Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| anthrax toxins: a weapon to systematically dismantle the host immune defenses. | successful colonization of the host by bacterial pathogens relies on their capacity to evade the complex and powerful defenses opposed by the host immune system, at least in the initial phases of infection. the two toxins of bacillus anthracis, lethal toxin and edema toxin, appear to have been shaped by evolution to assist the microorganism in this crucial function, in addition to act as general toxins acting on almost all cell types. edema toxin causes a consistent elevation of camp, an importa ... | 2009 | 19560486 |
| synthesis and assembly of a full-length human monoclonal antibody in algal chloroplasts. | monoclonal antibodies can be effective therapeutics against a variety of human diseases, but currently marketed antibody-based drugs are very expensive compared to other therapeutic options. here, we show that the eukaryotic green algae chlamydomonas reinhardtii is capable of synthesizing and assembling a full-length igg1 human monoclonal antibody (mab) in transgenic chloroplasts. this antibody, 83k7c, is derived from a human igg1 directed against anthrax protective antigen 83 (pa83), and has be ... | 2009 | 19562731 |
| membrane translocation by anthrax toxin. | much attention has been focused on anthrax toxin recently, both because of its central role in the pathogenesis of bacillus anthracis and because it has proven to be one of the most tractable toxins for studying how enzymic moieties of intracellularly acting toxins traverse membranes. the protective antigen (pa) moiety of the toxin, after being proteolytically activated at the cell surface, self-associates to form a heptameric pore precursor (prepore). the prepore binds up to three molecules of ... | 2009 | 19563824 |
| human naive and memory cd4+ t cell repertoires specific for naturally processed antigens analyzed using libraries of amplified t cells. | the enormous diversity of the naive t cell repertoire is instrumental in generating an immune response to virtually any foreign antigen that can be processed into peptides that bind to mhc molecules. the low frequency of antigen-specific naive t cells, their high activation threshold, and the constrains of antigen-processing and presentation have hampered analysis of naive repertoires to complex protein antigens. in this study, libraries of polyclonally expanded naive t cells were used to determ ... | 2009 | 19564353 |
| crystallization and initial crystallographic analysis of phosphoglucosamine mutase from bacillus anthracis. | the enzyme phosphoglucosamine mutase catalyzes the conversion of glucosamine 6-phosphate to glucosamine 1-phosphate, an early step in the formation of the nucleotide sugar udp-n-acetylglucosamine, which is involved in peptidoglycan biosynthesis. these enzymes are part of the large alpha-d-phosphohexomutase enzyme superfamily, but no proteins from the phosphoglucosamine mutase subgroup have been structurally characterized to date. here, the crystallization of phosphoglucosamine mutase from bacill ... | 2009 | 19574653 |
| bioaerosol analysis with raman chemical imaging microspectroscopy. | raman chemical imaging microspectroscopy is evaluated as a technology for waterborne pathogen and bioaerosol detection. raman imaging produces a three-dimensional data cube consisting of a raman spectrum at every pixel in a microscope field of view. binary and ternary mixtures including combinations of polystyrene beads, gram-positive bacillus anthracis, b. thuringiensis, and b. atrophaeus spores, and b. cereus vegetative cells were investigated by raman imaging for differentiation and character ... | 2009 | 19601631 |
| the surface of bacillus anthracis. | bacillus anthracis is a gram positive organism possessing a complex parietal structure. an s-layer, a bi-dimensional crystalline layer, and a peptidic capsule surround the thick peptidoglycan of bacilli harvested during infection. a review of the current literature indicates that elements from each of these three structures, as well as membrane components, have been studied. so-called cell-wall secondary polymers, be they attached to the cell-wall or to the membrane play important functions, eit ... | 2009 | 19607856 |
| synthesis, spectroscopic characterization and antibacterial activity of new cobalt(ii) complexes of unsymmetrical tetradentate (osn2) schiff base ligands. | cobalt ion complexes with the schiff bases, (4-x-2-{[2-(2-pyridine-2-yl-ethylsulfanyl)ethylimino]methyl}phenol (x=methoxy (ome), phenylazo (n(2)ph), bromo (br), nitro (no(2))),were synthesized and investigated by several techniques using elemental analysis (c, h, n), ftir, electronic spectra and molar conductivity. the thermal stability of free ligands and related cobalt complexes were studied by using differential scanning calorimetry (dsc) and thermogravimetric analyses (tga). cyclic voltammet ... | 2009 | 19608303 |
| functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore. | a key step of anthrax toxin action involves the formation of a protein-translocating pore within the endosomal membrane by the protective antigen (pa) moiety. formation of this transmembrane pore by pa involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel. | 2009 | 19609431 |
| solubilization and characterization of the anthrax toxin pore in detergent micelles. | proteolytically activated protective antigen (pa) moiety of anthrax toxin self-associates to form a heptameric ring-shaped oligomer (the prepore). acidic ph within the endosome converts the prepore to a pore that serves as a passageway for the toxin's enzymatic moieties to cross the endosomal membrane. prepore is stable in solution under mildly basic conditions, and lowering the ph promotes a conformational transition to an insoluble pore-like state. n-tetradecylphosphocholine (fos14) was the on ... | 2009 | 19609933 |
| the small acid soluble proteins (sasp alpha and sasp beta) of bacillus weihenstephanensis and bacillus mycoides group 2 are the most distinct among the bacillus cereus group. | the bacillus cereus group includes bacillus anthracis, b. cereus, bacillus thuringiensis, bacillus mycoides and bacillus weihenstephanensis. the small acid soluble spore protein (sasp) beta has been previously demonstrated to be among the biomarkers differentiating b. anthracis and b. cereus; sasp beta of b. cereus most commonly exhibits one or two amino acid substitutions when compared to b. anthracis. sasp alpha is conserved in sequence among these two species. neither sasp alpha nor beta for ... | 2009 | 19616612 |
| capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo. | anthrax toxin, a major virulence factor of bacillus anthracis, gains entry into target cells by binding to either of 2 von willebrand factor a domain-containing proteins, tumor endothelium marker-8 (tem8) and capillary morphogenesis protein-2 (cmg2). the wide tissue expression of tem8 and cmg2 suggest that both receptors could play a role in anthrax pathogenesis. to explore the roles of tem8 and cmg2 in normal physiology, as well as in anthrax pathogenesis, we generated tem8- and cmg2-null mice ... | 2009 | 19617532 |
| predicting hospital surge after a large-scale anthrax attack: a model-based analysis of cdc's cities readiness initiative prophylaxis recommendations. | background: a cri-compliant prophylaxis campaign starting 2 days after exposure would protect from 86% to 87% of exposed individuals from illness (assuming, in the base case, 90% antibiotic effectiveness and a 95% attack rate). each additional day needed to complete the campaign would result in, on average, 2.4% to 2.9% more hospitalizations in the exposed population; each additional day's delay to initiating prophylaxis beyond 2 days would result in 5.2% to 6.5% additional hospitalizations. the ... | 2009 | 19617582 |
| identification of linear epitopes in bacillus anthracis protective antigen bound by neutralizing antibodies. | protective antigen (pa), the binding subunit of anthrax toxin, is the major component in the current anthrax vaccine, but the fine antigenic structure of pa is not well defined. to identify linear neutralizing epitopes of pa, 145 overlapping peptides covering the entire sequence of the protein were synthesized. six monoclonal antibodies (mabs) and antisera from mice specific for pa were tested for their reactivity to the peptides by enzyme-linked immunosorbent assays. three major linear immunodo ... | 2009 | 19617628 |
| the physiologic responses of dutch belted rabbits infected with inhalational anthrax. | bacillus anthracis, the causative agent of anthrax, is a category a priority pathogen that causes extensive damage in humans. for this reason, b. anthracis has been the focus of numerous studies using various animal models. in this study, we explored physiologic parameters in dutch belted rabbits with inhalation anthrax to characterize the disease progression in this model. to this end, we infected dutch belted rabbits with 100 ld(50) b. anthracis ames spores by nasal instillation and continuous ... | 2009 | 19619416 |
| preparedness for an anthrax attack. | bacillus anthracis is a long-known bacterial organism with a uniquely stable spore stage. its stability and the lethal disease which results when the spore is inhaled made it a favorite of state-sponsored biological weapons programs throughout the cold war era. it is also believed to be high on the list of candidate microbial agents which could be used by terrorist groups or lone actors. its unique characteristics make protection of humans, especially civilians, from an intentional biological at ... | 2009 | 19619577 |
| investigation of new dominant-negative inhibitors of anthrax protective antigen mutants for use in therapy and vaccination. | the lethal toxin (letx) of bacillus anthracis plays a key role in the pathogenesis of anthrax. the protective antigen (pa) is a primary part of the anthrax toxin and forms letx by combination with lethal factor (lf). phenylalanine-427 (f427) is crucial for pa function. this study was designed to discover potential novel therapeutic agents and vaccines for anthrax. this was done by screening pa mutants that were mutated at the f427 residue for a dominant-negative inhibitory (dni) phenotype which ... | 2009 | 19620345 |
| nod1/nod2-mediated recognition plays a critical role in induction of adaptive immunity to anthrax after aerosol exposure. | toll-like receptors and nod-like receptors (nlr) play an important role in sensing invading microorganisms for pathogen clearance and eliciting adaptive immunity for protection against rechallenge. nod1 and nod2, members of the nlr family, are capable of detecting bacterial peptidoglycan motifs in the host cytosol for triggering proinflammatory cytokine production. in the current study, we sought to determine if nod1/nod2 are involved in sensing bacillus anthracis infection and eliciting protect ... | 2009 | 19620350 |
| anthrax lethal toxin enhances ikappab kinase activation and differentially regulates pro-inflammatory genes in human endothelium. | anthrax lethal toxin (lt) was previously shown to enhance transcriptional activity of nf-kappab in tumor necrosis factor-alpha-activated primary human endothelial cells. here we show that this lt-mediated increase in nf-kappab activation is associated with the enhanced degradation of the inhibitory proteins ikappabalpha and ikappabbeta but not ikappabepsilon. moreover, this was accompanied by enhanced activation of the ikappab kinase complex (ikk), which is responsible for targeting ikappab prot ... | 2009 | 19620708 |
| [preparation and characterization of monoclonal antibodies to the cholera toxin]. | monoclonal antibodies to cholera toxin were obtained. they do not cross-react with the termolabile toxin (lt) of escherichia coli, ricin, diphtherial toxin, staphylococcus enterotoxins of sea, seb, sei, seg, or the lethal factor and protective antigen of the anthrax toxin. pairs of antibodies for the quantitative measurement of the cholera toxin in sandwich enzyme immunoassay (eia) were selected. the detection limit of the toxin is 0.2 ng/ml for plate eia and 0.44 ng/ml for microchip eia. the pr ... | 2009 | 19621051 |
| [new immunoglobulin for treatment of anthrax]. | to experimentally assess activity and safety of anti-anthrax intravenous immunoglobulin manufactured on standard technology. | 2009 | 19621821 |
| [improvement of methods for identification of atypical anthrax strains and their differentiation from closely related bacilli]. | to study biologic characteristics of atypical strains of anthrax agent in order to improve methods of identification and differentiation from closely related bacilli. | 2009 | 19621825 |
| host-derived tumor endothelial marker 8 promotes the growth of melanoma. | tumor endothelial marker 8 (tem8) was initially identified as a gene overexpressed in the vasculature of human tumors and was subsequently identified as an anthrax toxin receptor. to assess the functional role of tem8, we disrupted the tem8 gene in mice by targeted homologous recombination. tem8(-/-) mice were viable and reached adulthood without defects in physiologic angiogenesis. however, histopathologic analysis revealed an excess of extracellular matrix in several tissues, including the ova ... | 2009 | 19622764 |
| gamma-phage lysin plyg sequence-based synthetic peptides coupled with qdot-nanocrystals are useful for developing detection methods for bacillus anthracis by using its surrogates, b. anthracis-sterne and b. cereus-4342. | previous reports of site-directed deletion analysis on gamma (gamma)-phage lysin protein (plyg) have demonstrated that removal of a short amino acid sequence in the c-terminal region encompassing a 10-amino acid motif (190lkmtadfilq199) abrogates its binding activity specific to the cell wall of bacillus anthracis. whether short synthetic peptides representing the10-amino acid plyg putative binding motif flanked by surrounding n- and c-terminal residues also selectively bind to the bacterial cel ... | 2009 | 19624851 |
| the protective antigen component of anthrax toxin forms functional octameric complexes. | the assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. we begin to address this question using anthrax toxin as a model. the protective antigen (pa) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (lf) and edema factor (ef), to form toxic complexes. to disrupt the host, these toxic complexes are endocytosed, suc ... | 2009 | 19627991 |
| isolation and chimerization of a highly neutralizing antibody conferring passive protection against lethal bacillus anthracis infection. | several studies have demonstrated that the passive transfer of protective antigen (pa)-neutralizing antibodies can protect animals against bacillus anthracis infection. the standard protocol for the isolation of pa-neutralizing monoclonal antibodies is based upon a primary selection of the highest pa-binders by elisa, and usually yields only few candidates antibodies. we demonstrated that by applying a pa-neutralization functionality-based screen as the primary criterion for positive clones, it ... | 2009 | 19629185 |
| healthcare coalitions: the new foundation for national healthcare preparedness and response for catastrophic health emergencies. | after 9/11 and the 2001 anthrax letters, it was evident that our nation's healthcare system was largely underprepared to handle the unique needs and large volumes of people who would seek medical care following catastrophic health events. in response, in 2002 congress established the hospital preparedness program (hpp) in the u.s. department of health and human services (hhs) to strengthen the ability of u.s. hospitals to prepare for and respond to bioterrorism and naturally occurring epidemics ... | 2009 | 19635000 |
| protection against anthrax and plague by a combined vaccine in mice and rabbits. | the protective antigen (pa) of bacillus anthracis and the fraction 1 capsular antigen (f1 antigen), v antigen of yersinia pestis have been demonstrated to be potential immunogens and candidate vaccine sub-units against anthrax and plague respectively. in this study, the authors have investigated the antibody responses and the protective efficacy when the antigens were administered separately or in combination intramuscularly formulation adsorbed to an aluminum hydroxide adjuvant. results show th ... | 2009 | 19635609 |
| ca-074me protection against anthrax lethal toxin. | anthrax lethal toxin (lt) activates the nlrp1b (nalp1b) inflammasome and caspase-1 in macrophages from certain inbred mouse strains, but the mechanism by which this occurs is poorly understood. we report here that similar to several nlrp3 (nalp3, cryopyrin)-activating stimuli, lt activation of the nlrp1b inflammasome involves lysosomal membrane permeabilization (lmp) and subsequent cytoplasmic cathepsin b activity. ca-074me, a potent cathepsin b inhibitor, protects lt-sensitive macrophages from ... | 2009 | 19635822 |
| novel broad-spectrum bis-(imidazolinylindole) derivatives with potent antibacterial activities against antibiotic-resistant strains. | given the limited number of structural classes of clinically available antimicrobial drugs, the discovery of antibacterials with novel chemical scaffolds is an important strategy in the development of effective therapeutics for both naturally occurring and engineered resistant strains of pathogenic bacteria. in this study, several diarylamidine derivatives were evaluated for their ability to protect macrophages from cell death following infection with bacillus anthracis, a gram-positive spore-fo ... | 2009 | 19635954 |
| bacillus cereus spores release alanine that synergizes with inosine to promote germination. | the first step of the bacterial lifecycle is the germination of bacterial spores into their vegetative form, which requires the presence of specific nutrients. in contrast to closely related bacillus anthracis spores, bacillus cereus spores germinate in the presence of a single germinant, inosine, yet with a significant lag period. | 2009 | 19636427 |
| cellular and systemic effects of anthrax lethal toxin and edema toxin. | anthrax lethal toxin (lt) and edema toxin (et) are the major virulence factors of anthrax and can replicate the lethality and symptoms associated with the disease. this review provides an overview of our current understanding of anthrax toxin effects in animal models and the cytotoxicity (necrosis and apoptosis) induced by lt in different cells. a brief reexamination of early historic findings on toxin in vivo effects in the context of our current knowledge is also presented. | 2009 | 19638283 |
| retroviruses and other latent viruses: the deadliest of pathogens are not necessarily the best candidates for bioterrorism. | hiv-1 (and other viral causes of latent, chronic infections) is not a likely candidate for bioterrorism. scenarios resulting in the introduction of retroviral infections into a large population generally seem impractical and unpredictable as bioterrorist plots, especially relative to the frightening simplicity of deadly anthrax spores or smallpox virions. as evidenced in the above discussion, contaminating the blood supply would require a highly sophisticated plan resulting in effects of rather ... | 2009 | 19639767 |
| through the looking glass, mechanistic insights from enantiomeric human defensins. | despite the small size and conserved tertiary structure of defensins, little is known at a molecular level about the basis of their functional versatility. for insight into the mechanism(s) of defensin function, we prepared enantiomeric pairs of four human defensins, hnp1, hnp4, hd5, and hbd2, and studied their killing of bacteria, inhibition of anthrax lethal factor, and binding to hiv-1 gp120. unstructured hnp1, hd5, and hbd3 and several other human alpha- and beta-defensins were also examined ... | 2009 | 19640840 |
| efficient methods for large-area surface sampling of sites contaminated with pathogenic microorganisms and other hazardous agents: current state, needs, and perspectives. | the recovery operations following the 2001 attacks with bacillus anthracis spores were complicated due to the unprecedented need for large-area surface sampling and decontamination protocols. since this event, multiple reports have been published describing recovery efficiencies of several surface sampling materials. these materials include fibrous swabs of various compositions, cloth wipes, vacuum socks, and adhesive tapes. these materials have reported recovery efficiencies ranging from approx ... | 2009 | 19644689 |
| implications of limits of detection of various methods for bacillus anthracis in computing risks to human health. | used for decades for biological warfare, bacillus anthracis (category a agent) has proven to be highly stable and lethal. quantitative risk assessment modeling requires descriptive statistics of the limit of detection to assist in defining the exposure. furthermore, the sensitivities of various detection methods in environmental matrices are vital information for first responders. a literature review of peer-reviewed journal articles related to methods for detection of b. anthracis was undertake ... | 2009 | 19648357 |
| novel and unique diagnostic biomarkers for bacillus anthracis infection. | a search for bacterium-specific biomarkers in peripheral blood following infection with bacillus anthracis was carried out with rabbits, using a battery of specific antibodies generated by dna vaccination against 10 preselected highly immunogenic bacterial antigens which were identified previously by a genomic/proteomic/serologic screen of the b. anthracis secretome. detection of infection biomarkers in the circulation of infected rabbits could be achieved only after removal of highly abundant s ... | 2009 | 19648366 |
| biofilm formation and cell surface properties among pathogenic and nonpathogenic strains of the bacillus cereus group. | biofilm formation by 102 bacillus cereus and b. thuringiensis strains was determined. strains isolated from soil or involved in digestive tract infections were efficient biofilm formers, whereas strains isolated from other diseases were poor biofilm formers. cell surface hydrophobicity, the presence of an s layer, and adhesion to epithelial cells were also examined. | 2009 | 19648377 |
| potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding. | this study describes the isolation and characterization of a neutralizing monoclonal antibody (mab) against anthrax edema factor, ef13d. ef13d neutralized edema toxin (et)-mediated cyclic amp (camp) responses in cells and protected mice from both et-induced footpad edema and systemic et-mediated lethality. the antibody epitope was mapped to domain iv of ef. the mab was able to compete with calmodulin (cam) for ef binding and displaced cam from ef-cam complexes. ef-mab binding affinity (0.05-0.12 ... | 2009 | 19651602 |
| the case for developing consensus standards for research in microbial pathogenesis: bacillus anthracis toxins as an example. | 2009 | 19651858 | |
| the global regulator cody regulates toxin gene expression in bacillus anthracis and is required for full virulence. | in gram-positive bacteria, cody is an important regulator of genes whose expression changes upon nutrient limitation and acts as a repressor of virulence gene expression in some pathogenic species. here, we report the role of cody in bacillus anthracis, the etiologic agent of anthrax. disruption of cody completely abolished virulence in a toxinogenic, noncapsulated strain, indicating that the activity of cody is required for full virulence of b. anthracis. global transcriptome analysis of a cody ... | 2009 | 19651859 |
| expression of nlrp1b inflammasome components in human fibroblasts confers susceptibility to anthrax lethal toxin. | anthrax lethal toxin causes macrophages and dendritic cells from some mouse strains to undergo caspase-1-dependent cell death. central to this process is the nod-like receptor nlrp1b (nalp1b), which detects intoxication and then self-associates to form a complex, termed an inflammasome, that is capable of activating the procaspase-1 zymogen. the nature of the signal detected directly by nlrp1b is not known, and the mechanisms of inflammasome assembly are poorly understood. here, we demonstrate t ... | 2009 | 19651869 |
| bacillus anthracis physiology and genetics. | bacillus anthracis is a member of the bacillus cereus group species (also known as the "group 1 bacilli"), a collection of gram-positive spore-forming soil bacteria that are non-fastidious facultative anaerobes with very similar growth characteristics and natural genetic exchange systems. despite their close physiology and genetics, the b. cereus group species exhibit certain species-specific phenotypes, some of which are related to pathogenicity. b. anthracis is the etiologic agent of anthrax. ... | 2009 | 19654018 |
| complete sequence of three plasmids from bacillus thuringiensis inta-fr7-4 environmental isolate and comparison with related plasmids from the bacillus cereus group. | bacillus thuringiensis is an insect pathogen used worldwide as a bioinsecticide. it belongs to the bacillus cereus sensu lato group as well as bacillus anthracis and b. cereus. plasmids from this group of organisms have been implicated in pathogenicity as they carry the genes responsible for different types of diseases that affect mammals and insects. some plasmids, like paw63 and pbt9727, encode a functional conjugation machinery allowing them to be transferred to a recipient cell. they also sh ... | 2009 | 19654019 |
| analysis of the fc gamma receptor-dependent component of neutralization measured by anthrax toxin neutralization assays. | anthrax toxin neutralization assays are used to measure functional antibody levels elicited by anthrax vaccines in both preclinical and clinical studies. in this study, we investigated the magnitude and molecular nature of fc gamma (fcgamma) receptor-dependent toxin neutralization observed in commonly used forms of the anthrax toxin neutralization assay. significantly more fcgamma receptor-dependent neutralization was observed in the j774a.1 cell-based assay than in the raw 264.7 cell-based assa ... | 2009 | 19656993 |
| bacterial inactivation by solar ultraviolet radiation compared with sensitivity to 254 nm radiation. | our goal was to derive a quantitative factor that would allow us to predict the solar sensitivity of vegetative bacterial cells to natural solar radiation from the wealth of data collected for cells exposed to uvc (254 nm) radiation. we constructed a solar effectiveness spectrum for inactivation of vegetative bacterial cells by combining the available action spectra for vegetative cell killing in the solar range with the natural sunlight spectrum that reaches the ground. we then analyzed previou ... | 2009 | 19659922 |
| the anthrax lethal factor and its mapk kinase-specific metalloprotease activity. | the anthrax lethal factor is a multi-domain protein toxin released by bacillus anthracis which enters cells in a process mediated by the protective antigen and specific cell receptors. in the cytosol, the lethal factor cleaves the n-terminal tail of many mapk kinases, thus deranging a major cell signaling pathway. the structural features at the basis of these activities of lf are reviewed here with particular attention to the proteolytic activity and to the identification of specific inhibitors. ... | 2009 | 19665472 |
| animal models of human anthrax: the quest for the holy grail. | anthrax is rare among humans, few data can be collected from infected individuals and they provide a fragmentary view of the dynamics of infection and human host-pathogen interactions. therefore, the development of animal models is necessary. anthrax has the particularity of being a toxi-infection, a combination of infection and toxemia. the ideal animal model would explore these two different facets and mimic human disease as much as possible. in the past decades, the main effort has been focus ... | 2009 | 19665473 |
| cd14-mac-1 interactions in bacillus anthracis spore internalization by macrophages. | anthrax, a potentially lethal disease of animals and humans, is caused by the gram-positive spore-forming bacterium bacillus anthracis. the outermost exosporium layer of b. anthracis spores contains an external hair-like nap formed by the glycoprotein bcla. recognition of bcla by the integrin mac-1 promotes spore uptake by professional phagocytes, resulting in the carriage of spores to sites of spore germination and bacterial growth in distant lymphoid organs. we show that cd14 binds to rhamnose ... | 2009 | 19666536 |
| the secret life of the anthrax agent bacillus anthracis: bacteriophage-mediated ecological adaptations. | ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. a central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alteratio ... | 2009 | 19672290 |
| insights into the mode of action of the two-peptide lantibiotic haloduracin. | haloduracin, a recently discovered two-peptide lantibiotic composed of the post-translationally modified peptides halalpha and halbeta, is shown to have high potency against a range of gram-positive bacteria and to inhibit spore outgrowth of bacillus anthracis. the two peptides display optimal activity in a 1:1 stoichiometry and have efficacy similar to that of the commercially used lantibiotic nisin. however, haloduracin is more stable at ph 7 than nisin. despite significant structural differen ... | 2009 | 19678697 |
| the bacillus anthracis spore. | in response to starvation, bacillus anthracis can form a specialized cell type called the spore, which is the infectious particle for the disease anthrax. the spore is largely metabolically inactive and can resist a wide range of stresses found in nature. in spite of its dormancy, the spore can sense the presence of nutrient and rapidly return to vegetative growth. these properties help the spore to persist for long periods of time in the environment, survive host defenses after entering the bod ... | 2009 | 19683018 |
| galactoxylomannan-mediated immunological paralysis results from specific b cell depletion in the context of widespread immune system damage. | the mechanisms responsible for polysaccharide-induced immunological paralysis have remained unexplained almost a century after this phenomenon was first described. cryptococcus neoformans capsular polysaccharides glucuronoxylomannan and galactoxylomannan (galxm) elicit little or no ab responses. this study investigates the immunological and biological effects of galxm in mice. galxm immunization elicits a state of immunological paralysis in mice characterized by the disappearance of ab-producing ... | 2009 | 19684080 |
| impact of spore biology on the rate of kill and suppression of resistance in bacillus anthracis. | bacillus anthracis is complex because of its spore form. the spore is invulnerable to antibiotic action. it also has an impact on the emergence of resistance. we employed the hollow-fiber infection model to study the impacts of different doses and schedules of moxifloxacin on the total-organism population, the spore population, and the subpopulations of vegetative- and spore-phase organisms that were resistant to moxifloxacin. we then generated a mathematical model of the impact of moxifloxacin, ... | 2009 | 19687233 |
| identification and quantitation of bacillus globigii using metal enhanced electrochemical detection and capillary biosensor. | presented herein are two detection strategies for the identification and quantification of bacillus globigii, a spore forming nonpathogenic simulant of bacillus anthracis. the first strategy involves a label-free, metal-enhanced electrochemical immunosensor for the quantitative detection of bacillus globigii (atrophaeus). the immunosensor comprises of antibacillus globigii (bg) antibody self-assembled onto a gold quartz crystal electrode via cystamine bond. a solid-phase monolayer of silver unde ... | 2009 | 19689112 |
| biochemical and structural characterization of alanine racemase from bacillus anthracis (ames). | bacillus anthracis is the causative agent of anthrax and a potential bioterrorism threat. here we report the biochemical and structural characterization of b. anthracis (ames) alanine racemase (alrbax), an essential enzyme in prokaryotes and a target for antimicrobial drug development. we also compare the native alrbax structure to a recently reported structure of the same enzyme obtained through reductive lysine methylation. | 2009 | 19695097 |
| pre-columbian origins for north american anthrax. | disease introduction into the new world during colonial expansion is well documented and had a major impact on indigenous populations; however, few diseases have been associated with early human migrations into north america. during the late pleistocene epoch, asia and north america were joined by the beringian steppe ecosystem which allowed animals and humans to freely cross what would become a water barrier in the holocene. anthrax has clearly been shown to be dispersed by human commerce and t ... | 2009 | 19283072 |
| biosecurity. paul keim on his life with the fbi during the anthrax investigation. interview by yudhijit bhattacharjee. | 2009 | 19286527 | |
| comparative transcriptional profiling of bacillus cereus sensu lato strains during growth in co2-bicarbonate and aerobic atmospheres. | bacillus species are spore-forming bacteria that are ubiquitous in the environment and display a range of virulent and avirulent phenotypes. this range is particularly evident in the bacillus cereus sensu lato group; where closely related strains cause anthrax, food-borne illnesses, and pneumonia, but can also be non-pathogenic. although much of this phenotypic range can be attributed to the presence or absence of a few key virulence factors, there are other virulence-associated loci that are co ... | 2009 | 19295911 |
| efficacy of recombinant anthrax vaccine against bacillus anthracis aerosol spore challenge: preclinical evaluation in rabbits and rhesus monkeys. | this report describes the immunogenicity and protective efficacy of escherichia coli-expressed recombinant protective antigen (rpa) in new zealand white rabbits and rhesus macaques against an aerosol challenge with bacillus anthracis spores (ivri strain, tox+cap+). a dose-ranging study was performed in which it became evident that the level of anti-pa igg and toxin-neutralizing antibody titer was directly proportional to the dose of rpa administered. however, the onset time of primary and second ... | 2009 | 19296443 |
| anthrax meningoencephalitis--declining trends in an uncommon but catastrophic cns infection in rural tamil nadu, south india. | anthrax, a cattle-born zoonosis has been a serious infectious disease and its meningoencephalitic form remains a rapidly fatal illness even now. | 2009 | 19304297 |
| distribution, diversity, and potential mobility of extrachromosomal elements related to the bacillus anthracis pxo1 and pxo2 virulence plasmids. | the presence of a pxo1- and/or pxo2-like plasmid(s) in clinical isolates of bacillus cereus sensu stricto and in strains of the biopesticide bacillus thuringiensis has been reported recently, and the pxo2-like plasmid pbt9727 and another pxo2-like plasmid, paw63, were found to be conjugative. in this study, a total of 1,000 b. cereus group isolates were analyzed for the presence of pxo1- and pxo2-like replicons and for the presence of pxo2-related conjugative modules. pxo1- and pxo2-like replico ... | 2009 | 19304837 |
| structure and complexity of a bacterial transcriptome. | although gene expression has been studied in bacteria for decades, many aspects of the bacterial transcriptome remain poorly understood. transcript structure, operon linkages, and information on absolute abundance all provide valuable insights into gene function and regulation, but none has ever been determined on a genome-wide scale for any bacterium. indeed, these aspects of the prokaryotic transcriptome have been explored on a large scale in only a few instances, and consequently little is kn ... | 2009 | 19304856 |
| label-free detection of b. anthracis spores using a surface plasmon resonance biosensor. | this study demonstrates the first use of surface plasmon resonance (spr) technology for the rapid, sensitive and label-free detection of whole b. anthracis spores. the approach involves the use of an spr biosensor (biacore 3000), and a monoclonal antibody which was raised against the b. anthracis spore (mab 8g3). by means of subtractive inhibition assays, whole b. anthracis spores with concentrations as low as 10(4) colony-forming units (cfu) ml(-1) can be detected within 40 min, and other relat ... | 2009 | 19305924 |
| cellular functions and x-ray structure of anthrolysin o, a cholesterol-dependent cytolysin secreted by bacillus anthracis. | anthrolysin o (alo) is a pore-forming, cholesterol-dependent cytolysin (cdc) secreted by bacillus anthracis, the etiologic agent for anthrax. growing evidence suggests the involvement of alo in anthrax pathogenesis. here, we show that the apical application of alo decreases the barrier function of human polarized epithelial cells as well as increases intracellular calcium and the internalization of the tight junction protein occludin. using pharmacological agents, we also found that barrier func ... | 2009 | 19307185 |
| bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase a and exchange protein activated by cyclic amp pathways. | bacillus anthracis, the etiological agent of anthrax, is a gram-positive spore-forming bacterium. it produces edema toxin (edtx), a powerful adenylate cyclase that increases cyclic amp (camp) levels in host cells. because other camp-increasing agents inhibit key macrophage (mphi) functions, such as phagocytosis, it was hypothesized that edtx would exhibit similar suppressive activities. our previous genechip data showed that edtx downregulated mphi genes involved in actin cytoskeleton remodeling ... | 2009 | 19307216 |
| structure of the diaminopimelate epimerase dapf from mycobacterium tuberculosis. | the meso (or d,l) isomer of diaminopimelic acid (dap), a precursor of l-lysine, is a key component of the pentapeptide linker in bacterial peptidoglycan. while the peptidoglycan incorporated in the highly complex cell wall of the pathogen mycobacterium tuberculosis structurally resembles that of escherichia coli, it is unique in that it can contain penicillin-resistant meso-dap-->meso-dap linkages. the interconversion of l,l-dap and meso-dap is catalysed by the dap epimerase dapf, a gene product ... | 2009 | 19307721 |
| norepinephrine in anthrax-associated shock: even worse than figs? | 2009 | 19318844 | |
| the solution structure of bacillus anthracis dihydrofolate reductase yields insight into the analysis of structure-activity relationships for novel inhibitors. | there is a significant need for new therapeutics to treat infections caused by the biodefense agent bacillus anthracis. in pursuit of drug discovery against this organism, we have developed novel propargyl-linked inhibitors that target the essential enzyme dihydrofolate reductase (dhfr) from b. anthracis. previously, we reported an initial series of these inhibitors and a high-resolution crystal structure of the ternary complex of the enzyme bound to its cofactor and one of the most potent inhib ... | 2009 | 19323450 |
| complement protein c3 binding to bacillus anthracis spores enhances phagocytosis by human macrophages. | alveolar macrophages are thought to play a central role in the pathogenesis of inhalational anthrax. receptors present on macrophages that mediate phagocytosis of bacillus anthracis spores have yet to be completely defined. to begin to determine if soluble factors that are present in the lung such as immunoglobulin and complement are involved, we characterized the binding of human igg and c3 to the surface of b. anthracis spores at different concentrations of nonimmune human serum. furthermore w ... | 2009 | 19328844 |
| molecular modification of t4 bacteriophage proteins and its potential application - review. | bacteriophage t4 is a virus with well-known genetics, structure, and biology. such techniques as x-ray crystallography, cryo-em, and three-dimensional (3d) image reconstruction allowed describing its structure very precisely. the genome of this bacteriophage was completely sequenced, which opens the way for the use of many molecular techniques, such as site-specific mutagenesis, which was widely applied, e.g., in investigating the functions of some essential t4 proteins. the phage-display method ... | 2009 | 19330539 |
| fusion protein of delta 27lfn and efn has the potential as a novel anthrax toxin inhibitor. | pa-binding domain of lf (lfn) or pa-binding domain of ef (efn) is the anthrax protective antigen (pa) binding domain of anthrax lethal factor (lf) or edema factor (ef). here we show the development of a novel anthrax toxin inhibitor, fusion protein of n-terminal 27 amino acids deletion of lfn (delta27lfn) and efn. in a cell model of intoxication, fusion protein of delta27lfn and efn (delta27lfn-efn) was a 62-fold more potent toxin inhibitor than lfn or efn, and this increased activity correspond ... | 2009 | 19332063 |
| idf's anthrax vaccine trial "violated helsinki convention". | 2009 | 19332445 | |
| inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small molecules. | furin is a ubiquitously expressed proprotein convertase (pc) that plays a vital role in numerous disease processes including cancer metastasis, bacterial toxin activation (e.g. anthrax and pseudomonas), and viral propagation (e.g. avian influenza and human immunodeficiency virus). to identify small molecule inhibitors of furin and related processing enzymes, we performed high-throughput screens of chemical diversity libraries utilizing both enzyme-based and cell-based assays. the screens identif ... | 2009 | 19332539 |
| localization and assembly of proteins comprising the outer structures of the bacillus anthracis spore. | bacterial spores possess a series of concentrically arranged protective structures that contribute to dormancy, survival and, ultimately, germination. one of these structures, the coat, is present in all spores. in bacillus anthracis, however, the spore is surrounded by an additional, poorly understood, morphologically complex structure called the exosporium. here, we characterize three previously discovered exosporium proteins called exsfa (also known as bxpb), exsfb (a highly related paralogue ... | 2009 | 19332815 |
| 27th annual jpmorgan healthcare conference--biocryst and emergent biosolutions. | 2009 | 19333891 | |
| existing antibacterial vaccines. | there are countless bacterial pathogens that cause disease in humans. many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. vaccines allow for reduction and potential eradication of such diseases. this article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, haemophilus influenza, cholera, ty ... | 2009 | 19335724 |
| extraordinary pleiotropy of protein kinase ck2 revealed by weblogo phosphoproteome analysis. | a weblogo has been generated from the sequences surrounding 433 ser/thr protein residues whose phosphorylation by protein kinase ck2 had been previously validated ("bona fide" ck2 phosphosites). this has been compared to the weblogo extracted from 2275 putative ck2 phosphosites displaying the motif ps/pt-x1-x2-d/e/ps (where x1 not=p) present in the human phosphoelm database including 10899 naturally occurring phosphosites. the two weblogos are strikingly similar supporting the notion that indeed ... | 2009 | 19339213 |
| anthrax lethal toxin impairs il-8 expression in epithelial cells through inhibition of histone h3 modification. | lethal toxin (lt) is a critical virulence factor of bacillus anthracis, the etiological agent of anthrax, whose pulmonary form is fatal in the absence of treatment. inflammatory response is a key process of host defense against invading pathogens. we report here that intranasal instillation of a b. anthracis strain bearing inactive lt stimulates cytokine production and polymorphonuclear (pmn) neutrophils recruitment in lungs. these responses are repressed by a prior instillation of an lt prepara ... | 2009 | 19343203 |
| lysozyme catalyzes the formation of antimicrobial silver nanoparticles. | hen egg white lysozyme acted as the sole reducing agent and catalyzed the formation of silver nanoparticles in the presence of light. stable silver colloids formed after mixing lysozyme and silver acetate in methanol and the resulting nanoparticles were concentrated and transferred to aqueous solution without any significant changes in physical properties. activity and antimicrobial assays demonstrated lysozyme-silver nanoparticles retained the hydrolase function of the enzyme and were effective ... | 2009 | 19344124 |
| rapid detection of the poly-gamma-d-glutamic acid capsular antigen of bacillus anthracis by latex agglutination. | latex agglutination has been used to detect capsular polysaccharides from a variety of bacteria in body fluids. a latex agglutination assay was constructed for detection of the poly-gamma-d-glutamic acid (gammadpga) capsular polypeptide of bacillus anthracis in serum from animal models of pulmonary anthrax. the assay was able to detect gammadpga in serum from infected animals at concentrations of 100 to 200 ng/ml. | 2009 | 19345041 |
| quantitative method to determine sporicidal decontamination of building surfaces by gaseous fumigants, and issues related to laboratory-scale studies. | chlorine dioxide gas and vaporous hydrogen peroxide sterilant have been used in the cleanup of building interiors contaminated with spores of bacillus anthracis. a systematic study, in collaboration with the u.s. environmental protection agency, was jointly undertaken by the u.s. army-edgewood chemical biological center to determine the sporicidal efficacies of these two fumigants on six building structural materials: carpet, ceiling tile, unpainted cinder block, painted i-beam steel, painted wa ... | 2009 | 19346341 |
| bacillus anthracis edema toxin impairs neutrophil actin-based motility. | inhalation anthrax results in high-grade bacteremia and is accompanied by a delay in the rise of the peripheral polymorphonuclear neutrophil (pmn) count and a paucity of pmns in the infected pleural fluid and mediastinum. edema toxin (et) is one of the major bacillus anthracis virulence factors and consists of the adenylate cyclase edema factor (ef) and protective antigen (pa). relatively low concentrations of et (100 to 500 ng/ml of pa and ef) significantly impair human pmn chemokinesis, chemot ... | 2009 | 19349425 |
| health concerns in uk armed forces personnel. | 2009 | 19349506 | |
| chlorine dioxide reactions with indoor materials during building disinfection: surface uptake. | chlorine dioxide received attention as a building disinfectant in the wake of bacillus anthracis contamination of several large buildings in the fall of 2001. it is increasingly used for the disinfection of homes and other indoor environments afflicted by mold. however, little is known regarding the interaction of chlorine dioxide and indoor materials, particularly as related to the removal of chlorine dioxide from air. such removal may be undesirable with respect to the subsequent formation of ... | 2009 | 19350899 |
| susceptibilities of bacillus subtilis, bacillus cereus, and avirulent bacillus anthracis spores to liquid biocides. | the susceptibility of spores of bacillus subtilis, bacillus cereus, and avirulent bacillus anthracis to treatment with hydrogen peroxide, peroxyacetic acid, a peroxy-fatty acid mixture, sodium hypochlorite, and acidified sodium chlorite was investigated. results indicated that b. cereus spores may be reasonable predictors of b. anthracis spore inactivation by peroxyacetic acid-based biocides. however, b. cereus was not a reliable predictor of b. anthracis inactivation by the other biocides. in s ... | 2009 | 19350981 |
| identification and characterization of immunodominant b-cell epitope of the c-terminus of protective antigen of bacillus anthracis. | bacillus anthracis is the etiological agent of anthrax. protective antigen (pa) has been established as the key protective immunogen and is the major component of anthrax vaccine. prior studies have indicated that c-terminus host cell receptor binding region contains dominant protective epitopes of pa. in the present study, we focused our attention on determining b-cell epitopes from this region, which could be employed as a vaccine. using b-cell epitope prediction systems, three regions were id ... | 2009 | 19356802 |
| structure-activity relationship studies of a novel series of anthrax lethal factor inhibitors. | we report on the identification of a novel small molecule inhibitor of anthrax lethal factor using a high-throughput screening approach. guided by molecular docking studies, we carried out structure-activity relationship (sar) studies and evaluated activity and selectivity of most promising compounds in in vitro enzyme inhibition assays and cellular assays. selected compounds were further analyzed for their in vitro adme properties, which allowed us to select two compounds for further preliminar ... | 2009 | 19359184 |
| substrate recognition of anthrax lethal factor examined by combinatorial and pre-steady-state kinetic approaches. | lethal factor (lf), a zinc-dependent protease of high specificity produced by bacillus anthracis, is the effector component of the binary toxin that causes death in anthrax. new therapeutics targeting the toxin are required to reduce systemic anthrax-related fatalities. in particular, new insights into the lf catalytic mechanism will be useful for the development of lf inhibitors. we evaluated the minimal length required for formation of bona fide lf substrates using substrate phage display. pha ... | 2009 | 19359249 |
| estimating the location and spatial extent of a covert anthrax release. | rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. we extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. a back-calculation method is developed allowing the cha ... | 2009 | 19360099 |
| crystal structure of the engineered neutralizing antibody m18 complexed to domain 4 of the anthrax protective antigen. | the virulence of bacillus anthracis is critically dependent on the cytotoxic components of the anthrax toxin, lethal factor (lf) and edema factor (ef). lf and ef gain entry into host cells through interactions with the protective antigen (pa), which binds to host cellular receptors such as cmg2. antibodies that neutralize pa have been shown to confer protection in animal models and are undergoing intense clinical development. a murine monoclonal antibody, 14b7, has been reported to interact with ... | 2009 | 19361425 |
| crystal structure of bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative rab1 provides a structural explanation of potency and selectivity. | bacillus anthracis possesses an innate resistance to the antibiotic trimethoprim due to poor binding to dihydrofolate reductase (dhfr); currently, there are no commercial antibacterials that target this enzyme in b. anthracis. we have previously reported a series of dihydrophthalazine-based trimethoprim derivatives that are inhibitors for this target. in the present work, we have synthesized one compound (rab1) displaying favorable 50% inhibitory concentration (54 nm) and mic (< or =12.8 microg/ ... | 2009 | 19364848 |
| framework for evaluating anthrax risk in buildings. | if bacillus anthracis (ba), the organism that causes anthrax, is known or suspected to have contaminated a building, a critical decision is what level of contamination is unacceptable. this decision has two components: (1) what is the relationship between the degree of contamination and the risk to occupants, (2) and what is an acceptable risk to occupants? these lead to a further decision: (3) how many samples must be taken to determine whether a building is unacceptably contaminated? we discus ... | 2009 | 19368172 |
| bacillus anthracis in china and its relationship to worldwide lineages. | the global pattern of distribution of 1033 b. anthracis isolates has previously been defined by a set of 12 conserved canonical single nucleotide polymorphisms (cansnp). these studies reinforced the presence of three major lineages and 12 sub-lineages and sub-groups of this anthrax-causing pathogen. isolates that form the a lineage (unlike the b and c lineages) have become widely dispersed throughout the world and form the basis for the geographical disposition of "modern" anthrax. an archival c ... | 2009 | 19368722 |
| vaccines for preventing anthrax. | anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine. | 2009 | 19370633 |
| antimicrobial ambiguine isonitriles from the cyanobacterium fischerella ambigua. | five new antibacterial ambiguine k-o isonitriles (1-5) and eight previously described indole alkaloids were isolated from the cultured cyanobacterium fischerella ambigua (utex 1903) by bioassay-guided fractionation. the planar structures of the new compounds were determined by spectroscopic analysis including ms and 1d and 2d nmr. x-ray crystallography was used to determine the absolute stereoconfiguration of ambiguine k isonitrile. the isolates were evaluated for their antibacterial activities ... | 2009 | 19371071 |
| matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis. | solid tumor growth is dependent on angiogenesis, the formation of neovasculature from existing vessels. endothelial activation of the extracellular signal-regulated kinase 1/2, c-jun nh(2)-terminal kinase, and p38 mitogen-activated protein kinase pathways is central to this process, and thus presents an attractive target for the development of angiogenesis inhibitors. anthrax lethal toxin (letx) has potent catalytic mitogen-activated protein kinase inhibition activity. preclinical studies showed ... | 2009 | 19372576 |
| x-ray structure of the ternary mtx.nadph complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design. | for reasons of bioterrorism and drug resistance, it is imperative to identify and develop new molecular points of intervention against anthrax. dihydrofolate reductase (dhfr) is a highly conserved enzyme and an established target in a number of species for a variety of chemotherapeutic programs. recently, the crystal structure of bacillus anthracis dhfr (badhfr) in complex with methotrexate (mtx) was determined and, based on the structure, proposals were made for drug design strategies directed ... | 2009 | 19374017 |
| sex differences in injection site reactions with human vaccines. | adverse events following immunization (aefi) are not uncommon, with injection site reactions (isrs) being the most common. predictors of injection site reactions are vaccine factors (antigen characteristics, antigen dose, dose number of antigen, antigen adjuvanting and type of diluent), vaccine administration factors (site and route of administration) and vaccinee factors (age and sex, the latter the subject of this review). 1,074 studies which reported isrs were retrieved by searching of on lin ... | 2009 | 19377279 |
| imaging specific cell surface protease activity in living cells using reengineered bacterial cytotoxins. | the scarcity of methods to visualize the activity of individual cell surface proteases in situ has hampered basic research and drug development efforts. in this chapter, we describe a simple, sensitive, and noninvasive assay that uses nontoxic reengineered bacterial cytotoxins with altered protease cleavage specificity to visualize specific cell surface proteolytic activity in single living cells. the assay takes advantage of the absolute requirement for site-specific endoproteolytic cleavage of ... | 2009 | 19377967 |