Publications

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[practical strategies against bioterrorism].bioterrorism is terrorism by intentional release of viruses, bacteria, toxins or other agents to cause illness or death in people. especially, anthrax, smallpox, plague, botulism, tularemia, and viral hemorrhagic fevers are important illness due to biological agents with a high potential for adverse public health impact. these biological agents can be spread through the air, through water, or in food and may cause disasters in the society. furthermore, difficulties in detection and identificatio ...200718069284
[bioterrorism: ideas of first resource medicine]. 200718069408
edema toxin impairs anthracidal phospholipase a2 expression by alveolar macrophages.bacillus anthracis, the etiological agent of anthrax, is a spore-forming gram-positive bacterium. infection with this pathogen results in multisystem dysfunction and death. the pathogenicity of b. anthracis is due to the production of virulence factors, including edema toxin (et). recently, we established the protective role of type-iia secreted phospholipase a2 (spla2-iia) against b. anthracis. a component of innate immunity produced by alveolar macrophages (ams), spla2-iia is found in human an ...200718069891
high-throughput sequence alignment using graphics processing units.the recent availability of new, less expensive high-throughput dna sequencing technologies has yielded a dramatic increase in the volume of sequence data that must be analyzed. these data are being generated for several purposes, including genotyping, genome resequencing, metagenomics, and de novo genome assembly projects. sequence alignment programs such as mummer have proven essential for analysis of these data, but researchers will need ever faster, high-throughput alignment tools running on ...200718070356
where and how do anthrax toxins exit endosomes to intoxicate host cells?the role of bacillus anthracis virulence factors in its pathogenesis has been subjected to intense investigation with the aim of finding novel preventive and therapeutic protocols. toxins that are endocytosed and act in the cytosol of host cells have a central role in b. anthracis infection. understanding of anthrax toxin cell entry has increased during the past few years and a composite picture is emerging. nevertheless, unanswered and controversial questions remain, particularly concerning the ...200717983750
cutaneous anthrax in the artibonite valley of haiti: 1992-2002.more cutaneous anthrax cases were noted at hospital albert schweitzer (has) in the artibonite valley of haiti. we examine the incidence of anthrax in the artibonite between 1992 and 2002, describe the clinical presentation of cutaneous anthrax, and determine risk factors for anthrax. in 1992 has reported 1 case of anthrax for an incidence of 4 cases per million persons/year. in 2002, there were 20 cases of anthrax for an incidence of 72 cases per million persons/year. this is a 17-fold increase ...200717984330
[mission oriented diagnostic real-time pcr].in out of area military missions soldiers are potentially exposed to bacteria that are endemic in tropical areas and can be used as biological agents. it can be difficult to culture these bacteria due to sample contamination, low number of bacteria or pretreatment with antibiotics. commercial biochemical identification systems are not optimized for these agents which can result in misidentification. immunological assays are often not commercially available or not specific. real-time pcr assays a ...200717987355
essential role of an active-site guanine in glms ribozyme catalysis.the glms ribozyme is a catalytic riboswitch that is activated for endonucleolytic cleavage by the coenzyme glucosamine-6-phosphate. using kinetic assays and x-ray crystallography, we identify an active-site mutation of a conserved guanine that abolishes catalysis without perturbing coenzyme binding. our results provide evidence that coenzyme function requires a specific nucleobase to interact with the nucleophile of the cleavage reaction.200717990888
cgas: a comparative genome annotation system.recent advances in genome sequencing technology and algorithms have made it possible to determine the sequence of a whole genome quickly in a cost-effective manner. as a result, there are more than 200 completely sequenced genomes. however, annotation of a genome is still a challenging task. one of the most effective methods to annotate a newly sequenced genome is to compare it with well-annotated and closely related genomes using computational tools and databases. comparing genomes requires use ...200717993671
genetic distribution of 295 bacillus cereus group members based on adk-screening in combination with mlst (multilocus sequence typing) used for validating a primer targeting a chromosomal locus in b. anthracis.the genetic distribution of 295 bacillus cereus group members has been investigated by using a modified multilocus sequence typing method (mlst). by comparing the nucleic acid sequence of the adk gene fragment, isolates of b. cereus group members most related to b. anthracis may be easily identified. the genetic distribution, with focus on the b. anthracis close neighbours, was used to evaluate a new primer set for specific identification of b. anthracis. this primer set, ba5510-1/2, targeted th ...200717997177
assessing the safety of anthrax immunization in us army aircrew members via physical examination.anthrax in weaponized form is the bioterrorism agent of most concern. questions raised about the safety of the anthrax vaccine can be addressed by comparing immunized and unimmunized people in population-based studies.200718000413
a staphylococcus aureus regulatory system that responds to host heme and modulates virulence.staphylococcus aureus, a bacterium responsible for tremendous morbidity and mortality, exists as a harmless commensal in approximately 25% of humans. identifying the molecular machinery activated upon infection is central to understanding staphylococcal pathogenesis. we describe the heme sensor system (hssrs) that responds to heme exposure and activates expression of the heme-regulated transporter (hrtab). inactivation of the hss or hrt systems leads to increased virulence in a vertebrate infect ...200718005689
bacterial characterization using protein profiling in a microchip separations platform.a rapid microanalytical protein-based approach to bacterial characterization is presented. chip gel electrophoresis (cge) coupled with lif detection was used to analyze lysates from different bacterial cell lines to obtain signature profiles of the soluble protein composition. the study includes escherichia coli, bacillus subtilis, and bacillus anthracis (delta sterne strain) vegetative cells as well as endospores formed from the latter two species as model organisms to demonstrate the method. a ...200718008300
critical role of the phosphatidylinositol 3-kinase/akt/glycogen synthase kinase-3 signaling pathway in recovery from anthrax lethal toxin-induced cell cycle arrest and mek cleavage in macrophages.anthrax lethal toxin (letx) is a virulence factor causing immune suppression and toxic shock of bacillus anthracis infected host. it inhibits cytokine production and cell proliferation/differentiation in various immune cells. this study showed that a brief exposure of letx caused a continual mek1 cleavage and prevented tumor necrosis factor-alpha (tnf) production in response to lipopolysaccharide (lps) in non-proliferating cells such as human peripheral blood mononuclear cells or mouse primary p ...200717951252
a study of the physiology of bacillus anthracis sterne during manufacture of the uk acellular anthrax vaccine.to analyse the growth of bacillus anthracis during simulations of the uk anthrax vaccine manufacturing process.200717953556
isolation and selection of bacillus spp. as potential biological agents for enhancement of water quality in culture of ornamental fish.to isolate, select and evaluate bacillus spp. as potential biological agents for enhancement of water quality in culture of ornamental fish.200717953558
rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant.abstract:200717953756
microwave-accelerated metal-enhanced fluorescence: application to detection of genomic and exosporium anthrax dna in <30 seconds.we describe the ultra-fast and sensitive detection of the gene encoding the protective antigen of bacillus anthracis the causative agent of anthrax. our approach employs a highly novel platform technology, microwave-accelerated metal-enhanced fluorescence (mamef), which combines the use of metal-enhanced fluorescence to enhance assay sensitivity and focused microwave heating to spatially and kinetically accelerate dna hybridization. genomic and exosporium target dna of bacillus anthracis spores ...200717955147
bacterial endospore inactivation caused by outgassing of vapourous hydrogen peroxide from polymethyl methacrylate (plexiglas).to investigate the cause and to eliminate the inactivation of bacillus anthracis strain sterne spores settled onto agar and stainless steel surfaces in plastic holders.200717958554
complement c3d conjugation to anthrax protective antigen promotes a rapid, sustained, and protective antibody response.b. anthracis is the causative agent of anthrax. pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (pa) to gain entry into the host cell. the current anthrax vaccine (ava, biothrax) consists of aluminum-adsorbed cell-free filtrates of unencapsulated b. anthracis, wherein pa is thought to be the principle target of neutralization. in this study, we evaluated the efficacy of the natural adjuvant, c3d, versus alum in eliciting an a ...200717940608
mutant anthrax toxin b moiety (protective antigen) inhibits angiogenesis and tumor growth.bacillus anthracis protective antigen (pa), the b subunit of the binary anthrax toxin, binds to the cellular receptors capillary morphogenesis gene 2 protein and tumor endothelial marker 8 with high affinity. both receptors are expressed on endothelial cells during angiogenesis. we sought to determine whether one could inhibit angiogenesis by interfering with the binding of these receptors to their endogenous ligands. here, we show that wild-type pa inhibits both vascular endothelial growth fact ...200717942931
cloning, expression and characterization of a fast self-sufficient p450: cyp102a5 from bacillus cereus.cyp102s represent a family of natural self-sufficient fusions of cytochrome p450 and cytochrome p450 reductase found in some bacteria. one member of this family, named cyp102a1 or more traditionally p450bm-3, has been widely studied as a model of human p450 cytochromes. remarkable detail of p450 structure and function has been revealed using this highly efficient enzyme. the recent rapid expansion of microbial genome sequences has revealed many relatives of cyp102a1, but to date only two from ba ...200717945181
the bayesian aerosol release detector: an algorithm for detecting and characterizing outbreaks caused by an atmospheric release of bacillus anthracis.early detection and characterization of outdoor aerosol releases of bacillus anthracis is an important problem. as health departments and other government agencies address this problem with newer methods of surveillance such as environmental surveillance through the biowatch program and enhanced medical surveillance, they increasingly have newer types of surveillance data available. however, existing methods for the statistical analysis of surveillance data do not account for recent meteorologic ...200717948918
exploring the evolution of the bacillus cereus group repeat element bcr1 by comparative genome analysis of closely related strains.bcr1 is a chromosomal approximately 155 bp repeated element found uniquely and ubiquitously in the bacillus cereus group of gram-positive bacteria; it exhibits several features characteristic of mobile elements, including a variable distribution pattern between strains. here, highly similar bcr1 elements in non-conserved genomic loci are identified in a set of closely related b. cereus and bacillus thuringiensis strains near the bacillus anthracis phylogenetic cluster. it is also shown that bcr1 ...200717975097
catalytically inactive anthrax toxin(s) are potential prophylactic agents.the anthrax exotoxin, which is a key mediator of anthrax related pathogenesis, is composed of two separate toxins formed by pairwise combinations of three proteins that are encoded on the pxo1 plasmid of bacillus anthracis. lethal toxin is composed of protective antigen (pa) combined with lethal factor (lf) while edema toxin is composed of pa and edema factor (ef). the present study found that the catalytic mutants of lf (lfe687a) and ef (efh351a) competitively inhibited lethal toxin and edema t ...200717980467
rapid clearance of bacteria and their toxins: development of therapeutic proteins.the emergence of pathogens and toxins with resistance against conventional drugs, vaccines, and host defense peptides and proteins warrants novel countermeasures that can efficiently capture and rapidly clear them. this article examines the utility of chimeric proteins with capture and clearance domains as a novel countermeasure against pathogens and their toxins. the capture and clearance domains are chosen from the large repertoire of host defense peptides and proteins. although individual cap ...200718197819
anthrax in red deer (cervus elaphus), italy. 200718214198
modeling the geographic distribution of bacillus anthracis, the causative agent of anthrax disease, for the contiguous united states using predictive ecological [corrected] niche modeling.the ecology and distribution of bacillus anthracis is poorly understood despite continued anthrax outbreaks in wildlife and livestock throughout the united states. little work is available to define the potential environments that may lead to prolonged spore survival and subsequent outbreaks. this study used the genetic algorithm for rule-set prediction modeling system to model the ecological niche for b. anthracis in the contiguous united states using wildlife and livestock outbreaks and severa ...200718165531
[the relationship between the conditions of cultivation and sporification of various bacillus strains and the results of the evaluation of the sporocidal activity of chemical desinfectants].the researchers compared the main microbiological characteristics of some bacillus antracoides strains after their cultivation in different nutrient media. the study found that the growth and sporification rate, r-s dissociation ability, and sensitivity to disinfectants are strain properties and significantly depend on the composition of the nutrient medium.200718228663
[evaluation of in vitro antibacterial activity of fosmidomycin and its derivatives].unlike the mammals, some species of pathogenic microorganisms synthesize isoprenoids by the mevalonate-independent pathway known as the methyl-erythritol phosphate pathway (mep). the macromolecules of the polyprenyl compounds play an essential role in the metabolism of the microbial cell. therefore, the mep enzymes can be targets for new antibiotics. antibacterial activity of fosmidomycin, an inhibitor of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (dxr), the key enzyme of mep in isoprenoid ...200718986018
defensive strategies of bacillus anthracis that promote a fatal disease.bacillus anthracis is a gram-positive bacterium that causes anthrax. bacterial spores that enter the host germinate into metabolically active bacilli that disseminate throughout the body and replicate to high numbers. two virulence factors are essential for this unrestrained growth. the first is a weakly immunogenic poly gamma-d-glutamic acid capsule that surrounds the bacilli and confers resistance to phagocytosis. the second virulence factor, anthrax toxin, disrupts multiple host functions to ...200719081825
variable number of tandem repeats (vntr) and its application in bacterial epidemiology.molecular epidemiology is the using of molecular techniques to study bacterial distribution in human populations. recently molecular epidemiologist benefit from several techniques such as variable number tandem repeat (vntr) typing method to typing bacterial strains. variable number tandem repeat (vntr) typing is a tool for genotyping and provides data in a simple and numeric format based on the number of repetitive sequences. vntr for first time identified in m. tuberculosis as mycobacterial in ...200719070072
decision theoretic analysis of improving epidemic detection.the potentially catastrophic impact of an epidemic specially these due to bioterrorist attack, makes developing effective detection methods essential for public health. current detection methods trade off reliability of alarms for early detection of outbreaks. the performance of these methods can be improved by disease-specific modeling techniques that take into account the potential costs and effects of an attack to provide optimal warnings and the cost and effectiveness of interventions. we st ...200718693857
[phage lytic enzymes--new hope in battle against bacterial infections].bacteriophage lytic enzymes are produced during phage replication cycle in bacterial cells. lysis of bacterial cell wall enables release of virus particles. bakteriophage enzymes activity are highly specific, therefore they are able to destroy selected bacterial species, also resistant to antibiotics. this creates new possibilities in therapy of bacterial infections.200718572503
informed consent in the military: the anthrax vaccination case. 200723228579
extending the bacillus cereus group genomics to putative food-borne pathogens of different toxicity.the bacillus cereus group represents sporulating soil bacteria containing pathogenic strains which may cause diarrheic or emetic food poisoning outbreaks. multiple locus sequence typing revealed a presence in natural samples of these bacteria of about 30 clonal complexes. application of genomic methods to this group was however biased due to the major interest for representatives closely related to bacillus anthracis. albeit the most important food-borne pathogens were not yet defined, existing ...200817434157
rat survival to anthrax lethal toxin is likely controlled by a single gene.we examined whether survival of different rat strains administered anthrax lethal toxin is genetically determined. a reproducible test population of first filial generation hybrid rats was bred based on the susceptibility of progenitors to anthrax lethal toxin and to maximize genetic diversity across the strains. these rats were then tested with varying doses of anthrax lethal toxin. we found that all 'sensitive' strains died within 2 h following systemic administration of 240 mug/kg lethal toxi ...200817440430
crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (ba3989) from bacillus anthracis at 2.4-a resolution. 200817894349
construction, crystal structure and application of a recombinant protein that lacks the collagen-like region of bcla from bacillus anthracis spores.spores of bacillus anthracis, the causative agent of anthrax, are enclosed by an exosporium, which consists of a basal layer surrounded by a nap of hair-like filaments. the major structural component of the filaments is called bcla, which comprises a central collagen-like region (clr) and a globular c-terminal domain. here, the entire clr coding sequence of bcla was removed, and the resulting protein (tbcla) produced in escherichia coli. the crystallographic structure of tbcla was determined to ...200817879302
nlr proteins: integral members of innate immunity and mediators of inflammatory diseases.the innate immune system is the first line of defense against microorganisms and is conserved in plants and animals. the nucleotide-binding domain, leucine rich containing (nlr) protein family is a recent addition to the members of innate immunity effector molecules. these proteins are characterized by a central oligomerization domain, termed nucleotide-binding domain (nbd) and a protein interaction domain, leucine-rich repeats (lrrs) at the c terminus. it has been shown that nlr proteins are lo ...200817875812
bactericidal activity of chlorine-loaded carbide-derived carbon against escherichia coli and bacillus anthracis.the authors investigated the bactericidal activity of high-chlorine-content nanoporous carbide-derived carbon (cdc) against the gram-positive, spore-forming bacterium bacillus anthracis and the common gram-negative enteric bacterium escherichia coli. chlorine-loaded nanoporous cdc produced by thermochemical etching of metals and metalloids by chlorination of carbides can retain up to 40 wt % of chlorine. etching temperature and the structure and composition of carbides allow tuning the porosity ...200817635016
modeling the structure of mab 14b7 bound to the anthrax protective antigen.the anthrax protective antigen (pa) is a key component of the tripartite anthrax toxin. monoclonal antibody (mab) 14b7 and its engineered, affinity-matured variants have been shown to be effective in blocking pa binding to cellular receptors and mitigating anthrax toxicity. here, we perform computational structural modeling of the mab 14b7-pa interaction. our objectives are to determine the structure of the 14b7-pa complex, to deduce a structural explanation for the affinity maturation from the ...200817671962
properties of bacillus anthracis spores prepared under various environmental conditions.bacillus anthracis makes highly stable, heat-resistant spores which remain viable for decades. effect of various stress conditions on sporulation in b. anthracis was studied in nutrient-deprived and sporulation medium adjusted to various ph and temperatures. the results revealed that sporulation efficiency was dependent on conditions prevailing during sporulation. sporulation occurred earlier in culture sporulating at alkaline ph or in pbs than control. spores formed in pbs were highly sensitive ...200817713759
paratope diversity in the human antibody response to bacillus anthracis protective antigen.the active component of the licensed human anthrax vaccine (biothrax, or ava) is a bacillus anthracis toxin known as protective antigen (pa). second generation anthrax vaccines currently under development are also based on a recombinant form of pa. since the current and future anthrax vaccines are based on this toxin, it is important that the immunobiology of this protein in vaccinated humans be understood in detail. we have isolated and analyzed the pa-specific antibody repertoire from an ava-v ...200817707509
anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome.anthrax lethal toxin (lt) is cytotoxic to macrophages from certain inbred mouse strains. the gene controlling macrophage susceptibility to lt is nalp1b. nalp1b forms part of the inflammasome, a multiprotein complex involved in caspase-1 activation and release of interleukin (il)-1beta and il-18. we confirm the role of caspase-1 in lt-mediated death by showing that caspase inhibitors differentially protected cells against lt, with the degree of protection corresponding to each compound's ability ...200817850338
imported tropical infectious ulcers in travelers.skin ulcers are a commonly encountered problem at departments of tropical dermatology in the western world. furthermore, the general dermatologist is likely to be consulted more often for imported chronic skin ulcers because of the ever-increasing travel to and from tropical countries. the most common cause of chronic ulceration throughout the world is probably pyoderma. however, in some parts of the world, cutaneous leishmaniasis is one of the most prevalent causes. mycobacterium ulcerans is an ...200818572973
[zoonoses with wildlife reservoirs: a threat to public health and the economy].the world is experiencing an increase in emergent infections as a result of anthropogenic changes of the biosphere and globalization. global warming unrestricted exploitation of natural resources such as forests and fisheries, urbanization, human migration, and industrialization of animal husbandry cause environmental destruction and fragmentation. these changes of the biosphere favor local emergence of zoonoses from their natural biotopes and their interaction with domestic animals and human po ...200818575667
antibacterial activity of labdane diterpenoids from stemodia foliosa.as part of a continuing interest in exploring the chemistry of brazilian medicinal plants, three new labdane diterpenoids, 6alpha-acetoxymanoyl oxide (1), 6alpha-malonyloxymanoyl oxide (2), and 6alpha-malonyloxy-n-butyl ester manoyl oxide (3), together with the known betulinic acid, lupeol, sitosterol, and stigmasterol, were isolated from the aerial parts of stemodia foliosa. the structures of 1-3 were established on the basis of interpretation of spectroscopic data, including hresims, and 1d an ...200818582112
biosynthesis of the 3,4-dihydroxybenzoate moieties of petrobactin by bacillus anthracis.the biosynthesis of the 3,4-dihydroxybenzoate moieties of the siderophore petrobactin, produced by b. anthracis str. sterne, was probed by isotopic feeding experiments in iron-deficient media with a mixture of unlabeled and d-[(13)c6]glucose at a ratio of 5:1 (w/w). after isolation of the labeled siderophore, analysis of the isotopomers was conducted via one-dimensional (1)h and (13)c nmr spectroscopy, as well as (13)c-(13)c dqfcosy spectroscopy. isotopic enrichment and (13)c-(13)c coupling cons ...200818582113
inhalation anthrax: dose response and risk analysis.the notion that inhalation of a single bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. the difficulty in ...200818582166
protein-protein docking and analysis reveal that two homologous bacterial adenylyl cyclase toxins interact with calmodulin differently.calmodulin (cam), a eukaryotic calcium sensor that regulates diverse biological activities, consists of n- and c-terminal globular domains (n-cam and c-cam, respectively). cam serves as the activator of cyaa, a 188-kda adenylyl cyclase toxin secreted by bordetella pertussis, which is the etiologic agent for whooping cough. upon insertion of the n-terminal adenylyl cyclase domain (acd) of cyaa to its targeted eukaryotic cells, cam binds to this domain tightly ( approximately 200 pm affinity). thi ...200818583346
an in vivo passive protection assay for the evaluation of immunity in ava-vaccinated individuals.samples of human plasma from anthrax vaccine adsorbed (ava, biothrax)-vaccinated individuals were used to demonstrate passive protection of a/j mice from a lethal challenge with the sterne strain of anthrax bacteria. the maximum concentration of human anti-protective antigen igg in mouse sera 24 h after injection of 260 microg of anti-pa igg was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). mice showed significant survival (p<or=0.001) after injection of serial dilutions ...200818586363
identification and characterization of bacillus anthracis spores by multiparameter flow cytometry.in response to the need for methods that can rapidly detect potentially virulent bacillus anthracis spores, we developed a two-color flow cytometric assay capable of simultaneously identifying b. anthracis spores and the presence of spore-associated protective antigen, a virulence marker for strains harboring the pxo1 plasmid.200818586967
assessment of acute injuries, exposure to environmental toxins, and five-year health surveillance of new york police department working dogs following the september 11, 2001, world trade center terrorist attack.to determine deployment logistics of new york police department (nypd) working dogs that assisted in relief efforts at the world trade center (wtc) site following the september 11, 2001, terrorist attack; establish types and rates of related acute injuries and illnesses; identify environmental toxin exposures; and determine long-term (ie, 5-year) health effects of deployment.200818593312
zoonosis update. anthrax. 200818593313
toxicity of anthrax toxin is influenced by receptor expression.anthrax toxin protective antigen (pa) binds to its cellular receptor, and seven subunits self-associate to form a heptameric ring that mediates the cytoplasmic entry of lethal factor or edema factor. the influence of receptor type on susceptibility to anthrax toxin components was examined using chinese hamster ovary (cho) cells expressing the human form of one of two pa receptors: tem8 or cmg2. unexpectedly, pa alone, previously believed to only mediate entry of lethal factor or edema factor, wa ...200818596206
zoonoses-with friends like this, who needs enemies?zoonoses are infections that are spread from animals to humans. most often, humans are "dead-end" hosts, meaning that there is no subsequent human-to-human transmission. if one considers most of the emerging infections that were recognized at the end of the last century and the beginning of this century, they would fall into the category of zoonoses. one of the most important common traits exhibited by infections that have been or can be eliminated from the face of the earth (e.g. smallpox, meas ...200818596867
genotyping of bacillus cereus strains by microarray-based resequencing.the ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. in this regard, bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the b. cereus group that can cause diverse diseases. we employed custom-designed resequencing arrays (ras) based on the genome sequence of bacillus anthr ...200818596941
birth defects among infants born to women who received anthrax vaccine in pregnancy.in response to bioterrorism threats, anthrax vaccine has been used by the us military and considered for civilian use. concerns exist about the potential for adverse reproductive health effects among vaccine recipients. this retrospective cohort evaluated birth defects, in relation to maternal anthrax vaccination, among all infants born to us military service women between 1998 and 2004. department of defense databases defined maternal vaccination and infant diagnoses; multivariable regression m ...200818599489
the vaccines development forum. 200818600591
a fluorimetric assay for real-time monitoring of adenylyl cyclase activity based on terbium norfloxacin.adenylyl cyclases catalyze the production of the second messenger cyclic amp from atp. until now, there has been no fluorescent adenylyl cyclase assay known that is applicable to high-throughput screening and kinetic determinations that can directly monitor the turnover of the unmodified substrate atp. in this study, a fluorescence-based assay is described using the ca(ii)- and calmodulin-dependent adenylyl cyclase edema factor (ef) from bacillus anthracis and tb(iii)-norfloxacin as probe for th ...200818601890
real-time pcr system targeting a chromosomal marker specific for bacillus anthracis.specific identification of bacillus anthracis and differentiation from closely related bacillus cereus and bacillus thuringiensis strains is still a major diagnostic problem. commercially available diagnostic kits targeting plasmid-markers cannot differentiate between b. anthracis, non-anthracis bacillus species harbouring anthrax-specific virulence plasmids, and plasmidless b. anthracis strains. a taqman pcr assay was designed targeting sequences of gene locus ba_5345 of the b. anthracis strain ...200818602986
efficacy of oritavancin in a murine model of bacillus anthracis spore inhalation anthrax.the inhaled form of bacillus anthracis infection may be fatal to humans. the current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. the potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against b. anthracis (mic against ames strain, 0.015 microg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. in postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of or ...200818606841
microbial forensics: dna fingerprinting of bacillus anthracis (anthrax). 200818609763
combating the threat of anthrax: a quantitative structure-activity relationship approach.bacterial agents or products more likely to be used as biological weapons of mass destruction are bacillus anthracis, francisella tularensis, yersinia pestis, and the neurotoxin of clostridium botulinum. anthrax is an acute infectious disease with a high mortality rate caused by bacillus anthracis, reinforcing the need for better adjunctive therapy and prevention strategies. in this paper, we developed 7 qsar models on penicillin-based inhibitors of the class a and b beta-lactamases from b. anth ...200818611038
[vaccines, biotechnology and their connection with induced abortion].diploid cells (wi-38, mrc-5) vaccines have their origin in induced abortions. among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis a, chickenpox, and herpes zoster. nowadays, other abortion tainted vaccines cultivated on transformed cells (293, per.c6) are in the pipeline: flu, respiratory syncytial and parainfluenza viruses, hiv, west nile virus, ebola, marburg and lassa, hepatitis b and c, foot and mouth disease, japanese encephalitis, dengue ...200818611078
novel inhibitors of anthrax edema factor.several pathogenic bacteria produce adenylyl cyclase toxins, such as the edema factor (ef) of bacillus anthracis. these disturb cellular metabolism by catalyzing production of excessive amounts of the regulatory molecule camp. here, a structure-based method, where a 3d-pharmacophore that fit the active site of ef was constructed from fragments, was used to identify non-nucleotide inhibitors of ef. a library of small molecule fragments was docked to the ef-active site in existing crystal structur ...200818620864
amide bonds assemble pili on the surface of bacilli.pilin precursors are the building blocks of pili on the surface of gram-positive bacteria; however, the assembly mechanisms of these adhesive fibers are unknown. here, we describe the chemical bonds that assemble bcpa pilin subunits on the surface of bacillus cereus. sortase d cleaves bcpa precursor between the threonine (t) and the glycine (g) residues of its lpxtg sorting signal and catalyzes formation of an amide bond between threonine (t) of the sorting signal and lysine (k) in the ypkn moti ...200818621716
anthrax lethal toxin suppresses chemokine production in human neutrophil nb-4 cells.microarray analysis was used to investigate the effects of bacillus anthracis lethal toxin (lt) on human neutrophil-like nb-4 cells to identify markers of intoxication. genes down-regulated after a 2h lt exposure included those encoding chemokines and transcription factors. significant decreases in the mrna of interleukin-8, ccl20, ccl3 and ccl4, which are important chemoattractants for immune cells, were observed using real-time pcr (12.3, 4.0, 4.1 and 2.2-fold (p<0.05), respectively). the decr ...200818625197
the crystal structure of ump kinase from bacillus anthracis (ba1797) reveals an allosteric nucleotide-binding site.uridine monophosphate (ump) kinase is a conserved enzyme that catalyzes the atp-driven conversion of uridylate monophosphate into uridylate diphosphate, an essential metabolic step. in prokaryotes, the enzyme exists as a homohexamer that is regulated by various metabolites. whereas the enzymatic mechanism of ump kinase (uk) is well-characterized, the molecular basis of its regulation remains poorly understood. here we report the crystal structure of uk from bacillus anthracis (ba1797) in complex ...200818625239
in vivo demonstration and quantification of intracellular bacillus anthracis in lung epithelial cells.inhalational anthrax is initiated by the entry of bacillus anthracis spores into the lung. a critical early event in the establishment of an infection is the dissemination of spores from the lung. using in vitro cell culture assays, we previously demonstrated that b. anthracis spores are capable of entering into epithelial cells of the lung and crossing a barrier of lung epithelial cells without apparent disruption of the barrier integrity, suggesting a novel portal for spores to disseminate fro ...200818625737
overview of the inactivation by 254 nm ultraviolet radiation of bacteria with particular relevance to biodefense.our goal was to ultimately predict the sensitivity of untested bacteria (including those of biodefense interest) to ultraviolet (uv) radiation. in this study, we present an overview and analysis of the relevant 254 nm data previously reported and available in the literature. the amount of variability in this data prevented us from determining an "average" response for any bacterium. therefore, we developed particular selection criteria to include the data in our analysis and suggested future gui ...200818627518
controlled plasmonic nanostructures for surface-enhanced spectroscopy and sensing.after its discovery more than 30 years ago, surface-enhanced raman spectroscopy (sers) was expected to have major impact as a sensitive analytical technique and tool for fundamental studies of surface species. unfortunately, the lack of reliable and reproducible fabrication methods limited its applicability. in recent years, sers has enjoyed a renaissance, and there is renewed interest in both the fundamentals and applications of sers. new techniques for nanofabrication, the design of substrates ...200818630932
recovery efficiencies of anthrax spores and ricin from nonporous or nonabsorbent and porous or absorbent surfaces by a variety of sampling methods*.the 2001 anthrax letter cases brought into focus the need to establish the most effective environmental sampling procedures. results are presented from two studies aimed at establishing the best procedures for everyday surfaces likely to be contaminated after the release of environmentally stable bioaggressive agents, as exemplified by anthrax spores and ricin. with anthrax spores, contact plates, with mean retrieval rates of 28-54%, performed better than other methods by a wide margin for flat ...200818637873
the type iii pantothenate kinase encoded by coax is essential for growth of bacillus anthracis.in bacillus anthracis, the novel type iii pantothenate kinase (pank(ba); encoded by coax) catalyzes the first committed step in coenzyme a biosynthesis. we have demonstrated by analyzing the growth characteristics of a conditional coax mutant that pank(ba) is an essential enzyme, thus contributing to its validation as a new antimicrobial target.200818641144
mechanistic modeling of emergency events: assessing the impact of hypothetical releases of anthrax.a modular system for source-to-dose-to-effect modeling analysis has been developed based on the modeling environment for total risk studies (mentor),((1)) and applied to study the impacts of hypothetical atmospheric releases of anthrax spores. the system, mentor-2e (mentor for emergency events), provides mechanistically consistent analysis of inhalation exposures for various release scenarios, while allowing consideration of specific susceptible subpopulations (such as the elderly) at the resolu ...200818643828
sizing the bacillus anthracis pa63 channel with nonelectrolyte poly(ethylene glycols).nonelectrolyte polymers of poly(ethylene glycol) (peg) were used to estimate the diameter of the ion channel formed by the bacillus anthracis protective antigen 63 (pa(63)). based on the ability of different molecular weight pegs to partition into the pore and reduce channel conductance, the pore appears to be narrower than the one formed by staphylococcus aureus alpha-hemolysin. numerical integration of the peg sample mass spectra and the channel conductance data were used to refine the estimat ...200818645196
the decline of antibiotic era--new approaches for antibacterial drug discovery.infectious diseases still remain the main cause of human premature deaths; especially in developing countries. the emergence and spread of pathogenic bacteria resistant to many antibiotics (multidrug-resistant strains) have created the need for the development of novel therapeutic agents. only two new classes of antibiotics of novel mechanisms of action (linezolid and daptomycin) have been introduced into the market during the last three decades. the recent progress in molecular biology and bact ...200818646395
a dual-purpose protein ligand for effective therapy and sensitive diagnosis of anthrax.this article reports the design of a bivalent protein ligand with dual use in therapy and diagnosis of anthrax caused by bacillus anthracis. the ligand specifically binds to pa and thereby blocks the intracellular delivery of lf and ef toxins that, respectively, cause cell lysis and edema. the ligand is a chimeric scaffold with two pa-binding domains (called vwa) linked to an igg-fc frame. molecular modeling and binding measurements reveal that the vwa-fc dimer binds to pa with high affinity (k( ...200818649128
responding to a bioterrorism attack--one scenario: part 1.this article continues the discussions introduced in an earlier article submitted to the health care manager entitled "epidemic simulation for syndromic surveillance," wherein a format for analysis of the incidence of a bioterrorist attack was presented. this article outlines a simulation conducted as part of a federal grant award administered through the center for biological defense at the university of south florida. the disease entity simulated was an attack of anthrax introduced into the ce ...200818695399
anthrax toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitis.anthrax meningitis is the main neurological complication of systemic infection with bacillus anthracis approaching 100% mortality. the presence of bacilli in brain autopsies indicates that vegetative bacteria are able to breach the blood-brain barrier (bbb). the bbb represents not only a physical barrier but has been shown to play an active role in initiating a specific innate immune response that recruits neutrophils to the site of infection. currently, the basic pathogenic mechanisms by which ...200818698416
a single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge.here we confirm that intranasal (in) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. the optimum dose of rpa in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150microg and therefore was chosen as the target dose for all subsequent experiments. rabbits received a single dose of either 150microg rpa, 150microg rpa+150microg of a conjugated 10-mer peptide representing the b ...200818703110
anthrax investigation. full-genome sequencing paved the way from spores to a suspect. 200818703714
anthrax case ignites new forensics field. 200818704053
molecular modeling and dynamics studies of shikimate kinase from bacillus anthracis.bacillus anthracis has been used as weapon in bioterrorist activities, with high mortality, despite anti-microbial treatment, which strongly indicates a need of new drugs to treat anthrax. shikimate pathway is a seven-step biosynthetic route which generates chorismic acid. the shikimate pathway is essential for many pathological organisms, whereas it is absent in mammals. therefore, these enzymes are potential targets for the development of non-toxic anti-microbial agents and herbicides and have ...200818706819
plant-produced hepatitis b core protein chimera carrying anthrax protective antigen domain-4.the hepatitis b core antigen (hbcag) can generate a strong immune response and is recognized as an effective carrier for foreign epitopes. the domain-4 epitope of the anthrax protective antigen (pa-d4) plays an essential role in generating protective immunity against virulent bacillus anthracis. here we report the successful production of a recombinant protein comprised of the antigenic pa-d4 integrated into the c/e1 loop of hbcag in transgenic low-alkaloid nicotiana tabacum. sera of mice inject ...200818707542
a novel approach to development of monoclonal antibodies using native antigen for immunization and recombinant antigen for screening.the production of monoclonal antibodies (mab) specific to microbes is rapidly growing. finding an appropriate antigen to screen hybridoma clones has become increasingly important. however, the conventional method, in which the purified antigen from the microbe is routinely used for screening, cannot avoid selection of false positive hybridoma clones, since even highly purified antigen is found to be contaminated with some other proteins from the microbe. in this study, mabs against anthrax prote ...200818707549
crystal structure of a family gt4 glycosyltransferase from bacillus anthracis orf ba1558. 200818712829
single-walled carbon nanotube as a unique scaffold for the multivalent display of sugars.single-walled carbon nanotube (swnt) is a pseudo-one-dimensional nanostructure capable of carrying/displaying a large number of bioactive molecules and species in aqueous solution. in this work, a series of dendritic beta-d-galactopyranosides and alpha-d-mannopyranosides with a terminal amino group were synthesized and used for the functionalization of swnts, which targeted the defect-derived carboxylic acid moieties on the nanotube surface. the higher-order sugar dendrons were more effective in ...200818712920
atomic resolution structures of escherichia coli and bacillus anthracis malate synthase a: comparison with isoform g and implications for structure-based drug discovery.enzymes of the glyoxylate shunt are important for the virulence of pathogenic organisms such as mycobacterium tuberculosis and candida albicans. two isoforms have been identified for malate synthase, the second enzyme in the pathway. isoform a, found in fungi and plants, comprises approximately 530 residues, whereas isoform g, found only in bacteria, is larger by approximately 200 residues. crystal structures of malate synthase isoform g from escherichia coli and mycobacterium tuberculosis were ...200818714089
functional interactions between anthrax toxin receptors and the wnt signalling protein lrp6.to exert its activity, anthrax toxin must be endocytosed and its enzymatic toxic subunits delivered to the cytoplasm. it has been proposed that, in addition to the anthrax toxin receptors (atrs), lipoprotein-receptor-related protein 6 (lrp6), known for its role in wnt signalling, is also required for toxin endocytosis. these findings have however been challenged. we show that lrp6 can indeed form a complex with atrs, and that this interaction plays a role both in wnt signalling and in anthrax to ...200818717822
anthrax investigation. fbi discusses microbial forensics--but key questions remain unanswered. 200818719254
anthrax investigation. six anthrax science questions the fbi has yet to answer. 200818719255
case not closed. 200818719537
fact sheet: anthrax. 200818720582
esat-6-like protein secretion in bacillus anthracis.proteins of the wxg100 family represent the prototypical substrates of bacterial type vii secretion systems that typically encompass 100 residues, lack canonical signal peptides, and form helix-turn-helix hairpin structures with wxg positioned in the turn element. bacillus anthracis encodes six wxg100 proteins, herein referred to as esxb, esxl, esxp, esxq, esxv, and esxw. with the exception of esxb, b. anthracis proteins harbor c-terminal extensions that are appended to canonical wxg domains. wh ...200818723613
assessing bioterrorism preparedness and response of rural veterinarians: experiences and training needs.veterinarians play a unique role in emergency preparedness and response, and federal agencies and academic institutions therefore allocate considerable resources to provide training to enhance their readiness. however, the level of preparedness of veterinarians in many rural regions is yet to be improved. this article reports an assessment of the bioterrorism preparedness, specifically the experience and training needs, of rural veterinarians in north texas. the study employed a cross-sectional ...200818723813
is 60 days of ciprofloxacin administration necessary for postexposure prophylaxis for bacillus anthracis?sixty days of ciprofloxacin administration at 500 mg every 12 h is currently recommended for the prophylaxis of inhalational exposure to bacillus anthracis. we examined bacillus anthracis (delta-sterne strain) in our hollow-fiber infection model. we measured the ciprofloxacin concentrations achieved and the number of organisms present before heat shock (total population) and after heat shock (spore population). we fit a mathematical model to these data. monte carlo simulation with differing init ...200818725437
preventing voltage-dependent gating of anthrax toxin channels using engineered disulfides.the channel-forming component of anthrax toxin, (pa(63))(7), is a heptameric water-soluble protein at neutral ph, but under acidic conditions it spontaneously inserts into lipid bilayers to form a 14-stranded beta-barrel ion-conducting channel. this channel plays a vital role in anthrax pathogenesis because it serves as a conduit for the membrane translocation of the two enzymatic components of anthrax toxin, lethal factor and edema factor. anthrax channels open and close in response to changes ...200818725530
bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin.acquisition of iron is necessary for the replication of nearly all bacterial pathogens; however, iron of vertebrate hosts is mostly sequestered by heme and bound to hemoglobin within red blood cells. in bacillus anthracis, the spore-forming agent of anthrax, the mechanisms of iron scavenging from hemoglobin are unknown. we report here that b. anthracis secretes isdx1 and isdx2, two neat domain proteins, to remove heme from hemoglobin, thereby retrieving iron for bacterial growth. unlike other gr ...200818725935
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