Publications

TitleAbstractYear
Filter
PMID
Filter
in vitro studies of peptidoglycan binding and hydrolysis by the bacillus anthracis germination-specific lytic enzyme sleb.the bacillus anthracis endospore loses resistance properties during germination when its cortex peptidoglycan is degraded by germination-specific lytic enzymes (gsles). although this event normally employs several gsles for complete cortex removal, the sleb protein alone can facilitate enough cortex hydrolysis to produce vulnerable spores. as a means to better understand its enzymatic function, sleb was overexpressed, purified, and tested in vitro for depolymerization of cortex by measurement of ...201020971910
glucose-dependent activation of bacillus anthracis toxin gene expression and virulence requires the carbon catabolite protein ccpa.sensing environmental conditions is an essential aspect of bacterial physiology and virulence. in bacillus anthracis, the causative agent of anthrax, transcription of the two major virulence factors, toxin and capsule, is triggered by bicarbonate, a major compound in the mammalian body. here it is shown that glucose is an additional signaling molecule recognized by b. anthracis for toxin synthesis. the presence of glucose increased the expression of the protective antigen toxin component-encodin ...201020971911
myd88-dependent signaling protects against anthrax lethal toxin-induced impairment of intestinal barrier function.myd88-deficient mice were previously shown to have increased susceptibility to bacillus anthracis infection relative to wild-type animals. to determine the mechanism by which myd88 protects against b. anthracis infection, knockout mice were challenged with nonencapsulated, toxigenic b. anthracis or with anthrax toxins. myd88-deficient mice had increased susceptibility to b. anthracis and anthrax lethal toxin but not to edema toxin. lethal toxin alone induced marked multifocal intestinal ulcers i ...201020974827
a modeled structure for amidase-03 from bacillus anthracis.homology models of amidase-03 from bacillus anthracis were constructed using modeller (9v2). modeller constructs protein models using an automated approach for comparative protein structure modeling by the satisfaction of spatial restraints. a template structure of listeria monocytogenes bacteriophage psa endolysin plypsa (pdb id: 1xov) was selected from protein databank (pdb) using blastp with blosum62 sequence alignment scoring matrix. we generated five models using the modeller default routin ...200920975917
studies on the nutritional requirements of bacillus anthracis. 194620983281
application of nutritional studies for development of practical culture media for bacillus anthracis. 194620983282
the capsular substance of bacillus anthracis. 194620989452
the capsular substance of bacillus anthracis. 194620989455
[not available]. 194620989755
[not available]. 194620990196
avirulent anthrax vaccine. 194620990776
cutaneous anthrax; report of twenty-five cases. 194620992839
anthrax; its diagnosis and treatment. 194620994281
chemotherapy of experimental anthrax infections. 194620998820
observations on the resistance of anthrax spores to heat. 194521005511
[treatment of anthrax]. 194521008645
[on the chemotherapy of experimental infection by anthrax]. 194521008748
a note on the efficacy of commercial anti-anthrax bacterins. 194521009458
[not available]. 194521011460
[not available]. 194521013359
anthrax treated with sulfadiazine; report of a case. 194621013959
anthrax. 194521015371
[not available]. 194521021176
[not available]. 194621025026
treatment of human anthrax with penicillin. 194521026573
cd and mcd spectroscopic studies of the two dps miniferritin proteins from bacillus anthracis: role of o2 and h2o2 substrates in reactivity of the diiron catalytic centers.dna protection during starvation (dps) proteins are miniferritins found in bacteria and archaea that provide protection from uncontrolled fe(ii)/o radical chemistry; thus the catalytic sites are targets for antibiotics against pathogens, such as anthrax. ferritin protein cages synthesize ferric oxymineral from fe(ii) and o(2)/h(2)o(2), which accumulates in the large central cavity; for dps, h(2)o(2) is the more common fe(ii) oxidant contrasting with eukaryotic maxiferritins that often prefer dio ...201021028901
photocatalytic inactivation of spores of bacillus anthracis using titania nanomaterials.studies on photocatalytic inactivation of spores of bacillus anthracis have been carried out using nanosized titania materials and uva light or sun light. results demonstrated pseudo first order behaviour of spore inactivation kinetics. the value of kinetic rate constant increased from 0.4h(-1) to 1.4h(-1) indicating photocatalysis facilitated by addition of nanosized titania. nanosized titania exhibited superior inactivation kinetics on par with large sized titania. the value of kinetic rate co ...201021035260
structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers.the protein transporter anthrax lethal toxin is composed of protective antigen (pa), a transmembrane translocase, and lethal factor (lf), a cytotoxic enzyme. after its assembly into holotoxin complexes, pa forms an oligomeric channel that unfolds lf and translocates it into the host cell. we report the crystal structure of the core of a lethal toxin complex to 3.1-å resolution; the structure contains a pa octamer bound to four lf pa-binding domains (lf(n)). the first α-helix and β-strand of each ...201021037566
role of purine biosynthesis in bacillus anthracis pathogenesis and virulence.bacillus anthracis, the etiological agent of anthrax, is a spore-forming, gram-positive bacterium and a category a biothreat agent. screening of a library of transposon-mutagenized b. anthracis spores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme purh. purh is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine imp. we constructed and characterized defined purh mutants of the virulent b ...201021041498
structure of dihydroorotase from bacillus anthracis at 2.6 å resolution.dihydroorotase (ec 3.5.2.3) catalyzes the reversible cyclization of n-carbamoyl-l-aspartate to l-dihydroorotate in the third step of the pyrimidine-biosynthesis pathway in bacillus anthracis. a comparison is made between the structures of dihydroorotase from four different organisms, including b. anthracis dihydroorotase, and reveals substantial variations in the active site, dimer interface and overall tertiary structure. these differences demonstrate the utility of exploring multiple structure ...201021045288
anthrax in a scottish intravenous drug user.anthrax, caused by bacillus anthracis, is an uncommon disease in the united kingdom. in december 2009, the first recorded case of injectable anthrax in the uk was diagnosed in glasgow, scotland. this case report describes the disease presentation in a detained person in police custody in dumfries, south west scotland. the case highlights to forensic physicians the clinical features of anthrax, particularly in relation to intravenous drug misuse and the importance of early recognition. anthrax an ...201021056883
alkaline earth metals are not required for the restoration of the apoform of anthrax lethal factor to its holoenzyme state.anthrax lethal factor (lf) is a zinc-dependent metalloendopeptidase previously shown to require calcium and magnesium for the restoration of its catalytic function upon exposure of the apoprotein (apolf) to zn(2+). since concrete ca(2+)/mg(2+) binding sites have not been identified in lf, the effects of alkaline earth metals on the enzymatic function of hololf (znlf) and on the reconstitution of apolf were reinvestigated. the current study reveals alkaline earth metals to be inhibitory at concen ...201021059339
cost-effective interrogation of single nucleotide polymorphisms using the mismatch amplification mutation assay and capillary electrophoresis.the ability to characterize snps is an important aspect of many clinical diagnostic, genetic and evolutionary studies. here, we designed a multiplexed snp genotyping method to survey a large number of phylogenetically informative snps within the genome of the bacterium bacillus anthracis. this novel method, ce universal tail mismatch amplification mutation assay (cuma), allows for pcr multiplexing and automatic scoring of snp genotypes, thus providing a rapid, economical and higher throughput al ...201021064143
[diagnostic of anthrax in russia]. 201021064225
the nutritional requirements of bacillus anthracis. 194621064683
anthrax lethal and edema toxins produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines.high mortality in the 2001 us and recent european anthrax outbreaks suggests that better understanding of the effects of the toxins produced by this bacterium is needed to improve treatment.201021067373
a dynamic dose-response model to account for exposure patterns in risk assessment: a case study in inhalation anthrax.the most commonly used dose-response models implicitly assume that accumulation of dose is a time-independent process where each pathogen has a fixed risk of initiating infection. immune particle neutralization of pathogens, however, may create strong time dependence; i.e. temporally clustered pathogens have a better chance of overwhelming the immune particles than pathogen exposures that occur at lower levels for longer periods of time. in environmental transmission systems, we expect different ...201021068030
anthrax toxins--roadblocks for exocytic trafficking.anthrax toxins cause vascular dysfunction, in part by perturbing the endothelial cell barrier. reporting in nature, guichard et al. shed new light on the mechanism by which this occurs and show that anthrax toxins interfere with exocytic delivery of cadherins to endothelial cell junctions by antagonizing the exocyst complex.201021074712
anthrax toxin delivers a one-two punch.although anthrax toxin was identified as a major bacillus anthracis virulence factor over 50 years ago, defining the physiologically relevant targets has been challenging. liu et al. demonstrate that intoxication of myeloid-derived cells contributes to establishing infection but is not required for mortality resulting from high toxin concentrations associated with end-stage disease.201021075350
anthrax toxin targeting of myeloid cells through the cmg2 receptor is essential for establishment of bacillus anthracis infections in mice.bacillus anthracis kills through a combination of bacterial infection and toxemia. anthrax toxin working via the cmg2 receptor mediates lethality late in infection, but its roles early in infection remain unclear. we generated myeloid-lineage specific cmg2-deficient mice to examine the roles of macrophages, neutrophils, and other myeloid cells in anthrax pathogenesis. macrophages and neutrophils isolated from these mice were resistant to anthrax toxin. however, the myeloid-specific cmg2-deficien ...201021075356
anthrax toxin receptor drives protective antigen oligomerization and stabilizes the heptameric and octameric oligomer by a similar mechanism.anthrax toxin is comprised of protective antigen (pa), lethal factor (lf), and edema factor (ef). these proteins are individually nontoxic; however, when pa assembles with lf and ef, it produces lethal toxin and edema toxin, respectively. assembly occurs either on cell surfaces or in plasma. in each milieu, pa assembles into a mixture of heptameric and octameric complexes that bind lf and ef. while octameric pa is the predominant form identified in plasma under physiological conditions (ph 7.4, ...201021079738
phase i study of safety and immunogenicity of an escherichia coli-derived recombinant protective antigen (rpa) vaccine to prevent anthrax in adults.the fatal disease caused by bacillus anthracis is preventable with a prophylactic vaccine. the currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. in this report we describe a phase i clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant escherichia coli-derived, b. anthracis protective antigen (rpa).201021079762
terrorism and the behavioral sciences.terrorism has existed for millennia and is a phenomenon well-known to many parts of the world. americans were forced to recognize this phenomenon, and our vulnerability to it, by two sets of events in 2001: the attacks on new york city and washington, dc, and the anthrax mailings that followed shortly thereafter. psychiatry, psychology, and other behavioral and social sciences have been looked to for assistance in collecting and analyzing intelligence data, understanding terrorism, and developin ...201021080775
protein-centric data integration for functional analysis of comparative proteomics data.high-throughput proteomic, microarray, protein interaction and other experimental methods all generate long lists of proteins and/or genes that have been identified or have varied in accumulation under the experimental conditions studied. these lists can be difficult to sort through for biologists to make sense of. here we describe a next step in data analysis--a bottom-up approach at data integration--starting with protein sequence identifications, mapping them to a common representation of the ...201121082443
clinical findings in children with cutaneous anthrax in eastern turkey.anthrax is a zoonosis produced by bacillus anthracis. the aim of this study was to evaluate the clinical findings, therapy, and outcome in children with cutaneous anthrax (ca). data on age, gender, occupation, clinical symptoms and findings, location and type of lesions, clinical history, laboratory findings, treatment, and outcome were recorded from patients' medical records, retrospectively. the study included 65 patients between 1 month and 18 years old (9.0±4.0 years), 37 patients (56.9%) we ...201021083757
characterization of an nadh-dependent persulfide reductase from shewanella loihica pv-4: implications for the mechanism of sulfur respiration via fad-dependent enzymes (,).the nadh-dependent persulfide reductase (npsr), a recently discovered member of the pndor family of flavoproteins that contains both the canonical flavoprotein reductase domain and a rhodanese domain, is proposed to be involved in the dissimilatory reduction of s(0) for shewanella loihica pv-4. we have previously shown that polysulfide is a substrate for this enzyme, and a recently determined structure of a closely related enzyme (coadr-rhod from bacillus anthracis) suggested the importance of a ...201021090815
identifying experimental surrogates for bacillus anthracis spores: a review.abstract: bacillus anthracis, the causative agent of anthrax, is a proven biological weapon. in order to study this threat, a number of experimental surrogates have been used over the past 70 years. however, not all surrogates are appropriate for b. anthracis, especially when investigating transport, fate and survival. although b. atrophaeus has been widely used as a b. anthracis surrogate, the two species do not always behave identically in transport and survival models. therefore, we devised a ...201021092338
accurate, rapid and high-throughput detection of strain-specific polymorphisms in bacillus anthracis and yersinia pestis by next-generation sequencing.abstract:201021092340
inhibition of poxvirus spreading by the anti-tumor drug gefitinib (iressa).the threat of smallpox virus as a bioterrorist weapon is raising international concerns again since the anthrax attacks in the usa in 2001. the medical readiness of treating patients suffering from such infections is a prerequisite of an effective civil defense system. currently the only therapeutic option for the treatment of poxvirus infections relies on the virostatic nulceosid analog cidofovir, although severe side effects and drug resistant strains have been described. a growing understandi ...201021094187
injection anthrax causing compartment syndrome and necrotising fasciitis. 201021097792
highly effective generic adjuvant systems for orphan or poverty-related vaccines.safe and effective adjuvants are needed for many vaccines with limited commercial appeal, such as vaccines to infrequent (orphan) diseases or to neglected and poverty-related diseases. here we found that three nonproprietary liposome formulations containing monophosphoryl lipid a each induced 3-fold to 5-fold increased titers of binding and neutralizing antibodies to anthrax protective antigen compared to aluminum hydroxide-adsorbed antigen in monkeys. all vaccinated monkeys were protected again ...201021115053
the phenotypic and genotypic characterization of bacillus anthracis isolates from iran.to understand epidemiology of bacillus anthracis in iran, the morphological, biochemical, and virulence specifications of 32 b. anthracis isolates, collected from human, sheep, cattle, goat, and environmental specimens obtained from throughout iran were examined by conventional and molecular approaches. b. anthracis isolates were characterized in multiple ways: (1) capsule formation both on bicarbonate agar and in defibrinated horse blood, (2) motility of vegetative forms, (3) hemolysis on 5% sh ...201021116715
case-control study investigating an anthrax outbreak in saskatchewan, canada--summer 2006.in 2006, an outbreak of anthrax in saskatchewan affected several species but most of the losses occurred in cattle. potential risk factors contributing to this outbreak were investigated through questionnaires involving 117 case farms and 259 control farms geographically representative of the saskatchewan beef herd. the occurrence of flooding [odds ratio (or) = 3.4; 95% confidence interval (ci): 1.8 to 6.4], wetter pastures (good: or = 3.5; 95% ci: 1.4 to 8.5; wet: or = 7.2; 95% ci: 2.9 to 18.1) ...201021119863
exploring the role of host cell chaperones/ppiases during cellular up-take of bacterial adp-ribosylating toxins as basis for novel pharmacological strategies to protect mammalian cells against these virulence factors.bacterial exotoxins exploit protein transport pathways of their mammalian target cells to deliver their enzymatic active moieties into the cytosol. there, they modify their specific substrate molecules resulting in cell damage and the clinical symptoms characteristic for each individual toxin. we have investigated the cellular uptake of the binary actin adp-ribosylating c2 toxin from clostridium botulinum and the binary lethal toxin from bacillus anthracis, a metalloprotease. both toxins are com ...201021120455
conformational dynamics of the anthrax lethal factor catalytic center.anthrax lethal factor (lf) is a zinc-metalloprotease that together with the protective antigen constitutes anthrax lethal toxin, which is the most prominent virulence factor of the anthrax disease. the solution nuclear magnetic resonance and in silico conformational dynamics of the 105 c-terminal residues of the lf catalytic core domain in its apo form are described here. the polypeptide adopts a compact structure even in the absence of the zn(2+) cofactor, while the 40 n-terminal residues compr ...201021121613
interferon-inducible cxc chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. no observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. here, we show that the murine interferon-inducible cxc chemokines cxcl9, cxcl10, and cxcl11 each exert direct antimicrobial eff ...201021124994
protection afforded by fluoroquinolones in animal models of respiratory infections with bacillus anthracis, yersinia pestis, and francisella tularensis.successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. bacillus anthracis ames, yersinia pestis co92, and francisella tularensis schu s4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited informat ...201021127743
structure and assembly of bacteriophage t4 head.the bacteriophage t4 capsid is an elongated icosahedron, 120 nm long and 86 nm wide, and is built with three essential proteins; gp23*, which forms the hexagonal capsid lattice, gp24*, which forms pentamers at eleven of the twelve vertices, and gp20, which forms the unique dodecameric portal vertex through which dna enters during packaging and exits during infection. the past twenty years of research has greatly elevated the understanding of phage t4 head assembly and dna packaging. the atomic s ...201021129201
bacillus anthracis sin locus and regulation of secreted proteases.bacillus anthracis shares many regulatory loci with the nonpathogenic bacillus species bacillus subtilis. one such locus is sinir, which in b. subtilis controls sporulation, biofilm formation, motility, and competency. as b. anthracis is not known to be motile, to be naturally competent, or to readily form biofilms, we hypothesized that the b. anthracis sinir regulon is distinct from that of b. subtilis. a genome-wide expression microarray analysis of b. anthracis parental and sinr mutant strain ...201021131488
particle release from respirators, part i: determination of the effect of particle size, drop height, and load.in late 2001, some u.s. postal service workers and a few members of congress were exposed to anthrax spores. this led to an increased effort to develop employable methods to protect workers from exposure to anthrax. some investigations focused on selection and use of respirators to protect workers against airborne anthrax. the present study evaluated the potential for several types of half-mask respirators to release deposited particles. four brands of the most commonly used filtering facepiece ...201121132594
entry of bacillus anthracis spores into epithelial cells is mediated by the spore surface protein bcla, integrin α2β1 and complement component c1q.inhalational anthrax is initiated by pulmonary exposure to bacillus anthracis spores. spore entry into lung epithelial cells is observed both in vitro and in vivo and evidence suggests it is important for bacterial dissemination and virulence. however the specific host receptor and spore factor that mediate the entry process were unknown. here, we report that integrin α2β1 is a major receptor for spore entry. this is supported by results from blocking antibodies, sirna knock-down, colocalization ...201021134100
o-acetylation of peptidoglycan is required for proper cell separation and s-layer anchoring in bacillus anthracis.o-acetylation of the murnac moiety of peptidoglycan is typically associated with bacterial resistance to lysozyme, a muramidase that serves as a central component of innate immunity. here, we report that the peptidoglycan of bacillus anthracis, the etiological agent of anthrax, is o-acetylated and that, unusually, this modification is produced by two unrelated families of o-acetyltransferases. also, in contrast to other bacteria, o-acetylation of b. anthracis peptidoglycan is combined with n-dea ...201021135105
proteomic analysis of the response of the human neutrophil-like cell line nb-4 after exposure to anthrax lethal toxin.we used 2-d dige to analyze the early response of nb-4 cells, a human promyelotic leukemia cell line, exposed to lethal toxin from bacillus anthracis at the proteome level. after a 2 h exposure, cells were still viable and 43% of spots (n = 1042) showed a significant change in protein level. we identified 59 spots whose expression had changed significantly, and these reflected cytoskeleton damage, mitochondrial lysis and endoplasmic reticulum stress. actin filament assembly was disrupted as evid ...200721136624
symmetry complementarity-guided design of anthrax toxin inhibitors based on β-cyclodextrin: synthesis and relative activities of face-selective functionalized polycationic clusters.three new series of potential anthrax toxin inhibitors based on the β-cyclodextrin (βcd) scaffold were developed by exploiting face-selective cu(i)-catalyzed azide-alkyne 1,3-cycloadditions, amine-isothiocyanate coupling, and allyl group hydroboration-oxidation/hydroxy → amine replacement reactions. the molecular design follows the "symmetry-complementarity" concept between homogeneously functionalized polycationic βcd derivatives and protective antigen (pa), a component of anthrax toxin known t ...201121140396
design of new chemotherapeutics against the deadly anthrax disease. docking and molecular dynamics studies of inhibitors containing pyrrolidine and riboamidrazone rings on nucleoside hydrolase from bacillus anthracis.anthrax is a disease caused by bacillus anthracis, a dangerous biological warfare agent already used for both military and terrorist purposes. an important selective target for chemotherapy against this disease is nucleoside hydrolase (nh), an enzyme still not found in mammals. having this in mind we have performed molecular docking studies, aiming to analyze the three-dimensional positioning of six known inhibitors of trypanosoma vivax nh (tvnh) in the active site of b. anthracis nh (banh). we ...201121142217
reliable detection of bacillus anthracis, francisella tularensis and yersinia pestis by using multiplex qpcr including internal controls for nucleic acid extraction and amplification.several pathogens could seriously affect public health if not recognized timely. to reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples.201021143837
yeast-hybrid based high-throughput assay for identification of anthrax lethal factor inhibitors.inhibitors of anthrax lethal factor (lf) are currently being sought as effective therapeutics for the treatment of anthrax. here we report a novel screening approach for inhibitors of lf, a yeast-hybrid-based assay system in which the expression of reporter genes from a gal4 promoter is repressed by lf proteolytic activity. yeast cells were co-transformed with lf and a chimeric transcription factor that contains an lf substrate sequence inserted between the dna-binding and activation domains of ...201021144836
raising awareness about terror medicine.terror medicine, which is related to emergency and disaster medicine, focuses on the constellation of medical issues uniquely related to terrorist attacks. it ranges from recognizing features of biologic and chemical agents such as bacillus anthracis (anthrax) and sarin to the treatment of multi-injury victims of suicide bombings. medical personnel will be involved in rescue, diagnosis, treatment and recovery from a terrorist attack. dermatologists could play a central role in diagnosis and trea ...201121146738
reduction of immunogenicity of anthrax vaccines subjected to thermal stress, as measured by a toxin neutralization assay.we report that a toxin neutralization assay (tna) can detect a decrease in the immunogenicity of anthrax vaccines as a consequence of brief exposure to elevated temperature. this attribute of tna may help in adopting immunogenicity as a replacement of the current potency test, which involves protection from lethal challenge.201021147935
auranofin protects against anthrax lethal toxin-induced activation of the nlrp1b inflammasome.anthrax lethal toxin (lt) is the major virulence factor for bacillus anthracis. the lethal factor (lf) component of this bipartite toxin is a protease which, when transported into the cellular cytoplasm, cleaves mitogen-activated protein kinase kinase (mek) family proteins and induces rapid toxicity in mouse macrophages through activation of the nlrp1b inflammasome. a high-throughput screen was performed to identify synergistic lt-inhibitory drug combinations from within a library of approved dr ...201021149629
inflammasome sensor nlrp1b-dependent resistance to anthrax is mediated by caspase-1, il-1 signaling and neutrophil recruitment.bacillus anthracis infects hosts as a spore, germinates, and disseminates in its vegetative form. production of anthrax lethal and edema toxins following bacterial outgrowth results in host death. macrophages of inbred mouse strains are either sensitive or resistant to lethal toxin depending on whether they express the lethal toxin responsive or non-responsive alleles of the inflammasome sensor nlrp1b (nlrp1b(s/s) or nlrp1b(r/r), respectively). in this study, nlrp1b was shown to affect mouse sus ...201021170303
sublethal doses of anthrax lethal toxin on the suppression of macrophage phagocytosis.lethal toxin (lt), the major virulence factor produced by bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of b. anthracis infections. it has been suggested that the suppression of mek/mapk signaling pathways of leukocytes contributes to lt-mediated immunosuppressive effects. however, the involvement of mapk independent pathways has not been clearly elucidated; nor has the crucial role played by lt in the early stages of infection. determ ...201021170330
cholera- and anthrax-like toxins are among several new adp-ribosyltransferases.chelt, a cholera-like toxin from vibrio cholerae, and certhrax, an anthrax-like toxin from bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. we also uncovered medically relevant toxins from mycobacterium avium and enterococcus faecalis. we found agriculturally relevant toxins in photorhabdus luminescens and vibrio splendidus. these toxins belong to the adp-ribosyltransferase family that has conserved structure d ...201021170356
a poster of pustules: representations of early twentieth century industrial anthrax in britain.in the decades around 1900, industrial anthrax attracted significant attention from medical practitioners, legislators and the general public in britain. attempts to reduce the incidence of the disease ranged from basic health measures - preventing workmen from eating inside factories and trialling the use of respirators - through to national legislation making disinfection of dangerous materials mandatory. another effort involved the production of industrial warning posters (or cautionary notic ...201021176968
crowd control: bacillus anthracis and quorum sensing.in 1965, dr. alexander tomasz identified a critical component of the dna uptake mechanism used by competent streptococcus pneumoniae: the pneumococci secrete a polypeptide that induces the expression of proteins to allow foreign dna to pass through the bacterium's cell wall. this hormone-like substance was the first of numerous "quorum-sensing" factors that have since been identified in many microbial processes.  detailed insights into the molecular mechanisms of quorum-sensing are now emerging, ...201021178417
role of luxs in bacillus anthracis growth and virulence factor expression.quorum-sensing (qs), the regulation of bacterial gene expression in response to changes in cell density, involves pathways that synthesize signaling molecules (auto-inducers). the luxs/ai-2-mediated qs system has been identified in both gram-positive and gram-negative bacteria. bacillus anthracis, the etiological agent of anthrax, possesses genes involved in luxs/ai-2-mediated qs, and deletion of luxs in b. anthracis sterne strain 34f2 results in inhibition of ai-2 synthesis and a growth defect. ...201021178420
development of a real time pcr taqman assay based on the tpi gene for simultaneous identification of clostridium chauvoei and clostridium septicum.in the present study, a taqman allelic discrimination assay based on three snps of the tpi gene is described. it was used as a differential diagnostic tool to detect blackleg and malignant edema. sudden deaths of grazing ruminants, such as cattle, sheep and goats, which show clinical signs related to hyperacute infective processes, encouraged the development of a rapid and precise diagnostic molecular method. specific primers and probes for clostridium septicum and clostridium chauvoei were desi ...201021182874
activation of human macrophages by bacterial components relieves the restriction on replication of an interferon-inducing parainfluenza virus 5 (piv5) p/v mutant.macrophages regulate immune responses during many viral infections, and can be a major determinant of pathogenesis, virus replication and immune response to infection. here, we have addressed the question of the outcome of infection of primary human macrophages with parainfluenza virus 5 (piv5) and a piv5 mutant (p/v-cpi-) that is unable to counteract interferon (ifn) responses. in cultures of naïve monocyte-derived macrophages (mdms), wt piv5 established a highly productive infection, whereas t ...201021185944
pre- and postexposure protection against virulent anthrax infection in mice by humanized monoclonal antibodies to bacillus anthracis capsule.one of the two essential virulence factors of bacillus anthracis is the poly-γ-d-glutamic acid (γdpga) capsule. five γdpga-specific antibody antigen-binding fragments (fabs) were generated from immunized chimpanzees. the two selected for further study, fabs 11d and 4c, were both converted into full-length igg1 and igg3 mabs having human igg1 or igg3 constant regions. these two mabs had similar binding affinities, in vitro opsonophagocytic activities, and in vivo efficacies, with the igg1 and igg ...201021187383
identifying chelators for metalloprotein inhibitors using a fragment-based approach.fragment-based lead design (fbld) has been used to identify new metal-binding groups for metalloenzyme inhibitors. when screened at 1 mm, a chelator fragment library (cfl-1.1) of 96 compounds produced hit rates ranging from 29% to 43% for five matrix metalloproteases (mmps), 24% for anthrax lethal factor (lf), 49% for 5-lipoxygenase (5-lo), and 60% for tyrosinase (ty). the ligand efficiencies (le) of the fragment hits are excellent, in the range of 0.4-0.8 kcal/mol. the mmp enzymes all generally ...201021189019
discovery of mouse spleen signaling responses to anthrax using label-free quantitative phosphoproteomics via mass spectrometry.inhalational anthrax is caused by spores of the bacterium bacillus anthracis (b. anthracis), and is an extremely dangerous disease that can kill unvaccinated victims within 2 weeks. modern antibiotic-based therapy can increase the survival rate to ∼50%, but only if administered presymptomatically (within 24-48 h of exposure). to discover host signaling responses to presymptomatic anthrax, label-free quantitative phosphoproteomics via liquid chromatography coupled to mass spectrometry was used to ...201021189417
the effect of cationic liposomes encapsulating pcdna3.1+pa plasmids on humoral immune response in mice.dna vaccines are third generation vaccines which have made promises to combat infectious diseases. cationic liposomes are used as effective delivery systems for dna vaccines to generate stronger immunity.201021189443
you cannot b. cereus.this month's genome watch looks at the different bacillus species that can cause anthrax.201021189478
adulterants in illicit drugs: a review of empirical evidence.widespread public perception is that illicit drugs contain substances that are a serious risk to health, even though adulterants are often not considered in clinical or forensic toxicology. this review attempts to present an evidence-based overview of adulterants in illicit drugs, and their associated toxicity. adulterants are deliberately added to increase bulk, enhance or mimic a pharmacological effect, or to facilitate drug delivery. those present unintentionally are as a result of poor manuf ...201021191909
development of an aerosol surface inoculation method for bacillus spores.a method was developed to deposit bacillus subtilis spores via aerosolization onto various surface materials for biological agent decontamination and detection studies. this new method uses an apparatus coupled with a metered dose inhaler to reproducibly deposit spores onto various surfaces. a metered dose inhaler was loaded with bacillus subtilis spores, a surrogate for bacillus anthracis. five different material surfaces (aluminum, galvanized steel, wood, carpet, and painted wallboard paper) w ...201021193670
viability of bacillus licheniformis and bacillus thuringiensis spores as a model for predicting the fate of bacillus anthracis spores during composting of dead livestock.safe disposal of dead livestock and contaminated manure is essential for the effective control of infectious disease outbreaks. composting has been shown to be an effective method of disposal, but no information exists on its ability to contain diseases caused by spore-forming bacteria, such as bacillus anthracis. duplicate composters (east and west), each containing 16 dead cattle, were constructed (final capacity, 85,000 kg). spores (10(7) cfu/g manure) of bacillus licheniformis and bacillus t ...201021193674
multivariate bayesian modeling of known and unknown causes of events-an application to biosurveillance.this paper investigates bayesian modeling of known and unknown causes of events in the context of disease-outbreak detection. we introduce a multivariate bayesian approach that models multiple evidential features of every person in the population. this approach models and detects (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively n ...201021195503
targeting the anthrax receptors, tem-8 and cmg-2, for anti-angiogenic therapy.the anthrax toxin receptors tumor endothelial marker-8 (tem-8) and capillary morphogenesis gene-2 (cmg-2) are responsible for allowing entry of anthrax toxin into host cells. these receptors were first discovered due to their enhanced expression on endothelial cells undergoing blood vessel growth or angiogenesis in model systems. inhibition of angiogenesis is an important strategy for current anti-cancer therapies and treatment of retinal diseases. functional roles for tem-8 and cmg-2 in angioge ...201121196249
progress and novel strategies in vaccine development and treatment of anthrax.the lethal anthrax disease is caused by spores of the gram-positive bacillus anthracis, a member of the cereus group of bacilli. although the disease is very rare in the western world, development of anthrax countermeasures gains increasing attention due to the potential use of b. anthracis spores as a bio-terror weapon. protective antigen (pa), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into ...201121198675
biomass transformation webs provide a unified approach to consumer-resource modelling.an approach to modelling food web biomass flows among live and dead compartments within and among species is formulated using metaphysiological principles that characterise population growth in terms of basal metabolism, feeding, senescence and exploitation. this leads to a unified approach to modelling interactions among plants, herbivores, carnivores, scavengers, parasites and their resources. also, dichotomising sessile miners from mobile gatherers of resources, with relevance to feeding and ...201021199247
papillation in bacillus anthracis colonies: a tool for finding new mutators.colonies of bacillus anthracis sterne allow the growth of papillation after 6 days of incubation at 30°c on luria-bertani medium. the papillae are due to mutations that allow the cells to overcome the barriers to continued growth. cells isolated from papillae display two distinct gross phenotypes (group a and group b). we determined that group a mutants have mutations in the nprr gene including frameshifts, deletions, duplications and base substitutions. we used papillation as a tool for finding ...201121205011
crystallization and preliminary x-ray analysis of the vwa domain of human anthrax toxin receptor 1.the gram-positive spore-forming bacterium bacillus anthracis causes anthrax by secreting anthrax toxin, which consists of protective antigen (pa), lethal factor and oedema factor. binding of pa to receptors triggers the multi-step process of anthrax toxin entry into target cells. two distinct cellular receptors, antxr1 (also known as tumour endothelial marker 8; tem8) and antxr2 (also known as capillary morphogenesis protein 2; cmg2), for anthrax toxin have been identified. although the crystal ...201021206026
therapeutic immunization in hiv infected ugandans receiving stable antiretroviral treatment: a phase i safety study.therapeutic immunizations in hiv infection may boost immunity during antiretroviral treatment. we report on the first therapeutic vaccine trial in uganda, africa. this open label phase i trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic hiv-1 vaccine candidate. thirty hiv positive volunteers receiving a stable regimen of antiretroviral therapy with cd4 counts >400 were recruited for the safety evaluation of lfn-p24c, a detoxified anthrax-derived polypeptid ...201121211581
synthesis of bi-substrate state mimics of dihydropteroate synthase as potential inhibitors and molecular probes.the increasing emergence of resistant bacteria drives us to design and develop new antimicrobial agents. pursuant to that goal, a new targeting approach of the dihydropteroate synthase enzyme, which serves as the site of action for the sulfonamide class of antimicrobial agents, is being explored. using structural information, a new class of transition state mimics has been designed and synthesized that have the capacity to bind to the pterin, phosphate and para-amino binding sites. the design, s ...201021216602
structural insights into inhibition of bacillus anthracis sporulation by a novel class of non-heme globin sensor domains.pathogenesis by bacillus anthracis requires coordination between two distinct activities: plasmid-encoded virulence factor expression (which protects vegetative cells from immune surveillance during outgrowth and replication) and chromosomally encoded sporulation (required only during the final stages of infection). sporulation is regulated by at least five sensor histidine kinases that are activated in response to various environmental cues. one of these kinases, ba2291, harbors a sensor domain ...201121216948
anthrax edema toxin has camp-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model.while anthrax edema toxin produces pronounced tachycardia and lethal toxin depresses left ventricular (lv) ejection fraction in in vivo models, whether these changes reflect direct cardiac effects as opposed to indirect ones related to preload or afterload alterations is unclear. in the present study, the effects of edema toxin and lethal toxin were investigated in a constant pressure isolated perfused rat heart model. compared with control hearts, edema toxin at doses comparable to or less than ...201121217068
comparative proteome analysis of bacillus anthracis with pxo1 plasmid content.bacillus anthracis the causative agent of anthrax, is an important pathogen among the bacillus cereus group of species because of its physiological characteristics and its importance as a biological warfare agent. tripartite anthrax toxin proteins and a poly-d-glutamic acid capsule are produced by b. anthracis vegetative cells during mammalian hosts infection and when cultured in conditions that are thought to mimic the host environment. to identify the factors regulating virulence in b. anthrac ...201021221933
bacillus gaemokensis sp. nov., isolated from foreshore tidal flat sediment from the yellow sea.a gram-positive, rod-shaped, endospore-forming organism, strain bl3-6(t), was isolated from tidal flat sediments of the yellow sea in the region of tae-an. a 16s rrna gene sequence analysis demonstrated that this isolate belongs to the bacillus cereus group, and is closely related to bacillus mycoides (99.0% similarity), bacillus thuringiensis (99.0%), bacillus weihenstephanensis (99.0%), bacillus cereus (98.9%), bacillus anthracis (98.8%), and bacillus pseudomycoides (98.1%). the phylogenetic d ...201021221948
continuing challenge of infectious diseases in india.in india, the range and burden of infectious diseases are enormous. the administrative responsibilities of the health system are shared between the central (federal) and state governments. control of diseases and outbreaks is the responsibility of the central ministry of health, which lacks a formal public health department for this purpose. tuberculosis, malaria, filariasis, visceral leishmaniasis, leprosy, hiv infection, and childhood cluster of vaccine-preventable diseases are given priority ...201121227500
monoclonal antibodies directed against protective antigen of bacillus anthracis enhance lethal toxin activity in vivo.protective antigen (pa) from bacillus anthracis binds to cellular receptors, combines with lethal factor (lf) forming lethal toxin (letx), and facilitates the translocation of lf into the cytosol. letx is cytotoxic for j774a.1 cells, a murine macrophage cell line, and causes death of fisher 344 rats when injected intravenously. pa is also the major protective component in anthrax vaccines. antibody-dependent enhancement has been reported for several viral diseases, a bacterial infection, and for ...201121231965
Displaying items 6701 - 6800 of 9033