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development of metal-chelating inhibitors for the class ii fructose 1,6-bisphosphate (fbp) aldolase.it has long been suggested that the essential and ubiquitous enzyme fructose 1,6-bisphosphate (fbp) aldolase could be a good drug target against bacteria and fungi, since lower organisms possess a metal-dependant (class ii) fbp aldolase, as opposed to higher organisms which possess a schiff-base forming (class i) fbp aldolase. we have tested the capacity of derivatives of the metal-chelating compound dipicolinic acid (dpa), as well a thiol-containing compound, to inhibit purified recombinant cla ...201222546686
increased membrane turnover in the brain in cutaneous anthrax without central nervous system disorder: a magnetic resonance spectroscopy study.cutaneous anthrax, caused by bacillus anthracis contacting the skin, is the most common form of human anthrax. recent studies implicate the presence of additional, possibly toxin-related subtle changes, even in patients without neurological or radiological findings. in this study, the presence of subtle changes in cutaneous anthrax was investigated at the metabolite level using magnetic resonance spectroscopy. study subjects were consisted of 10 patients with cutaneous anthrax without co-morbid ...201222543072
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
trace detection of meglumine and diatrizoate from bacillus spore samples using liquid chromatography/mass spectrometry.following the september 11, 2001 terrorist attacks, letters containing bacillus anthracis were distributed through the united states postal system killing five people. a complex forensic investigation commenced to identify the perpetrator of these mailings. a novel liquid chromatography/mass spectrometry protocol for the qualitative detection of trace levels of meglumine and diatrizoate in dried spore preparations of b. anthracis was developed. meglumine and diatrizoate are components of radiogr ...201222537353
proteolytic processing of nlrp1b is required for inflammasome activity.nlrp1b is a nod-like receptor that detects the catalytic activity of anthrax lethal toxin and subsequently co-oligomerizes into a pro-caspase-1 activation platform known as an inflammasome. nlrp1b has two domains that promote oligomerization: a nacht domain, which is a member of the aaa+ atpase family, and a poorly characterized function to find domain (fiind). here we demonstrate that proteolytic processing within the fiind generates n-terminal and c-terminal cleavage products of nlrp1b that re ...201222536155
functional hybrid nickel nanostructures as recyclable sers substrates: detection of explosives and biowarfare agents.we present the synthesis of highly anisotropic nickel nanowires (nws) and large area, free-standing carpets extending over cm(2) area by simple solution phase chemistry. the materials can be post-synthetically manipulated to produce hybrid tubes, wires, and carpets by galvanic exchange reactions with au(3+), ag(+), pt(2+), and pd(2+). all of these structures, especially the hybrid carpets and tubes, have been prepared in bulk and are surface enhanced raman scattering (sers) active substrates. mo ...201222535435
anthrax toxin receptor 2 functions in ecm homeostasis of the murine reproductive tract and promotes mmp activity.anthrax toxin receptor proteins function as receptors for anthrax toxin, however physiological activity remains unclear. to evaluate the biological role of antxr2, we generated antxr2-/- mice. antxr2-/- mice were viable, however antxr2 is required for parturition in young females and for preserving fertility in older female mice. histological analysis of the uterus and cervix revealed aberrant deposition of extracellular matrix proteins such as type i collagen, type vi collagen and fibronectin. ...201222529944
real-time polymerase chain reaction assay for rapid and sensitive detection of anthrax spores in spiked soil and talcum powder.real-time polymerase chain reaction (real-time pcr) is a laboratory technique based on pcr. this technique is able to detect sequence-specific pcr products as they accumulate in "real time" during the pcr amplification, and also to quantify the number of substrates present in the initial pcr mixture before amplification begins. in the present study, real-time pcr assay was employed for rapid and real-time detection of bacillus anthracis spores spiked in 0.1 g of soil and talcum powder ranging fr ...201222528297
an overview of anthrax infection including the recently identified form of disease in injection drug users.bacillus anthracis infection (anthrax) can be highly lethal. two recent outbreaks related to contaminated mail in the usa and heroin in the uk and europe and its potential as a bioterrorist weapon have greatly increased concerns over anthrax in the developed world.201222527064
expression of either lethal toxin or edema toxin by bacillus anthracis is sufficient for virulence in a rabbit model of inhalational anthrax.the development of therapeutics against biothreats requires that we understand the pathogenesis of the disease in relevant animal models. the rabbit model of inhalational anthrax is an important tool in the assessment of potential therapeutics against bacillus anthracis. we investigated the roles of b. anthracis capsule and toxins in the pathogenesis of inhalational anthrax in rabbits by comparing infection with the ames strain versus isogenic mutants with deletions of the genes for the capsule ...201222526673
structural and functional characterization of microcin c resistance peptidase mccf from bacillus anthracis.microcin c (mcc) is heptapeptide adenylate antibiotic produced by escherichia coli strains carrying the mccabcdef gene cluster encoding enzymes, in addition to the heptapeptide structural gene mcca, necessary for mcc biosynthesis and self-immunity of the producing cell. the heptapeptide facilitates mcc transport into susceptible cells, where it is processed releasing a non-hydrolyzable aminoacyl adenylate that inhibits an essential aminoacyl-trna synthetase. the self-immunity gene mccf encodes a ...201222516613
immunogenicity and efficacy of an anthrax/plague dna fusion vaccine in a mouse model.the efficacy of multi-agent dna vaccines consisting of a truncated gene encoding bacillus anthracis lethal factor (lfn) fused to either yersinia pestis v antigen (v) or y . pestis f1 was evaluated. a/j mice were immunized by gene gun and developed predominantly igg1 responses that were fully protective against a lethal aerosolized b. anthracis spore challenge but required the presence of an additional dna vaccine expressing anthrax protective antigen to boost survival against aerosolized y. pest ...201222515653
effect of animal sera on bacillus anthracis sterne spore germination and vegetative cell growth.the aims of this work were to investigate the effects of sera on b. anthracis sterne germination and growth. sera examined included human, monkey and rabbit sera, as well as sera from eight other species.201222515644
variance in bacillus anthracis virulence assessed through bayesian hierarchical dose-response modelling.to develop a predictive dose-response model for describing the survival of animals exposed to bacillus anthracis to support risk management options.201222515543
evaluation of sample preparation methods for maldi-tof ms identification of highly dangerous bacteria.to propose a universal workflow of sample preparation method for the identification of highly pathogenic bacteria by maldi-tof ms.201222512320
delayed toxicity associated with soluble anthrax toxin receptor decoy-ig fusion protein treatment.soluble receptor decoy inhibitors, including receptor-immunogloubulin (ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. these agents act by binding to the receptor-interaction site on the protective antigen (pa) toxin subunit, thereby blocking toxin binding to cell surface receptors. here we have made the surprising observation that co-administration of receptor decoy-ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax letha ...201222511955
protective effect of bacillus anthracis surface protein ea1 against anthrax in mice.bacillus anthracis spores germinate to vegetative forms in host cells, and produced fatal toxins. a toxin-targeting prophylaxis blocks the effect of toxin, but may allow to grow vegetative cells which create subsequent toxemia. in this study, we examined protective effect of extractable antigen 1 (ea1), a major s-layer component of b. anthracis, against anthrax. mice were intranasally immunized with recombinant ea1, followed by a lethal challenge of b. anthracis spores. mucosal immunization with ...201222507985
biosecurity aspects and pathogen inactivation in acidified high risk animal by-products.the aim of the study was to investigate the effects of formic acid addition to ground high risk animal by-products (abp 1) in terms of stabilization and pathogen inactivation and to evaluate the biosecurity risk connected with the abp 1 based combustion fuel biomal. laboratory studies were performed on the persistence of salmonella typhimurium, bacillus cereus spores, porcine herpes virus, avian influenza virus, bovine viral diarrhea virus, equine rhinitis a virus and porcine parvovirus in bioma ...201222506709
raman spectroscopic detection of anthrax endospores in powder samples. 201222505355
gerhard hansen: discoverer of the organism of leprosy.this year marks the hundredth anniversary of the death, on 12 february 1912, of the norwegian leprologist, gerhard hansen, who was the first to describe the mycobacterium leprae (hansen's bacillus). it was, in fact, only the second specific disease-causing organism to be discovered, the first being the bacillus of anthrax.201222504759
role of chondroitin sulfate c in the action of anthrax toxin.anthrax toxin is produced by bacillus anthracis, the causative agent of anthrax, and is responsible for the majority of disease symptoms. the toxin consists of 3 proteins, protective antigen (pa), lethal factor (lf), and edema factor (ef), which combine to form lethal and edema toxin. glycosaminoglycans, which are present on the surface of cells, were investigated with regard to their role in toxicity resulting from anthrax toxin exposure. lethal toxin-induced cytotoxicity of the raw 264.7 cells ...201222503668
laccase- and chloroperoxidase-nanotube paint composites with bactericidal and sporicidal activity.laccase and chloroperoxidase (cpo) were separately immobilized onto multi-walled carbon nanotubes (mwnts) and subsequently mixed with a commercial eco-friendly paint to generate biocatalytic coatings. the laccase-nanotube based paints showed >99% bactericidal activity against escherichia coli and staphylococcus aureus (both challenged with 10⁶ cfu/ml) within 30 min and >98% sporicidal activity against bacillus cereus and bacillus anthracis-δsterne (initially challenged with 10⁴ cfu/ml) within 12 ...201222500892
bounds on the effect of vaccine induced immune response on outcome.a major goal of vaccine development is the identification of immune responses that are responsible for vaccine efficacy. in theory, modest vaccines could be successfully improved by increasing such immune responses. and for a vaccine with a great benefit in one population, inducing such immune response in a different population could help one conclude the vaccine would have great benefit there. such identification is tricky because the immune response to vaccination can only be measured in the v ...201222499733
invariant gly residue is important for α-defensin folding, dimerization, and function: a case study of the human neutrophil α-defensin hnp1.the human α-defensins (hnp) are synthesized in vivo as inactive prodefensins, and contain a conserved glycine, gly(17), which is part of a β-bulge structure. it had previously been shown that the glycine main chain torsion angles are in a d-configuration, and that d-amino acids but not l-alanine could be substituted at that position to yield correctly folded peptides without the help of a prodomain. in this study, the glycine to l-alanine mutant defensin was synthesized in the form of a prodefen ...201222496447
black-backed jackal exposure to rabies virus, canine distemper virus, and bacillus anthracis in etosha national park, namibia.canine distemper virus (cdv) and rabies virus (rabv) occur worldwide in wild carnivore and domestic dog populations and pose threats to wildlife conservation and public health. in etosha national park (enp), namibia, anthrax is endemic and generates carcasses frequently fed on by an unusually dense population of black-backed jackals (canis mesomelas). using serology, phylogenetic analyses (on samples obtained from february 2009-july 2010), and historical mortality records (1975-2011), we assesse ...201222493112
anthrax outbreaks in bangladesh, 2009-2010.during august 2009-october 2010, a multidisciplinary team investigated 14 outbreaks of animal and human anthrax in bangladesh to identify the etiology, pathway of transmission, and social, behavioral, and cultural factors that led to these outbreaks. the team identified 140 animal cases of anthrax and 273 human cases of cutaneous anthrax. ninety one percent of persons in whom cutaneous anthrax developed had history of butchering sick animals, handling raw meat, contact with animal skin, or were ...201222492157
distributed and grid computing projects with research focus in human health.distributed systems and grid computing systems are used to connect several computers to obtain a higher level of performance, in order to solve a problem. during the last decade, projects use the world wide web to aggregate individuals' cpu power for research purposes. this paper presents the existing active large scale distributed and grid computing projects with research focus in human health. there have been found and presented 11 active projects with more than 2000 processing units (pus) eac ...201222491123
[two new sequence type isolates of bacillus anthracis by multilocus sequence typing].to define the sequence type (st) isolates of bacillus anthracis by multilocus sequence typing (mlst).201222489469
production of protocatechuic acid in bacillus thuringiensis atcc33679.protocatechuic acid, or 3,4-dihydroxybenzoic acid, is produced by both soil and marine bacteria in the free form and as the iron binding component of the siderophore petrobactin. the soil bacterium, bacillus thuringiensis kurstaki atcc 33679, contains the asb operon, but does not produce petrobactin. iron restriction resulted in diminished b. thuringiensis kurstaki atcc 33679 growth and the production of catechol(s). the gene product responsible for protocatechuic acid (asbf) and its receptor (f ...201222489181
membrane pores in the pathogenesis of neurodegenerative disease.the neurodegenerative diseases described in this volume, as well as many nonneurodegenerative diseases, are characterized by deposits known as amyloid. amyloid has long been associated with these various diseases as a pathological marker and has been implicated directly in the molecular pathogenesis of disease. however, increasing evidence suggests that these proteinaceous congo red staining deposits may not be toxic or destructive of tissue. recent studies strongly implicate smaller aggregates ...201222482454
anthrax lethal factor cleavage of nlrp1 is required for activation of the inflammasome.nod-like receptor (nlr) proteins (nlrps) are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis) and maturation of il-1β and il-18. anthrax lethal toxin (lt) induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from cer ...201222479187
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
lung b cells promote early pathogen dissemination and hasten death from inhalation anthrax.sampling of mucosal antigens regulates immune responses but may also promote dissemination of mucosal pathogens. lung dendritic cells (ldcs) capture antigens and traffic them to lung-draining lymph nodes (ldlns) dependent on the chemokine receptor ccr7 (chemokine (c-c motif) receptor 7). ldcs also capture lung pathogens such as bacillus anthracis (ba). however, we show here that the initial traffic of ba spores from lungs to ldlns is largely independent of ldcs and ccr7, occurring instead in ass ...201222472773
human-animal anthrax outbreak in the luangwa valley of zambia in 2011.there has been a reduction of incidences of anthrax in the developed countries but it is still a public health problem in the developing countries where communities live in interface areas with wildlife. an outbreak of anthrax in hippopotamus amphibious was observed in zambia. following the death of hippopotamuses, suspected human cases were reported. the objective of this study was to isolate and confirm bacillus anthracis and to determine the antimicrobial susceptibility for the management of ...201222472314
benchmark dose analysis for bacillus anthracis inhalation exposures in the nonhuman primate.there is considerable variability in the published lethality values for inhalation exposures of bacillus anthracis. the lack of consensus on an acceptable dose-response relationship poses a significant challenge in the development of risk-based management approaches for use following a terrorist release of b. anthracis spores. this article reviewed available b. anthracis dose-response modeling and literature for the nonhuman primate, evaluated the use of the u.s. environmental protection agency' ...201222469218
active control of silver nanoparticles spacing using dielectrophoresis for surface-enhanced raman scattering.we demonstrate an active microfluidic platform that integrates dielectrophoresis for the control of silver nanoparticles spacing, as they flow in a liquid channel. by careful control of the nanoparticles spacing, we can effectively increase the surface-enhanced raman scattering (sers) signal intensity based on augmenting the number of sers-active hot-spots, while avoiding irreversible aggregation of the particles. the system is benchmarked using dipicolinate (2,6-pyridinedicarboxylic acid) (dpa) ...201222468827
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
ultrafast kinetic dna hybridization assay based on the visualization of threshold turbidity.we report herein the development of an ultrafast kinetic dna hybridization assay system based on the visualization of threshold turbidity associated with the assembly of polystyrene nanospheres. initial testing of our diagnostic protocol on a sequence associated with the anthrax lethal factor indicates that a visually identifiable, turbidity-definitive, and kinetic threshold state could be reached at a time as short as 1 min. the assay scheme allows for both target concentration quantification a ...201222458673
assessing a decade of public health preparedness: progress on the precipice?september 11 and the subsequent anthrax attacks marked the beginning of significant investment by the federal government to develop a national public health emergency response capability. recognizing the importance of the public health sector's contribution to the burgeoning homeland security enterprise, this investment was intended to convey a "dual benefit" by strengthening the overall public health infrastructure while building preparedness capabilities. in many instances, federal funds were ...201222455679
a decade of countering bioterrorism: incremental progress, fundamental failings.the fear and disruption caused by the 2001 anthrax attacks understandably led americans to seek enhanced biodefenses. however, the path followed since those attacks has left the country inadequately prepared to face further risks from biological attacks. why has security against these threats been only partially achieved? this article suggests that our responses over the past decade can be sorted into 4 levels in order of increasing difficulty. first, we rapidly appropriated funds, augmented per ...201222455678
the evolution of law in biopreparedness.the decade following the terrorist attacks on september 11, 2001, and ensuing anthrax exposures that same fall has seen significant legal reforms designed to improve biopreparedness nationally. over the past 10 years, a transformative series of legal changes have effectively (1) rebuilt components of federal, state, and local governments to improve response efforts; (2) created an entire new legal classification known as "public health emergencies"; and (3) overhauled existing legal norms defini ...201222455677
public health surveillance and infectious disease detection.emerging infectious diseases, such as hiv/aids, sars, and pandemic influenza, and the anthrax attacks of 2001, have demonstrated that we remain vulnerable to health threats caused by infectious diseases. the importance of strengthening global public health surveillance to provide early warning has been the primary recommendation of expert groups for at least the past 2 decades. however, despite improvements in the past decade, public health surveillance capabilities remain limited and fragmented ...201222455675
fluoroquinolone-induced tendinopathy: etiology and preventive measures.tendinopathy is a serious health problem and its etiology is not fully elucidated. among intrinsic and extrinsic predisposing factors of tendinopathy, the impact of therapeutic agents, especially fluoroquinolone (fq) group antibiotics, is recently being recognized. fqs are potent bactericidal agents widely used in various infectious diseases, including community acquired pneumonia and bronchitis, chronic osteomyelitis, traveler's diarrhea, typhoid fever, shigellosis, chronic bacterial prostatiti ...201222452935
bacillus anthracis protease inha regulates bsla-mediated adhesion in human endothelial cells.to achieve widespread dissemination in the host, bacillus anthracis cells regulate their attachment to host endothelium during infection. previous studies identified bsla (bacillus anthracis s-layer protein a), a virulence factor of b. anthracis, as necessary and sufficient for adhesion of vegetative cells to human endothelial cells. while some factors have been identified, bacteria-specific contributions to bsla mediated adhesion remain unclear. using the attenuated vaccine sterne 7702 strain o ...201222452315
sterilization effect of uv light on bacillus spores using tio(2) films depends on wavelength.uv light and photocatalysts such as titanium dioxide (tio(2)) and silver (ag) are useful for disinfection of water and surfaces. however, the effect of uv wavelength on photocatalytic disinfection of spores is not well understood. inactivation of bacillus spores has been examined using different uv wavelengths and tio(2) or tio(2)/ag composite materials. the level of uva disinfection of bacillus anthracis and bacillus brevis vegetative cells increased with the presence of the tio(2) and ag photo ...201222449993
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
antimicrobial susceptibility and molecular subtyping of 55 turkish bacillus anthracis strains using 25-loci multiple-locus vntr analysis.anthrax, which is caused by the bacterium bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. the differentiation of b. anthracis strains is difficult because of their highly homogeneous genomes. we used multiple-locus variable-number tandem repeat analysis (mlva) with 25 markers to genotype 55 b. anthracis isolates from 16 distinct regions of turkey. the antimicrobial susceptibility of the isolates was investigated using the agar dilution method ...201222445310
[epidemiologic surveillance for anthrax foci by using standard case definition]. 201222442983
thermal inactivation of bacillus anthracis surrogate spores in a bench-scale enclosed landfill gas flare.a bench-scale landfill flare system was designed and built to test the potential for landfilled biological spores that migrate from the waste into the landfill gas to pass through the flare and exit into the environment as viable. the residence times and temperatures of the flare were characterized and compared to full-scale systems. geobacillus stearothermophilus and bacillus atrophaeus, nonpathogenic spores that may serve as surrogates for bacillus anthracis, the causative agent for anthrax, w ...201222442931
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
targeting bacterial toxins.protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin-mediated pathogenicity. despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. this review presents the state of the art i ...201222441768
analysis of defined combinations of monoclonal antibodies in anthrax toxin neutralization assays and their synergistic action.antibodies against the protective antigen (pa) component of anthrax toxin play an important role in protection against disease caused by bacillus anthracis. in this study, we examined defined combinations of pa-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. we observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. synergistic toxin-neutral ...201222441391
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
a platform for combined dna and protein microarrays based on total internal reflection fluorescence.we have developed a novel microarray technology based on total internal reflection fluorescence (tirf) in combination with dna and protein bioassays immobilized at the tirf surface. unlike conventional microarrays that exhibit reduced signal-to-background ratio, require several stages of incubation, rinsing and stringency control, and measure only end-point results, our tirf microarray technology provides several orders of magnitude better signal-to-background ratio, performs analysis rapidly in ...201222438738
novel approaches to the treatment of systemic anthrax.anthrax continues to generate concern as an agent of bioterrorism and as a natural cause of sporadic disease outbreaks. despite the use of appropriate antimicrobial agents and advanced supportive care, the mortality associated with the systemic disease remains high. this is primarily due to the pathogenic exotoxins produced by bacillus anthracis as well as other virulence factors of the organism. for this reason, new therapeutic strategies that target events in the pathogenesis of anthrax and ma ...201222438345
[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
in vivo activity of oritavancin in animal infection models and rationale for a new dosing regimen in humans.oritavancin is a novel glycopeptide antibiotic with concentration-dependent killing of gram-positive cocci and pharmacokinetics characterized by extensive tissue distribution and a long terminal half-life. its development was hindered by a 16- to 32-fold underestimation of activity against staphylococci and enterococci because of oritavancin's sticking to vials and tubes. dose-fractionation studies in animal models suggested the peak concentration was the major index for efficacy. once-daily int ...201222431852
multiple abc transporters are involved in the acquisition of petrobactin in bacillus anthracis.in bacillus anthracis the siderophore petrobactin is vital for iron acquisition and virulence. the petrobactin-binding receptor fpua is required for these processes. here additional components of petrobactin reacquisition are described. to identify these proteins, mutants of candidate permease and atpase genes were generated allowing for characterization of multiple petrobactin atp-binding cassette (abc)-import systems. either of two distinct permeases, fpub or fatcd, is required for iron acquis ...201222429808
human monoclonal antibodies generated following vaccination with ava provide neutralization by blocking furin cleavage but not by preventing oligomerization.in order to identify the combination of antibody-mediated mechanisms of neutralization that result from vaccination with anthrax vaccine adsorbed (ava), we isolated antibody secreting cells from a single donor seven days after booster vaccination with ava and generated nine fully human monoclonal antibodies (hmab) with high specificity for protective antigen (pa). two of the antibodies were able to neutralize lethal toxin in vitro at low concentrations (ic(50): p6c01, 0.12 μg/ml and p6f01, 0.45 ...201222425791
structure, assembly, and dna packaging of the bacteriophage t4 head.the bacteriophage t4 head is an elongated icosahedron packed with 172 kb of linear double-stranded dna and numerous proteins. the capsid is built from three essential proteins: gp23*, which forms the hexagonal capsid lattice; gp24*, which forms pentamers at 11 of the 12 vertices; and gp20, which forms the unique dodecameric portal vertex through which dna enters during packaging and exits during infection. intensive work over more than half a century has led to a deep understanding of the phage ...201222420853
structure-based design of novel pyrimido[4,5-c]pyridazine derivatives as dihydropteroate synthase inhibitors with increased affinity.dihydropteroate synthase (dhps) is the validated drug target for sulfonamide antimicrobial therapy. however, due to widespread drug resistance and poor tolerance, the use of sulfonamide antibiotics is now limited. the pterin binding pocket in dhps is highly conserved and is distinct from the sulfonamide binding site. it therefore represents an attractive alternative target for the design of novel antibacterial agents. we previously carried out the structural characterization of a known pyridazin ...201222416048
distribution and molecular evolution of bacillus anthracis genotypes in namibia.the recent development of genetic markers for bacillus anthracis has made it possible to monitor the spread and distribution of this pathogen during and between anthrax outbreaks. in namibia, anthrax outbreaks occur annually in the etosha national park (enp) and on private game and livestock farms. we genotyped 384 b. anthracis isolates collected between 1983-2010 to identify the possible epidemiological correlations of anthrax outbreaks within and outside the enp and to analyze genetic relation ...201222413024
rugged single domain antibody detection elements for bacillus anthracis spores and vegetative cells.significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. while numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. in an effort to overcome these ...201222412927
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
differential function of lip residues in the mechanism and biology of an anthrax hemophore.to replicate in mammalian hosts, bacterial pathogens must acquire iron. the majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, isdx1 and isdx2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. both proteins ...201222412371
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
ultra-fast pg/ml anthrax toxin (protective antigen) detection assay based on microwave-accelerated metal-enhanced fluorescence.rapid presymptomatic diagnosis of bacillus anthracis at early stages of infection plays a crucial role in prompt medical intervention to prevent rapid disease progression and accumulation of lethal levels of toxin. to detect low levels of the anthrax protective antigen (pa) exotoxin in biological fluids, we have developed a metal-enhanced fluorescence (mef)-pa assay using a combination of the mef effect and microwave-accelerated pa protein surface absorption. the assay is based on a modified ver ...201222406431
variable lymphocyte receptor recognition of the immunodominant glycoprotein of bacillus anthracis spores.variable lymphocyte receptors (vlrs) are the adaptive immune receptors of jawless fish, which evolved adaptive immunity independent of other vertebrates. in lieu of the immunoglobulin fold-based t and b cell receptors, lymphocyte-like cells of jawless fish express vlrs (vlra, vlrb, or vlrc) composed of leucine-rich repeats and are similar to toll-like receptors (tlrs) in structure, but antibodies (vlrb) and t cell receptors (vlra and vlrc) in function. here, we present the structural and biochem ...201222405006
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
determinants of emergency response willingness in the local public health workforce by jurisdictional and scenario patterns: a cross-sectional survey.the all-hazards willingness to respond (wtr) of local public health personnel is critical to emergency preparedness. this study applied a threat-and efficacy-centered framework to characterize these workers' scenario and jurisdictional response willingness patterns toward a range of naturally-occurring and terrorism-related emergency scenarios.201222397547
the mountain meadows massacre and "poisoned springs": scientific testing of the more recent, anthrax theory.it has been recorded that one of the possible causes that eventually escalated into the 1857 manslaughter at mountain meadows in southern utah was the poisoning of an open spring by the fancher-baker party as they crossed the utah territory on their way from arkansas to california. historical accounts report that a number of cattle died, followed by human casualties from those that came in contact with the dead animals. even after the arkansas party departed, animals continued to perish and peop ...201322395921
[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
debridement increases survival in a mouse model of subcutaneous anthrax.anthrax is caused by infection with bacillus anthracis, a spore-forming gram-positive bacterium. a major virulence factor for b. anthracis is an immunomodulatory tripartite exotoxin that has been reported to alter immune cell chemotaxis and activation. it has been proposed that b. anthracis infections initiate through entry of spores into the regional draining lymph nodes where they germinate, grow, and disseminate systemically via the efferent lymphatics. if this model holds true, it would be p ...201222393351
the aminoglycoside antibiotic kanamycin damages dna bases in escherichia coli: caffeine potentiates the dna-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in escherichia coli and bacillus anthracis.the distribution of mutants in the keio collection of escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. strains lacking one of a number of glycosylases (e.g., alka, yzab, ogt, ksga) or other specific repair proteins (alkb, phrb, smbc) are more sensitive to these antibiotics. mutants lacking alkb display the strongest sensitivity among the gly ...201222391551
[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
identification of 2 novel antxr2 mutations in patients with hyaline fibromatosis syndrome and proposal of a modified grading system.juvenile hyaline fibromatosis (jhf) and infantile systemic hyalinosis (ish) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (antxr2) located on chromosome 4q21. characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. the present report describes a pair o ...201222383261
amphiphilic polyanhydride nanoparticles stabilize bacillus anthracis protective antigen.advancements toward an improved vaccine against bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (pa) adsorbed to aluminum hydroxide. however, due to the labile nature of pa, antigen stability is a primary concern for vaccine development. thus, there is a need for a delivery system capable of preserving the immunogenicity of pa through all the steps of vaccine fabrication, storage, and administration. in this work, we demonstrate ...201222380593
ratcheting up protein translocation with anthrax toxin.energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. they are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. biological nanomachines that catalyze protein transport, kno ...201222374876
sverdlovsk revisited: pulmonary pathology of inhalational anthrax versus anthraxlike bacillus cereus pneumonia. 201222372894
finding the smoking gun: protein tyrosine phosphatases as tools and targets of unicellular microorganisms and viruses.protein tyrosine phosphatases (ptps) are increasingly recognized as important effectors of host-pathogen interactions. since guan and dixon reported in 1990 that phosphatase yoph serves as an essential virulence determinant of yersinia, the field shifted significantly forward, and dozens of ptps were identified in various microorganisms and even in viruses. the discovery of extensive tyrosine signaling networks in non-metazoan organisms refuted the moth-eaten paradigm claiming that these organis ...201222360485
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
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
genetic variation and linkage disequilibrium in bacillus anthracis.we performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 bacillus anthracis strains. we used an efficient algorithm contained within a custom software program, uniquemer, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. we discovered a total of 240 single nuc ...201122355684
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
updating perspectives on the initiation of bacillus anthracis growth and dissemination through its host.since 1957, it has been proposed that the dissemination of inhalational anthrax required spores to be transported from the lumena of the lungs into the lymphatic system. in 2002, this idea was expanded to state that alveolar macrophages act as a "trojan horse" capable of transporting spores across the lung epithelium into draining mediastinal lymph nodes. since then, the trojan horse model of dissemination has become the most widely cited model of inhalational infection as well as the focus of t ...201222354031
sporicidal/bactericidal textiles via the chlorination of silk.bacterial spores, such as those of the bacillus genus, are extremely resilient, being able to germinate into metabolically active cells after withstanding harsh environmental conditions or aggressive chemical treatments. the toughness of the bacterial spore in combination with the use of spores, such as those of bacillus anthracis, as a biological warfare agent necessitates the development of new antimicrobial textiles. in this work, a route to the production of fabrics that kill bacterial spore ...201222352921
decontamination after a release of b. anthracis spores.decontaminating civilian facilities or large urban areas following an attack with bacillus anthracis poses daunting challenges because of the lack of resources and proven technologies. nevertheless, lessons learned from the 2001 cleanups together with advances derived from recent research have improved our understanding of what is required for effective decontamination. this article reviews current decontamination technologies appropriate for use in outdoor environments, on material surfaces, wi ...201222352747
identification of the first known inhibitors of o-acetylpeptidoglycan esterase: a potential new antibacterial target.the o-acetylation of peptidoglycan (pg) is now known to occur in 53 species, including numerous human pathogens such as, staphylococcus aureus, bacillus anthracis, species of enterococcus, campylobacter jejuni, helicobacter pylori, neisseria gonorrhoeae and n. meningitidis. this modification, which occurs at the c-6 hydroxyl of n-acetylmuramoyl residues within pg, serves to regulate autolytic activity during pg metabolism and contributes to pathogenesis and persistence within a host. o-acetylpep ...201222351512
development of an in vitro potency assay for anti-anthrax lethal toxin neutralizing antibodies.lethal toxin (lt) of bacillus anthracis reduces the production of a number of inflammatory mediators, including transcription factors, chemokines and cytokines in various human cell lines, leading to down-regulation of the host inflammatory response. previously we showed that the reduction of interleukin-8 (il-8) is a sensitive marker of lt-mediated intoxication in human neutrophil-like nb-4 cells and that il-8 levels are restored to normality when therapeutic monoclonal antibodies (mab) with to ...201222347621
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
characterization of a novel lytic protein encoded by the bacillus cereus e33l gene ampd as a bacillus anthracis antimicrobial protein.lytic proteins encoded by bacterial genomes have been implicated in cell wall biosynthesis and recycling. the bacillus cereus e33l ampd gene encodes a putative n-acetylmuramoyl-l-alanine amidase. this gene, expressed in vitro, produced a very stable, highly active lytic protein. very low concentrations rapidly and efficiently lyse vegetative bacillus anthracis cells.201222344637
naturally occurring cutaneous anthrax: antibiotic treatment and outcome.cutaneous anthrax (ca) is the most common clinical presentation in human anthrax, but the duration of antibiotic therapy in naturally occurring ca is controversial. the aim of this study was to compare the clinical outcomes of patients receiving antibiotic treatment for either 3-5 days (group 1) or 7-10 days (group 2) in uncomplicated ca.201222343361
in vitro and in vivo analyses of the bacillus anthracis spore cortex lytic protein slel.the bacterial endospore is the most resilient biological structure known. multiple protective integument layers shield the spore core and promote spore dehydration and dormancy. dormancy is broken when a spore germinates and becomes a metabolically active vegetative cell. germination requires the breakdown of a modified layer of peptidoglycan (pg) known as the spore cortex. this study reports in vitro and in vivo analyses of the bacillus anthracis slel protein. slel is a spore cortex lytic enzym ...201222343356
antidotes to anthrax lethal factor intoxication. part 3: evaluation of core structures and further modifications to the c2-side chain.four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (lf) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro adme profiles, and relative efficacy in a rat lethal toxin (lt) model of lf intoxication. poor efficacy in the rat lt model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. specific molecular interactions contributing to the high affinity of inhibitors wit ...201222342144
tem8/antxr1 blockade inhibits pathological angiogenesis and potentiates tumoricidal responses against multiple cancer types.current antiangiogenic agents used to treat cancer only partially inhibit neovascularization and cause normal tissue toxicities, fueling the need to identify therapeutic agents that are more selective for pathological angiogenesis. tumor endothelial marker 8 (tem8), also known as anthrax toxin receptor 1 (antxr1), is a highly conserved cell-surface protein overexpressed on tumor-infiltrating vasculature. here we show that genetic disruption of tem8 results in impaired growth of human tumor xenog ...201222340594
bacteria and their toxins tamed for immunotherapy.bacterial toxins share the ability to enter host cells to target various intracellular proteins and to modulate host immune responses. over the last 20 years, toxins and their mutated variants, as well as live attenuated bacteria, have been exploited for vaccination and immunotherapy of various infectious, malignant and autoimmune diseases. the ability of bordetella pertussis adenylate cyclase toxin to translocate its adenylate cyclase domain across the host cell membrane, as well as the pathway ...201222339216
anthrax--update on diagnosis and management.human anthrax is difficult to contain. this is primarily because it is a zoonotic disease and the disease has never been contained in the livestock of india due to lack of adequate vaccination facilities. animal anthrax is very common in many parts of india. the problem of anthrax is further compounded by lack of awareness on the part of village folk who unwittingly handle the hide and share the dead animal meat and this causes cutaneous and gastrointestinal forms of anthrax respectively. hemorr ...201122334971
frequency of epitope-specific naive cd4(+) t cells correlates with immunodominance in the human memory repertoire.the frequency of epitope-specific naive cd4(+) t cells in humans has not been extensively examined. in this study, a systematic approach was used to examine the frequency of cd4(+) t cells that recognize the protective ag of bacillus anthracis in both anthrax vaccine-adsorbed vaccinees and nonvaccinees with hla-drb1*01:01 haplotypes. three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine. average naive precursor frequencies of t cell ...201222327072
multiplexed electrochemical detection of yersinia pestis and staphylococcal enterotoxin b using an antibody microarray.the combimatrix antibody microarray is a versatile, sensitive detection platform based on the generation and transduction of electrochemical signals following antigen binding to surface antibodies. the sensor chip described herein is comprised of microelectrodes coupled to an adjacent bio-friendly matrix coated with antibodies to the biological pathogens yersinia pestis and bacillus anthracis, and the bacterial toxin staphylococcal enterotoxin b (seb). using this system, we were able to detect s ...201022319302
predictability of anthrax infection in the serengeti, tanzania.anthrax is endemic throughout africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. however, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood.we explored rec ...201122318563
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