Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
the emilin/multimerin family.elastin microfibrillar interface proteins (emilins) and multimerins (emilin1, emilin2, multimerin1, and multimerin2) constitute a four member family that in addition to the shared c-terminus gc1q domain typical of the gc1q/tnf superfamily members contain a n-terminus unique cysteine-rich emi domain. these glycoproteins are homotrimeric and assemble into high molecular weight multimers. they are predominantly expressed in the extracellular matrix and contribute to several cellular functions in pa ...201122566882
exploiting human memory b cell heterogeneity for improved vaccine efficacy.the major goal in vaccination is establishment of long-term, prophylactic humoral memory to a pathogen. two major components to long-lived humoral memory are plasma cells for the production of specific immunoglobulin and memory b cells that survey for their specific antigen in the periphery for later affinity maturation, proliferation, and differentiation. the study of human b cell memory has been aided by the discovery of a general marker for b cell memory, expression of cd27; however, new data ...201122566866
[evaluation of molecular biology reagents used in plcr-tergeted rsi-pcr assay for b. anthracis identification and their influence on time necessary for obtaining results].fast and reliable identification of b. anthracis is crucial for a successful therapy of persons exposed to anthrax spores. use of molecular biology techniques significantly reduces time necessary for obtaining results. however, the molecular identification is hampered by the high genetic similarity of the b. cereus group bacteria. a lot of published b. antharcis identification approaches turned out to be non-specific. nevertheless, theplcr-targeted rsi-pcr assay described in 2007 is still regard ...201122384665
[landscape components favouring the occurrence of anthrax in the flooding pampa grasslands (buenos aires province, argentina)].the authors studied the landscape components that favour the occurrence of anthrax in the flooding pampa grasslands (buenos aires province, argentina). they made spatial locations of anthrax outbreaks diagnosed by registered veterinary laboratories in the study area's zone of influence. as variables for study, they differentiated areas that are flooded for 20% of the time or more from primary and secondary runoff channels. they also identified areas with low-productivity pasture. logistic regres ...201122435200
[necrotic lesion of the lip and cough with fever: cutaneous and pulmonary anthrax].anthrax disease is an anthropozoonosis caused by bacillus anthracis. it appears in three clinical forms: pulmonary, intestinal, and cutaneous. we report a case of pulmonary and cutaneous anthrax in a one-year-old moroccan infant.201122393634
recent progress in the development of anthrax vaccines.bacillus anthracis is the etiological agent of anthrax. although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. the potential use of b. anthracis spores as biowarfare agent has led to immense attention. prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. this highlights the need for alternative anthrax countermeasures. a number of approaches are being investigated to substitute o ...201122360464
pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor.antibiotic treatment may fail to protect individuals, if not started early enough, after infection with bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. stable and easily stored inhibitors of the edema factor toxin (ef), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. the toxin's basic activity is to convert atp to camp, and it is thus in principle a simple phosphatase, which means that many ...201223202316
identification of novel and cross-species seroreactive proteins from bacillus anthracis using a ligation-independent cloning-based, sos-inducible expression system.the current standard for bacillus anthracis vaccination is the anthrax vaccine adsorbed (ava, biothrax). while effective, the licensed vaccine schedule requires five intramuscular injections in the priming series and yearly boosters to sustain protection. one potential approach to maintain or improve the protection afforded by an anthrax vaccine, but requiring fewer doses, is through the use of purified proteins to enhance an antibody response, which could be used on their own or in combination ...201222975444
molecular motions as a drug target: mechanistic simulations of anthrax toxin edema factor function led to the discovery of novel allosteric inhibitors.edema factor (ef) is a component of bacillus anthracis toxin essential for virulence. its adenylyl cyclase activity is induced by complexation with the ubiquitous eukaryotic cellular protein, calmodulin (cam). ef and its complexes with cam, nucleotides and/or ions, have been extensively characterized by x-ray crystallography. those structural data allowed molecular simulations analysis of various aspects of ef action mechanism, including the delineation of ef and cam domains through their associ ...201223012649
binding of regulatory subunits of cyclic amp-dependent protein kinase to cyclic cmp agarose.the bacterial adenylyl cyclase toxins cyaa from bordetella pertussis and edema factor from bacillus anthracis as well as soluble guanylyl cyclase α(1)β(1) synthesize the cyclic pyrimidine nucleotide ccmp. these data raise the question to which effector proteins ccmp binds. recently, we reported that ccmp activates the regulatory subunits riα and riiα of camp-dependent protein kinase. in this study, we used two ccmp agarose matrices as novel tools in combination with immunoblotting and mass spect ...201222808067
bacillus anthracis edema factor substrate specificity: evidence for new modes of action.since the isolation of bacillus anthracis exotoxins in the 1960s, the detrimental activity of edema factor (ef) was considered as adenylyl cyclase activity only. yet the catalytic site of ef was recently shown to accomplish cyclization of cytidine 5'-triphosphate, uridine 5'-triphosphate and inosine 5'-triphosphate, in addition to adenosine 5'-triphosphate. this review discusses the broad ef substrate specificity and possible implications of intracellular accumulation of cyclic cytidine 3':5'-mo ...201222852066
cellular and physiological effects of anthrax exotoxin and its relevance to disease.bacillus anthracis, the causative agent of anthrax, secretes a tri-partite exotoxin that exerts pleiotropic effects on the host. the purification of the exotoxin components, protective antigen, lethal factor, and edema factor allowed the rapid characterization of their physiologic effects on the host. as molecular biology matured, interest focused on the molecular mechanisms and cellular alterations induced by intoxication. only recently have researchers begun to connect molecular and cellular k ...201222919667
cytoskeleton as an emerging target of anthrax toxins.bacillus anthracis, the agent of anthrax, has gained virulence through its exotoxins produced by vegetative bacilli and is composed of three components forming lethal toxin (lt) and edema toxin (et). so far, little is known about the effects of these toxins on the eukaryotic cytoskeleton. here, we provide an overview on the general effects of toxin upon the cytoskeleton architecture. thus, we shall discuss how anthrax toxins interact with their receptors and may disrupt the interface between ext ...201222474568
mechanisms of nk cell-macrophage bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.nk cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. bacillus anthracis spores can efficiently drive ifn-γ production by nk cells. the present study provides insights into the mechanisms of cytokine and cellular signaling that underlie the process of nk-cell activation by b. anthracis and the bacterial strategies to subvert and evade this response. infection with non-toxigenic encapsulated b. anthracis i ...201222253596
functional and structural analysis of the siderophore synthetase asbb through reconstitution of the petrobactin biosynthetic pathway from bacillus anthracis.petrobactin, a mixed catechol-carboxylate siderophore, is required for full virulence of bacillus anthracis, the causative agent of anthrax. the asbabcdef operon encodes the biosynthetic machinery for this secondary metabolite. here, we show that the function of five gene products encoded by the asb operon is necessary and sufficient for conversion of endogenous precursors to petrobactin using an in vitro system. in this pathway, the siderophore synthetase asbb catalyzes formation of amide bonds ...201222408253
genomic characterization of the bacillus cereus sensu lato species: backdrop to the evolution of bacillus anthracis.the key genes required for bacillus anthracis to cause anthrax have been acquired recently by horizontal gene transfer. to understand the genetic background for the evolution of b. anthracis virulence, we obtained high-redundancy genome sequences of 45 strains of the bacillus cereus sensu lato (s.l.) species that were chosen for their genetic diversity within the species based on the existing multilocus sequence typing scheme. from the resulting data, we called more than 324,000 new genes repres ...201222645259
sortase-conjugation generates a capsule vaccine that protects guinea pigs against bacillus anthracis.capsules protect bacteria against phagocytic clearance. capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. linking capsular material to a carrier protein stimulates its presentation to the immune system. for many conjugate vaccines this is achieved by a process of random chemical cross-linking. here we describe a new technology, designated sortase-conjugation, which g ...201222449424
activation of the classical complement pathway by bacillus anthracis is the primary mechanism for spore phagocytosis and involves the spore surface protein bcla.interactions between spores of bacillus anthracis and macrophages are critical for the development of anthrax infections, as spores are thought to use macrophages as vehicles to disseminate in the host. in this study, we report a novel mechanism for phagocytosis of b. anthracis spores. murine macrophage-like cell line raw264.7, bone marrow-derived macrophages, and primary peritoneal macrophages from mice were used. the results indicated that activation of the classical complement pathway (ccp) w ...201222442442
maximal adjuvant activity of nasally delivered il-1α requires adjuvant-responsive cd11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.il-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. we vaccinated il-1r1 bone marrow (bm) chimeric mice to determine whether il-1r1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered il-1α as determined by the acute induction of cytokine responses and induction of bacillus anthracis lethal factor (lf)-specific adaptive immunity. cytokine and chemokine responses ind ...201222345651
standoff detection of biological agents using laser induced fluorescence-a comparison of 294 nm and 355 nm excitation wavelengths.standoff detection measuring the fluorescence spectra of seven different biological agents excited by 294 nm as well as 355 nm wavelength laser pulses has been undertaken. the biological warfare agent simulants were released in a semi-closed aerosol chamber at 210 m standoff distance and excited by light at either of the two wavelengths using the same instrument. significant differences in several of the agents' fluorescence response were seen at the two wavelengths. the anthrax simulants' fluor ...201223162732
anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.a variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (mapk) signaling pathways, including bacillus anthracis. anthrax lethal toxin (lt) has specific proteolytic activity against the upstream regulators of mapks, the mapk kinases (mkks). using a murine model of intoxication, we show that lt causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. this pathology correlates w ...201222438953
θ-defensins: cyclic peptides with endless potential.θ-defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. human θ-defensin genes contain a premature stop codon that prevents effective translation of ...201222700960
effects of over-expression of tlr2 in transgenic goats on pathogen clearance and role of up-regulation of lysozyme secretion and infiltration of inflammatory cells.toll-like receptor 2 (tlr2) is important to host recognition of invading gram-positive microbes. in goats, these microbes can cause serious mastitis, anthrax, tetanus, and other problems. transgenic goats constitutively over-expressing tlr2 in many tissues serve as a suitable model for the study of the role of tlr2 over-expression in bacterial clearance.201223082910
swab protocol for rapid laboratory diagnosis of cutaneous anthrax.the clinical laboratory diagnosis of cutaneous anthrax is generally established by conventional microbiological methods, such as culture and directly straining smears of clinical specimens. however, these methods rely on recovery of viable bacillus anthracis cells from swabs of cutaneous lesions and often yield negative results. this study developed a rapid protocol for detection of b. anthracis on clinical swabs. three types of swabs, flocked-nylon, rayon, and polyester, were evaluated by 3 ext ...201223035192
anthrax lethal toxin and the induction of cd4 t cell immunity.bacillus anthracis secretes exotoxins which act through several mechanisms including those that can subvert adaptive immunity with respect both to antigen presenting cell and t cell function. the combination of protective antigen (pa) and lethal factor (lf) forming lethal toxin (lt), acts within host cells to down-regulate the mitogen activated protein kinase (mapk) signaling cascade. until recently the mapk kinases were the only known substrate for lt; over the past few years it has become evid ...201223162703
unusual bacterial infections and the pleura.rickettsiosis, q fever, tularemia, and anthrax are all bacterial diseases that can affect the pleura. rocky mountain spotted fever (rmsf) and mediterranean spotted fever (msf) are caused by rickettsia rickettsii and rickettsia conorii, respectively. pleural fluid from a patient with msf had a neutrophil-predominant exudate. coxiellaburnetii is the causative agent of q fever. of the two cases described in the literature, one was an exudate with a marked eosinophilia while the other case was a tra ...201222977649
rapid vascular responses to anthrax lethal toxin in mice containing a segment of chromosome 11 from the cast/ei strain on a c57bl/6 genetic background.host allelic variation controls the response to b. anthracis and the disease course of anthrax. mouse strains with macrophages that are responsive to anthrax lethal toxin (lt) show resistance to infection while mouse strains with lt non-responsive macrophages succumb more readily. b6.cast.11m mice have a region of chromosome 11 from the cast/ei strain (a lt responsive strain) introgressed onto a lt non-responsive c57bl/6j genetic background. previously, b6.cast.11m mice were found to exhibit a r ...201222792226
the potential of taqman array cards for detection of multiple biological agents by real-time pcr.the taqman array card architecture, normally used for gene expression studies, was evaluated for its potential to detect multiple bacterial agents by real-time pcr. ten pcr assays targeting five biological agents (bacillus anthracis, burkholderia mallei, burkholderia pseudomallei, francisella tularensis, and yersinia pestis) were incorporated onto array cards. a comparison of pcr performance of each pcr in array card and singleplex format was conducted using dna extracted from pure bacterial cul ...201222540014
phage-based platforms for the clinical detection of human bacterial pathogens.bacteriophages (phages) have been utilized for decades as a means for uniquely identifying their target bacteria. due to their inherent natural specificity, ease of use, and straightforward production, phage possess a number of desirable attributes which makes them particularly suited as bacterial detectors. as a result, extensive research has been conducted into the development of phage, or phage-derived products to expedite the detection of human pathogens. however, very few phage-based diagno ...201223050221
prioritizing risks and uncertainties from intentional release of selected category a pathogens.this paper synthesizes available information on five category a pathogens (bacillus anthracis, yersinia pestis, francisella tularensis, variola major and lassa) to develop quantitative guidelines for how environmental pathogen concentrations may be related to human health risk in an indoor environment. an integrated model of environmental transport and human health exposure to biological pathogens is constructed which 1) includes the effects of environmental attenuation, 2) considers fomite cont ...201222412915
development and comparison of two assay formats for parallel detection of four biothreat pathogens by using suspension microarrays.microarrays provide a powerful analytical tool for the simultaneous detection of multiple pathogens. we developed diagnostic suspension microarrays for sensitive and specific detection of the biothreat pathogens bacillus anthracis, yersinia pestis, francisella tularensis and coxiella burnetii. two assay chemistries for amplification and labeling were developed, one method using direct hybridization and the other using target-specific primer extension, combined with hybridization to universal arr ...201222355407
bacillus anthracis factors for phagosomal escape.the mechanism of phagosome escape by intracellular pathogens is an important step in the infectious cycle. during the establishment of anthrax, bacillus anthracis undergoes a transient intracellular phase in which spores are engulfed by local phagocytes. spores germinate inside phagosomes and grow to vegetative bacilli, which emerge from their resident intracellular compartments, replicate and eventually exit from the plasma membrane. during germination, b. anthracis secretes multiple factors th ...201222852067
rapid and high-throughput detection of highly pathogenic bacteria by ibis plex-id technology.in this manuscript, we describe the identification of highly pathogenic bacteria using an assay coupling biothreat group-specific pcr with electrospray ionization mass spectrometry (pcr/esi-ms) run on an ibis plex-id high-throughput platform. the biothreat cluster assay identifies most of the potential bioterrorism-relevant microorganisms including bacillus anthracis, francisella tularensis, yersinia pestis, burkholderia mallei and pseudomallei, brucella species, and coxiella burnetii. dna from ...201222768173
comparison of two suspension arrays for simultaneous detection of five biothreat bacterial in powder samples.we have developed novel bio-plex assays for simultaneous detection of bacillus anthracis, yersinia pestis, brucella spp., francisella tularensis, and burkholderia pseudomallei. universal primers were used to amplify highly conserved region located within the 16s rrna amplicon, followed by hybridized to pathogen-specific probes for identification of these five organisms. the other assay is based on multiplex pcr to simultaneously amplify five species-specific pathogen identification-targeted regi ...201222690123
peptide conjugated phosphorodiamidate morpholino oligomers increase survival of mice challenged with ames bacillus anthracis.targeting bacterial essential genes using antisense phosphorodiamidate morpholino oligomers (pmos) represents an important strategy in the development of novel antibacterial therapeutics. pmos are neutral dna analogues that inhibit gene expression in a sequence-specific manner. in this study, several cationic, membrane-penetrating peptides were conjugated to pmos (ppmos) that target 2 bacterial essential genes: acyl carrier protein (acpp) and gyrase a (gyra). these were tested for their ability ...201222978365
panning of a phage display library against a synthetic capsule for peptide ligands that bind to the native capsule of bacillus anthracis.bacillus anthracis is the causative agent of anthrax with the ability to not only produce a tripartite toxin, but also an enveloping capsule comprised primarily of γ-d-glutamic acid residues. the purpose of this study was to isolate peptide ligands capable of binding to the native capsule of b. anthracis from a commercial phage display peptide library using a synthetic form of the capsule consisting of 12 γ-d-glutamic acid residues. following four rounds of selection, 80 clones were selected ran ...201223029033
the structure of mlc titration factor a (mtfa/yeei) reveals a prototypical zinc metallopeptidase related to anthrax lethal factor.mtfa of escherichia coli (formerly yeei) was previously identified as a regulator of the phosphoenolpyruvate (pep)-dependent:glucose phosphotransferase system. mtfa homolog proteins are highly conserved, especially among beta- and gammaproteobacteria. we determined the crystal structures of the full-length mtfa apoenzyme from klebsiella pneumoniae and its complex with zinc (holoenzyme) at 2.2 and 1.95 å, respectively. mtfa contains a conserved h(149)e(150)xxh(153)+e(212)+y(205) metallopeptidase ...201222467785
germination and amplification of anthrax spores by soil-dwelling amoebas.while anthrax is typically associated with bioterrorism, in many parts of the world the anthrax bacillus (bacillus anthracis) is endemic in soils, where it causes sporadic disease in livestock. these soils are typically rich in organic matter and calcium that promote survival of resilient b. anthracis spores. outbreaks of anthrax tend to occur in warm weather following rains that are believed to concentrate spores in low-lying areas where runoff collects. it has been concluded that elevated spor ...201222983962
anthrax toxin protective antigen integrates poly-γ-d-glutamate and ph signals to sense the optimal environment for channel formation.many toxins assemble into oligomers on the surface of cells. local chemical cues signal and trigger critical rearrangements of the oligomer, inducing the formation of a membrane-fused or channel state. bacillus anthracis secretes two virulence factors: a tripartite toxin and a poly-γ-d-glutamic acid capsule (γ-dpga). the toxin's channel-forming component, protective antigen (pa), oligomerizes to create a prechannel that forms toxic complexes upon binding the two other enzyme components, lethal f ...201223100533
rapid induction of inflammatory lipid mediators by the inflammasome in vivo.detection of microbial products by host inflammasomes is an important mechanism of innate immune surveillance. inflammasomes activate the caspase-1 (casp1) protease, which processes the cytokines interleukin (il)-1β and il-18, and initiates a lytic host cell death called pyroptosis. to identify novel casp1 functions in vivo, we devised a strategy for cytosolic delivery of bacterial flagellin, a specific ligand for the naip5 (nlr family, apoptosis inhibitory protein 5)/nlrc4 (nlr family, card-dom ...201222902502
coatings capable of germinating and neutralizing bacillus anthracis endospores.endospores are formed by various bacterial families, including bacillus and clostridium, in response to environmental stresses as a means to survive conditions inhospitable to vegetative growth. although metabolically inert, the endospore must interact with its environment to determine an optimal time to return to a vegetative state, a process known as germination. germination has been shown to occur in response to a variety of chemical stimuli from specific nutrient germinants including amino a ...201222211260
detecting anthrax in the mail by coherent raman microspectroscopy.in this report, we show the collection of spatial information through a turbid medium by coherent raman microspectroscopic imaging. in particular, the technique is capable of identifying anthrax endospores inside a sealed paper envelope.201222215594
nanohole-based spr instruments with improved spectral resolution quantify a broad range of antibody-ligand binding kinetics.we demonstrate an affordable low-noise spr instrument based on extraordinary optical transmission (eot) in metallic nanohole arrays and quantify a broad range of antibody-ligand binding kinetics with equilibrium dissociation constants ranging from 200 pm to 40 nm. this nanohole-based spr instrument is straightforward to construct, align, and operate, since it is built around a standard microscope and a portable fiber-optic spectrometer. the measured refractive index resolution of this platform i ...201222235895
structural studies on antd: an n-acyltransferase involved in the biosynthesis of d-anthrose.the unusual dideoxysugar d-anthrose has been identified as an important component in the endospores of such infectious agents as bacillus anthracis and bacillus cereus. specifically, it is the terminal sugar on the bacterium's exosporium, and it provides a point of interaction between the spore and the host. the biosynthesis of d-anthrose involves numerous steps starting from α-d-glucose-1-phosphate. here we present a combined structural and functional investigation of antd from b. cereus. this ...201222220494
curing of plasmid pxo1 from bacillus anthracis using plasmid incompatibility.the large plasmid pxo1 encoding the anthrax toxin is important for the virulence of bacillus anthracis. it is essential to cure pxo1 from b. anthracis to evaluate its role in the pathogenesis of anthrax infection. because conventional methods for curing plasmids (e.g., curing agents or growth at elevated temperatures) can induce mutations in the host chromosomal dna, we developed a specific and reliable method to eliminate pxo1 from b. anthracis using plasmid incompatibility. three putative repl ...201222253811
zoonoses: a potential obstacle to the growing wildlife industry of namibia.zoonoses, which account for approximately 75% of emerging human infectious diseases worldwide, pose a re-emerging threat to public health. with an ever-increasing interrelationship between humans, livestock and wildlife species, the threat to human health will rise to unprecedented levels. wildlife species contribute to the majority of emerging diseases; therefore, there is an urgent need to define control systems of zoonoses of wildlife origin but very little information exists. in this review, ...201223077724
a new generation microarray for the simultaneous detection and identification of yersinia pestis and bacillus anthracis in food.the use of microarrays as a multiple analytic system has generated increased interest and provided a powerful analytical tool for the simultaneous detection of pathogens in a single experiment. a wide array of applications for this technology has been reported. a low density oligonucleotide microarray was generated from the genetic sequences of y. pestis and b. anthracis and used to fabricate a microarray chip. the new generation chip, consisting of 2,240 spots in 4 quadrants with the capability ...201223125935
insights from genomic comparisons of genetically monomorphic bacterial pathogens.some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called 'genetically monomorphic bacteria'. it has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. the genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. some ...201222312053
crystal structures of putative phosphoglycerate kinases from b. anthracis and c. jejuni.phosphoglycerate kinase (pgk) is indispensable during glycolysis for anaerobic glucose degradation and energy generation. here we present comprehensive structure analysis of two putative pgks from bacillus anthracis str. sterne and campylobacter jejuni in the context of their structural homologs. they are the first pgks from pathogenic bacteria reported in the protein data bank. the crystal structure of pgk from bacillus anthracis str. sterne (bapgk) has been determined at 1.68 å while the struc ...201222403005
mhc class ii and non-mhc class ii genes differentially influence humoral immunity to bacillus anthracis lethal factor and protective antigen.anthrax lethal toxin consists of protective antigen (pa) and lethal factor (lf), and current vaccination strategies focus on eliciting antibodies to pa. in human vaccination, the response to pa can vary greatly, and the response is often directed toward non-neutralizing epitopes. variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both mhc class ii and other genes playing roles. here, we investigated the relative contribution of mhc class ii v ...201223342680
the receptors that mediate the direct lethality of anthrax toxin.tumor endothelium marker-8 (tem8) and capillary morphogenesis protein-2 (cmg2) are the two well-characterized anthrax toxin receptors, each containing a von willebrand factor a (vwa) domain responsible for anthrax protective antigen (pa) binding. recently, a cell-based analysis was used to implicate another vwa domain-containing protein, integrin β1 as a third anthrax toxin receptor. to explore whether proteins other than tem8 and cmg2 function as anthrax toxin receptors in vivo, we challenged m ...201223271637
quantitative assessment of anthrax vaccine immunogenicity using the dried blood spot matrix.the collection, processing and transportation to a testing laboratory of large numbers of clinical samples during an emergency response situation present significant cost and logistical issues. blood and serum are common clinical samples for diagnosis of disease. serum preparation requires significant on-site equipment and facilities for immediate processing and cold storage, and significant costs for cold-chain transport to testing facilities. the dried blood spot (dbs) matrix offers an alterna ...201223266055
soft-x-ray-enhanced electrostatic precipitation for protection against inhalable allergens, ultrafine particles, and microbial infections.protection of the human lung from infectious agents, allergens, and ultrafine particles is difficult with current technologies. high-efficiency particulate air (hepa) filters remove airborne particles of >0.3 μm with 99.97% efficiency, but they are expensive to maintain. electrostatic precipitation has been used as an inexpensive approach to remove large particles from airflows, but it has a collection efficiency minimum in the submicrometer size range, allowing for a penetration window for some ...201223263945
recombinant groel enhances protective antigen-mediated protection against bacillus anthracis spore challenge.the fatal inhalation infection caused by bacillus anthracis results from a complex pathogenic cycle involving release of toxins by bacteria that germinate from spores. currently available vaccines against anthrax consist of protective antigen (pa), one of the anthrax toxin components. however, these pa-based vaccines are only partially protective against spore challenge in mice. this shows that exclusive elicitation of high anti-pa titer does not directly correlate with protection. here, we demo ...201223263010
investigation of an outbreak of cutaneous anthrax in banlu village, lianyungang, china, 2012.after notification of a suspected case of anthrax following the slaughtering of a sick cow in banlu village, an area that has not had any anthrax cases for decades, we aimed to confirm the outbreak, determine the transmission mechanism and implement control measures.201223908932
anthrax and the taiga. 201223543935
zoonotic infections among employees from great smoky mountains and rocky mountain national parks, 2008-2009.u.s. national park service employees may have prolonged exposure to wildlife and arthropods, placing them at increased risk of infection with endemic zoonoses. to evaluate possible zoonotic risks present at both great smoky mountains (grsm) and rocky mountain (romo) national parks, we assessed park employees for baseline seroprevalence to specific zoonotic pathogens, followed by evaluation of incident infections over a 1-year study period. park personnel showed evidence of prior infection with a ...201222835153
bacillus anthracis inosine 5'-monophosphate dehydrogenase in action: the first bacterial series of structures of phosphate ion-, substrate-, and product-bound complexes.inosine 5'-monophosphate dehydrogenase (impdh) catalyzes the first unique step of the gmp branch of the purine nucleotide biosynthetic pathway. this enzyme is found in organisms of all three kingdoms. impdh inhibitors have broad clinical applications in cancer treatment, as antiviral drugs and as immunosuppressants, and have also displayed antibiotic activity. we have determined three crystal structures of bacillus anthracis impdh, in a phosphate ion-bound (termed "apo") form and in complex with ...201222788966
climate change and zoonotic infections in the russian arctic.climate change in the russian arctic is more pronounced than in any other part of the country. between 1955 and 2000, the annual average air temperature in the russian north increased by 1.2°c. during the same period, the mean temperature of upper layer of permafrost increased by 3°c. climate change in russian arctic increases the risks of the emergence of zoonotic infectious diseases. this review presents data on morbidity rates among people, domestic animals and wildlife in the russian arctic, ...201222868189
unusual epidemic events: a new method of early orientation and differentiation between natural and deliberate epidemics.to develop a model for quick and accurate evaluation of unusual epidemic events (uee), based on the original model of bioterrorism risk assessment.201222136700
differential role of the interleukin-17 axis and neutrophils in resolution of inhalational anthrax.the roles of interleukin-17 (il-17) and neutrophils in the lung have been described as those of two intricate but independent players. here we identify neutrophils as the primary il-17-secreting subset of cells in a model of inhalation anthrax using a/j and c57bl/6 mice. with il-17 receptor a knockout (il-17ra(-/-)) mice, we confirmed that il-17a/f signaling is instrumental in the self-recruitment of this population. we also show that the il-17a/f axis is critical for surviving pulmonary infecti ...201222025514
three probable cases of cutaneous anthrax in autonomous province of vojvodina, serbia, june 2011. 201222264812
sometimes it takes two to tango: contributions of dimerization to functions of human α-defensin hnp1.human myeloid α-defensins called hnps play multiple roles in innate host defense. the trp26 residue of hnp1 was previously shown to contribute importantly to its ability to kill s. aureus, inhibit anthrax lethal factor (lf), bind gp120 of hiv-1, dimerize, and undergo further self-association. to gain additional insights into the functional significance of dimerization, we compared wild-type hnp1 to dimerization-impaired, n-methylated hnp1 monomers and to disulfide-tethered obligate hnp1 dimers. ...201222270360
biosurveillance: a review and update.since the terrorist attacks and anthrax release in 2001, almost $32 billion has been allocated to biodefense and biosurveillance in the usa alone. surveillance in health care refers to the continual systematic collection, analysis, interpretation, and dissemination of data. when attempting to detect agents of bioterrorism, surveillance can occur in several ways. syndromic surveillance occurs by monitoring clinical manifestations of certain illnesses. laboratory surveillance occurs by looking for ...201222242207
kinetic characterization of a slow-binding inhibitor of bla2: thiomaltol.the increasing prevalence of drug resistant bacteria is a pandemic problem. metallo-β-lactamases (mbls) are one of the main causes of drug resistance due to hydrolysis of β-lactam antibiotics. thus, the development of effective inhibitors of mbls remains urgent. the compound thiomaltol was used as a lead compound to investigate its ability to inhibit metallo-β-lactamase from bacillus anthracis (bla2), which causes anthrax. kinetic evaluation with nitrocefin as a substrate indicates that thiomalt ...201222233540
inhibition of bacterial carbonic anhydrases and zinc proteases: from orphantargets to innovative new antibiotic drugs.zinc-containing enzymes, such as carbonic anhydrases (cas) and metalloproteases (mps) play critical functions in bacteria, being involved in various steps of their life cycle, which are important for survival, colonization, acquisition of nutrients for growth and proliferation, facilitation of dissemination, invasion and pathogenicity. the development of resistance to many classes of clinically used antibiotics emphasizes the need of new antibacterial drug targets to be explored. there is a weal ...201222214451
protective antigen antibody augments hemodynamic support in anthrax lethal toxin shock in canines.background. anthrax-associated shock is closely linked to lethal toxin (lt) release and is highly lethal despite conventional hemodynamic support. we investigated whether protective antigen-directed monoclonal antibody (pa-mab) treatment further augments titrated hemodynamic support.methods and results. forty sedated, mechanically ventilated, instrumented canines challenged with anthrax lt were assigned to no treatment (controls), hemodynamic support alone (protocol-titrated fluids and norepinep ...201222223857
bacillus anthracis-derived edema toxin (et) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway.abstract: background: a common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (pmns) in infected tissues in the face of abundant circulating pmns. a major virulence determinant of anthrax is edema toxin (et), which is formed by the combination of two proteins produced by the organism, edema factor (ef), which is an adenyl cyclase, and protective antigen (pa). since camp, a product of adenyl cyclase, is known to enhance endothelial barrier integri ...201222230035
two independent replicons can support replication of the anthrax toxin-encoding plasmid pxo1 of bacillus anthracis.the large pxo1 plasmid (181.6kb) of bacillus anthracis encodes the anthrax toxin proteins. previous studies have shown that two separate regions of pxo1 can support replication of pxo1 miniplasmids when introduced into plasmid-less strains of this organism. no information is currently available on the ability of the above two replicons, termed repx and orfs 14/16 replicons, to support replication of the full-length pxo1 plasmid. we generated mutants of the full-length pxo1 plasmid in which eithe ...201222239982
comparative analysis of virulence factors secreted by bacillus anthracis sterne at host body temperature.aims:  for the analysis of virulence factors produced and secreted by bacillus anthracis vegetative cells during mammalian host infection, we evaluated the secretome of b. anthracis sterne exposed to host-specific factors specifically to host body temperature. methods and results:  we employed a comparative proteomics-based approach to analyze the proteins secreted by b. anthracis sterne under host-specific body temperature conditions. a total of 17 proteins encoded on a single chromosome and th ...201222268495
effect of the mammalian arginase inhibitor 2(s)-amino-6-boronohexanoic acid on bacillus anthracis arginase.macrophages, upon phagocytosing endospores of bacillus anthracis, up-regulate the expression of the immunological isoform of nitric oxide synthase, nos 2, concomitant with production of nitric oxide (no•) from metabolism of l: -arginine. we have previously demonstrated that macrophages that secrete no• kill the bacilli of b. anthracis. to circumvent this microbicidal activity of no•, b. anthracis has evolved pathways that include the enzyme arginase, which metabolizes l: -arginine to ornithine a ...201222271269
probing the substrate and acceptor specificity of the γ-glutamyltranspeptidase.abstract. γ-glutamyl transpeptidase (ggt) is a two-substrate enzyme that plays a central role in glutathione metabolism and is a potential target for drug design. ggt catalyze the cleavage of γ-glutamyl donor substrates, and the transfer of the γ-glutamyl moiety to an amine of an acceptor substrate or water. although structures of bacterial ggt have revealed details of the protein-ligand interactions at the donor site, the acceptor substrate site is relatively undefined. the recent identificatio ...201222257032
health-related quality of life in the anthrax vaccination program for workers in the laboratory response network.background: in 2002 cdc initiated the anthrax vaccination program (avp) to provide voluntary pre-exposure vaccination with anthrax vaccine adsorbed (ava) for persons at high risk of exposure to bacillus anthracis spores. there has been concern that ava could be associated with long term impairment of physical and/or mental health. objectives: to ascertain whether physical and mental functional status, as measured by the sf-36v2 health survey (medical outcomes trust, boston, ma), of ava recipient ...201222230591
gold nanoparticles with asymmetric polymerase chain reaction for colorimetric detection of dna sequence.we developed a novel strategy for rapid colorimetric analysis of a specific dna sequence by combining gold nanoparticles (aunps) with an asymmetric polymerase chain reaction (as-pcr). in the presence of the correct dna template, the bound oligonucleotides on the surface of aunps selectively hybridized to form complementary sequences of single-stranded dna (ssdna) target generated from as-pcr. dna hybridization resulted in self-assembly and aggregation of aunps, and a concomitant color change fro ...201222243128
Reviewing the role of peptide rarity in bacterial toxin immunomics.In the past decade, renewed efforts have been made toward the development of vaccines against cancers, infectious agents, autoimmune diseases, and allergies. These efforts have led to the accumulation of numerous peptide sequences experimentally validated as epitopes. However, the factors that render a peptide immunogenic and, more generally, the nature of the antigen-antibody recognition process remain unclear. Based on the hypothesis that potential epitopes correspond to rare sequences and/or ...201222202055
Anthrax toxin protective antigen-Insights into molecular switching from prepore to pore.The protective antigen is a key component of the anthrax toxin, as it allows entry of the enzymatic components edema factor and lethal factor into the host cell, through the formation of a membrane spanning pore. This event is absolutely critical for the pathogenesis of anthrax, and although we have yet to understand the mechanism of pore formation, recent developments have provided key insights into how this process may occur. Based on the available data, a model is proposed for the kinetic ste ...201222095644
microchip capillary electrophoresis of multi-locus vntr analysis for genotyping of bacillus anthracis and yersinia pestis in microbial forensic cases.bacillus anthracis and yersinia pestis are etiological agents of anthrax and plague respectively, and are also considered among the most feared potential bioterrorism agents. these microorganisms show intraspecies genome homogeneity, making strains differentiation difficult, while strains identification and comparison with known genotypes may be crucial for naturally occurring outbreaks vs. bioterrorist events discrimination.here an mlva application for b. anthracis and y. pestis strains differe ...201222139674
Application of nanoparticles for the detection and sorting of pathogenic bacteria by flow-cytometry.In this paper we will describe a new developed contribution of fluorescence nano-crystal (q-dots) as a fluorescence label for detecting pathogenic bacteria by flow cytometry (FCM) and the use of nano-magnetic particles to improve bacterial sorting by Flow cytometry cell sorting (FACS).FCM or FACS systems are based upon single cell detection by light scatter and Immunofluorescence labeling signals. The common FACS systems are based upon single or dual excitation as excitation source both for ligh ...201222101709
Platelets, inflammatory cells, von Willebrand factor, syndecan-1, fibrin, fibronectin, and bacteria co-localize in the liver thrombi of Bacillus anthracis-infected mice.Vascular dysfunction and thrombosis have been described in association with anthrax infection in humans and animals but the mechanisms of these dysfunctions, as well as the components involved in thrombi formation are poorly understood. Immunofluorescent microscopy was used to define the composition of thrombi in the liver of mice challenged with the Bacillus anthracis Sterne spores. Lethal infection with the toxigenic Sterne strain, in contrast to the non-lethal, non-toxigenic delta-Sterne stra ...201222001909
Natural biopolymer for preservation of microorganisms during sampling and storage.Stability of microbial cultures during sampling and storage is a vital issue in various fields of medicine, biotechnology, food science, and forensics. We have developed a unique bacterial preservation process involving a non-toxic, water-soluble acacia gum polymer that eliminates the need for refrigerated storage of samples. The main goal of this study is to characterize the efficacy of acacia gum polymer for preservation of pathogenic bacteria (Bacillus anthracis and methicillin-resistant Stap ...201222093998
effects by anthrax toxins on hematopoiesis: a key role for cytokines as mediators.an understanding of anthrax toxins on the emerging immune system and blood production are significant to medicine. this study examined the effects of anthrax toxin on hematopoiesis and determined roles for cytokines. anthrax holotoxin toxin is three components: protective antigen (pa) binds to the target cell and mediates the entry of lethal factor (lf) and edema factor (ef). anthrax toxin dramatically inhibits signaling in immune cells. we first identified the cell subsets that interacted with ...201222082805
anthrax vaccine antigen-adjuvant formulations completely protect new zealand white rabbits against challenge with bacillus anthracis ames strain spores.in an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (pa)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using bacillus anthracis ames strain spores. the vaccine formulations include pa adsorbed to alhydrogel, pa encapsulated in liposomes containing monophosphoryl lipid a, stable liposomal pa oil-in-water ...201222089245
differential effects of linezolid and ciprofloxacin on toxin production by bacillus anthracis in an in vitro pharmacodynamic system.bacillus anthracis causes anthrax. ciprofloxacin is a gold standard for the treatment of anthrax. previously, using the non-toxin-producing δsterne strain of b. anthracis, we demonstrated that linezolid was equivalent to ciprofloxacin for reducing the total (vegetative and spore) bacterial population. with ciprofloxacin therapy, the total population consisted of spores. with linezolid therapy, the population consisted primarily of vegetative bacteria. linezolid is a protein synthesis inhibitor, ...201222064542
Web interface for brownian dynamics simulation of ion transport and its applications to beta-barrel pores.Brownian dynamics (BD) based on accurate potential of mean force is an efficient and accurate method for simulating ion transport through wide ion channels. Here, a web-based graphical user interface (GUI) is presented for carrying out grand canonical Monte Carlo (GCMC) BD simulations of channel proteins: http://www.charmm-gui.org/input/gcmcbd. The webserver is designed to help users avoid most of the technical difficulties and issues encountered in setting up and simulating complex pore systems ...201222102176
Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis.Bacterial lipoproteins play a crucial role in virulence in some Gram-positive bacteria. However, the role of lipoprotein biosynthesis in Bacillus anthracis is unknown. We created a B. anthracis mutant strain altered in lipoproteins by deleting the lgt gene encoding the enzyme prolipoprotein diacylglyceryl transferase, which attaches the lipid anchor to prolipoproteins. (14) C-palmitate labelling confirmed that the mutant strain lacked lipoproteins, and hydrocarbon partitioning showed it to have ...201222103323
Structure-based redesign of an edema toxin inhibitor.Edema factor (EF) toxin of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3',5'-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an ...201222154558
Antibacterial Role for Natural Killer Cells in Host Defense to Bacillus anthracis.Natural killer (NK) cells have innate antibacterial activity that could be targeted for clinical interventions for infectious disease caused by naturally occurring or weaponized bacterial pathogens. To determine a potential role for NK cells in immunity to Bacillus anthracis, we utilized primary human and murine NK cells, in vitro assays, and in vivo NK cell depletion in a murine model of inhalational anthrax. Our results demonstrate potent antibacterial activity by human NK cells against B. ant ...201222006566
The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits.Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T ...201222020310
Domain flexibility modulates the heterogeneous assembly mechanism of anthrax toxin protective antigen.The three protein components of anthrax toxin are nontoxic individually, but they form active holotoxin complexes upon assembly. The role of the protective antigen (PA) component of the toxin is to deliver two other enzyme components, lethal factor and edema factor, across the plasma membrane and into the cytoplasm of target cells. PA is produced as a proprotein, which must be proteolytically activated; generally, cell surface activation is mediated by a furin family protease. Activated PA can t ...201222063095
Characterization of Type II and III Restriction-Modification Systems from Bacillus cereus Strains ATCC 10987 and ATCC 14579.The genomes of two Bacillus cereus strains (ATCC 10987 and ATCC 14579) have been sequenced. Here, we report the specificities of type II/III restriction (R) and modification (M) enzymes. Found in the ATCC 10987 strain, BceSI is a restriction endonuclease (REase) with the recognition and cut site CGAAG 24-25/27-28. BceSII is an isoschizomer of AvaII (G/GWCC). BceSIII cleaves at ACGGC 12/14. The BceSIII C terminus resembles the catalytic domains of AlwI, MlyI, and Nt.BstNBI. BceSIV is composed of ...201222037402
Serum amyloid A protects murine macrophages from lethal toxin-mediated death.Lethal toxin, a key virulence factor produced by Bacillus anthracis, induces cell death, in part by disrupting numerous signaling pathways, in mouse macrophages. However, exposure to sublethal doses of lethal toxin allows some cells to survive. Because these pro-survival signaling events occur within a few hours after exposure to sublethal doses, we hypothesized that acute phase proteins might influence macrophage survival. Our data show that serum amyloid A (SAA) is produced in response to leth ...201222082566
Anthrax sub-unit vaccine: The structural consequences of binding rPA83 to Alhydrogel®.An anthrax sub-unit vaccine, comprising recombinant Protective Antigen (rPA83) and aluminium hydroxide adjuvant (Alhydrogel®) is currently being developed. Here, a series of biophysical techniques have been applied to free and adjuvant bound antigen. Limited proteolysis and fluorescence identified no changes in rPA83 tertiary structure following binding to Alhydrogel and the bound rPA83 retained two structurally important calcium ions. For adsorbed rPA83, differential scanning calorimetry reveal ...201221964315
in vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria.silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. here, the bactericidal activity of four silver carbene complexes (sccs) with different formulations, including nanoparticles (nps) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections.201221972270
spectroscopic, catalytic and binding properties of bacillus subtilis no synthase-like protein: comparison with other bacterial and mammalian no synthases.genome sequencing has shown the presence of genes coding for no-synthase (nos)-like proteins in bacteria. the roles and properties of these proteins remain unclear. uv-visible spectroscopy was used to characterize the recombinant nos-like protein from bacillus subtilis (bsnos) in its ferric and ferrous states in the presence of various fe(iii)- and fe(ii)-heme-ligands and of a series of l-arginine (l-arg) analogs. bsnos exhibited several spectroscopic and binding properties in common with bacill ...201222119809
serological correlate of protection in guinea pigs for a recombinant protective antigen anthrax vaccine produced from bacillus brevis.recombinant protective antigen (rpa) is the active pharmaceutical ingredient of a second generation anthrax vaccine undergoing clinical trials both in korea and the usa. by using the rpa produced from bacillus brevis pnu212 expression system, correlations of serological immune response to anthrax protection efficacy were analyzed in a guinea pig model.201224159510
synthetic studies toward the anthrax tetrasaccharide: alternative synthesis of this antigen.the synthesis of the anthrax tetrasaccharide, amenable for conjugation, has been envisaged by both [2+2] and [1+3] approaches from d-fucose and l-rhamnose. the successful route reported herein relies on a [1+3] strategy in which the 1,2-trans-glycosidic linkages have been secured using a participating group at the 2-position of the donors using conventional thio as well as trichloroacetimidate glycosylation chemistry. the exchange of the ester to benzyl protective groups on the rhamnosyl moiety ...201222356927
rational design of a fluorescent receptor for the recognition of anthrax biomarker dipicolinate.a new carbazole-2,7-dicarboxamide derivative has been synthesised and has been proved to effectively bind the dipicolinate anion, which is commonly used as an anthrax biomarker. the fluorescent response from this synthetic receptor offers a selective colour change in an organic-aqueous environment that is of valuable analytical use.201223070516
role of n-terminal his6-tags in binding and efficient translocation of polypeptides into cells using anthrax protective antigen (pa).it is of interest to define bacterial toxin biochemical properties to use them as molecular-syringe devices in order to deliver enzymatic activities into host cells. binary toxins of the ab(7/8)-type are among the most potent and specialized bacterial protein toxins. the b subunits oligomerize to form a pore that binds with high affinity host cell receptors and the enzymatic a subunit. this allows the endocytosis of the complex and subsequent injection of the a subunit into the cytosol of the ho ...201223056543
draft genome sequence of bacillus anthracis ur-1, isolated from a german heroin user.we report the draft genome sequence of bacillus anthracis ur-1, isolated from a fatal case of injectional anthrax in a german heroin user. analysis of the genome sequence of strain ur-1 may aid in describing phylogenetic relationships between virulent heroin-associated isolates of b. anthracis isolated in the united kingdom, germany, and other european countries.201223045504
effect of the bacillus atrophaeus subsp. globigii spo0f h101r mutation on strain fitness.sporulation is a critical developmental process in bacillus spp. that, once initiated, removes the possibility of further growth until germination. therefore, the threshold conditions triggering sporulation are likely to be subject to evolutionary constraint. our previous studies revealed two spontaneous hypersporulating mutants of bacillus atrophaeus subsp. globigii, both containing point mutations in the spo0f gene. one of these strains (detrick-2; contains the spo0f101 allele with a c:t [his1 ...201223042165
Refresh
firstprev
...71727374757677787980...
nextlast
Displaying items 7201 - 7300 of 9033