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[type i interferon and bacterial infection].interferons (ifns) are cytokines playing an important role in immune responses. interferons are classified into two distinct types according to specific interferon receptors(ifnr). type i ifns include ifn-α and ifn-β, whereas ifn-γ is type ii ifn. it is well known that type i ifns have important roles in the host defense against viruses through activation of interferon receptor a (ifnar). however, many recent studies have also demonstrated that type i ifns have effects on immune responses to bac ...201222927085
light-activated porphyrin-based formulations to inactivate bacterial spores.the objective of this study was to develop porphyrin-based formulations to inactivate bacillus spores. we probed the effect of porphyrins alone and in combination with germinants against both bacillus cereus and bacillus anthracis spores in the presence of light.201222925067
inhalational anthrax (ames aerosol) in naïve and vaccinated new zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.there is a need to better understand inhalational anthrax in relevant animal models. this understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. the aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (> 100 ld(50)) of bacillus anthracis (ames) spores immediately following exposure through 36 h. the primary goal of collecting the data was to sup ...201222919678
achieving consistent multiple daily low-dose bacillus anthracis spore inhalation exposures in the rabbit model.repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. this is especially true for persistent agents such as b. anthracis spores, the causative agent of anthrax. studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 10(6) colony forming units (cfu) of b. anthracis spores) and included a pilot feasibility characterization study, acute exposure stu ...201222919662
combined bacillus licheniformis and bacillus subtilis infection in a patient with oesophageal perforation.species of the genus bacillus are a common laboratory contaminant, therefore, isolation of these organisms from blood cultures does not always indicate infection. in fact, except for bacillus anthracis and bacillus cereus, most species of the genus bacillus are not considered human pathogens, especially in immunocompetent individuals. here, we report an unusual presentation of bacteraemia and mediastinitis due to co-infection with bacillus subtilis and bacillus licheniformis, which were identifi ...201222918867
cutaneous infection caused by bacillus anthracis in larissa, thessaly, central greece, july 2012.in july 2012, a confirmed case of cutaneous anthraxinfection in a stockbreeder in the prefecture of larissa, thessaly, central greece was reported. the investigation revealed five related deaths in animals (two dogs and three sheep). control measures have been taken immediately in order to prevent further spread in humans and animals.201222913937
broad expression analysis of human antxr1/tem8 transcripts reveals differential expression and novel splizce variants.tumor endothelial marker 8 (tem8; antxr1) is one of two anthrax toxin receptors; the other is capillary morphogenesis gene 2 protein (cmg2; antxr2). tem8 shows enhanced expression in certain tumor endothelia, and is thought to be a player in tumor vasculature formation. however, a comprehensive expression profile of individual tem8 variants in normal or cancerous tissues is lacking. in this work we carried out an extensive analysis of all splice variants of human tem8 in 12 digestive tissues, an ...201222912819
comparison of the structural stability and dynamic properties of recombinant anthrax protective antigen and its 2-fluorohistidine-labeled analogue.protective antigen (pa) is the primary protein antigenic component of both the currently used anthrax vaccine and related recombinant vaccines under development. an analogue of recombinant pa (2-fhis rpa) has been recently shown to block the key steps of pore formation in the process of inducing cytotoxicity in cells, and thus can potentially be used as an antitoxin or a vaccine. this rpa analogue was produced by fermentation to incorporate the unnatural amino acid 2-fluorohistidine (2-fhis). in ...201222911632
evaluation of two multiplex real-time pcr screening capabilities for the detection of bacillus anthracis, francisella tularensis and yersinia pestis in blood samples generated from murine infection models.two multiplex pcr screening capabilities (taqman array cards and filmarray) were evaluated for their ability to detect bacillus anthracis, francisella tularensis and yersinia pestis in blood samples obtained from respective murine infection models. blood samples were obtained from infected mice at 24 h intervals after exposure. multiplex pcr results were compared with standard blood culture and singleplex real-time pcr. across all three models, 71 mice were tested in total, within which a subset ...201222899777
test method development to evaluate hot, humid air decontamination of materials contaminated with bacillus anthracis ∆sterne and b. thuringiensis al hakam spores.to develop test methods and evaluate the survival of bacillus anthracis ∆sterne and bacillus thuringiensis al hakam spores after exposure to hot, humid air.201222897143
attachment of bacillus anthracis spores on multi-walled carbon nanotube coated surfaces.in this study, two types of carbon nanotube (cnt) modified surfaces for the attachment of bacillus anthracis spores were examined. multi-walled carbon nanotube (mwcnt) forest on silicon wafer and mwcnt sheet on poly(methyl methacrylate) (pmma) film were used. both types of mwcnt surfaces significantly increased surface hydrophobicity (p < 0.05) and increased the attachment of spores on their surfaces compared to the uncoated substrates, respectively. however, no inhibitory effect was observed on ...201222888754
risk analysis of an anthrax outbreak in cattle and humans of sesheke district of western zambia.an anthrax outbreak occurred in november 2010 in five villages of sesheke district in western zambia. control measures and data collection was carried out immediately the outbreak was reported. the prevalence of the disease in cattle was estimated at 7.4% (45/609) while the average herd size of infected cattle in affected villages was estimated at 121.8 (95% ci 48.8-194.8). individual mortality per herd varied between 1.70% (3/179) and 20.25% (6/79). the relative risk of infection of cattle in t ...201222885011
[study on the single nucleotide polymorphism in capsule plasmid gene of bacillus anthracis in the china isolates].to study the characteristic of single nucleotide polymorphism (snp) in capsule plasmid gene of bacillus anthracis isolated from china.201222883267
louis pasteur, from crystals of life to vaccination.louis pasteur (1822-1895) is an exceptional scientist who opened a new era in medicine and biology. starting from studies on crystals of by-products of wine fermentation, he first defined a distinct chemistry between dead and living matters. he then showed the role of living microbes in the fermentation and putrefaction processes. this brought him to challenge the two-millennium-old theory of spontaneous generation, using remarkably well-designed experiments. his observations on epidemics in sil ...201222882766
genomic determinants of sporulation in bacilli and clostridia: towards the minimal set of sporulation-specific genes.three classes of low-g+c gram-positive bacteria (firmicutes), bacilli, clostridia and negativicutes, include numerous members that are capable of producing heat-resistant endospores. spore-forming firmicutes include many environmentally important organisms, such as insect pathogens and cellulose-degrading industrial strains, as well as human pathogens responsible for such diseases as anthrax, botulism, gas gangrene and tetanus. in the best-studied model organism bacillus subtilis, sporulation in ...201222882546
impact of particulate antigens, such as bacillus anthracis, on the uniformity of response across a biosensor flow cell as determined by gc-spr.biosensors are desired for the detection of a wide range of analytes in various scenarios, for example environmental monitoring for biological threats, from toxins to viruses and bacteria. ideally a single sensor will be capable of simultaneous multianalyte detection. the varying nature, and in particular disparate size, of such a variety of analytes poses a significant challenge in the development of effective high-confidence instruments. many existing biosensors employ functionalized flow cell ...201222881408
disability among us army veterans vaccinated against anthrax.to protect troops against the use of anthrax as a biological weapon, the us department of defense began an anthrax vaccination program in 1998. 14 years after the inception of the vaccination program, there is no evidence suggesting vaccination against anthrax carries long-term health risks for active duty soldiers.201222874851
it's in the genes! human genetic diversity and the response to anthrax vaccines. 201222873120
reaerosolization of bacillus spp. in outdoor environments: a review of the experimental literature.reaerosolization or resuspension-that is, the reintroduction of previously airborne particles into the atmosphere-is a complex phenomenon. microbial reaerosolization is particularly poorly understood because few studies have been done in this area, and many of the studies that have been performed are not in the peer-reviewed literature. the reaerosolization of bacillus anthracis in outdoor environments is of particular concern because of its stability and potential for use as a biological weapon ...201222871211
a novel mechanism for antibody-based anthrax toxin neutralization: inhibition of prepore-to-pore conversion.protective antigen (pa), a key component of anthrax toxin, mediates the entry of lethal factor (lf) or edema factor (ef) through a membranal pore into target cells. we have previously reported the isolation and chimerization of cab29, an anti-pa monoclonal antibody that effectively neutralizes anthrax toxin in an unknown mechanism. the aim of this study was to elucidate the neutralizing mechanism of this antibody in vitro and to test its ability to confer post-exposure protection against anthrax ...201222869370
hal is a bacillus anthracis heme acquisition protein.the metal iron is a limiting nutrient for bacteria during infection. bacillus anthracis, the causative agent of anthrax and a potential weapon of bioterrorism, grows rapidly in mammalian hosts, which suggests that it efficiently attains iron during infection. recent studies have uncovered both heme (isd) and siderophore-mediated (asb) iron transport pathways in this pathogen. whereas deletion of the asb genes results in reduced virulence, the loss of three surface components from isd had no effe ...201222865843
ph effects on binding between the anthrax protective antigen and the host cellular receptor cmg2.the anthrax protective antigen (pa) binds to the host cellular receptor capillary morphogenesis protein 2 (cmg2) with high affinity. to gain a better understanding of how ph may affect binding to the receptor, we have investigated the kinetics of binding as a function of ph to the full-length monomeric pa and to two variants: a 2-fluorohistidine-labeled pa (2-fhispa), which is ∼1 ph unit more stable to variations in ph than wt, and an ∼1 ph unit less stable variant in which trp346 in the domain ...201222855243
genome wide search for identification of potential drug targets in bacillus anthracis.with the heightened interest in bacillus anthracis as a potential biological threat agent, novel drug targets identification is of great importance in drug discovery. this study considered a genome-wide approach to identify 270 non-redundant, non-human homologous genes and 103 essential genes of the bacteria as putative drug targets. sub-cellular localisation of each drug target was annotated using psortb 3.0 and confirmation by a hybrid support vector machine analysis identified 16 membrane-bou ...201222854124
effect of single-walled carbon nanotubes on bacillus anthracis cell growth, sporulation, and spore germination.in this study, the effect of single-walled carbon nanotubes (swcnts) on b. anthracis cell growth, spore formation, and spore germination was studied. we found that swcnts at a concentration of 100 microg/ml exhibited obvious antimicrobial activity on 10(6) cfu/ml b. anthracis cells. at 300 microg/ml, 1 h of swcnts treatment could inactivate b. anthracis cells by approximately 2 log viable cell reduction. the swcnt treatment did not induce spore formation. we also found that swcnts were not effec ...201222852312
filament formation of the ftsz/tubulin-like protein tubz from the bacillus cereus pxo1 plasmid.stable maintenance of low-copy-number plasmids requires partition (par) systems that consist of a nucleotide hydrolase, a dna-binding protein, and a cis-acting dna-binding site. the ftsz/tubulin-like gtpase tubz was identified as a partitioning factor of the virulence plasmids pbtoxis and pxo1 in bacillus thuringiensis and bacillus anthracis, respectively. tubz exhibits high gtpase activity and assembles into polymers both in vivo and in vitro, and its "treadmilling" movement is required for pla ...201222847006
cost-effectiveness comparison of response strategies to a large-scale anthrax attack on the chicago metropolitan area: impact of timing and surge capacity.rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. however, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. we conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the chicago metropolitan area beginning either day 2 or day 5 after the attack. these strategies correspond ...201222845046
synthesis of bacillithiol and the catalytic selectivity of fosb-type fosfomycin resistance proteins.bacillithiol (bsh) has been prepared on the gram scale from the inexpensive starting material, d-glucosamine hydrochloride, in 11 steps and 8-9% overall yield. the bsh was used to survey the substrate and metal-ion selectivity of fosb enzymes from four gram-positive microorganisms associated with the deactivation of the antibiotic fosfomycin. the in vitro results indicate that the preferred thiol substrate and metal ion for the fosb from staphylococcus aureus are bsh and ni(ii), respectively. ho ...201223030527
relacin, a novel antibacterial agent targeting the stringent response.finding bacterial cellular targets for developing novel antibiotics has become a major challenge in fighting resistant pathogenic bacteria. we present a novel compound, relacin, designed to inhibit (p)ppgpp production by the ubiquitous bacterial enzyme rela that triggers the stringent response. relacin inhibits rela in vitro and reduces (p)ppgpp production in vivo. moreover, relacin affects entry into stationary phase in gram positive bacteria, leading to a dramatic reduction in cell viability. ...201223028324
cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol enrichment, hyperpolarization, and reactive oxygen species generation through downregulating mln64 in macrophages.cellular adaptation to different stresses related to survival and function has been demonstrated in several cell types. anthrax lethal toxin (letx) induces rapid cell death, termed "pyroptosis," by activating nlrp1b/caspase-1 in murine macrophages. we and others (s. d. ha et al., j. biol. chem. 282:26275-26283, 2007; i. i. salles et al., proc. natl. acad. sci. u. s. a. 100:12426 -12431, 2003) have shown that raw264.7 cells preexposed to sublethal doses of letx become resistant to subsequent high ...201223028046
bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.the lung is the site of entry for bacillus anthracis in inhalation anthrax, the deadliest form of the disease. bacillus anthracis produces virulence toxins required for disease. alveolar macrophages were considered the primary target of the bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of mek signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. our current results s ...201223027535
bacillus anthracis thioredoxin systems, characterization and role as electron donors for ribonucleotide reductase.bacillus anthracis is the causative agent of anthrax, which is associated with a high mortality rate. like several medically important bacteria, b. anthracis lacks glutathione but encodes many genes annotated as thioredoxins, thioredoxin reductases, and glutaredoxin-like proteins. we have cloned, expressed, and characterized three potential thioredoxins, two potential thioredoxin reductases, and three glutaredoxin-like proteins. of these, thioredoxin 1 (trx1) and nrdh reduced insulin, 5,5'-dithi ...201223012357
bioterrorism: pathogens as weapons.biowarfare has been used for centuries. the use of biological weapons in terrorism remains a threat. biological weapons include infectious agents (pathogens) and toxins. the most devastating bioterrorism scenario would be the airborne dispersal of pathogens over a concentrated population area. characteristics that make a specific pathogen a high-risk for bioterrorism include a low infective dose, ability to be aerosolized, high contagiousness, and survival in a variety of environmental condition ...201223011963
synthesis and immunochemical evaluation of a non-methylated disaccharide analogue of the anthrax tetrasaccharide.anthrax tetrasaccharide is an oligosaccharide expressed at the outermost surface of the bacillus anthracis spores, featuring three rhamnoses and a rare sugar called anthrose. this motif has now been identified as a plausible component of future human vaccines against anthrax. we report herein the synthesis of a 2-o-demethylated-β-d-anthropyranosyl-(1→3)-α-l-rhamnopyranose disaccharide analogue of this tetrasaccharide from a cyclic sulfate intermediate. this disaccharide conjugated to bsa induces ...201223010801
effect of ph on the electrophoretic mobility of spores of bacillus anthracis and its surrogates in aqueous solutions.the electrophoretic mobility (epm) of endospores of bacillus anthracis and surrogates was measured in aqueous solution across a broad ph range and several ionic strengths. epm values trended around phylogenetic clustering based on the 16s rrna gene. measurements reported here provide new insight for bacillus anthracis surrogate selection and for attachment/detachment and transport studies.201223001659
genetic barcodes for improved environmental tracking of an anthrax simulant.the development of realistic risk models that predict the dissemination, dispersion and persistence of potential biothreat agents have utilized nonpathogenic surrogate organisms such as bacillus atrophaeus subsp. globigii or commercial products such as bacillus thuringiensis subsp. kurstaki. comparison of results from outdoor tests under different conditions requires the use of genetically identical strains; however, the requirement for isogenic strains limits the ability to compare other desira ...201223001658
the effect of seasonal variation on anthrax epidemiology in the upper zambezi floodplain of western zambia.anthrax has become endemic throughout the upper zambezi floodplain located in the western province of zambia over the recent years. to date, no comprehensive study has been carried out to determine whether recurrence of anthrax outbreaks may be linked to differences in precipitation and human activities. retrospective data for the period 1999 to 2007 showed that a total of 1,216 bovine cases of anthrax were reported. during the same period, 1,790 human anthrax cases and a corresponding case fata ...201223000586
interactions of high-affinity cationic blockers with the translocation pores of b. anthracis, c. botulinum, and c. perfringens binary toxins.cationic β-cyclodextrin derivatives were recently introduced as highly effective, potentially universal blockers of three binary bacterial toxins: anthrax toxin of bacillus anthracis, c2 toxin of clostridium botulinum, and iota toxin of clostridium perfringens. the binary toxins are made of two separate components: the enzymatic a component, which acts on certain intracellular targets, and the binding/translocation b component, which forms oligomeric channels in the target cell membrane. here we ...201222995493
structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria.some bacterial type ii fatty-acid synthesis (fas ii) enzymes have been shown to be important candidates for drug discovery. the scientific and medical quest for new fas ii protein targets continues to stimulate research in this field. one of the possible additional candidates is the acyl-carrier-protein synthase (acps) enzyme. its holo form post-translationally modifies the apo form of an acyl carrier protein (acp), which assures the constant delivery of thioester intermediates to the discrete e ...201222993090
certhrax toxin, an anthrax-related adp-ribosyltransferase from bacillus cereus.we identified certhrax, the first anthrax-like mart toxin from the pathogenic g9241 strain of bacillus cereus. certhrax shares 31% sequence identity with anthrax lethal factor from bacillus anthracis; however, we have shown that the toxicity of certhrax resides in the mart domain, whereas anthrax uses a metalloprotease mechanism. like anthrax lethal factor, certhrax was found to require protective antigen for host cell entry. this two-domain enzyme was shown to be 60-fold more toxic to mammalian ...201222992735
reversible blindness in bilateral optic neruritis associated with nasal flu vaccine.various case reports have shown possible associations between optic neuritis and different vaccines. some of the vaccines include influenza, hepatitis b and anthrax201222989339
assembly of the bclb glycoprotein into the exosporium and evidence for its role in the formation of the exosporium 'cap' structure in bacillus anthracis.the outermost layer of the bacillus anthracis spore consists of an exosporium comprised of an outer hair-like nap layer and an internal basal layer. a major component of the hair-like nap is the glycosylated collagen-like protein bcla. a second collagen-like protein, bclb, is also present in the exosporium. bclb possesses an n-terminal sequence that targets it to the exosporium and is similar in sequence to a cognate targeting region in bcla. bclb lacks, however, sequence similarity to the regio ...201222989026
isolation of bacillus anthracis from soil in selected high-risk areas of zimbabwe.to isolate bacillus anthracis from cattle carcass burial sites from high-risk districts in zimbabwe.201222984812
immunomagnetic capture of bacillus anthracis spores from food.food is a vulnerable target for potential bioterrorist attacks; therefore, a critical mitigation strategy is needed for the rapid concentration and detection of biothreat agents from food matrices. magnetic beads offer a unique advantage in that they have a large surface area for efficient capture of bacteria. we have demonstrated the efficient capture and concentration of bacillus anthracis (sterne) spores using immunomagnetic beads for a potential food application. magnetic beads from three di ...201222980007
quantitative analysis of the mechanism of dna binding by bacillus dnaa protein.dnaa protein has the sole responsibility of initiating a new round of dna replication in prokaryotic organisms. it recognizes the origin of dna replication, and initiates chromosomal dna replication in the bacterial genome. in gram-negative escherichia coli, a large number of dnaa molecules bind to specific dna sequences (known as dnaa boxes) in the origin of dna replication, oric, leading to the activation of the origin. we have cloned, expressed, and purified full-length dnaa protein in large ...201222974984
solution structure of the sortase required for efficient production of infectious bacillus anthracis spores.bacillus anthracis forms metabolically dormant endospores that upon germination can cause lethal anthrax disease in humans. efficient sporulation requires the activity of the srtc sortase (basrtc), a cysteine transpeptidase that covalently attaches the bash and basi proteins to the peptidoglycan of the forespore and predivisional cell, respectively. to gain insight into the molecular basis of protein display, we used nuclear magnetic resonance to determine the structure and backbone dynamics of ...201222974341
anthrax vaccine-induced antibodies provide cross-species prediction of survival to aerosol challenge.because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the food and drug administration's "animal rule," a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. u.s. government-sponsored animal studies have shown anthrax vaccine efficacy in a variety of settings. we examined data from 21 of ...201222972844
d-proline-based peptidomimetic inhibitors of anthrax lethal factor.in this work we reported the generation of d-proline-derived hydroxamic acids as inhibitors of anthrax lethal factor (lf), taking advantage of a pyrrolidine ring as the central scaffold and a hydroxamate group as the zn(2+) chelating agent. the introduction of two hydrophobic groups addressing the s1' subsite and a long substrate-binding groove was conceived by overlapping the bioactive conformations of two reported lf inhibitors. micromolar affinity of compound 38 suggested cis-3-substituted-1- ...201222960696
development of an inhalational bacillus anthracis exposure therapeutic model in cynomolgus macaques.appropriate animal models are required to test medical countermeasures to bioterrorist threats. to that end, we characterized a nonhuman primate (nhp) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the u.s. food and drug administration animal rule. a clinical profile was recorded for each nhp exposed to a lethal dose of bacillus anthracis ames spores. specific diagnostic parameters were detected relatively early in disease progr ...201222956657
small molecule inhibitors of bacillus anthracis protective antigen proteolytic activation and oligomerization.protective antigen (pa), lethal factor, and edema factor, the protein toxins of bacillus anthracis , are among its most important virulence factors and play a key role in infection. we performed a virtual ligand screen of a library of 10000 members to identify compounds predicted to bind to pa and prevent its oligomerization. four of these compounds slowed pa association in a fret-based oligomerization assay, and two of those protected cells from intoxication at concentrations of 1-10 μm. explor ...201222954387
identification of new dominant-negative mutants of anthrax protective antigen using directed evolution.the anthrax toxin is composed of three proteins: protective antigen (pa), lethal factor (lf), and edema toxin (ef). the pa moiety carries ef and lf into the cytosol of mammalian cells via a mechanism that depends on the oligomerization of pa and transmembrane pore formation by the pa oligomer. certain mutants of pa, termed dominant-negative (dn) mutants, can co-oligomerize with wild-type pa and disrupt the translocation ability of the pore. here, we constructed a pa mutant library by introducing ...201222948605
[genotype diversity of the bacillus anthracis strains isolated from the caucasus region].the study of the genotypes of bacillus anthracis strains isolated from the caucasus region was performed using mlva. among 149 strains, 32 distinctive mlva-8 genotypes belonging to ala, a3a, a4 and b1 molecular diversity groups were identified. 9 genotypes were not described previously; 6 genotypes were not found in other geographic regions and could be considered as endemic for caucasus. the majority of the identified genotypes are widespread not only in caucasus, but also throughout eurasia, a ...201222937567
[identification of the differences in the genes responsible for methionine biosynthesis in bacillus anthracis strains and phylogeny-related species].the comparative analysis of the gene sequences encoding the synthesis of enzymes responsible for the intermediary metabolism of methionine in bacillus anthracis strains and in closely related bacterial species was carried out. deletion of 42 nucleotides in the hom2 gene, which determines the homoserinedehydrogenase, is detected in all tested bacillus anthracis strains. in the strains of other bacillar species hom2 gene mutation, which blocks up the tracts of methionine and threonine biosynthesis ...201222937566
strand-specific rna-seq reveals ordered patterns of sense and antisense transcription in bacillus anthracis.although genome-wide transcriptional analysis has been used for many years to study bacterial gene expression, many aspects of the bacterial transcriptome remain undefined. one example is antisense transcription, which has been observed in a number of bacteria, though the function of antisense transcripts, and their distribution across the bacterial genome, is still unclear.201222937038
both lethal and edema toxins of bacillus anthracis disrupt the human dendritic cell chemokine network.bacillus anthracis, the agent of anthrax, produces two main virulence factors: a capsule and two toxins. both lethal toxin (lt) and edema toxin (et) paralyze the immune defense system. here, we analyze the effects of lt and et on the capacity of human monocyte-derived dendritic cells (modc) to produce proinflammatory chemokines. we show that both toxins disrupt proinflammatory chemokine production. lt has more pronounced effects than et on cxcl8 production, which is correlated with impaired recr ...201222937027
endolysins of bacillus anthracis bacteriophages recognize unique carbohydrate epitopes of vegetative cell wall polysaccharides with high affinity and selectivity.bacteriophages express endolysins which are the enzymes that hydrolyze peptidoglycan resulting in cell lysis and release of bacteriophages. endolysins have acquired stringent substrate specificities, which have been attributed to cell wall binding domains (cbd). although it has been realized that cbds of bacteriophages that infect gram-positive bacteria target cell wall carbohydrate structures, molecular mechanisms that confer selectivity are not understood. a range of oligosaccharides, derived ...201222935003
identification of exosite-targeting inhibitors of anthrax lethal factor by high-throughput screening.protease inhibitor discovery has focused almost exclusively on compounds that bind to the active site. inhibitors targeting protease exosites, regions outside of the active site that influence catalysis, offer potential advantages of increased specificity but are difficult to systematically discover. here, we describe an assay suitable for detecting exosite-targeting inhibitors of the metalloproteinase anthrax lethal factor (lf) based on cleavage of a full-length mitogen-activated protein kinase ...201222840775
molecular epidemiologic investigation of an anthrax outbreak among heroin users, europe.in december 2009, two unusual cases of anthrax were diagnosed in heroin users in scotland. a subsequent anthrax outbreak in heroin users emerged throughout scotland and expanded into england and germany, sparking concern of nefarious introduction of anthrax spores into the heroin supply. to better understand the outbreak origin, we used established genetic signatures that provided insights about strain origin. next, we sequenced the whole genome of a representative bacillus anthracis strain from ...201222840345
characterization of a therapeutic model of inhalational anthrax using an increase in body temperature in new zealand white rabbits as a trigger for treatment.the development of an appropriate animal therapeutic model is essential to assess the potential efficacy of therapeutics for use in the event of a bacillus anthracis exposure. we conducted a natural history study that showed new zealand white rabbits exhibited a significant increase in body temperature (sibt), changes in hematologic parameters, and increases in c-reactive protein and succumbed to disease with an average time to death of approximately 73 h following aerosol challenge with b. anth ...201222837095
global health surveillance.awareness of the importance of global health surveillance increased in the latter part of the 20th century with the global emergence of human immunodeficiency virus and novel strains of influenza. in the first decade of the 21st century, several events further highlighted global shared interests in and vulnerability to infectious diseases. bioterrorist use of anthrax spores in 2001 raised awareness of the value of public health surveillance for national security. the epidemic of severe acute res ...201222832992
a multiplex pcr assay for the simultaneous identification of virulent & avirulent bacillus anthracis targeting genes of plasmids & chromosomal dna. 201222825613
monoclonal antibodies and toxins--a perspective on function and isotype.antibody therapy remains the only effective treatment for toxin-mediated diseases. the development of hybridoma technology has allowed the isolation of monoclonal antibodies (mabs) with high specificity and defined properties, and numerous mabs have been purified and characterized for their protective efficacy against different toxins. this review summarizes the mab studies for 6 toxins--shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and staphylococcal enterotoxin b ( ...201222822456
bacillus anthracis lethal toxin induces complex changes in sympathetic nerve discharge regulation.bacillus anthracis lethal toxin (letx) alters blood pressure and visceral sympathetic nerve discharge (snd) regulation (garcia et al., 2012). the present results indicate that letx infusions produce similar response profiles in peripheral (lumbar) and visceral (renal) snd; an initial widespread activation of sympathetic nerve outflow, followed by a generalized reduction in lumbar and renal snd from peak levels, although the sympathoinhibition tended to be attenuated in lumbar snd. combined hypox ...201222818628
razor ex anthrax air detection system.the razor ex anthrax air detection system, developed by idaho technology, inc. (iti), is a qualitative method for the detection of bacillus anthracis spores collected by air collection devices. this system comprises a dna extraction kit, a freeze-dried pcr reagent pouch, and the razor ex real-time pcr instrument. each pouch contains three assays, which distinguish potentially virulent b. anthracis from avirulent b. anthracis and other bacillus species. these assays target the pxo1 and pxo2 plasm ...201222816278
complete genome sequence of bacillus anthracis h9401, an isolate from a korean patient with anthrax.bacillus anthracis h9401 (nccp 12889) is an isolate from a korean patient with gastrointestinal anthrax. the whole genome of h9401 was sequenced. it is a circular chromosome containing 5,480 open reading frames (orfs) and two plasmids, pxo1 containing 202 orfs and pxo2 containing 110 orfs. h9401 shows high pathogenicity and genome sequence similarity to ames ancestor.201222815438
structural and immunological analysis of anthrax recombinant protective antigen adsorbed to aluminum hydroxide adjuvant.new anthrax vaccines currently under development are based on recombinant protective antigen (rpa) and formulated with aluminum adjuvant. because long-term stability is a desired characteristic of these vaccines, an understanding of the effects of adsorption to aluminum adjuvants on the structure of rpa is important. using both biophysical and immunological techniques, we compared the structure and immunogenicity of freshly prepared rpa-alhydrogel formulations to that of formulations stored for ...201222815152
cationic quaternized aminocalix[4]arenes: cytotoxicity, haemolytic and antibacterial activities.this study reports the characterization of three cationic amphiphillic aminocalix[4]arenes as potential antimicrobial agents in vitro. in cytotoxicity tests on mouse macrophage raw 264.7 cells aminocalix[4]arenes 1 and 3 showed no toxicity up to 200 and 100 μm concentrations, respectively, while 2 was non-toxic only up to 50 μm. with regard to the haemolytic activity on rabbit red blood cells, 1 was not active at concentrations up to 100 μm in contrast to the other two studied macrocycles. compo ...201324157345
selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses.pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. one common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. to identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. here we report that 4-bromobenzaldehyde n-( ...201324191014
structural and biological studies on bacterial nitric oxide synthase inhibitors.nitric oxide (no) produced by bacterial nos functions as a cytoprotective agent against oxidative stress in staphylococcus aureus, bacillus anthracis, and bacillus subtilis. the screening of several nos-selective inhibitors uncovered two inhibitors with potential antimicrobial properties. these two compounds impede the growth of b. subtilis under oxidative stress, and crystal structures show that each compound exhibits a unique binding mode. both compounds serve as excellent leads for the future ...201324145412
a multiplex bead-based suspension array assay for interrogation of phylogenetically informative single nucleotide polymorphisms for bacillus anthracis.single nucleotide polymorphisms (snps) are abundant in genomes of all species and represent informative dna markers extensively used to analyze phylogenetic relationships between strains. medium to high throughput, open methodologies able to test many snps in a minimum time are therefore in great need. by using the versatile luminex® xtag technology, we developed an efficient multiplexed snp genotyping assay to score 13 phylogenetically informative snps within the genome of bacillus anthracis. t ...201324140576
bacillus cereus sensu lato genomes: basis for identifying anthrax disease strain sources. 201324092785
whole-genome sequences of 94 environmental isolates of bacillus cereus sensu lato.bacillus cereus sensu lato is a species complex that includes the anthrax pathogen bacillus anthracis and other bacterial species of medical, industrial, and ecological importance. their phenotypes of interest are typically linked to large plasmids that are closely related to the anthrax plasmids pxo1 and pxo2. here, we present the draft genome sequences of 94 isolates of b. cereus sensu lato, which were chosen for their plasmid content and environmental origins.201324092776
calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis.the protective antigen component of bacillus anthracis toxins can interact with at least three distinct proteins on the host cell surface, capillary morphogenesis gene 2 (cmg2), tumor endothelial marker 8, and β1-integrin, and, with the assistance of other host proteins, enters targeted cells by receptor-mediated endocytosis. using an antisense-based phenotypic screen, we discovered the role of calpains in this process. we show that functions of a ubiquitous ca(2+)-dependent cysteine protease, c ...201324085852
prophylaxis and treatment of anthrax in pregnant women.to review the safety and pharmacokinetics of antimicrobials recommended for anthrax postexposure prophylaxis and treatment in pregnant women.201324084549
influence of temperature and organic load on chemical disinfection of geobacillus steareothermophilus spores, a surrogate for bacillus anthracis.this study evaluated the influence of temperature and organic load on the effectiveness of domestic bleach (db), surface decontamination foam (sdf), and virkon in inactivating geobacillus stearothermophilus spores, which are a surrogate for bacillus anthracis spores. the spores were suspended in light or heavy organic preparations and the suspension was applied to stainless steel carrier disks. the dried spore inoculum was covered with the disinfectants and the disks were then incubated at vario ...201324082400
bacillus anthracis, virulence factors, pcr, and interpretation of results. 201324067452
a chemically synthesized capture agent enables the selective, sensitive, and robust electrochemical detection of anthrax protective antigen.we report on a robust and sensitive approach for detecting protective antigen (pa) exotoxin from bacillus anthracis in complex media. a peptide-based capture agent against pa was developed by improving a bacteria display-developed peptide into a highly selective biligand through in situ click screening against a large, chemically synthesized peptide library. this biligand was coupled with an electrochemical enzyme-linked immunosorbent assay utilizing nanostructured gold electrodes. the resultant ...201324063758
modified aoac three step method (officialmethod 2008.05): consolidation of fractions b and c.the aoac quantitative three step method (tsm; aoac official method sm 2008.05) is validated for testing the efficacy of liquid sporicides against spores of bacillus subtilis and bacillus anthracis on selected hard, nonporous, and porous surfaces. the tsm uses 5x5x1 mm inoculated coupons (carriers), which are placed in 400 microl liquid sporicidal agent contained in a microcentrifuge tube. following exposure of inoculated carriers to the test chemical and subsequent neutralization, viable spores ...201324282930
hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin.anthrax lethal toxin is a classical ab toxin comprised of two components: protective antigen (pa) and lethal factor (lf). here, we show that following assembly and endocytosis, pa forms a channel that translocates lf, not only into the cytosol, but also into the lumen of endosomal intraluminal vesicles (ilvs). these ilvs can fuse and release lf into the cytosol, where lf can proteolyze and disable host targets. we find that lf can persist in ilvs for days, fully sheltered from proteolytic degrad ...201324239351
single, double and quadruple alanine substitutions at oligomeric interfaces identify hydrophobicity as the key determinant of human neutrophil alpha defensin hnp1 function.hnp1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including tyr¹⁶, ile²⁰, leu²⁵, and phe²⁸. previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: i20a-hnp1 and l25a-hnp1, plus the double alanine mutants i20a/l25a-hnp1 and y16a/f28a-hnp1, an ...201324236072
a hierarchical distance sampling approach to estimating mortality rates from opportunistic carcass surveillance data.distance sampling is widely used to estimate the abundance or density of wildlife populations. methods to estimate wildlife mortality rates have developed largely independently from distance sampling, despite the conceptual similarities between estimation of cumulative mortality and the population density of living animals. conventional distance sampling analyses rely on the assumption that animals are distributed uniformly with respect to transects and thus require randomized placement of trans ...201324224079
an unusual mechanism of isopeptide bond formation attaches the collagenlike glycoprotein bcla to the exosporium of bacillus anthracis. 201324222492
development of a comparative risk ranking system for agents posing a bioterrorism threat to human or animal populations.various systems for prioritizing biological agents with respect to their applicability as biological weapons are available, ranging from qualitative to (semi)quantitative approaches. this research aimed at generating a generic risk ranking system applicable to human and animal pathogenic agents based on scientific information. criteria were evaluated and clustered to create a criteria list. considering availability of data, a number of 28 criteria separated by content were identified that can be ...201323971819
mass spectrometric detection of protein-based toxins.this review focuses on mass spectrometric detection of protein-based toxins, which are among the most toxic substances known. special emphasis is given to the bacterial toxins botulinum neurotoxin from clostridium botulinum and anthrax toxins from bacillus anthracis as well as the plant toxin ricin produced by ricinus communis. a common feature, apart from their extreme toxicity, is that they are composed of 2 polypeptide chains, one of which is responsible for cell uptake and another that has e ...201323971809
genetic diversity of bacillus anthracis in europe: genotyping methods in forensic and epidemiologic investigations.bacillus anthracis, the etiological agent of anthrax, a zoonosis relatively common throughout the world, can be used as an agent of bioterrorism. in naturally occurring outbreaks and in criminal release of this pathogen, a fast and accurate diagnosis is crucial to an effective response. microbiological forensics and epidemiologic investigations increasingly rely on molecular markers, such as polymorphisms in dna sequence, to obtain reliable information regarding the identification or source of a ...201323971802
a generic open-source software framework supporting scenario simulations in bioterrorist crises.since the 2001 anthrax attack in the united states, awareness of threats originating from bioterrorism has grown. this led internationally to increased research efforts to improve knowledge of and approaches to protecting human and animal populations against the threat from such attacks. a collaborative effort in this context is the extension of the open-source spatiotemporal epidemiological modeler (stem) simulation and modeling software for agro- or bioterrorist crisis scenarios. stem, origina ...201323971799
comparative evaluation of vacuum-based surface sampling methods for collection of bacillus spores.in this study, four commonly-used sampling devices (vacuum socks, 37 mm 0.8 μm mixed cellulose ester (mce) filter cassettes, 37 mm 0.3 μm polytetrafluoroethylene (ptfe) filter cassettes, and 3m™ forensic filters) were comparatively evaluated for their ability to recover surface-associated spores. aerosolized spores (~10(5)cfucm(-2)) of a bacillus anthracis surrogate were allowed to settle onto three material types (concrete, carpet, and upholstery). ten replicate samples were collected using eac ...201324184017
[diagnosis and treatment of anthrax in palpebral localization: report of a case and review of literature]. 201324171070
surface plasmon resonance biosensor for detection of bacillus anthracis, the causative agent of anthrax from soil samples targeting protective antigen.bacillus anthracis, the causative agent of anthrax is one of the most important biological warfare agents. in this study, surface plasmon resonance (spr) technology was used for indirect detection of b. anthracis by detecting protective antigen (pa), a common toxin produced by all live b. anthracis bacteria. for development of biosensor, a monoclonal antibody raised against b. anthracis pa was immobilized on carboxymethyldextran modified gold chip and its interaction with pa was characterized in ...201324426078
reverse line blot macroarray for simultaneous detection and characterization of four biological warfare agents.the need for a rapid detection and characterization of biowarfare (bw) agents cannot be over emphasized. with diverse array of potential bw pathogen available presently, rapid identification of the pathogen is crucial, so that specific therapy and control measures can be initiated. we have developed a multiplex polymerase chain reaction based reverse line blot macroarray to simultaneously detect four pathogens of bw importance viz. bacillus anthracis, yersinia pestis, brucella melitensis and bur ...201324426077
quantitative anti-pa igg elisa; assessment and comparability with the anthrax toxin neutralization assay in goats.presently, few data exist on the level and duration of anti-protective antigen (pa) igg in vaccinated livestock. various adaptation of enzyme-linked immunosorbent assays (elisas) have been developed in studies to assess immune response following vaccination, albeit mostly in laboratory rodent models. the quantitative anti-anthrax igg elisa in this study describes a method of enumerating the concentration of anti-pa specific igg present in sera of immunized goats, with the aid of an affinity-puri ...201324373579
allelic-dependent expression of an activating fc receptor on b cells enhances humoral immune responses.b cells are pivotal regulators of acquired immune responses, and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of b cell function can substantially alter immunological responses. the balance of negative and positive signals in maintaining an appropriate b cell activation threshold is critical in b lymphocyte immune tolerance and autoreactivity. fcγriib (cd32b), the only recognized fcγ receptor on b cells, provides immunoglobulin ...201324353158
applications of docking and molecular dynamic studies on the search for new drugs against the biological warfare agents bacillus anthracis and yersinia pestis.the fear of biological warfare agents (bwa) use by terrorists is the major concern of the security agencies and health authorities worldwide today. the non-existence of vaccines or drugs against most bwa and the possibility of genetic modified strains has turned the search for new drugs to a state of urgency. fast in silico techniques are, therefore, perfect tools for this task once they can quickly provide structures of several new lead compounds for further experimental work. here we try to pr ...201324341424
identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins.clostridium difficile is a major cause of infectious diarrhea worldwide. although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. also, apart from the toxins, proteins exported by c. difficile into the extracellular milieu have been poorly studied. in order to identify novel extracellular factors of c. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and r20291, using liq ...201324303041
introduction of the republic of korea-the united states of america's joint exercise against biothreats in 2013: able response 13.the republic of korea (rok) and the the united states of america (usa) has held joint exercises to respond to biothreats in the korean peninsula since 2011. the exercise was called able response (ar) and it aims to coordinate interministerial procedures inside korea and international procedures in requesting the medical resources urgently between rok and usa, and among rok and the united nations, and nongovernmental organizations. ar13 was a functional exercise with a scenario that presumed a se ...201324298445
risk practices for animal and human anthrax in bangladesh: an exploratory study.from august 2009 to october 2010, international centre for diarrheal disease research, bangladesh and the institute of epidemiology, disease control and research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program.201324298326
[the experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated against plague and anthrax].the article deals with experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated with plague and anthrax live dry vaccines. it is established that the introduction of plague and anthrax live dry vaccines into organism of vaccinated persons ignites immunologic rearrangement manifested by reliable increase of level of blood concentration of th1-lymphocytes (immunologic memory cells) against the background of vaccination. the highe ...201324640112
ante- and postmortem diagnostic techniques for anthrax: rethinking pathogen exposure and the geographic extent of the disease in wildlife.although antemortem approaches in wildlife disease surveillance are common for most zoonoses, they have been used infrequently in anthrax surveillance. classically, anthrax is considered a disease with extremely high mortality. this is because anthrax outbreaks are often detected ex post facto through wildlife or livestock fatalities or spillover transmission to humans. as a result, the natural prevalence of anthrax infection in animal populations is largely unknown. however, in the past 20 yr, ...201324502707
[bioterrorism and pathogenic microorganisms].in recent years the use of pathogenic microorganisms in acts of bioterrorism has been the subject of major concern in many countries. this paper presents a possible application of viruses and bacteria for warfare and terrorist purposes, as well as a laboratory diagnosis to identify those agents. the viruses of smallpox (orthopoxvirus), of hemorrhagic fever and those belonging to filovirus have been highlighted, inter alia, as agents of human infection with bioterrorist intent. among the bacteria ...201324473660
historical review of the list of occupational diseases recommended by the international labour organization (ilo).the list of occupational diseases established in the international and national legal system has played important roles in both prevention of and compensation for workers' diseases. this report reviewed the historical development in the ilo list of occupational diseases and suggested implications of the trends. since the first establishment of the ilo list of occupational diseases in 1925, the list has played a key role in harmonizing the development of policies on occupational diseases at the i ...201324472440
haem-based sensors: a still growing old superfamily.the haem-based sensors are chimeric multi-domain proteins responsible for the cellular adaptive responses to environmental changes. the signal transduction is mediated by the sensing capability of the haem-binding domain, which transmits a usable signal to the cognate transmitter domain, responsible for providing the adequate answer. four major families of haem-based sensors can be recognized, depending on the nature of the haem-binding domain: (i) the haem-binding pas domain, (ii) the co-sensit ...201324054793
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