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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
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
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
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
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
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
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
inhibition of anthrax lethal factor: lability of hydroxamate as a chelating group.the metalloprotease activity of lethal factor (lf) from bacillus anthracis (b. anthracis) is a main source of toxicity in the lethality of anthrax infection. thus, the understanding of the enzymatic activity and inhibition of b. anthracis lf is of scientific and clinical interests. we have designed, synthesized, and studied a peptide inhibitor of lf, r9lf-1, with the structure nh(2)-(d: -arg)(9)-val-leu-arg-co-nhoh in which the c-terminal hydroxamic acid is commonly used in the inhibitors of met ...201222270239
rapid detection methods for bacillus anthracis in environmental samples: a review.bacillus anthracis is a gram-positive, spore-forming bacterium, which causes anthrax, an often lethal disease of animals and humans. although the disease has been well studied since the nineteenth century, it has witnessed a renewed interest during the past decade, due to its use as a bioterrorist agent in the fall of 2001 in the usa. a number of techniques aimed at rapidly detecting b. anthracis, in environmental samples as well as in point-of-care settings for humans suspected of exposure to t ...201222262227
hiv vaccine candidates generate in vitro t cell response to putative epitopes in chinese-origin rhesus macaques.the indian rhesus macaque is the established animal model for hiv infection and vaccine research. growing evidence suggests that the more readily available chinese rhesus macaque may be a more relevant option. as increasing numbers of novel chinese rhesus mhc alleles are reported, we decided to explore potential hiv vaccine epitopes in this model. we immunized forty chinese rhesus macaques with three different hiv vaccine candidates either individually or following a prime/boost strategy. we use ...201222261410
pharmacological inhibition of the clpxp protease increases bacterial susceptibility to host cathelicidin antimicrobial peptides and cell envelope-active antibiotics.the clpxp protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. here we identified a pharmacological inhibitor of the clpxp protease, f2, and evaluated its action in bacillus anthracis and staphylococcus aureus. we found that f2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane, such as penicillin and daptomycin, in b. anthracis and drug- ...201222252821
gc/ms method for positive detection of bacillus anthracis endospores.a simple method was developed for detection of bacillus anthracis (ba) endospores and for differentiation of them from other species in the bacillus cereus group. chemical profiles that include lipids (i.e., fatty acids), carbohydrates (i.e., sugars), and the spore-specific biomarker, dipicolinic acid, were generated by one-step thermochemolysis (tcm) at 140 °c in 5 min to provide specific biomarker signatures. anthrose, which is a biomarker characteristic of the b. cereus group of bacteria, was ...201222243393
comparison of quantitative pcr and culture-based methods for evaluating dispersal of bacillus thuringiensis endospores at a bioterrorism hoax crime scene.since the anthrax mail attacks of 2001, law enforcement agencies have processed thousands of suspicious mail incidents globally, many of which are hoax bioterrorism threats. bio-insecticide preparations containing bacillus thuringiensis (bt) spores have been involved in several such threats in australia, leading to the requirement for rapid and sensitive detection techniques for this organism, a close relative of bacillus anthracis. here we describe the development of a quantitative pcr (qpcr) m ...201222227150
apoptosis, antimicrobial and antioxidant activities of phytochemicals from garcinia malaccensis hk.f.to study the chemical constituents of stembark of garcinia malaccensis (g. malaccensis) together with apoptotic, antimicrobial and antioxidant activities.201222221758
binding and cell intoxication studies of anthrax lethal toxin.anthrax lethal toxin (lt) is a major virulence factor of bacillus anthracis. the vast majority of the anthrax toxin-related literature describes the assembly of lt as a cell-dependent process. however, some reports have provided evidence for the existence of a fully assembled lt, either in vitro or in the bloodstream of anthrax-infected animals. to follow up on this work, we present studies on fully-assembled lt. we first demonstrate facile and cell-free assembly and purification of lt. we then ...201222219086
development of aptamer beacons for rapid presumptive detection of bacillus spores.a library of 92 dna aptamer sequences was developed against bacillus anthracis (nonpathogenic sterne strain) spores and anthrose sugar immobilized on magnetic beads. the selected dna sequences were studied for similarities and potential binding pockets between the b. anthracis spore and anthrose aptamers. several recurring loop structures were identified and tested for their potential to act as aptamer beacons when labeled with tye 665 dye on their 5' ends and iowa black quencher on their 3' end ...201222218972
human genetic variation altering anthrax toxin sensitivity.the outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. some host genes encode defense mechanisms, whereas others assist pathogen functions. genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causality is limited. here we demonstrate that human genetic variation affecting capillary morphogenesis gene 2 (cmg2), which encodes a host membrane protein exploited by anthrax toxin a ...201222315420
increased affinity and solubility of peptides used for direct peptide elisa on polystyrene surfaces through fusion with a polystyrene-binding peptide tag.peptide reagents can serve as alternatives or replacements to antibodies in sensing or diagnostic applications. the passive adsorption of peptides onto polystyrene surfaces can limit the target binding capability, especially for short, positively charged, or hydrophobic sequences. in this report, we show that fusing a peptide with a previously characterized 12-amino acid polystyrene binding sequence (ps-tag) improves overall peptide solubility and enzyme-linked immunosorbent assay (elisa) result ...201222313407
total decontamination cost of the anthrax letter attacks.all of the costs associated with decontamination following the 2001 anthrax letter attacks were summarized, estimated, and aggregated based on existing literature and news media reports. a comprehensive list of all affected structures was compiled. costs were analyzed by building class and decontamination type. sampling costs and costs of worker relocation were also included. our analysis indicates that the total cost associated with decontamination was about $320 million.201222313022
on-column labeling of gram-positive bacteria with a boronic acid functionalized squarylium cyanine dye for analysis by polymer-enhanced capillary transient isotachophoresis.a new asymmetric, squarylium cyanine dye functionalized by boronic acid ("sq-ba") was designed and synthesized for on-capillary labeling of gram-positive bacteria to provide for high sensitivity detection by way of a modified form of capillary electrophoresis with laser induced fluorescence detection (ce-lif). the ce-based separation employed a polymer-enhanced buffer with capillary transient isotachophoresis in a new hybrid method dubbed "pecti." it was found that the addition of various monosa ...201222304241
binding of filamentous actin to anthrax toxin receptor 1 decreases its association with protective antigen.antxr1 is a type i membrane protein that binds the protective antigen (pa) component of anthrax toxin. the cytosolic domain of antxr1 has a novel actin-binding region that influences the interaction of the ectodomain with pa. here, we have investigated features of the cytosolic domain of antxr1 that reduce the association of the receptor with pa. we mutated a stretch of conserved acidic amino acids adjacent to the actin-binding region and found that the mutation increased the affinity for monome ...201222303962
infantile systemic hyalinosis associated with a putative splice-site mutation in the antxr2 gene.infantile systemic hyalinosis (ish) is a rare autosomal recessive genetic disorder characterized by dermal and subcutaneous fibromatosis, joint contractures and bone deformities. the condition usually presents at birth, resulting in death in infancy. ish is caused by mutations in the anthrax toxin receptor 2 gene, antxr2, also known as cmg2. we report an indian child with ish in whom we identified a homozygous acceptor splice site mutation, ivs2-4g>a. in silico analysis of this sequence showed t ...201222300424
lethality in a murine model of pulmonary anthrax is reduced by combining nuclear transport modifier with antimicrobial therapy.in the last ten years, bioterrorism has become a serious threat and challenge to public health worldwide. pulmonary anthrax caused by airborne bacillus anthracis spores is a life-threatening disease often refractory to antimicrobial therapy. inhaled spores germinate into vegetative forms that elaborate an anti-phagocytic capsule along with potent exotoxins which disrupt the signaling pathways governing the innate and adaptive immune responses and cause endothelial cell dysfunction leading to vas ...201222291977
genomic and snp analyses demonstrate a distant separation of the hospital and community-associated clades of enterococcus faecium.recent studies have pointed to the existence of two subpopulations of enterococcus faecium, one containing primarily commensal/community-associated (ca) strains and one that contains most clinical or hospital-associated (ha) strains, including those classified by multi-locus sequence typing (mlst) as belonging to the cc17 group. the ha subpopulation more frequently has is16, pathogenicity island(s), and plasmids or genes associated with antibiotic resistance, colonization, and/or virulence. supp ...201222291916
design and characterization of novel hybrid antimicrobial peptides based on cecropin a, ll-37 and magainin ii.antimicrobial peptides (amps) are a naturally occurring component of the innate immune response of many organisms and can have activity against both gram-negative and gram-positive bacterial species. in order to optimize and improve the direct antimicrobial effect of amps against a broad spectrum of bacterial species, novel synthetic hybrids were rationally designed from cecropin a, ll-37 and magainin ii. amps were selected based on their α-helical secondary structure and fragments of these were ...201222289499
serum albumin disrupts cryptococcus neoformans and bacillus anthracis extracellular vesicles.for both pathogenic fungi and bacteria, extracellular vesicles have been shown to contain many microbial components associated with virulence, suggesting a role in pathogenesis. however, there are many unresolved issues regarding vesicle synthesis and stability, including the fact that vesicular packaging for extracellular factors involved in virulence must also have a mechanism for vesicle unloading. consequently, we studied the kinetics of vesicle production and stability using [1-(14) c] palm ...201222289081
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
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: has the clinical milieu changed since 2001?since the anthrax attacks of 2001 (amerithrax), several important improvements in the knowledge of bacillus anthracis and the clinical condition it causes have occurred. while much remains to be known about the optimal management of anthrax patients, several approaches that were not widely utilized, available, or known in 2001 would be used in the treatment of critically ill anthrax patients in 2012.201223882372
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
the african buffalo: a villain for inter-species spread of infectious diseases in southern africa.the african buffalo (syncerus caffer) is a large wild bovid which until recently ranged across all but the driest parts of sub-saharan africa, and their local range being limited to about 20 km from surface water. they are of high ecological value due to their important role as bulk feeders in the grazing hierarchy. they also have high economic value, because they are one of the sought after 'big five' in the eco-tourism industry. in africa, buffaloes have been recognised for some time as an imp ...201223327373
new aspects of the infection mechanisms of bacillus anthracis.articles concerning new aspects of b. anthracis mechanisms of infection were reviewed. it was found, that the hair follicle plays an important role in the spore germination process. the hair follicle represent an important portal of entry in the course of the cutaneous form of disease infections. after mouse exposition to aerosol of spores prepared from b. anthracis strains, an increase in the level of tnf-α cytokines was observed. the tnf-α cytokines were produced after intrusion into the host ...201223311776
computational studies on molecular interactions of 6-thioguanosine analogs with anthrax toxin receptor 1.dormant endospores of bacillus anthracis are the causative agent of anthrax, which is an acute disease for both human and animals. anthrax has been practised as biological weapon because of two attributes: i) short duration of spore germination, and ii) lethal toxaemia of the vegetative stage. pathogenesis is caused by the activity of edema toxin and lethal toxin. protective antigen (pa), is an essential component of both complexes, binds to anthrax toxin receptor (atr) and mediates the lethalit ...201223292691
development of a high throughput assay for indirectly measuring phage growth using the omnilog(tm) system.the conventional and most accepted method of measuring the lytic activity of a phage against its bacterial host is the plaque assay. this method is laborious, time consuming and expensive, especially in high throughput analyses where multiple phage-bacterial interactions are required to be monitored simultaneously. it can also vary considerably with the experimenter and by the growth and plating conditions. alternatively, the lytic activity can be measured indirectly by following the decrease in ...201223275867
genetic populations of bacillus anthracis isolates from korea.bacillus (b.) anthracis is the pathogen that causes fatal anthrax. strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial population genetics. in the present study, we employed molecular approaches including multiple-locus variable-number tandem repeat analysis (mlva) and canonical single-nucleotide polymorphism (cansnp) analysis to perform molecular typing of b. anthracis strains isolated in korea. according to the mlva, 17 b. anthracis is ...201223271180
injection anthrax--a new outbreak in heroin users.injection anthrax is a rare disease that affects heroin users and is caused by bacillus anthracis. in 2012, there were four cases in germany, one of which was fatal, as well as a small number of cases in other european countries, including denmark, france, and the united kingdom. three cases among drug users occurred in germany in 2009/2010, in the setting of a larger outbreak centered on scotland, where there were 119 cases. case presentation and clinical course: we present three cases of injec ...201223267409
analysing the spatial patterns of livestock anthrax in kazakhstan in relation to environmental factors: a comparison of local (gi*) and morphology cluster statistics.we compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle) and small (sheep and goats) domestic ruminants across kazakhstan. the getis-ord (gi*) statistic and a multidirectional optimal ecotope algorithm (amoeba) were compared using 1st, 2nd and 3rd order rook contiguity matrices. multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the amoeba and gi* tests. a logistic regression ...201223242686
critical challenges and impediments affecting rural physicians during a public health emergency.disaster preparedness has become a health policy priority for the united states in the aftermath of the anthrax attacks, 9/11, and other calamities. it is important for rural health care professionals to be prepared for a bioterrorist attack or other public health emergency. we sought to determine the barriers impeding rural physicians from being prepared for a human-induced disaster such as a bioterrorist attack.201223241464
the differential susceptibility of spores from virulent and attenuated bacillus anthracis strains to aldehyde- and hypochlorite-based disinfectants.this study compared the sensitivity of spores from virulent and attenuated bacillus anthracis strains in suspension to inactivation by various chemical disinfectants. spore suspensions from two virulent strains (a0256 and a0372) and two attenuated strains (sterne and a0141) of b. anthracis were tested against two aldehyde-based disinfectants and one hypochlorite-based disinfectant. a novel statistical model was used to estimate 4-log(10) reduction times for each disinfectant/strain combination. ...201223233190
coumarin-based inhibitors of bacillus anthracis and staphylococcus aureus replicative dna helicase: chemical optimization, biological evaluation, and antibacterial activities.the increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9-18-fold increased potency against staphylococcus aureus (sa) and bacillus anthracis (ba) helicases. compounds 20 and ...201223231076
[detection and identification of highly pathogenic bacteria within the framework of the eqadeba project--part ii: samples containing inactivated pathogens].the aim of the studies was analysis of methods applied and results of detection and identification of bacillus anthracis, yersinia pestis, francisella tularensis, brucella sp., bulkholderia mallei and b. pseudomallei in inactivated samples obtained within the framework of the third external quality assessment exercise (eqae) in the project ,,establishment of quality assurances for detection of highly pathogenic bacteria of potential bioterrorism risk (eqadeba)".201223230707
[safe from biothreats? legislation protects you and society].the 9/11 terror attacks, followed by mailing of letters containing anthrax spores, changed our comprehension on threats towards modern society. finland is committed by international treaties to develop biosafety and biosecurity legislation, and general awareness of the legislation. however, the rapidly developing field of biosciences cannot be extensively regulated by legislation. awareness of the risks and challenges involved in handling of biological agents is an important tool in threat preve ...201223210284
effects of epidemic diseases on the distribution of bonobos.this study examined how outbreaks and the occurrence of anthrax, ebola, monkeypox and trypanosomiasis may differentially affect the distribution of bonobos (pan paniscus). using a combination of mapping, jaccard overlapping coefficients and binary regressions, the study determined how each disease correlated with the extent of occurrence of, and the areas occupied by, bonobos. anthrax has only been reported to occur outside the range of bonobos and so was not considered further. ebola, monkeypox ...201223251431
public response to an anthrax attack: a multiethnic perspective.the 2001 anthrax attacks emphasized the need to develop outreach that would more effectively support racial/ethnic minority populations during a bioterrorism incident. given the importance of antibiotic prophylaxis in a future anthrax attack, it should be a priority to better support racial/ethnic minorities in mass dispensing programs. to examine the needs and perspectives of racial/ethnic minorities, this study used a nationally representative poll of 1,852 adults, including 1,240 whites, 261 ...201223244501
using a bacteriocin structure to engineer a phage lysin that targets yersinia pestis.purified phage lysins present an alternative to traditional antibiotics and work by hydrolysing peptidoglycan. phage lysins have been developed against gram-positive pathogens such as bacillus anthracis and streptococcus pneumoniae, where the peptidoglycan layer is exposed on the cell surface. addition of the lysin to a bacterial culture results in rapid death of the organism. gram-negative bacteria are resistant to phage lysins because they contain an outer membrane that protects the peptidogly ...201223176506
activated protein c ameliorates bacillus anthracis lethal toxin-induced lethal pathogenesis in rats.lethal toxin (lt) is a major virulence factor of bacillus anthracis. sprague dawley rats manifest pronounced lung edema and shock after lt treatments, resulting in high mortality. the heart failure that is induced by lt has been suggested to be a principal mechanism of lung edema and mortality in rodents. since lt-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of lt-induced p ...201223170801
clinical and forensic signs related to opioids abuse.for a good performance in clinical and forensic toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. this manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administ ...201223170787
anthrax cases in pregnant and postpartum women: a systematic review.to describe the worldwide experience of bacillus anthracis infection reported in pregnant, postpartum, and lactating women.201223168771
inactivation of bacillus anthracis spores by single-walled carbon nanotubes coupled with oxidizing antimicrobial chemicals.in this study, we investigated the sporicidal effects of single-walled carbon nanotubes (swcnts) and swcnts combined with oxidizing antimicrobial chemicals, h₂o₂ and naocl, on b. anthracis spores. the results indicated that treatment with swcnts alone exhibited little sporicidal effect on b. anthracis spores, while treatment with h₂o₂ or naocl alone showed moderate sporicidal effect. the combination treatment with swcnts (100 μg/ml) and h₂o₂ (1.5%) or naocl (0.25%) exhibited much stronger sporic ...201223167544
[analysis of outbreak of anthrax in omsk region in 2010].carrying out analysis of epizootologic-epidemiologic situation on anthrax that had emerged in omsk region in 2010 when horse meat from epizootic focus of anthrax was used in production of meat semi-finished products.201223163033
anthrax lethal factor cleaves mouse nlrp1b in both toxin-sensitive and toxin-resistant macrophages.anthrax lethal factor (lf) is the protease component of anthrax lethal toxin (lt). lt induces pyroptosis in macrophages of certain inbred mouse and rat strains, while macrophages from other inbred strains are resistant to the toxin. in rats, the sensitivity of macrophages to toxin-induced cell death is determined by the presence of an lf cleavage sequence in the inflammasome sensor nlrp1. lf cleaves rat nlrp1 of toxin-sensitive macrophages, activating caspase-1 and inducing cell death. toxin-res ...201223152930
cell-wall preparation containing poly-γ-d-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection.bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. many vaccine strategies were described to counteract anthrax infection. in contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent. however, in animal models this vaccine is less efficient than the live vaccine. in this study, we analyzed the protection afforded by a single extractable surface element. ...201223122993
[present status and prospects for the detection of bacillus anthracis--a review].anthrax, as a fulminating infectious disease, threatens human' s health seriously. bacillus anthracis, the agent of anthrax, was classified into the second kinds of pathogenic microorganisms (one kind of the highly pathogenic microorganism) in the list of human pathogenic microorganisms issued by the chinese government. the spores formed by b. anthracis are potential material for biological warfare agent and biological terror. therefore, it is very important and pressing to develop sensitive, ef ...201223115964
electrostatic ratchet in the protective antigen channel promotes anthrax toxin translocation.central to the power-stroke and brownian-ratchet mechanisms of protein translocation is the process through which nonequilibrium fluctuations are rectified or ratcheted by the molecular motor to transport substrate proteins along a specific axis. we investigated the ratchet mechanism using anthrax toxin as a model. anthrax toxin is a tripartite toxin comprised of the protective antigen (pa) component, a homooligomeric transmembrane translocase, which translocates two other enzyme components, let ...201223115233
multi-platform comparison of ten commercial master mixes for probe-based real-time polymerase chain reaction detection of bioterrorism threat agents for surge preparedness.the centers for disease control and prevention and united states army research institute for infectious diseases have developed real-time pcr assays for the detection of bioterrorism threat agents. these assays all rely on a limited number of approved real-time pcr master mixes. because the availability of these reagents is a critical element of bioterrorism preparedness, we undertook a joint national preparedness exercise to address the potential surge needs resulting from a large-scale bio-eme ...201223107058
draft genome sequence of bacillus anthracis bf-1, isolated from bavarian cattle.bacillus anthracis bf-1 was isolated from a cow in bavaria (germany) that had succumbed to anthrax. here, we report the draft genome sequence of this strain, which belongs to the european b2 subclade of b. anthracis. the closest phylogenetic neighbor of strain bf-1 is a strain isolated from cattle in france.201223105087
outbreak of cutaneous anthrax in musalimadugu village, chittoor district, andhra pradesh, india, july-august 2011.in august 2011, chittoor district authorities reported a cluster of suspected human anthrax cases to the andhra pradesh state surveillance unit. we investigated this cluster to confirm its etiology, describe its magnitude, identify potential risk factors, and make recommendations for preventing similar outbreaks in the future.201223103890
kinetics and thermodynamics of binding reactions as exemplified by anthrax toxin channel blockage with a cationic cyclodextrin derivative.the thermodynamics of binding reactions is usually studied in the framework of the linear van't hoff analysis of the temperature dependence of the equilibrium constant. the logarithm of the equilibrium constant is plotted versus inverse temperature to discriminate between two terms: an enthalpic contribution that is linear in the inverse temperature, and a temperature-independent entropic contribution. when we apply this approach to a particular case-blockage of the anthrax pa(63) channel by a m ...201223100532
cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.lethal and edema toxins secreted by bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. however, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. this study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction.201223134810
a novel mode of regulation of the staphylococcus aureus catabolite control protein a (ccpa) mediated by stk1 protein phosphorylation.the staphylococcus aureus serine/threonine protein kinase stk1 (also known as pknb) affects different key pathways such as cell wall metabolism, antibiotic susceptibility, and regulation of virulence. here we report that the catabolite control protein a (ccpa), a highly conserved regulator of carbon catabolite repression and virulence in a number of gram-positive pathogens, was efficiently phosphorylated in vitro and in vivo by stk1 in s. aureus, whereas the ccpa homologues of bacillus subtilis ...201223132867
identification of bacillus anthracis via raman spectroscopy and chemometric approaches.raman micro-spectroscopy was applied to compile a large-scale database of raman spectra of single bacillus endospores and to calculate classification functions, which were trained to discriminate between endospores of 66 strains from 13 bacillus and bacillus-related species including b. anthracis. the developed two-stage classification system comprising two support vector machines and one linear discriminant analysis classifier was then challenged by a test set of 27 samples to simulate the case ...201223098322
whole genome sequencing of phage resistant bacillus anthracis mutants reveals an essential role for cell surface anchoring protein csab in phage ap50c adsorption.spontaneous bacillus anthracis mutants resistant to infection by phage ap50c (ap50r) exhibit a mucoid colony phenotype and secrete an extracellular matrix.201223098174
[joining forces in the fight against epidemics--priority task in cooperation between russia and kazakhstan].this problem has historically existed for russia and kazakhstan. traditionally plague, crimean-congo hemorrhagic fever anthrax, cholera, and other diseases have been a matter of greater public health concern in the above countries. under russia's chairmanship in the group of eight in 2006 and in the shanghai cooperation organization in 2008-2009, these countries were first to join their effects to control epidemics. as for kazakhstan, its cooperation with russia has been reinforced only by a sol ...201223088106
the contribution of residents who cooperate with ring-vaccination measures against smallpox epidemic.establishing containment measures against the potential spread of the smallpox virus has become a major issue in the public health field since the 2001 anthrax attacks in the united states. the primary objective of the study was to investigate the relationship between the level of activity of public health agencies and the voluntary cooperation of residents with ring-vaccination measures against a smallpox epidemic.201223077270
disrupting the luxs quorum sensing gene does not significantly affect bacillus anthracis virulence in mice or guinea pigs.many bacterial species use secreted quorum-sensing autoinducer molecules to regulate cell density- and growth phase-dependent gene expression, including virulence factor production, as sufficient environmental autoinducer concentrations are achieved. bacillus anthracis, the causative agent of anthrax, contains a functional autoinducer (ai-2) system, which appears to regulate virulence gene expression. to determine if the ai-2 system is necessary for disease, we constructed a luxs ai-2 synthase-d ...201223076278
a three-dose intramuscular injection schedule of anthrax vaccine adsorbed generates sustained humoral and cellular immune responses to protective antigen and provides long-term protection against inhalation anthrax in rhesus macaques.a 3-dose (0, 1, and 6 months) intramuscular (3-im) priming series of a human dose (huava) and dilutions of up to 1:10 of anthrax vaccine adsorbed (ava) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. serum anti-protective antigen (anti-pa) igg and lethal toxin neutralization activity (tna) were detectable following a single injection of huava or 1:5 ava or following two injections of diluted vaccine (1:10, 1:20 ...201222933399
sequence-specific nucleic acid detection from binary pore conductance measurement.we describe a platform for sequence-specific nucleic acid (na) detection utilizing a micropipet tapered to a 2 μm diameter pore and 3 μm diameter polystyrene beads to which uncharged peptide nucleic acid (pna) probe molecules have been conjugated. as the target nas hybridize to the complementary pna-beads, the beads acquire negative charge and become electrophoretically mobile. an applied electric field guides these na-pna-beads toward the pipet tip, which they obstruct, leading to an indefinite ...201222931376
inhibition of bacterial dihydrofolate reductase by 6-alkyl-2,4-diaminopyrimidines.(±)-6-alkyl-2,4-diaminopyrimidine-based inhibitors of bacterial dihydrofolate reductase (dhfr) have been prepared and evaluated for biological potency against bacillus anthracis and staphylococcus aureus. biological studies revealed attenuated activity relative to earlier structures lacking substitution at c6 of the diaminopyrimidine moiety, though minimum inhibitory concentration (mic) values are in the 0.125-8 μg ml(-1) range for both organisms. this effect was rationalized from three- dimensi ...201222930550
a novel electrochemical biosensor for highly selective detection of protease biomarker from bacillus licheniformis with d-amino acid containing peptide.a simple, selective and sensitive electrochemical biosensor has been developed to detect protease biomarker from bacillus licheniformis, a recognized model of the biochemical warfare agent bacillus anthracis. in this assay, the biosensor is constructed using a d-amine acid containing substrate peptide via self-assembly of cysteine residual at the c-terminal. a biotin modifier is labelled at the n-terminal of the substrate peptide. this enables sensitive electrochemical detection of the intact su ...201222930190
recent outbreak of cutaneous anthrax in bangladesh: clinico-demographic profile and treatment outcome of cases attended at rajshahi medical college hospital.human cutaneous anthrax results from skin exposure to b. anthracis, primarily due to occupational exposure. bangladesh has experienced a number of outbreaks of cutaneous anthrax in recent years. the last episode occurred from april to august, 2011 and created mass havoc due to its dreadful clinical outcome and socio-cultural consequences. we report here the clinico-demographic profile and treatment outcome of 15 cutaneous anthrax cases attended at the dermatology outpatient department of rajshah ...201222929128
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