Publications

structure determination of ba0150, a putative polysaccharide deacetylase from bacillus anthracis.	polysaccharide deacetylases are bacterial enzymes that catalyze the deacetylation of acetylated sugars on the membranes of gram-positive bacteria, allowing them to be unrecognized by host immune systems. inhibition of these enzymes would disrupt such pathogenic defensive mechanisms and therefore offers a promising route for the development of novel antibiotic therapeutics. here, the first x-ray crystal structure of ba0150, a putative polysaccharide deacetylase from bacillus anthracis, is reporte ...	2014	24637747
identification of peptide sequences as a measure of anthrax vaccine stability during storage.	the uk anthrax vaccine is an alum precipitate of a sterile filtrate of bacillus anthracis sterne culture (avp). an increase in shelf life of avp from 3 to 5 years prompted us to investigate the in vivo potency and the antigen content of 12 batches with a shelf life of 6.4 to 9.9 years and one bulk with a shelf life of 23.8 years. all batches, except for a 9.4-year-old batch, passed the potency test. mass spectrometry (ms) and in-gel difference 2-dimensional gel electrophoresis (dige) were used t ...	2014	24637775
[the experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated against plague and anthrax].	the article deals with experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated with plague and anthrax live dry vaccines. it is established that the introduction of plague and anthrax live dry vaccines into organism of vaccinated persons ignites immunologic rearrangement manifested by reliable increase of level of blood concentration of th1-lymphocytes (immunologic memory cells) against the background of vaccination. the highe ...	2013	24640112
three eyelid localized cutaneous anthrax cases.	anthrax is primarily seen in the developing countries, but it can be a worldwide medical concern due to bioterrorism threats. palpebral anthrax is a rare form of cutaneous anthrax. untreated cutaneous anthrax can be lethal. patients with palpebral anthrax can develop complications including cicatrisation and ectropion. thus, anthrax should be considered in differential diagnosis for patients presenting with preseptal cellulitis in high-risk regions. herein, we report three anthrax cases (with di ...	2014	24641116
a protective antigen mutation increases the ph threshold of anthrax toxin receptor 2-mediated pore formation.	anthrax toxin protective antigen (pa) binds cellular receptors and self-assembles into oligomeric prepores. a prepore converts to a protein translocating pore after it has been transported to an endosome where the low ph triggers formation of a membrane-spanning β-barrel channel. formation of this channel occurs after some pa-receptor contacts are broken to allow pore formation, while others are retained to preserve receptor association. the interaction between pa and anthrax toxin receptor 1 (a ...	2014	24641616
synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against bacillus anthracis.	due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. as a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against bacillus anthracis. the structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an n-acryloyl-substituted 1,2-dihydrophthalazine ring. vario ...	2014	24642909
the il-23/th17 axis is involved in the adaptive immune response to bacillus anthracis in humans.	the neutralization of toxins is considered essential for protection against lethal infection with bacillus anthracis (ba), a select agent and bioterrorism threat. however, toxin-neutralizing activity alone would not be expected to provide sterile immunity. therefore, we hypothesized that the development of an adaptive immune response against ba is required for bacterial clearance. we found that human monocyte-derived dendritic cells (hdcs) kill germinated ba bacilli, but not nongerminated ba spo ...	2014	24643777
structural basis of bacillus anthracis moxxt disruption and the modulation of moxt ribonuclease activity by rationally designed peptides.	bacillus anthracis moxxt is a type ii proteic toxin-antitoxin (ta) module wherein moxt is a ribonuclease that cleaves rna specifically while moxx interacts with moxt and inhibits its activity. disruption of the ta interaction has been proposed as a novel antibacterial strategy. peptides, either based on antitoxin sequence or rationally designed, have previously been reported to disrupt the moxxt interaction but cause a decrease in moxt ribonuclease activity. in the present study, we report the c ...	2015	24650157
transcriptome analysis identifies bacillus anthracis genes that respond to co2 through an atxa-dependent mechanism.	upon infection of a mammalian host, bacillus anthracis responds to host cues, and particularly to elevated temperature (37°c) and bicarbonate/co2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer. this response requires the presence of the pxo1 virulence plasmid-encoded pleiotropic regulator atxa. to better understand the genetic basis of this response, we utilized a controlled in vitro system and next generation seque ...	2014	24661624
x-ray structures of human furin in complex with competitive inhibitors.	furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal bacillus anthracis or the pandemic influenza virus. development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. here we present a novel preparation of human furin and the first crystal structures of this enzyme in complex with noncovalent inhibito ...	2014	24666235
capillary morphogenesis gene 2 inhibits growth of breast cancer cells and is inversely correlated with the disease progression and prognosis.	capillary morphogenesis gene 2 (cmg2) also known as anthrax toxin receptor 2 was identified as a gene being up-regulated in capillary morphogenesis. it has been shown to be involved in cell adhesion and motility which are critical functions for cancerous cells to disseminate. the present study aimed to examine the expression of cmg2 in breast cancer and its implication in the disease progression.	2014	24667935
asymmetric dimethylarginine levels in patients with cutaneous anthrax: a laboratory analysis.	asymmetric dimethylarginine (adma), the main endogenous inhibitor of nitric oxide synthase, is considered to be associated with endothelial dysfunction. high adma levels have been shown to be related with disorders causing vascular inflammation such as hypertension, hypercholesterolemia, atherosclerosis, chronic heart failure, stroke and sepsis. cutaneous anthrax (ca) is a serious infectious disease which may cause vasculitis. the aim of the study was to investigate the serum adma levels in pati ...	2014	24669818
bidirectional effect of wnt signaling antagonist dkk1 on the modulation of anthrax toxin uptake.	lrp6, a co-receptor for the morphogen wnt, aids endocytosis of anthrax complexes. here we report that dickkopf1 (dkk1) protein, a secreted lrp6 ligand and antagonist, is also a modulator of anthrax toxin sensitivity. shrna-mediated gene silencing or talen-mediated gene knockout of dkk1 reduced sensitivity of cells to pa-dependent hybrid toxins. however, unlike the solely inhibitory effect on wnt signaling, the effects of dkk1 overexpression on anthrax toxicity were bidirectional, depending on it ...	2014	24671437
two-component system cross-regulation integrates bacillus anthracis response to heme and cell envelope stress.	two-component signaling systems (tcss) are one of the mechanisms that bacteria employ to sense and adapt to changes in the environment. a prototypical tcs functions as a phosphorelay from a membrane-bound sensor histidine kinase (hk) to a cytoplasmic response regulator (rr) that controls target gene expression. despite significant homology in the signaling domains of hks and rrs, tcss are thought to typically function as linear systems with little to no cross-talk between non-cognate hk-rr pairs ...	2014	24675902
cutaneous anthrax in southeast anatolia of turkey.	anthrax is a rare disease cause by bacillus anthracis, a gram-positive, rod-shaped endospore-forming capsuled bacterium. anthrax is manifest in three primary forms: cutaneous, respiratory, and gastrointestinal. cutaneous anthrax accounts for approximately 95% of all cases of anthrax in humans.	2015	24678748
unusual cause of fatal anthrax meningitis.	we report the case of fatal anthrax meningoencephalitis in the province of muş located in eastern anatolia, turkey. the organism isolated from cerebrospinal fluid was identified as bacillus anthracis. the patient was treated with crystallized penicillin g (24 mu/day iv) and ciprofloxacin (2 × 400/day iv), but died 5 days after hospitalization. although it is a rare case, we consider that the patients who have skin, respiratory and neurological systems might also have hemorrhagic meningitis.	2015	24678752
anthrax lethal and edema toxins in anthrax pathogenesis.	the pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. b. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the usa. the exotoxins secreted by b. anthracis use capillary morphogenesis protein 2 (cmg2) as the major ...	2014	24684968
standard method for deposition of dry, aerosolized, silica-coated bacillus spores onto inanimate surfaces.	to evaluate a standard aerosolization method for uniformly depositing threat-representative spores onto surfaces.	2014	24690070
detection of the urban release of a bacillus anthracis simulant by air sampling.	in 2005 and 2009, the pentagon force protection agency (pfpa) staged deliberate releases of a commercially available organic pesticide containing bacillus amyloliquefaciens to evaluate pfpa's biothreat response protocols. in concert with, but independent of, these releases, the department of homeland security sponsored experiments to evaluate the efficacy of commonly employed air and surface sampling techniques for detection of an aerosolized biological agent. high-volume air samplers were place ...	2014	24697146
the planning, execution, and evaluation of a mass prophylaxis full-scale exercise in cook county, il.	increasing threats of bioterrorism and the emergence of novel disease agents, including the recent international outbreaks of h7n9 influenza and mers-cov, have stressed the importance and highlighted the need for public health preparedness at local, regional, and national levels. to test plans that were developed for mass prophylaxis scenarios, in april 2013 the cook country department of public health (ccdph) and the triple community (tripcom) medical reserve corps (mrc) executed a full-scale m ...	2014	24697783
rapid detection of bacillus spore aerosol particles by direct in situ analysis using maldi-tof mass spectrometry.	accurate and rapid analytical methods are essential for the detection and identification of biological warfare agents (bwa). although various studies have investigated the use of maldi-tof ms for bacterial classification, only a few studies have examined the applicability of method for the identification of bwas. this study aimed to generate, collect and analyse bacillus spore aerosol particles of 2-10 μm, the optimal size of a bwa. bacillus spore aerosol particles of 2-10 μm were rapidly analys ...	2014	24702137
design of monodisperse and well-defined polypeptide-based polyvalent inhibitors of anthrax toxin.	the design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. the ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. to that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding pept ...	2014	24706570
proteases as activators for cytotoxic prodrugs in antitumor therapy.	proteases are often overexpressed in tumor cells and/or the stromal compartment and can thus be exploited in tumor therapy to activate cytotoxic prodrugs as, for example, in cytolytic fusion proteins, and for tumor imaging. specifically, we discuss cathepsin b-activated prodrug conjugates, antibody-directed prodrug therapy, protease-activated peptide-thapsigargin conjugates, protease-activated cytotoxic receptor ligands and other cytotoxic proteins, protease-mediated activation of anthrax toxin, ...	2014	24709544
high-throughput screening of a crispr/cas9 library for functional genomics in human cells.	targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. in contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. here we report the development of a focused crispr/cas-based (clustered regularly interspaced short palindromic repeats/crispr-associated) lentiviral library in hum ...	2014	24717434
spectrally-resolved fluorescence cross sections of aerosolized biological live agents and simulants using five excitation wavelengths in a bsl-3 laboratory.	a system for measuring spectrally-resolved fluorescence cross sections of single bioaerosol particles has been developed and employed in a biological safety level 3 (bsl-3) facility at edgewood chemical and biological center (ecbc). it is used to aerosolize the slurry or solution of live agents and surrogates into dried micron-size particles, and to measure the fluorescence spectra and sizes of the particles one at a time. spectrally-resolved fluorescence cross sections were measured for (1) bac ...	2014	24718194
simultaneous and rapid detection of salmonella typhi, bacillus anthracis, and yersinia pestis by using multiplex polymerase chain reaction (pcr).	salmonella typhi, bacillus anthracis, and yersinia pestis are some serious human pathogens, which their early diagnosis is of great importance. salmonella typhi, bacillus anthracis, and yersinia pestis cause typhoid fever, anthrax, and plague respectively. these bacteria can be used to make biologic weapons.	2013	24719692
[knowledge of zoonoses transmission routes and of the species concerned among rural workers].	the aim of this study was to evaluate the level of awareness of zoonoses among rural workers and their potential associations with socio-demographic factors. a cross-sectional study was performed by holding personal interviews (n=110, n=94) using a structured questionnaire. the statistical analysis included the χ(2) test, the student's t test and pearson and spearman correlations. the highest level of awareness was found for trichinosis, rabies and scabies. species transmitting brucellosis, tube ...	2014	24721268
tabanids: neglected subjects of research, but important vectors of disease agents!	tabanids are nuisance pests for people and livestock because of their painful and irritating bite, persistent biting behavior, and blood ingestion. about 4400 tabanid species have been described; they are seasonally present in all kinds of landscapes, latitudes, and altitudes. high populations have a significant economic impact on outdoor activities, tourism, and livestock production. tabanids are also vectors of animal disease agents, including viruses, bacteria and parasites. however, tabanids ...	2014	24727644
fast identification of yersinia pestis, bacillus anthracis and francisella tularensis based on conventional pcr.	rapid and accurate diagnostic tools for detection and identification of y pestis, b. anthracis and f. tularensis are essential for timely initial appropriate treatment of exposed individuals, which will be critical to their survival, as well as for reduction of the public health impact and the spread of the disease. the paper presents application of fast polymerases and fast dry electrophoresis in conventional pcr as an alternative for real-time pcr application for detection and identification o ...	2013	24730142
efficacy and safety of avp-21d9, an anthrax monoclonal antibody, in animal models and humans.	anthrax is an acute infectious disease caused by the spore-forming bacterium bacillus anthracis. timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. however, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. an anthrax antitoxin, avp-21d9, also known as thravixa (fully human anthrax monoclonal antibody), is being ...	2014	24733473
high-throughput sequencing of bacillus anthracis in france: investigating genome diversity and population structure using whole-genome snp discovery.	single nucleotide polymorphisms (snps) are ideal signatures for subtyping monomorphic pathogens such as bacillus anthracis. here we report the use of next-generation sequencing technology to investigate the historical, geographic and genetic diversity of bacillus anthracis in france. 122 strains isolated over a 60-years period throughout the country were whole-genome sequenced and comparative analyses were carried out with a focus on snps discovery to discriminate regional sub-groups of strains.	2014	24734872
anthracimycin activity against contemporary methicillin-resistant staphylococcus aureus.	anthracimycin is a recently discovered novel marine-derived compound with activity against bacillus anthracis. we tested anthracimycin against an expanded panel of staphylococcus aureus strains in vitro and in vivo. all strains of s. aureus tested, including methicillin-susceptible, methicillin-resistant (mrsa) and vancomycin-resistant strains of s. aureus, were susceptible to anthracimycin at mic values of ⩽0.25 mg l(-1). although its postantibiotic effects were minimal, anthracimycin exhibited ...	2014	24736856
antxr2 is a potential causative gene in the genome-wide association study of the blood pressure locus 4q21.	hypertension is the most prevalent cardiovascular disease worldwide, but its genetic basis is poorly understood. recently, genome-wide association studies identified 33 genetic loci that are associated with blood pressure. however, it has been difficult to determine whether these loci are causative owing to the lack of functional analyses. of these 33 genome-wide association studies (gwas) loci, the 4q21 locus, known as the fibroblast growth factor 5 (fgf5) locus, has been linked to blood pressu ...	2014	24739539
targeted silencing of anthrax toxin receptors protects against anthrax toxins.	anthrax spores can be aerosolized and dispersed as a bioweapon. current postexposure treatments are inadequate at later stages of infection, when high levels of anthrax toxins are present. anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 (tem8) and capillary morphogenesis protein 2 (cmg2). we hypothesized that host cells would be protected from anthrax toxins if anthrax toxin receptor expression was effectively silenced using rna interference (rna ...	2014	24742682
reductive methylation and mutation of an anthrax toxin fusion protein modulates its stability and cytotoxicity.	we characterized an anti-cancer fusion protein consisting of anthrax lethal factor (lf) and the catalytic domain of pseudomonas exotoxin a by (i) mutating the n-terminal amino acids and by (ii) reductive methylation to dimethylate all lysines. dimethylation of lysines was achieved quantitatively and specifically without affecting binding of the fusion protein to pa or decreasing the enzymatic activity of the catalytic moiety. ubiquitination in vitro was drastically decreased for both the n-termi ...	2014	24755540
age of bioterrorism: are you prepared? review of bioweapons and their clinical presentation for otolaryngologists.	this review on category a bioweapons is intended to help otolaryngologists (1) understand the concepts of bioterrorism, (2) identify a bioterrorism attack, and (3) recognize specific otolaryngologic symptoms and signs of category a bioweapons.	2014	24757076
crosstalk between the coagulation and complement systems in sepsis.	sepsis is a potent activator of the hemostatic and complement systems. while local activation of these proteolytic cascades contributes to the host defense, their uncontrolled systemic activation has major tissue damaging effects that lead to multiple organ failure and death. we have extensively studied the activation of complement and coagulation cascades in experimental sepsis using baboons challenged with live bacteria, such as gram-negative escherichia coli or gram-positive staphylococcus au ...	2014	24759136
in trans complementation of lethal factor reveal roles in colonization and dissemination in a murine mouse model.	lethal factor (lf) is a component of the b. anthracis exotoxin and critical for pathogenesis. the roles of lf in early anthrax pathogenesis, such as colonization and dissemination from the initial site of infection, are poorly understood. in mice models of infection, lf-deficient strains either have altered dissemination patterns or do not colonize, precluding analysis of the role of lf in colonization and dissemination from the portal of entry. previous reports indicate rabbit and guinea pig mo ...	2014	24763227
online monitoring of escherichia coli and bacillus thuringiensis spore inactivation after advanced oxidation treatment.	various studies have shown that advanced oxidation processes (aops) such as uv light in combination with hydrogen peroxide is an efficient process for the removal of a large variety of emerging contaminants including microorganisms. the mechanism of destruction in the presence of hydrogen peroxide (h2o2) is the enhanced formation of hydroxyl (·oh) radicals, which have a high oxidation potential. the goal of this study was to utilize in-line advanced oxidation to inactivate microbes, and document ...	2014	24766594
evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin g on injection site adverse events following anthrax vaccine adsorbed (ava) in the cdc ava human clinical trial.	anthrax vaccine adsorbed (ava) administered intramuscularly (im) results in fewer adverse events (aes) than subcutaneous (sq) administration. women experience more aes than men. antibody response, female hormones, race, and body mass index (bmi) may contribute to increased frequency of reported injection site aes.	2014	24768633
protective immune response against bacillus anthracis induced by intranasal introduction of a recombinant adenovirus expressing the protective antigen fused to the fc-fragment of igg2a.	anthrax is a particularly dangerous infectious disease that affects humans and livestock. it is characterized by intoxication, serosanguineous skin lesions, development of lymph nodes and internal organs, and may manifest itsself in either a cutaneous or septic form. the pathogenic agent is bacillus anthracis, a grampositive, endospore-forming, rod-shaped aerobic bacterium. efficacious vaccines that can rapidly induce a long-term immune response are required to prevent anthrax infection in human ...	2014	24772330
pediatric anthrax clinical management: executive summary.		2014	24777221
pediatric anthrax clinical management.	anthrax is a zoonotic disease caused by bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. because b anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. this document provides clinical guidance f ...	2014	24777226
descriptive epidemiology of detected anthrax outbreaks in wild wood bison (bison bison athabascae) in northern canada, 1962-2008.	we inventoried and assessed historical anthrax outbreak data from 1962-2008 in wild wood bison (bison bison athabascae) in wood buffalo national park and the slave river lowlands (srl), northwest territories, canada. we compared these results with a 2010 outbreak in the srl. anthrax outbreaks have occurred in 12 of the years between 1962 and 2008 in wild wood bison with 1,515 anthrax deaths detected. the average number of carcasses found each outbreak year was 126 (range 1-363), though local ave ...	2014	24779457
[anthrax meningoencephalitis: a case following a cutaneous lesion in morocco].	anthrax meningoencephalitis is very rare especially following skin location. we report a case of meningoencephalitis secondary to skin lesion. the diagnosis is based on clinical presentation and confirmed by microbiological tests. its evolution remains fatal despite aggressive resuscitation.	2014	24784916
anthrax lethal factor as an immune target in humans and transgenic mice and the impact of hla polymorphism on cd4+ t cell immunity.	bacillus anthracis produces a binary toxin composed of protective antigen (pa) and one of two subunits, lethal factor (lf) or edema factor (ef). most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. we characterized cd4+ t cell immunity to lf in a panel of humanized hla-dr and dq transgenic mice and in naturally exposed patien ...	2014	24788397
substrate specificity and kinetic characterization of peptidoglycan o-acetyltransferase b from neisseria gonorrhoeae.	the o-acetylation of the essential cell wall polymer peptidoglycan is a major virulence factor identified in many bacteria, both gram-positive and gram-negative, including staphylococcus aureus, bacillus anthracis, neisseria gonorrhoeae, and neisseria meningitidis. with gram-negative bacteria, the translocation of acetyl groups from the cytoplasm is performed by an integral membrane protein, pata, for its transfer to peptidoglycan by o-acetyltransferase patb, whereas a single bimodal membrane pr ...	2014	24795044
factors associated with healthcare worker acceptance of vaccination: a systematic review and meta-analysis.	healthcare workers experience occupational risk of infection and may transmit infections to patients. vaccination provides an efficient means of protecting workers and patients, but uptake may be low. we sought to identify factors influencing vaccine acceptance by healthcare workers in order to obtain insights leading to more effective vaccination programs in this population.	2014	24799647
nanopore biosensor for label-free and real-time detection of anthrax lethal factor.	we report a label-free real-time nanopore sensing method for the detection of anthrax lethal factor, a component of the anthrax toxin, by using a complementary single-stranded dna as a molecular probe. the method is rapid and sensitive: sub-nanomolar concentrations of the target anthrax lethal factor dna could be detected in ∼1 min. further, our method is selective, which can differentiate the target dna from other single-stranded dna molecules at the single-base resolution. this sequence-specif ...	2014	24806593
raxibacumab: potential role in the treatment of inhalational anthrax.	anthrax is a highly contagious and potentially fatal human disease caused by bacillus anthracis, an aerobic, gram-positive, spore-forming rod-shaped bacterium with worldwide distribution as a zoonotic infection in herbivore animals. bioterrorist attacks with inhalational anthrax have prompted the development of more effective treatments. antibodies against anthrax toxin have been shown to decrease mortality in animal studies. raxibacumab is a recombinant human monoclonal antibody developed again ...	2014	24812521
endospore surface properties of commonly used bacillus anthracis surrogates vary in aqueous solution.	the hydrophobic character and electrophoretic mobility (epm) of microorganisms are vital aspects of understanding their interactions with the environment. these properties are fundamental in fate-and-transport, physiological, and virulence studies, and thus integral in surrogate selection. hydrophobic and electrostatic forces are significant contributors to particle and microorganism mobility in the environment. herein, the surface properties of commonly used bacillus anthracis surrogate endospo ...	2014	24817579
a model of federal interagency cooperation: the national interagency confederation for biological research.	the terrorist attacks of september 11 and the anthrax mailings a month later prompted a sweeping response by the federal government to improve the preparedness of the us to meet the potential threat posed by a terrorist using a biological agent. this response transcended traditional interagency boundaries, creating new opportunities while producing unique fiscal and leadership challenges. the national interagency confederation for biological research has made significant progress over the past 1 ...	2015	24819736
extracellular vesicles produced by the gram-positive bacterium bacillus subtilis are disrupted by the lipopeptide surfactin.	previously, extracellular vesicle production in gram-positive bacteria was dismissed due to the absence of an outer membrane, where gram-negative vesicles originate, and the difficulty in envisioning how such a process could occur through the cell wall. however, recent work has shown that gram-positive bacteria produce extracellular vesicles and that the vesicles are biologically active. in this study, we show that bacillus subtilis produces extracellular vesicles similar in size and morphology ...	2014	24826903
undecaprenyl diphosphate synthase inhibitors: antibacterial drug leads.	there is a significant need for new antibiotics due to the rise in drug resistance. drugs such as methicillin and vancomycin target bacterial cell wall biosynthesis, but methicillin-resistant staphylococcus aureus (mrsa) and vancomycin-resistant enterococci (vre) have now arisen and are of major concern. inhibitors acting on new targets in cell wall biosynthesis are thus of particular interest since they might also restore sensitivity to existing drugs, and the cis-prenyl transferase undecapreny ...	2014	24827744
monitoring endocytic trafficking of anthrax lethal factor by precise and quantitative protein labeling.	coupling the genetic code expansion technique with bioorthogonal reactions enables precise control over the conjugation site as well as the choice of fluorescent probes during protein labeling. however, the advantages of this strategy over bulky and rigid fluorescent proteins (fps) remain to be fully explored. here we applied site-specific bioorthogonal labeling on anthrax lethal factor (lf) to visualize its membrane translocation inside live cells. in contrast to the previously reported fp tags ...	2014	24828812
impaired colonic b-cell responses by gastrointestinal bacillus anthracis infection.	ingestion of bacillus anthracis spores causes gastrointestinal (gi) anthrax. humoral immune responses, particularly immunoglobulin a (iga)-secreting b-1 cells, play a critical role in the clearance of gi pathogens. here, we investigated whether b. anthracis impacts the function of colonic b-1 cells to establish active infection. gi anthrax led to significant inhibition of immunoglobulins (eg, iga) and increased expression of program death 1 on b-1 cells. furthermore, infection also diminished ty ...	2014	24829464
cu(i)-mediated allosteric switching in a copper-sensing operon repressor (csor).	the copper-sensing operon repressor (csor) is representative of a major cu(i)-sensing family of bacterial metalloregulatory proteins that has evolved to prevent cytoplasmic copper toxicity. it is unknown how cu(i) binding to tetrameric csors mediates transcriptional derepression of copper resistance genes. a phylogenetic analysis of 227 duf156 protein members, including biochemically or structurally characterized csor/rcnr repressors, reveals that geobacillus thermodenitrificans (gt) csor charac ...	2014	24831014
n-acetylglucosamine deacetylases modulate the anchoring of the gamma-glutamyl capsule to the cell wall of bacillus anthracis.	bacillus anthracis has a complex cell wall structure composed of a peptidoglycan (pg) layer to which major structures are anchored such as a neutral polysaccharide, an s-layer, and a poly-γ-d-glutamate (pdga) capsule. many of these structures have central roles in the biology of b. anthracis, particularly, in virulence. however, little attention has been devoted to structurally study the pg and how it is modified in the presence of these secondary cell wall components. we present here the fine s ...	2014	24833281
disaster preparedness, pediatric considerations in primary blast injury, chemical, and biological terrorism.	both domestic and foreign terror incidents are an unfortunate outgrowth of our modern times from the oklahoma city bombings, sarin gas attacks in japan, the madrid train bombing, anthrax spores in the mail, to the world trade center on september 11(th), 2001. the modalities used to perpetrate these terrorist acts range from conventional weapons to high explosives, chemical weapons, and biological weapons all of which have been used in the recent past. while these weapons platforms can cause sign ...	2014	24834398
anthrax vaccine adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.	whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. we applied the noninferiority analysis model to this prospective study comparing the bacillus anthracis protective antigen (pa) igg antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (ava) (biothrax®) administered on schedule or delayed. a total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed ...	2014	24837771
identification of stringent response-related and potential serological proteins released from bacillus anthracis overexpressing the rela/spot homolog, rsh bant.	rela and spot synthesize ppgpp, a key effector molecule that facilitates the adaptation of bacteria to nutrient starvation and other stresses, known as the stringent response. to investigate the role of rsh bant , a putative rela/spot homolog (encoded by bas4302) in bacillus anthracis, we examined the alteration of the secretome profiles after the overexpression of a functional his-rsh bant protein in the b. anthracis strain sterne at the stationary growth phase. in the ppgpp-deficient e. coli m ...	2014	24838666
clinical microbiologists facing an anthrax alert.	microbiological war and terrorist attacks are made to weaken populations by transmitting pathogenic and epidemic microorganisms. these bacteria or viruses are often difficult to diagnose. anthrax alerts following september 2001 showed that most clinical microbiology laboratories were not adequately prepared, using obsolete diagnostic methods or being too slow to use accurate tools when facing a major threat. following this period, most microbiology laboratories were prepared for bioterrorism ale ...	2014	24845109
detection of anthrax protective antigen (pa) using europium labeled anti-pa monoclonal antibody and time-resolved fluorescence.	inhalation anthrax is a rare but acute infectious disease following adsorption of bacillus anthracis spores through the lungs. the disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. the early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time pcr. consequently, there may be a significant delay in diagnosis and target ...	2014	24857756
cutaneous anthrax in a school teacher.	cutaneous anthrax is an infection of the skin caused by bacillus anthracis. this is a report of a case of cutaneous anthrax attending outpatients of mymensingh medical college hospital in october, 2010. the infected person was a retired school teacher with a very good body build. he reported to handle cow flesh about 4-5 days ago, developed few painless papules over shin of right leg, which gradually became large bullae and blackish eschar developed over the lesion. smears from the lesions were ...	2014	24858169
more or less is fine: an undercover work of dkk1 in anthrax toxin uptake.		2014	24865625
glycan surface antigens from bacillus anthracis as vaccine targets: current status and future perspectives.	over recent years great attention has been directed to the discovery of novel antigens from bacillus anthracis, because of the potential of its spores in the development of weapons for mass destruction. substantial effort has been directed to the identification and immunochemical evaluation of glycans that might be used for specific diagnostic detection of the spores or immune-mediated prevention of anthrax. carbohydrate structures found on surfaces of vegetative cells and spores are herein disc ...	2014	24867680
draft genome sequence of bacillus cereus strain bcfl2013, a clinical isolate similar to g9241.	bacillus cereus strains, such as g9241, causing anthrax-like illnesses have recently been discovered. we report the genome sequence of a clinical strain, b. cereus bcfl2013, which is similar to g9241, recovered from a patient in florida.	2014	24874674
combination of biobarcode assay with on-chip capillary electrophoresis for ultrasensitive and multiplex biological agent detection.	early diagnosis of biological agents is of paramount importance to prevent the casualties and fatal disease in human during bioterrorism or biological warfare. in this study, we reported an efficient and sensitive multiplex biological agent detection method based on the dna biobarcode assay and the micro-capillary electrophoresis (μce) technology. monoplex as well as multiplex pathogen identification was performed using five targets including bacillus anthracis, francisella tularensis, yersinia ...	2014	24878840
evaluation of the relationship between the adenosine triphosphate (atp) bioluminescence assay and the presence of bacillus anthracis spores and vegetative cells.	the adenosine triphosphate (atp) bioluminescence assay was utilized in laboratory evaluations to determine the presence and concentration of vegetative and spore forms of bacillus anthracis sterne 34f2.	2014	24879485
robert koch (1843-1910) and dermatology on his 171st birthday.	robert koch (1843-1910) received the nobel prize in medicine in 1905 for his studies of tuberculosis. he contributed significantly to microbiology, isolating also cholera and anthrax pathogens, and introducing several postulates in this field. in addition, he developed staining methods, as well as culturing and microscopic techniques. many of his achievements have also influenced dermatology. this contribution reviews his life and major achievements on the occasion of the 171st anniversary of hi ...	2014	24887990
exposure to bacillus anthracis capsule results in suppression of human monocyte-derived dendritic cells.	the antiphagocytic capsule of bacillus anthracis is a major virulence factor. we hypothesized that it may also mediate virulence through inhibition of the host's immune responses. during an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. we sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (idcs). human monocytes were differentiated into idcs by interleukin-4 (il-4) and granuloc ...	2014	24891109
history of biological warfare and bioterrorism.	bioterrorism literally means using microorganisms or infected samples to cause terror and panic in populations. bioterrorism had already started 14 centuries before christ, when the hittites sent infected rams to their enemies. however, apart from some rare well-documented events, it is often very difficult for historians and microbiologists to differentiate natural epidemics from alleged biological attacks, because: (i) little information is available for times before the advent of modern micro ...	2014	24894605
efficiency and effectiveness of using nonmedical staff during an urgent mass prophylaxis response.	using a simulated anthrax scenario, the philadelphia department of public health tested the readiness of a nonmedical closed point-of-dispensing (pod) site to see how rapidly and accurately it could provide medication to its internal population. this closed pod had developed and exercised its mass prophylaxis plan in conjunction with the local health department twice before, and the department was interested in assessing the impact of having no onsite department involvement. two sessions were co ...	2014	24896307
structure-activity relationship of semicarbazone ega furnishes photoaffinity inhibitors of anthrax toxin cellular entry.	ega, 1, prevents the entry of multiple viruses and bacterial toxins into mammalian cells by inhibiting vesicular trafficking. the cellular target of 1 is unknown, and a structure-activity relationship study was conducted in order to develop a strategy for target identification. a compound with midnanomolar potency was identified (2), and three photoaffinity labels were synthesized (3-5). for this series, the expected photochemistry of the phenyl azide moiety is a more important factor than the i ...	2014	24900841
genotyping of french bacillus anthracis strains based on 31-loci multi locus vntr analysis: epidemiology, marker evaluation, and update of the internet genotype database.	bacillus anthracis is known to have low genetic variability. in spite of this lack of diversity, multiple-locus variable-number tandem repeat (vntr) analysis (mlva) and single nucleotide polymorphisms (snps) including the canonical snps assay (cansnp) have proved to be highly effective to differentiate strains. five different mlva schemes based on a collection of 31 vntr loci (mlva8, mlva15, mlva20, mlva25 and mlva31) with increased resolving power have been described.	2014	24901417
neglected zoonotic diseases-the long and winding road to advocacy.	years of advocacy for the neglected tropical diseases (ntds) have focused the world's attention on these diseases of the poor, resulting most recently in the 2012 "london declaration" and the recent world health assembly resolution wha66.12 on ntds in may 2013. control of the endemic neglected zoonotic diseases (nzds) would benefit from a similar campaign, which needs the support of a global community.	2014	24901769
interactions between bacillus anthracis and plants may promote anthrax transmission.	environmental reservoirs are essential in the maintenance and transmission of anthrax but are poorly characterized. the anthrax agent, bacillus anthracis was long considered an obligate pathogen that is dormant and passively transmitted in the environment. however, a growing number of laboratory studies indicate that, like some of its close relatives, b. anthracis has some activity outside of its vertebrate hosts. here we show in the field that b. anthracis has significant interactions with a gr ...	2014	24901846
bacillus thuringiensis hd-1 cry- : development of a safe, non-insecticidal simulant for bacillus anthracis.	a representative simulant for spores of bacillus anthracis is needed for field testing. bacillus thuringiensis is gaining recognition as a suitable organism. a strain that does not form the insecticidal, parasporal crystals that are characteristic of this species is a more accurate physical representative of b. anthracis spores. we developed noninsecticidal derivatives of two isolates of b. thuringiensis hd-1.	2014	24903218
application of r-pfe hyperimmune sera for concurrent detection of bacillus anthracis, yersinia pestis and staphylococcal enterotoxin b.	to evaluate the potential of an intergeneric multidomain recombinant chimeric protein for the simultaneous detection of bacillus anthracis, yersinia pestis and staphylococcal enterotoxin b.	2014	24905217
the genetic diversity of cereulide biosynthesis gene cluster indicates a composite transposon tnces in emetic bacillus weihenstephanensis.	cereulide is a cyclic dodecadepsipeptide ionophore, produced via non-ribosomal peptide synthetases (nrps), which in rare cases can lead to human death. early studies had shown that emetic toxin formation belongs to a homogeneous group of bacillus cereus sensu stricto and the genetic determinants of cereulide (a 24-kb gene cluster of ceshptabcd) are located on a 270-kb plasmid related to the bacillus anthracis virulence plasmid pxo1.	2014	24906385
negative impact of laws regarding biosecurity and bioterrorism on real diseases.	research on highly pathogenic microorganisms in biosafety level 3 and 4 laboratories is very important for human public health, as it provides opportunities for the development of vaccines and novel therapeutics as well as diagnostic methods to prevent epidemics. however, in recent years, after the anthrax and world trade center attacks in 2001 in the usa, the threat of bioterrorism has grown for both the public and the authorities. as a result, technical and physical containment measures and bi ...	2014	24909400
structure of the ldcb ld-carboxypeptidase reveals the molecular basis of peptidoglycan recognition.	peptidoglycan surrounds the bacterial cytoplasmic membrane to protect the cell against osmolysis. the biosynthesis of peptidoglycan, made of glycan strands crosslinked by short peptides, is the target of antibiotics like β-lactams and glycopeptides. nascent peptidoglycan contains pentapeptides that are trimmed by carboxypeptidases to tetra- and tripeptides. the well-characterized dd-carboxypeptidases hydrolyze the terminal d-alanine from the stem pentapeptide to produce a tetrapeptide. however, ...	2014	24909784
identification of three noncontiguous regions on bacillus anthracis plasmid pxo1 that are important for its maintenance.	bacillus anthracis pxo1 minireplicon (mr) plasmid consisting of open reading frames (orfs) gbaa_pxo1_0020 to gbaa_pxo1_0023 is not stably maintained in b. anthracis, whereas the full-size parent pxo1 plasmid (having 181,677 bp and 217 orfs) is extremely stable under the same growth conditions. two genetic tools developed for dna manipulation in b. anthracis (cre-loxp and flp-frt systems) were used to identify pxo1 regions important for plasmid stability. we localized a large segment of pxo1 that ...	2014	24914182
gnez, a udp-glcnac 2-epimerase, is required for s-layer assembly and vegetative growth of bacillus anthracis.	bacillus anthracis, the causative agent of anthrax, forms an s-layer atop its peptidoglycan envelope and displays s-layer proteins and bacillus s-layer-associated (bsl) proteins with specific functions to support cell separation of vegetative bacilli and growth in infected mammalian hosts. s-layer and bsl proteins bind via the s-layer homology (slh) domain to the pyruvylated secondary cell wall polysaccharide (scwp) with the repeat structure [→4)-β-mannac-(1→4)-β-glcnac-(1→6)-α-glcnac-(1→]n, whe ...	2014	24914184
[pregnancy and vaccinoprevention].	vaccinations protect woman and her fetus against different infectious diseases, but their application on pregnant should be extremely responsible. in this review i present information about some infectious diseases and vaccines during pregnancy. women, planning to get pregnant should be advised to do serological tests in order to find out their immune status against some infections, leading to fetal congenital malformations (rubella, chicken pox, hepatitis b) and if necessary to get vaccinated a ...	2014	24919344
cholesterol depletion induces antxr2-dependent activation of mmp-2 via erk1/2 phosphorylation in neuroglioma u251 cell.	cholesterol is a critical component of lipid rafts implicated in regulating multiple signal transduction. the anthrax toxin receptor 2 (antxr2) is a type i membrane protein acting as the second receptor for the anthrax toxin. in this study, we first investigated the association between cholesterol and antxr2. we provided the evidence that cholesterol depletion by methyl-beta-cyclodextrin (mβcd) promoted antxr2 expression in u251 neuroglioma cell, which was reversed by cholesterol supplement. mβc ...	2014	24924630
complete genome sequence of bacillus cereus sensu lato bacteriophage bcp1.	bacillus cereus sensu lato organisms are an ecologically diverse group that includes etiologic agents of food poisoning, periodontal disease, and anthrax. the recently identified bcp1 bacteriophage infects b. cereus sensu lato and is being developed as a therapeutic decontamination agent and diagnostic countermeasure. we announce the complete genome sequence of bcp1.	2014	24926042
effect of inoculation method on the determination of decontamination efficacy against bacillus spores.	decontamination studies investigating the effectiveness of products and processes for the inactivation of bacillus species spores have traditionally utilized metering viable spores in a liquid suspension onto test materials (coupons). the current study addresses the representativeness of studies using this type of inoculation method compared to when coupons are dosed with a metered amount of aerosolized spores. the understanding of this comparability is important in order to assess the represent ...	2014	24928258
capillary morphogenesis gene 2 regulates adhesion and invasiveness of prostate cancer cells.	capillary morphogenesis gene 2 (cmg2), also known as anthrax toxin receptor 2, has been indicated in the formation of new vasculature and in the internalisation of the anthrax toxin. anti-angiogenesis therapy that targets this molecule has been investigated. however, our recent studies of this molecule have indicated that this gene may also play certain roles in cancer cells. the present study aimed to examine the expression of cmg2 in prostate cancer tissues and cell lines, and also its impact ...	2014	24932305
cytotoxicity of the vibrio vulnificus martx toxin effector duf5 is linked to the c2a subdomain.	the multifunctional-autoprocessing repeats-in-toxin (martx) toxins are bacterial protein toxins that serve as delivery platforms for cytotoxic effector domains. the domain of unknown function in position 5 (duf5) effector domain is present in at least six different species' martx toxins and as a hypothetical protein in photorhabdus spp. its presence increases the potency of the vibrio vulnificus martx toxin in mouse virulence studies, indicating duf5 directly contributes to pathogenesis. in this ...	2014	24935440
distinct regions of nlrp1b are required to respond to anthrax lethal toxin and metabolic inhibition.	pattern recognition receptors monitor for signs of infection or cellular dysfunction and respond to these events by initiating an immune response. nlrp1b is a receptor that upon activation recruits multiple copies of procaspase-1, which promotes cytokine processing and a proinflammatory form of cell death termed pyroptosis. nlrp1b detects anthrax lethal toxin when the toxin cleaves an amino-terminal fragment from the protein. in addition, nlrp1b is activated when cells are deprived of glucose or ...	2014	24935976
decontamination efficacy of three commercial-off-the-shelf (cots) sporicidal disinfectants on medium-sized panels contaminated with surrogate spores of bacillus anthracis.	in the event of a wide area release and contamination of a biological agent in an outdoor environment and to building exteriors, decontamination is likely to consume the nation's remediation capacity, requiring years to cleanup, and leading to incalculable economic losses. this is in part due to scant body of efficacy data on surface areas larger than those studied in a typical laboratory (5×10-cm), resulting in low confidence for operational considerations in sampling and quantitative measureme ...	2014	24940605
characterization of bacillus strains and hoax agents by protein profiling using automated microfluidic capillary electrophoresis.	in recent times, but especially since 2001, bioterrorism has been of increasing concern. in addition to the use of biological agents, including bacillus anthracis (anthrax), there have been numerous hoax white powder "scares." it is imperative to rapidly and accurately identify any suspicious powder as hazardous or hoax. classical methods for identification typically rely on time-consuming cultivation or highly specific molecular tests which are limited if the agent is unknown. faster and field ...	2014	24943711
nmr conformational properties of an anthrax lethal factor domain studied by multiple amino acid-selective labeling.	nmr-based structural biology urgently needs cost- and time-effective methods to assist both in the process of acquiring high-resolution nmr spectra and their subsequent analysis. especially for bigger proteins (>20 kda) selective labeling is a frequently used means of sequence-specific assignment. in this work we present the successful overexpression of a polypeptide of 233 residues, corresponding to the structured part of the n-terminal domain of anthrax lethal factor, using escherichia coli ex ...	2014	24944022
bacillus anthracis-like bacteria and other b. cereus group members in a microbial community within the international space station: a challenge for rapid and easy molecular detection of virulent b. anthracis.	for some microbial species, such as bacillus anthracis, the etiologic agent of the disease anthrax, correct detection and identification by molecular methods can be problematic. the detection of virulent b. anthracis is challenging due to multiple virulence markers that need to be present in order for b. anthracis to be virulent and its close relationship to bacillus cereus and other members of the b. cereus group. this is especially the case in environments where build-up of bacillus spores can ...	2014	24945323
colonic immune suppression, barrier dysfunction, and dysbiosis by gastrointestinal bacillus anthracis infection.	gastrointestinal (gi) anthrax results from the ingestion of bacillus anthracis. herein, we investigated the pathogenesis of gi anthrax in animals orally infected with toxigenic non-encapsulated b. anthracis sterne strain (pxo1+ pxo2-) spores that resulted in rapid animal death. b. anthracis sterne induced significant breakdown of intestinal barrier function and led to gut dysbiosis, resulting in systemic dissemination of not only b. anthracis, but also of commensals. disease progression signific ...	2014	24945934
clpc operon regulates cell architecture and sporulation in bacillus anthracis.	the clpc operon is known to regulate several processes such as genetic competence, protein degradation and stress survival in bacteria. here, we describe the role of clpc operon in bacillus anthracis. we generated knockout strains of the clpc operon genes to investigate the impact of ctsr, mcsa, mcsb and clpc deletion on essential processes of b. anthracis. we observed that growth, cell division, sporulation and germination were severely affected in mcsb and clpc deleted strains, while none of d ...	2015	24947607
response surface modeling for hot, humid air decontamination of materials contaminated with bacillus anthracis ∆sterne and bacillus thuringiensis al hakam spores.	response surface methodology using a face-centered cube design was used to describe and predict spore inactivation of bacillus anthracis ∆sterne and bacillus thuringiensis al hakam spores after exposure of six spore-contaminated materials to hot, humid air. for each strain/material pair, an attempt was made to fit a first or second order model. all three independent predictor variables (temperature, relative humidity, and time) were significant in the models except that time was not significant ...	2014	24949256
cationic pamam dendrimers as pore-blocking binary toxin inhibitors.	dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. here we identified poly(amido amine) (pamam) dendrimers as novel blockers for the pore-forming b components of the binary anthrax toxin (pa63) and clostridium botulinum c2 toxin (c2iia). these pores are essential for delivery of the enzymatic a components of the internalized toxins from endosomes into the cytosol of target cells. we demonstrate that at low μm concentration ...	2014	24954629
lessons for control of heroin-associated anthrax in europe from 2009-2010 outbreak case studies, london, uk.	outbreaks of serious infections associated with heroin use in persons who inject drugs (pwids) occur intermittently and require vigilance and rapid reporting of individual cases. here, we give a firsthand account of the cases in london during an outbreak of heroin-associated anthrax during 2009-2010 in the united kingdom. this new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. during 2012-13, additional cases of heroin-associated anthrax ...	2014	24959910