Publications

health-related quality of life in the anthrax vaccination program for workers in the laboratory response network.	background: in 2002 cdc initiated the anthrax vaccination program (avp) to provide voluntary pre-exposure vaccination with anthrax vaccine adsorbed (ava) for persons at high risk of exposure to bacillus anthracis spores. there has been concern that ava could be associated with long term impairment of physical and/or mental health. objectives: to ascertain whether physical and mental functional status, as measured by the sf-36v2 health survey (medical outcomes trust, boston, ma), of ava recipient ...	2012	22230591
kinetic characterization of a slow-binding inhibitor of bla2: thiomaltol.	the increasing prevalence of drug resistant bacteria is a pandemic problem. metallo-β-lactamases (mbls) are one of the main causes of drug resistance due to hydrolysis of β-lactam antibiotics. thus, the development of effective inhibitors of mbls remains urgent. the compound thiomaltol was used as a lead compound to investigate its ability to inhibit metallo-β-lactamase from bacillus anthracis (bla2), which causes anthrax. kinetic evaluation with nitrocefin as a substrate indicates that thiomalt ...	2012	22233540
nanohole-based spr instruments with improved spectral resolution quantify a broad range of antibody-ligand binding kinetics.	we demonstrate an affordable low-noise spr instrument based on extraordinary optical transmission (eot) in metallic nanohole arrays and quantify a broad range of antibody-ligand binding kinetics with equilibrium dissociation constants ranging from 200 pm to 40 nm. this nanohole-based spr instrument is straightforward to construct, align, and operate, since it is built around a standard microscope and a portable fiber-optic spectrometer. the measured refractive index resolution of this platform i ...	2012	22235895
two independent replicons can support replication of the anthrax toxin-encoding plasmid pxo1 of bacillus anthracis.	the large pxo1 plasmid (181.6kb) of bacillus anthracis encodes the anthrax toxin proteins. previous studies have shown that two separate regions of pxo1 can support replication of pxo1 miniplasmids when introduced into plasmid-less strains of this organism. no information is currently available on the ability of the above two replicons, termed repx and orfs 14/16 replicons, to support replication of the full-length pxo1 plasmid. we generated mutants of the full-length pxo1 plasmid in which eithe ...	2012	22239982
allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to bacillus anthracis.	anthrax is a potentially fatal disease resulting from infection with bacillus anthracis. the outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (lt), as well as by genetic variation within the host. to identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the lt-responsive cast/ei strain introgressed on a lt-resistant c57bl/6 (b6) background was screened for ...	2011	22241984
biosurveillance: a review and update.	since the terrorist attacks and anthrax release in 2001, almost $32 billion has been allocated to biodefense and biosurveillance in the usa alone. surveillance in health care refers to the continual systematic collection, analysis, interpretation, and dissemination of data. when attempting to detect agents of bioterrorism, surveillance can occur in several ways. syndromic surveillance occurs by monitoring clinical manifestations of certain illnesses. laboratory surveillance occurs by looking for ...	2012	22242207
gold nanoparticles with asymmetric polymerase chain reaction for colorimetric detection of dna sequence.	we developed a novel strategy for rapid colorimetric analysis of a specific dna sequence by combining gold nanoparticles (aunps) with an asymmetric polymerase chain reaction (as-pcr). in the presence of the correct dna template, the bound oligonucleotides on the surface of aunps selectively hybridized to form complementary sequences of single-stranded dna (ssdna) target generated from as-pcr. dna hybridization resulted in self-assembly and aggregation of aunps, and a concomitant color change fro ...	2012	22243128
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 ...	2012	22243393
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- ...	2012	22252821
mechanisms of nk cell-macrophage bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.	nk cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. bacillus anthracis spores can efficiently drive ifn-γ production by nk cells. the present study provides insights into the mechanisms of cytokine and cellular signaling that underlie the process of nk-cell activation by b. anthracis and the bacterial strategies to subvert and evade this response. infection with non-toxigenic encapsulated b. anthracis i ...	2012	22253596
curing of plasmid pxo1 from bacillus anthracis using plasmid incompatibility.	the large plasmid pxo1 encoding the anthrax toxin is important for the virulence of bacillus anthracis. it is essential to cure pxo1 from b. anthracis to evaluate its role in the pathogenesis of anthrax infection. because conventional methods for curing plasmids (e.g., curing agents or growth at elevated temperatures) can induce mutations in the host chromosomal dna, we developed a specific and reliable method to eliminate pxo1 from b. anthracis using plasmid incompatibility. three putative repl ...	2012	22253811
probing the substrate and acceptor specificity of the γ-glutamyltranspeptidase.	abstract. γ-glutamyl transpeptidase (ggt) is a two-substrate enzyme that plays a central role in glutathione metabolism and is a potential target for drug design. ggt catalyze the cleavage of γ-glutamyl donor substrates, and the transfer of the γ-glutamyl moiety to an amine of an acceptor substrate or water. although structures of bacterial ggt have revealed details of the protein-ligand interactions at the donor site, the acceptor substrate site is relatively undefined. the recent identificatio ...	2012	22257032
rapid assembly of a multimeric membrane protein pore.	we have observed the assembly of the staphylococcal pore-forming toxin α-hemolysin using single-molecule fluorescence imaging. surprisingly, assembly from the monomer to the complete heptamer is extremely rapid, occurring in <5 ms. no lower order oligomeric intermediates are detected. monte carlo simulation of our experiment shows that assembly is diffusion limited, and pore formation is dependent on the stability of intermediate species. there are close similarities between bacterial pore-formi ...	2011	22261056
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 ...	2012	22261410
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 ...	2012	22262227
three probable cases of cutaneous anthrax in autonomous province of vojvodina, serbia, june 2011.		2012	22264812
comparative analysis of virulence factors secreted by bacillus anthracis sterne at host body temperature.	aims: for the analysis of virulence factors produced and secreted by bacillus anthracis vegetative cells during mammalian host infection, we evaluated the secretome of b. anthracis sterne exposed to host-specific factors specifically to host body temperature. methods and results: we employed a comparative proteomics-based approach to analyze the proteins secreted by b. anthracis sterne under host-specific body temperature conditions. a total of 17 proteins encoded on a single chromosome and th ...	2012	22268495
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 ...	2012	22270239
sometimes it takes two to tango: contributions of dimerization to functions of human α-defensin hnp1.	human myeloid α-defensins called hnps play multiple roles in innate host defense. the trp26 residue of hnp1 was previously shown to contribute importantly to its ability to kill s. aureus, inhibit anthrax lethal factor (lf), bind gp120 of hiv-1, dimerize, and undergo further self-association. to gain additional insights into the functional significance of dimerization, we compared wild-type hnp1 to dimerization-impaired, n-methylated hnp1 monomers and to disulfide-tethered obligate hnp1 dimers. ...	2012	22270360
effect of the mammalian arginase inhibitor 2(s)-amino-6-boronohexanoic acid on bacillus anthracis arginase.	macrophages, upon phagocytosing endospores of bacillus anthracis, up-regulate the expression of the immunological isoform of nitric oxide synthase, nos 2, concomitant with production of nitric oxide (no•) from metabolism of l: -arginine. we have previously demonstrated that macrophages that secrete no• kill the bacilli of b. anthracis. to circumvent this microbicidal activity of no•, b. anthracis has evolved pathways that include the enzyme arginase, which metabolizes l: -arginine to ornithine a ...	2012	22271269
[bacillus anthracis: a molecular look at a famous pathogen].	bacillus anthracis, a gram-positive rod belonging to the bacillus cereus group, has an extremely monomorphic genome, and presents high structural and physiological similarity with b. cereus and bacillus thuringiensis. in this work, the new molecular methods for the identification and typing of b. anthracis developed in the last years, based on variable number tandem repeats or on genetic differences detected through sequencing, are described. the molecular aspects of traditional virulence factor ...	2013	22274828
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 ...	2012	22289081
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 ...	2012	22289499
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 ...	2012	22291916
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 ...	2012	22291977
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 ...	2012	22300424
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 ...	2012	22303962
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 ...	2012	22304241
insights from genomic comparisons of genetically monomorphic bacterial pathogens.	some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called 'genetically monomorphic bacteria'. it has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. the genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. some ...	2012	22312053
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.	2012	22313022
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 ...	2012	22313407
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 ...	2012	22315420
binary fingerprints at fluctuation-enhanced sensing.	we have developed a simple way to generate binary patterns based on spectral slopes in different frequency ranges at fluctuation-enhanced sensing. such patterns can be considered as binary "fingerprints" of odors. the method has experimentally been demonstrated with a commercial semiconducting metal oxide (taguchi) sensor exposed to bacterial odors (escherichia coli and anthrax-surrogate bacillus subtilis) and processing their stochastic signals. with a single taguchi sensor, the situations of e ...	2010	22315545
predictability of anthrax infection in the serengeti, tanzania.	anthrax is endemic throughout africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. however, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood.we explored rec ...	2011	22318563
multiplexed electrochemical detection of yersinia pestis and staphylococcal enterotoxin b using an antibody microarray.	the combimatrix antibody microarray is a versatile, sensitive detection platform based on the generation and transduction of electrochemical signals following antigen binding to surface antibodies. the sensor chip described herein is comprised of microelectrodes coupled to an adjacent bio-friendly matrix coated with antibodies to the biological pathogens yersinia pestis and bacillus anthracis, and the bacterial toxin staphylococcal enterotoxin b (seb). using this system, we were able to detect s ...	2010	22319302
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 ...	2012	22327072
anthrax--update on diagnosis and management.	human anthrax is difficult to contain. this is primarily because it is a zoonotic disease and the disease has never been contained in the livestock of india due to lack of adequate vaccination facilities. animal anthrax is very common in many parts of india. the problem of anthrax is further compounded by lack of awareness on the part of village folk who unwittingly handle the hide and share the dead animal meat and this causes cutaneous and gastrointestinal forms of anthrax respectively. hemorr ...	2011	22334971
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 ...	2012	22339216
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 ...	2012	22340594
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 ...	2012	22342144
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 ...	2012	22343356
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.	2012	22343361
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.	2012	22344637
maximal adjuvant activity of nasally delivered il-1α requires adjuvant-responsive cd11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.	il-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. we vaccinated il-1r1 bone marrow (bm) chimeric mice to determine whether il-1r1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered il-1α as determined by the acute induction of cytokine responses and induction of bacillus anthracis lethal factor (lf)-specific adaptive immunity. cytokine and chemokine responses ind ...	2012	22345651
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 ...	2012	22347621
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 ...	2012	22351512
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 ...	2012	22352747
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 ...	2012	22352921
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 ...	2012	22354031
development and comparison of two assay formats for parallel detection of four biothreat pathogens by using suspension microarrays.	microarrays provide a powerful analytical tool for the simultaneous detection of multiple pathogens. we developed diagnostic suspension microarrays for sensitive and specific detection of the biothreat pathogens bacillus anthracis, yersinia pestis, francisella tularensis and coxiella burnetii. two assay chemistries for amplification and labeling were developed, one method using direct hybridization and the other using target-specific primer extension, combined with hybridization to universal arr ...	2012	22355407
genetic variation and linkage disequilibrium in bacillus anthracis.	we performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 bacillus anthracis strains. we used an efficient algorithm contained within a custom software program, uniquemer, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. we discovered a total of 240 single nuc ...	2011	22355684
synthetic studies toward the anthrax tetrasaccharide: alternative synthesis of this antigen.	the synthesis of the anthrax tetrasaccharide, amenable for conjugation, has been envisaged by both [2+2] and [1+3] approaches from d-fucose and l-rhamnose. the successful route reported herein relies on a [1+3] strategy in which the 1,2-trans-glycosidic linkages have been secured using a participating group at the 2-position of the donors using conventional thio as well as trichloroacetimidate glycosylation chemistry. the exchange of the ester to benzyl protective groups on the rhamnosyl moiety ...	2012	22356927
recent progress in the development of anthrax vaccines.	bacillus anthracis is the etiological agent of anthrax. although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. the potential use of b. anthracis spores as biowarfare agent has led to immense attention. prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. this highlights the need for alternative anthrax countermeasures. a number of approaches are being investigated to substitute o ...	2011	22360464
finding the smoking gun: protein tyrosine phosphatases as tools and targets of unicellular microorganisms and viruses.	protein tyrosine phosphatases (ptps) are increasingly recognized as important effectors of host-pathogen interactions. since guan and dixon reported in 1990 that phosphatase yoph serves as an essential virulence determinant of yersinia, the field shifted significantly forward, and dozens of ptps were identified in various microorganisms and even in viruses. the discovery of extensive tyrosine signaling networks in non-metazoan organisms refuted the moth-eaten paradigm claiming that these organis ...	2012	22360485
sverdlovsk revisited: pulmonary pathology of inhalational anthrax versus anthraxlike bacillus cereus pneumonia.		2012	22372894
ratcheting up protein translocation with anthrax toxin.	energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. they are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. biological nanomachines that catalyze protein transport, kno ...	2012	22374876
amphiphilic polyanhydride nanoparticles stabilize bacillus anthracis protective antigen.	advancements toward an improved vaccine against bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (pa) adsorbed to aluminum hydroxide. however, due to the labile nature of pa, antigen stability is a primary concern for vaccine development. thus, there is a need for a delivery system capable of preserving the immunogenicity of pa through all the steps of vaccine fabrication, storage, and administration. in this work, we demonstrate ...	2012	22380593
identification of 2 novel antxr2 mutations in patients with hyaline fibromatosis syndrome and proposal of a modified grading system.	juvenile hyaline fibromatosis (jhf) and infantile systemic hyalinosis (ish) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (antxr2) located on chromosome 4q21. characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. the present report describes a pair o ...	2012	22383261
[evaluation of molecular biology reagents used in plcr-tergeted rsi-pcr assay for b. anthracis identification and their influence on time necessary for obtaining results].	fast and reliable identification of b. anthracis is crucial for a successful therapy of persons exposed to anthrax spores. use of molecular biology techniques significantly reduces time necessary for obtaining results. however, the molecular identification is hampered by the high genetic similarity of the b. cereus group bacteria. a lot of published b. antharcis identification approaches turned out to be non-specific. nevertheless, theplcr-targeted rsi-pcr assay described in 2007 is still regard ...	2011	22384665
the aminoglycoside antibiotic kanamycin damages dna bases in escherichia coli: caffeine potentiates the dna-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in escherichia coli and bacillus anthracis.	the distribution of mutants in the keio collection of escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. strains lacking one of a number of glycosylases (e.g., alka, yzab, ogt, ksga) or other specific repair proteins (alkb, phrb, smbc) are more sensitive to these antibiotics. mutants lacking alkb display the strongest sensitivity among the gly ...	2012	22391551
debridement increases survival in a mouse model of subcutaneous anthrax.	anthrax is caused by infection with bacillus anthracis, a spore-forming gram-positive bacterium. a major virulence factor for b. anthracis is an immunomodulatory tripartite exotoxin that has been reported to alter immune cell chemotaxis and activation. it has been proposed that b. anthracis infections initiate through entry of spores into the regional draining lymph nodes where they germinate, grow, and disseminate systemically via the efferent lymphatics. if this model holds true, it would be p ...	2012	22393351
[necrotic lesion of the lip and cough with fever: cutaneous and pulmonary anthrax].	anthrax disease is an anthropozoonosis caused by bacillus anthracis. it appears in three clinical forms: pulmonary, intestinal, and cutaneous. we report a case of pulmonary and cutaneous anthrax in a one-year-old moroccan infant.	2011	22393634
the mountain meadows massacre and "poisoned springs": scientific testing of the more recent, anthrax theory.	it has been recorded that one of the possible causes that eventually escalated into the 1857 manslaughter at mountain meadows in southern utah was the poisoning of an open spring by the fancher-baker party as they crossed the utah territory on their way from arkansas to california. historical accounts report that a number of cattle died, followed by human casualties from those that came in contact with the dead animals. even after the arkansas party departed, animals continued to perish and peop ...	2013	22395921
determinants of emergency response willingness in the local public health workforce by jurisdictional and scenario patterns: a cross-sectional survey.	the all-hazards willingness to respond (wtr) of local public health personnel is critical to emergency preparedness. this study applied a threat-and efficacy-centered framework to characterize these workers' scenario and jurisdictional response willingness patterns toward a range of naturally-occurring and terrorism-related emergency scenarios.	2012	22397547
crystal structures of putative phosphoglycerate kinases from b. anthracis and c. jejuni.	phosphoglycerate kinase (pgk) is indispensable during glycolysis for anaerobic glucose degradation and energy generation. here we present comprehensive structure analysis of two putative pgks from bacillus anthracis str. sterne and campylobacter jejuni in the context of their structural homologs. they are the first pgks from pathogenic bacteria reported in the protein data bank. the crystal structure of pgk from bacillus anthracis str. sterne (bapgk) has been determined at 1.68 å while the struc ...	2012	22403005
variable lymphocyte receptor recognition of the immunodominant glycoprotein of bacillus anthracis spores.	variable lymphocyte receptors (vlrs) are the adaptive immune receptors of jawless fish, which evolved adaptive immunity independent of other vertebrates. in lieu of the immunoglobulin fold-based t and b cell receptors, lymphocyte-like cells of jawless fish express vlrs (vlra, vlrb, or vlrc) composed of leucine-rich repeats and are similar to toll-like receptors (tlrs) in structure, but antibodies (vlrb) and t cell receptors (vlra and vlrc) in function. here, we present the structural and biochem ...	2012	22405006
ultra-fast pg/ml anthrax toxin (protective antigen) detection assay based on microwave-accelerated metal-enhanced fluorescence.	rapid presymptomatic diagnosis of bacillus anthracis at early stages of infection plays a crucial role in prompt medical intervention to prevent rapid disease progression and accumulation of lethal levels of toxin. to detect low levels of the anthrax protective antigen (pa) exotoxin in biological fluids, we have developed a metal-enhanced fluorescence (mef)-pa assay using a combination of the mef effect and microwave-accelerated pa protein surface absorption. the assay is based on a modified ver ...	2012	22406431
functional and structural analysis of the siderophore synthetase asbb through reconstitution of the petrobactin biosynthetic pathway from bacillus anthracis.	petrobactin, a mixed catechol-carboxylate siderophore, is required for full virulence of bacillus anthracis, the causative agent of anthrax. the asbabcdef operon encodes the biosynthetic machinery for this secondary metabolite. here, we show that the function of five gene products encoded by the asb operon is necessary and sufficient for conversion of endogenous precursors to petrobactin using an in vitro system. in this pathway, the siderophore synthetase asbb catalyzes formation of amide bonds ...	2012	22408253
differential function of lip residues in the mechanism and biology of an anthrax hemophore.	to replicate in mammalian hosts, bacterial pathogens must acquire iron. the majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, isdx1 and isdx2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. both proteins ...	2012	22412371
prioritizing risks and uncertainties from intentional release of selected category a pathogens.	this paper synthesizes available information on five category a pathogens (bacillus anthracis, yersinia pestis, francisella tularensis, variola major and lassa) to develop quantitative guidelines for how environmental pathogen concentrations may be related to human health risk in an indoor environment. an integrated model of environmental transport and human health exposure to biological pathogens is constructed which 1) includes the effects of environmental attenuation, 2) considers fomite cont ...	2012	22412915
rugged single domain antibody detection elements for bacillus anthracis spores and vegetative cells.	significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. while numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. in an effort to overcome these ...	2012	22412927
distribution and molecular evolution of bacillus anthracis genotypes in namibia.	the recent development of genetic markers for bacillus anthracis has made it possible to monitor the spread and distribution of this pathogen during and between anthrax outbreaks. in namibia, anthrax outbreaks occur annually in the etosha national park (enp) and on private game and livestock farms. we genotyped 384 b. anthracis isolates collected between 1983-2010 to identify the possible epidemiological correlations of anthrax outbreaks within and outside the enp and to analyze genetic relation ...	2012	22413024
structure-based design of novel pyrimido[4,5-c]pyridazine derivatives as dihydropteroate synthase inhibitors with increased affinity.	dihydropteroate synthase (dhps) is the validated drug target for sulfonamide antimicrobial therapy. however, due to widespread drug resistance and poor tolerance, the use of sulfonamide antibiotics is now limited. the pterin binding pocket in dhps is highly conserved and is distinct from the sulfonamide binding site. it therefore represents an attractive alternative target for the design of novel antibacterial agents. we previously carried out the structural characterization of a known pyridazin ...	2012	22416048
structure, assembly, and dna packaging of the bacteriophage t4 head.	the bacteriophage t4 head is an elongated icosahedron packed with 172 kb of linear double-stranded dna and numerous proteins. the capsid is built from three essential proteins: gp23, which forms the hexagonal capsid lattice; gp24, which forms pentamers at 11 of the 12 vertices; and gp20, which forms the unique dodecameric portal vertex through which dna enters during packaging and exits during infection. intensive work over more than half a century has led to a deep understanding of the phage ...	2012	22420853
human monoclonal antibodies generated following vaccination with ava provide neutralization by blocking furin cleavage but not by preventing oligomerization.	in order to identify the combination of antibody-mediated mechanisms of neutralization that result from vaccination with anthrax vaccine adsorbed (ava), we isolated antibody secreting cells from a single donor seven days after booster vaccination with ava and generated nine fully human monoclonal antibodies (hmab) with high specificity for protective antigen (pa). two of the antibodies were able to neutralize lethal toxin in vitro at low concentrations (ic(50): p6c01, 0.12 μg/ml and p6f01, 0.45 ...	2012	22425791
multiple abc transporters are involved in the acquisition of petrobactin in bacillus anthracis.	in bacillus anthracis the siderophore petrobactin is vital for iron acquisition and virulence. the petrobactin-binding receptor fpua is required for these processes. here additional components of petrobactin reacquisition are described. to identify these proteins, mutants of candidate permease and atpase genes were generated allowing for characterization of multiple petrobactin atp-binding cassette (abc)-import systems. either of two distinct permeases, fpub or fatcd, is required for iron acquis ...	2012	22429808
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 ...	2012	22431852
[landscape components favouring the occurrence of anthrax in the flooding pampa grasslands (buenos aires province, argentina)].	the authors studied the landscape components that favour the occurrence of anthrax in the flooding pampa grasslands (buenos aires province, argentina). they made spatial locations of anthrax outbreaks diagnosed by registered veterinary laboratories in the study area's zone of influence. as variables for study, they differentiated areas that are flooded for 20% of the time or more from primary and secondary runoff channels. they also identified areas with low-productivity pasture. logistic regres ...	2011	22435200
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 ...	2012	22438345
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 ...	2012	22438738
anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.	a variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (mapk) signaling pathways, including bacillus anthracis. anthrax lethal toxin (lt) has specific proteolytic activity against the upstream regulators of mapks, the mapk kinases (mkks). using a murine model of intoxication, we show that lt causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. this pathology correlates w ...	2012	22438953
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 ...	2012	22441391
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 ...	2012	22441768
activation of the classical complement pathway by bacillus anthracis is the primary mechanism for spore phagocytosis and involves the spore surface protein bcla.	interactions between spores of bacillus anthracis and macrophages are critical for the development of anthrax infections, as spores are thought to use macrophages as vehicles to disseminate in the host. in this study, we report a novel mechanism for phagocytosis of b. anthracis spores. murine macrophage-like cell line raw264.7, bone marrow-derived macrophages, and primary peritoneal macrophages from mice were used. the results indicated that activation of the classical complement pathway (ccp) w ...	2012	22442442
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 ...	2012	22442931
[epidemiologic surveillance for anthrax foci by using standard case definition].		2012	22442983
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 ...	2012	22445310
sortase-conjugation generates a capsule vaccine that protects guinea pigs against bacillus anthracis.	capsules protect bacteria against phagocytic clearance. capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. linking capsular material to a carrier protein stimulates its presentation to the immune system. for many conjugate vaccines this is achieved by a process of random chemical cross-linking. here we describe a new technology, designated sortase-conjugation, which g ...	2012	22449424
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 ...	2012	22449993
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 ...	2012	22452315
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 ...	2012	22452935
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 ...	2012	22455675
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 ...	2012	22455677
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 ...	2012	22455678
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 ...	2012	22455679
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 ...	2012	22458673
the structure of mlc titration factor a (mtfa/yeei) reveals a prototypical zinc metallopeptidase related to anthrax lethal factor.	mtfa of escherichia coli (formerly yeei) was previously identified as a regulator of the phosphoenolpyruvate (pep)-dependent:glucose phosphotransferase system. mtfa homolog proteins are highly conserved, especially among beta- and gammaproteobacteria. we determined the crystal structures of the full-length mtfa apoenzyme from klebsiella pneumoniae and its complex with zinc (holoenzyme) at 2.2 and 1.95 å, respectively. mtfa contains a conserved h(149)e(150)xxh(153)+e(212)+y(205) metallopeptidase ...	2012	22467785
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) ...	2012	22468827
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' ...	2012	22469218
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 ...	2012	22472314