostic markers is suggested for simultaneous detection. the assay yielded a 400 bp amplicon for the groel gene from all the b. cereus group bacteria, and a 253 bp amplicon from b. anthracis, 475 bp amplicon from b. cereus, 299 bp amplicon from b. thuringiensis, and 604 bp amplicon f ...	2007	18051330
cutaneous anthrax involving the genital area.	a 5-year-old girl was admitted with a lesion of the labia majora which was found to be owing to anthrax. she had been licked on the hand by a sick cow (which subsequently died) 5 days prior to admission to a health clinic and 8 days before admission to hospital.	2007	18053349
anthrax: from reality to exercise.		2007	17968209