Publications

comparison of air sampling methods for aerosolized spores of b. anthracis sterne.	bacillus anthracis sterne spores were aerosolized within a chamber at concentrations ranging from 1 x 10³ to 1.7 x 104 spores per cubic meter of air (particles (p)/m³) to compare three different sampling methods: andersen samplers, gelatin filters, and polytetrafluoroethylene (ptfe) membrane filters. three samples of each type were collected during each of 19 chamber runs. chamber concentration was determined by an aerodynamic particle sizer (aps) for the size range of 1.114-1.596 µm. runs were ...	2011	21347959
function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size.	changes in effective population size impinge on patterns of molecular evolution. notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. this prediction has been validated empirically for several endosymbiont and island taxa. here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidate ...	2011	21349981
high-level production of a single chain antibody against anthrax toxin in escherichia coli by high cell density cultivation.	previously, we isolated the m18 scfv, which is an affinity matured antibody against the anthrax toxin pa, and observed that its single chain antibody (scab) form (m18 scab) exhibited superior stability compared to the scfv. here, we report high cell density cultivations for preparative scale production of m18 scab in a 3.5 l fermenter. briefly, a ph-stat feeding strategy was employed in fed-batch cultivation, and four different cell densities (od(600) of 40, 80, 120, and 150) were examined for t ...	2011	21350955
chemical dissection of protein translocation through the anthrax toxin pore.		2011	21351339
mek2 is sufficient but not necessary for proliferation and anchorage-independent growth of sk-mel-28 melanoma cells.	mitogen-activated protein kinase kinases (mkk or mek) 1 and 2 are usually treated as redundant kinases. however, in assessing their relative contribution towards erk-mediated biologic response investigators have relied on tests of necessity, not sufficiency. in response we developed a novel experimental model using lethal toxin (letx), an anthrax toxin-derived pan-mkk protease, and genetically engineered protease resistant mkk mutants (mkkcr) to test the sufficiency of mek signaling in melanoma ...	2011	21365009
the role of hla-dr-dq haplotypes in variable antibody responses to anthrax vaccine adsorbed.	host genetic variation, particularly within the human leukocyte antigen (hla) loci, reportedly mediates heterogeneity in immune response to certain vaccines; however, no large study of genetic determinants of anthrax vaccine response has been described. we searched for associations between the immunoglobulin g antibody to protective antigen (abpa) response to anthrax vaccine adsorbed (ava) in humans, and polymorphisms at hla class i (hla-a, -b, and -c) and class ii (hla-drb1, -dqa1, -dqb1, -dpb1 ...	2011	21368772
purification development and characterization of the zinc-dependent metallo-ß-lactamase from bacillus anthracis.	metallo-ß-lactamase from bacillus anthracis (bla2) catalyzes the hydrolysis of ß-lactam antibiotics which are commonly prescribed to combat bacterial infections. bla2 contributes to the antibiotic resistance of this bacterium. an understanding of it is necessary to design potential inhibitors that can be introduced with current antibiotics for effective eradication of anthrax infections. we have purified bla2 using ni(2+)-affinity chromatography with over 140-fold increase in activity with a yie ...	2011	21369909
peptide-based fluorescence resonance energy transfer protease substrates for the detection and diagnosis of bacillus species.	we describe the development of a highly specific enzyme-based fluorescence resonance energy transfer (fret) assay for easy and rapid detection both in vitro and in vivo of bacillus spp., among which are the members of the b. cereus group. synthetic substrates for b. anthracis proteases were designed and exposed to secreted enzymes of a broad spectrum of bacterial species. the rational design of the substrates was based on the fact that the presence of d-amino acids in the target is highly specif ...	2011	21370823
two capsular polysaccharides enable bacillus cereus g9241 to cause anthrax-like disease.	bacillus cereus g9241 causes an anthrax-like respiratory illness in humans; however, the molecular mechanisms of disease pathogenesis are not known. genome sequencing identified two putative virulence plasmids proposed to provide for anthrax toxin (pbcxo1) and/or capsule expression (pbc218). we report here that b. cereus g9241 causes anthrax-like disease in immune-competent mice, which is dependent on each of the two virulence plasmids. pbcxo1 encodes paga1, the homologue of anthrax protective a ...	2011	21371137
analogues of peptide smap-29 with comparable antimicrobial potency and reduced cytotoxicity.	smap-29 (sheep myeloid antimicrobial peptide-29) is a peptide with potent antibacterial properties. however, it is also highly cytotoxic both to human red blood cells (hrbcs) and human embryonic kidney (hek) cells. in this study, some of the amino acids of smap-29 were changed in an attempt to reduce haemolytic activity whilst maintaining high antibacterial efficacy. these analogues, plus other analogues described in the literature with potent antimicrobial activity against gram-positive bacteri ...	2011	21377841
bacillus anthracis comparative genome analysis in support of the amerithrax investigation.	before the anthrax letter attacks of 2001, the developing field of microbial forensics relied on microbial genotyping schemes based on a small portion of a genome sequence. amerithrax, the investigation into the anthrax letter attacks, applied high-resolution whole-genome sequencing and comparative genomics to identify key genetic features of the letters' bacillus anthracis ames strain. during systematic microbiological analysis of the spore material from the letters, we identified a number of m ...	2011	21383169
bacillus anthracis spore interactions with mammalian cells: relationship between germination state and the outcome of in vitro.	during inhalational anthrax, internalization of bacillus anthracis spores by host cells within the lung is believed to be a key step for initiating the transition from the localized to disseminated stages of infection. despite compelling in vivo evidence that spores remain dormant within the bronchioalveolar spaces of the lungs, and germinate only after uptake into host cells, most in vitro studies of infection have been conducted under conditions that promote rapid germination of spores within ...	2011	21356113
cutting edge: primary innate immune cells respond efficiently to polymeric peptidoglycan, but not to peptidoglycan monomers.	the cell wall of bacteria induces proinflammatory cytokines in monocytes and neutrophils in human blood. the nature of the stimulating component of bacterial cell walls is not well understood. we have previously shown polymeric peptidoglycan (pgn) has this activity, and the cytokine response requires pgn internalization and trafficking to lysosomes. in this study, we demonstrate that peptidoglycan monomers such as muramyl dipeptide and soluble peptidoglycan fail to induce robust cytokine product ...	2011	21357534
subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis.	anthrax is extremely rare in the western world but is endemic to areas of south and central asia. in early 2010 an outbreak was identified in heroin-injecting intravenous drug users in the united kingdom and europe. afghanistan is currently the principal source of heroin which reaches the united kingdom. when anthrax occurs, cutaneous disease accounts for over 95% of cases. at least 47 cases with 13 deaths have been confirmed so far. we present three cases presenting during this time with marked ...	2011	21357967
antibody responses to a spore carbohydrate antigen as a marker of nonfatal inhalation anthrax in rhesus macaques.	the bacillus anthracis exosporium protein bcla contains an o-linked antigenic tetrasaccharide whose terminal sugar is known as anthrose (j. m. daubenspeck et al., j. biol. chem. 279:30945-30953, 2004). we hypothesized that serologic responses to anthrose may have diagnostic value in confirming exposure to aerosolized b. anthracis. we evaluated the serologic responses to a synthetic anthrose-containing trisaccharide (ats) in a group of five rhesus macaques that survived inhalation anthrax followi ...	2011	21389148
serologic surveillance of anthrax in the serengeti ecosystem, tanzania, 1996-2009.	bacillus anthracis, the bacterium that causes anthrax, is responsible for varying death rates among animal species. difficulties in case detection, hazardous or inaccessible carcasses, and misdiagnosis hinder surveillance. using case reports and a new serologic assay that enables multispecies comparisons, we examined exposure to and illness caused by b. anthracis in different species in the serengeti ecosystem in tanzania during 1996-2009 and the utility of serosurveillance. high seroprevalence ...	2011	21392428
nature of allosteric inhibition in glutamate racemase: discovery and characterization of a cryptic inhibitory pocket using atomistic md simulations and pka calculations.	enzyme inhibition via allostery, in which the ligand binds remotely from the active site, is a poorly understood phenomenon and represents a significant challenge to structure-based drug design. dipicolinic acid (dpa), a major component of bacillus spores, is shown to inhibit glutamate racemase from bacillus anthracis , a monosubstrate/monoproduct enzyme, in a novel allosteric fashion. glutamate racemase has long been considered an important drug target for its integral role in bacterial cell wa ...	2011	21395329
secreted bacillus anthracis proteases target the host fibrinolytic system.	the fibrinolytic system is often the target for pathogenic bacteria, resulting in increased fibrinolysis, bacterial dissemination, and inflammation. the purpose of this study was to explore whether proteases nprb and inha secreted by bacillus anthracis could activate the host's fibrinolytic system. nprb efficiently activated human pro-urokinase plasminogen activator (pro-upa), a key protein in the fibrinolytic cascade. conversely, inha had little effect on pro-upa. plasminogen activator inhibito ...	2011	21395696
the effect of growth medium on b. anthracis sterne spore carbohydrate content.	the expressed characteristics of biothreat agents may be impacted by variations in the culture environment, including growth medium formulation. the carbohydrate composition of b. anthracis spores has been well studied, particularly for the exosporium, which is the outermost spore structure. the carbohydrate composition of the exosporium has been demonstrated to be distinct from the vegetative form containing unique monosaccharides. we have investigated the carbohydrate composition of b. anthrac ...	2011	21396405
subsite specificity of anthrax lethal factor and its implications for inhibitor development.	the lethal factor of bacillus anthracis is a major factor for lethality of anthrax infection by this bacterium. with the aid of the protective antigen, lethal factor gains excess to the cell cytosol where it manifests toxicity as a metalloprotease. for better understanding of its specificity, we have determined its residue preferences of 19 amino acids in six subsites (from p3 to p3') as relative k(cat)/k(m) values (specificity constants). these results showed that lethal factor has a broad spec ...	2011	21396916
the early humoral immune response to bacillus anthracis toxins in patients infected with cutaneous anthrax.	bacillus anthracis, the causative agent of anthrax, produces a tripartite toxin composed of two enzymatically active subunits, lethal factor (lf) and edema factor (ef), which, when associated with a cell-binding component, protective antigen (pa), form lethal toxin and edema toxin, respectively. in this preliminary study, we characterized the toxin-specific antibody responses observed in 17 individuals infected with cutaneous anthrax. the majority of the toxin-specific antibody responses observe ...	2011	21401726
the anthrax toxin channel: a barrel of lfs.		2011	21402885
trapping a translocating protein within the anthrax toxin channel: implications for the secondary structure of permeating proteins.	anthrax toxin consists of three proteins: lethal factor (lf), edema factor (ef), and protective antigen (pa). this last forms a heptameric channel, (pa(63))(7), in the host cell's endosomal membrane, allowing the former two (which are enzymes) to be translocated into the cytosol. (pa(63))(7) incorporated into planar bilayer membranes forms a channel that translocates lf and ef, with the n terminus leading the way. the channel is mushroom-shaped with a cap containing the binding sites for ef and ...	2011	21402886
quantitative mass spectrometry for bacterial protein toxins--a sensitive, specific, high-throughput tool for detection and diagnosis.	matrix-assisted laser-desorption time-of-flight (maldi-tof) mass spectrometry (ms) is a valuable high-throughput tool for peptide analysis. liquid chromatography electrospray ionization (lc-esi) tandem-ms provides sensitive and specific quantification of small molecules and peptides. the high analytic power of ms coupled with high-specificity substrates is ideally suited for detection and quantification of bacterial enzymatic activities. as specific examples of the ms applications in disease dia ...	2011	21403598
scratching the surface: the history of skin, its diseases and their treatment--history of medicine unit, university of birmingham, october 29-30, 2010.		2011	21409964
a new peptide motif present in the protective antigen of anthrax toxin exerts its efficiency on the cellular uptake of liposomes and applications for a dual-ligand system.	protective antigen (pa) is a nontoxic protein present in anthrax toxin. domain 4 of pa (pa-d4) acts as a receptor binding site for tumor endothelial marker 8 (tem8). in this study, kynd motif from pa-d4 was utilized as a ligand against tem8. the efficiency of kynd motif on cellular association was assessed by evaluating the cellular uptake of pegylated liposomes (peg-lps) in tem8 positive and negative cells. the peptide was attached on the top of the peg of peg-lp. compared to peg-lp, kynd modif ...	2011	21414394
a practical liquid plug flow-through polymerase chain-reaction system based on a heat-resistant resin chip.	flow-through polymerase chain reaction (pcr) microfluidic systems for fast, small-volume dna amplification on a single chip are significantly impacting medical and bioanalytical research. we have fabricated an improved, practical flow-through pcr chip by weighting a pressure-sensitive polyolefin (psp) film onto a cyclo-olefin polymer (cop) substrate. the substrate was cut so as to produce microchannels, and was used to amplify dna using a small moving liquid plug, in contrast to conventional con ...	2011	21415501
anthrax vaccination induced anti-lethal factor igg: fine specificity and neutralizing capacity.	the efficacy biomarker of the currently licensed anthrax vaccine (ava) is based on quantity and neutralizing capacity of anti-protective antigen (anti-pa) antibodies. however, animal studies have demonstrated that antibodies to lethal factor (lf) can provide protection against in vivo bacterial spore challenges. improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin prepa ...	2011	21420416
therapeutic recommendations for the management of patients exposed to bacillus anthracis in natural settings.		2011	21420809
secondary cell wall polysaccharides from bacillus cereus strains g9241, 03bb87 and 03bb102 causing fatal pneumonia share similar glycosyl structures with the polysaccharides from bacillus anthracis.	secondary cell wall polysaccharides (scwps) are important structural components of the bacillus cell wall and contribute to the array of antigens presented by these organisms in both spore and vegetative forms. we previously found that antisera raised to bacillus anthracis spore preparations cross-reacted with scwps isolated from several strains of pathogenic b. cereus, but did not react with other phylogenetically related but nonpathogenic bacilli, suggesting that the scwp from b. anthracis and ...	2011	21421577
anthrax lethal factor activates k(+) channels to induce il-1ß secretion in macrophages.	anthrax lethal toxin (letx) is a virulence factor of bacilillus anthracis that is a bivalent toxin, containing lethal factor (lf) and protective ag proteins, which causes cytotoxicity and altered macrophage function. letx exposure results in early k(+) efflux from macrophages associated with caspase-1 activation and increased il-1ß release. the mechanism of this toxin-induced k(+) efflux is unknown. the goals of the current study were to determine whether letx-induced k(+) efflux from macrophage ...	2011	21421849
mechanism of reactant and product dissociation from the anthrax edema factor: a locally enhanced sampling and steered molecular dynamics study.	the anthrax edema factor is a toxin overproducing damaging levels of cyclic adenosine monophosphate (camp) and pyrophosphate (ppi) from atp. here, mechanisms of dissociation of atp and products (camp, ppi) from the active site are studied using locally enhanced sampling (les) and steered molecular dynamics simulations. various substrate conformations and ionic binding modes found in crystallographic structures are considered. les simulations show that ppi and camp dissociate through different so ...	2011	21425348
cys-cys cross-linking shows contact between the n-terminus of lethal factor and phe427 of the anthrax toxin pore.	electrophysiological studies of wild-type and mutated forms of anthrax protective antigen (pa) suggest that the phe clamp, a structure formed by the phe427 residues within the lumen of the oligomeric pa pore, binds the unstructured n-terminus of the lethal factor and the edema factor during initiation of translocation. we now show by electrophysiological measurements and gel shift assays that a single cys introduced into the phe clamp can form a disulfide bond with a cys placed at the n-terminus ...	2011	21425869
detection of ascitic fluid infections in patients with liver cirrhosis and ascites.	ascitic fluid infections (afis) are the frequent complications of advanced liver disease. bacterial translocation is considered a key step in the pathogenesis of gut-derived bacterial infections; mainly spontaneous bacterial peritonitis (sbp) in cirrhotic patients. bacterial dna (bactdna) in ascitic fluid and serum has been suggested as a surrogate marker for bacterial translocation. we attempted at the isolation and identification of bacteria in ascitic fluid in cirrhotic patients and the asses ...	2011	21429450
bacillus anthracis protease inha increases blood-brain barrier permeability and contributes to cerebral hemorrhages.	hemorrhagic meningitis is a fatal complication of anthrax, but its pathogenesis remains poorly understood. the present study examined the role of b. anthracis-secreted metalloprotease inha on monolayer integrity and permeability of human brain microvasculature endothelial cells (hbmecs) which constitute the blood-brain barrier (bbb). treatment of hbmecs with purified inha resulted in a time-dependent decrease in trans-endothelial electrical resistance (teer) accompanied by zonula occluden-1 (zo- ...	2011	21437287
the unfolding story of anthrax toxin translocation.	the essential cellular functions of secretion and protein degradation require a molecular machine to unfold and translocate proteins either across a membrane or into a proteolytic complex. protein translocation is also critical for microbial pathogenesis, namely bacteria can use translocase channels to deliver toxic proteins into a target cell. anthrax toxin (atx), a key virulence factor secreted by bacillus anthracis, provides a robust biophysical model to characterize transmembrane protein tra ...	2011	21443527
[immunogenicity of protective antigen extracted from asporogenic recombinant strain bacillus anthracis].	to study the ability of recombinant protective antigen (pa) to stimulate adaptive immune response in laboratory animals.	2011	21446166
investigating the genome diversity of b. cereus and evolutionary aspects of b. anthracis emergence.	here we report the use of a multi-genome dna microarray to investigate the genome diversity of bacillus cereus group members and elucidate the events associated with the emergence of bacillus anthracis the causative agent of anthrax-a lethal zoonotic disease. we initially performed directed genome sequencing of seven diverse b. cereus strains to identify novel sequences encoded in those genomes. the novel genes identified, combined with those publicly available, allowed the design of a "species" ...	2011	21447378
anthrax investigation. army missed warning signs about alleged anthrax mailer.		2011	21454766
analysis of bacillus anthracis nucleoside hydrolase via in silico docking with inhibitors and molecular dynamics simulation.	as the enzyme nucleoside hydrolase (nh) is widely found in nature but has not yet been detected in mammals, it is considered an ideal target in the development of chemotherapy against parasitic diseases and bacterial infections like anthrax. considering the risk that this biological warfare agent represents nowadays, the search for new drugs and new molecular targets in the development of chemotherapy against anthrax is imperative. on this basis, we performed docking studies of six known nh inhi ...	2011	21318235
evaluation of the effect of syringe surfaces on protein formulations.	packaging of drugs in prefillable syringes offers considerable advantages over conventional vials. almost all major biotech molecules are available on the market today in prefilled syringes, and are safe and efficacious. newer high-concentration liquid formulations, especially fusion proteins, however, can suffer from instability in prefilled syringes due to syringe components like silicone oil. to assess the effect of siliconized and modified syringe surfaces on protein formulations, the stabil ...	2011	21319164
bacillus anthracis interacts with plasmin(ogen) to evade c3b-dependent innate immunity.	the causative agent of anthrax, bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. it has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. however, interference of b. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as t ...	2011	21464960
a tpo receptor agonist, alxn4100tpo, mitigates radiation-induced lethality and stimulates hematopoiesis in cd2f1 mice.	abstract thrombopoietin (tpo) receptor agonists lacking sequence homology to tpo were designed by grafting a known peptide sequence into the hinge and/or kappa constant regions of a human anti-anthrax antibody. some of these proteins were equipotent to tpo in stimulating cmpl-r activity in vitro and in increasing platelet levels in vivo. alxn4100tpo (4100tpo), the best agonist in this series with a k(d) of 30 nm for cmpl-r, exhibited potent activity as a radiation countermeasure in cd2f1 mice ex ...	2011	21476857
a new approach to in silico snp detection and some new snps in the bacillus anthracis genome.	abstract:	2011	21477306
adenomatous polyposis coli protein associates with c/ebp {beta} and increases bacillus anthracis edema toxin-stimulated gene expression in macrophages.	the production of camp from bacillus anthracis edema toxin (et) activates gene expression in macrophages through a complex array of signaling pathways, most of which remain poorly defined. in this study, the tumor suppressor protein adenomatous polyposis coli (apc) was found to be important for the up-regulation of previously defined et-stimulated genes (vegfa, ptgs2, arg2, cxcl2, sdc1, and cebpb). a reduction in the expression of these genes after et exposure was observed when apc was disrupted ...	2011	21487015
a combination of the tlr4 agonist cia05 and alum promotes the immune responses to bacillus anthracis protective antigen in mice.	anthrax is an infectious disease caused by bacillus anthracis. the currently licensed human anthrax vaccines contain protective antigen (pa) as a major protective component and alum as an adjuvant. in this study, we investigated whether cia05, a tlr4 agonist, is able to promote the immune response to an anthrax vaccine adjuvanted with alum. balb/c mice were immunized intraperitoneally three times at 2-week intervals with a recombinant b. anthracis pa alone or in combination with cia05 in the abs ...	2011	21492746
peptide epitope identification by affinity selection on bacteriophage ms2 virus-like particles.	filamentous phages are now the most widely used vehicles for phage display and provide efficient means for epitope identification. however, the peptides they display are not very immunogenic because they normally fail to present foreign epitopes at the very high densities required for efficient b-cell activation. meanwhile, systems based on virus-like particles (vlps) permit the engineered high-density display of specific epitopes but are incapable of peptide library display and affinity selecti ...	2011	21501621
internet-based reporting to the vaccine adverse event reporting system: a more timely and complete way for providers to support vaccine safety.	on march 22, 2002, internet-based reports (ibrs) were added to the vaccine adverse event reporting system (vaers) to allow rapid, expedited reporting of adverse events (aes) in anticipation of wider use of counter-bioterrorism vaccines such as those against smallpox and anthrax.	2011	21502243
crystal structure of the vibrio cholerae cytolysin heptamer reveals common features among disparate pore-forming toxins.	pore-forming toxins (pfts) are potent cytolytic agents secreted by pathogenic bacteria that protect microbes against the cell-mediated immune system (by targeting phagocytic cells), disrupt epithelial barriers, and liberate materials necessary to sustain growth and colonization. produced by gram-positive and gram-negative bacteria alike, pfts are released as water-soluble monomeric or dimeric species, bind specifically to target membranes, and assemble transmembrane channels leading to cell dama ...	2011	21502531
a plant based protective antigen [pa(div)] vaccine expressed in chloroplasts demonstrates protective immunity in mice against anthrax.	the currently available anthrax vaccines are limited by being incompletely characterized, potentially reactogenic and have an expanded dosage schedule. plant based vaccines offer safe alternative for vaccine production. in the present study, we expressed domain iv of bacillus anthracis protective antigen gene [pa(div)] in planta (by nuclear agrobacterium and chloroplast transformation) and e. coli [rpa(div)]. the presence of transgene and the expression of pa(div) in planta was confirmed by mole ...	2011	21504775
phemadb: a solution for storage, retrieval, and analysis of high throughput phenotype data.	abstract:	2011	21507258
charge requirements for proton gradient-driven translocation of anthrax toxin.	anthrax lethal toxin is used as a model system to study protein translocation. the toxin is composed of a translocase channel, called protective antigen (pa), and an enzyme, called lethal factor (lf). a proton gradient (δph) can drive lf unfolding and translocation through pa channels; however, the mechanism of δph- mediated force generation, substrate unfolding, and the establishment of directionality are poorly understood. one recent hypothesis suggests that the δph may act through changes in ...	2011	21507946
acr appropriateness criteria® acute respiratory illness in immunocompetent patients.	acute respiratory illness is defined as one or more of the following: cough, sputum production, chest pain, or dyspnea (with or without fever). the workup of these patients depends on many factors, including clinical presentation and the suspected etiology. this study reviews the literature on the indications and usefulness of radiologic studies for the evaluation of acute respiratory illness in the immunocompetent patient. the following recommendations are the result of evidence-based consensus ...	2011	21508726
one-step synthesized silver micro-dendrites used as novel separation mediums and their applications in multi-dna analysis.	a new kind of silver micro-dendrites have been synthesized for the separation and multiplex detection of dna merely by earth gravity. through this approach, the dna strands of the sickle cell disease, human t-lymphotropic virus type i, the anthrax lethal factor can be detected down to 100 pm with the detection range from 100 pm to 100 nm at the same time.	2011	21512713
larvicidal, antimicrobial and brine shrimp activities of extracts from cissampelos mucronata and tephrosia villosa from coast region, tanzania.	abstract:	2011	21513544
mechanism of inhibition of bacillus anthracis spore outgrowth by the lantibiotic nisin.	the lantibiotic nisin inhibits growth of vegetative gram-positive bacteria by binding to lipid ii, which disrupts cell wall biosynthesis and facilitates pore formation. nisin also inhibits the outgrowth of bacterial spores, including spores of bacillus anthracis, whose structural and biochemical properties are fundamentally different from those of vegetative bacteria. the molecular basis of nisin inhibition of spore outgrowth had not been identified, as previous studies suggested that inhibition ...	2011	21517116
contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis.	bacillus anthracis is a gram-positive spore forming bacterium that causes anthrax disease in humans and animals. systemic infection is characterized by septicemia, toxemia, and meningitis, the main neurological complication associated with high mortality. we have shown previously that b. anthracis sterne is capable of blood-brain barrier (bbb) penetration establishing the classic signs of meningitis, and that infection is dependent on the expression of both major anthrax toxins, lethal toxin (lt ...	2011	21518787
european risk assessment guidance for infectious diseases transmitted on aircraft - the ragida project.		2011	21527131
post-exposure therapy of inhalational anthrax in the common marmoset.	the aim of this study was to compare the pharmacokinetics and efficacy of ciprofloxacin as post-exposure therapy against inhalational anthrax in the common marmoset (callithrix jacchus) with other non-human primate models in order to determine whether the marmoset is a suitable model to test post-exposure therapies for anthrax. pharmacokinetic (pk) and efficacy studies with ciprofloxacin were performed in the marmoset. ciprofloxacin plasma pharmacokinetics were determined in six animals in separ ...	2011	21530184
the cody pleiotropic repressor controls virulence in gram-positive pathogens.	cody is involved in the adaptive response to starvation in at least 30 different low g+c gram-positive bacteria. after dimerization and activation by cofactor binding, cody binds to a consensus palindromic dna sequence, leading to the repression of approximately 5% of the genome. cody represses the transcription of target genes when bound to dna by competition with the rna polymerase for promoter binding, or by interference with transcriptional elongation as a roadblock. cody displays enhanced a ...	2011	21539625
multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies.	multivalent display of heterologous proteins on viral nanoparticles forms a basis for numerous applications in nanotechnology, including vaccine development, targeted therapeutic delivery, and tissue-specific bioimaging. in many instances, precise placement of proteins is required for optimal functioning of the supramolecular assemblies, but orientation- and site-specific coupling of proteins to viral scaffolds remains a significant technical challenge. we have developed two strategies that allo ...	2011	21545187
recombinant expression and functional analysis of proteases from streptococcus pneumoniae, bacillus anthracis, and yersinia pestis.	abstract: background: uncharacterized proteases naturally expressed by bacterial pathogens represents important topic in infectious disease research, because these enzymes may have critical roles in pathogenicity and cell physiology. it has been observed that cloning, expression and purification of proteases often fail due to their catalytic functions which, in turn, cause toxicity in the e. coli heterologous host. results: in order to address this problem systematically, a modified pipeline of ...	2011	21545736
sensitive detection of an anthrax biomarker using a glassy carbon electrode with a consecutively immobilized layer of polyaniline/carbon nanotube/peptide.	sensitivity of anthrax protective antigen (pa) detection has been improved by directly immobilizing a pa-specific peptide onto a multi-wall carbon nanotube (mwcnt). the mwcnt was covalently immobilized onto a polyaniline (pani) electrode, which was prepared via electropolymerization of the aniline monomer onto a glassy carbon electrode (gce). then, the pa-specific peptide was covalently immobilized to the mwcnt layer for measurement. when comparing this technique to that of pa immobilization on ...	2011	21550226
symmetry requirements for the effective blocking of pore-forming toxins: comparative study with {alpha}-, {beta}-, and {gamma}-cyclodextrin derivatives.	we compared the ability of structurally related cationic cyclodextrins to inhibit bacillus anthracis lethal toxin and staphylococcus aureus α-hemolysin. we found that both β- and γ-cyclodextrin derivatives effectively inhibited anthrax toxin action by blocking the trans-membrane oligomeric pores formed by the pa subunit of the toxin, whereas α-cyclodextrins were ineffective. in contrast, α-hemolysin was selectively blocked only by β- cyclodextrin derivatives, demonstrating that both symmetry and ...	2011	21555769
characterization of bacilli isolated from the confined environments of the antarctic concordia station and the international space station.	abstract bacillus and related genera comprise opportunist and pathogen species that can threaten the health of a crew in confined stations required for long-term missions. in this study, 43 bacilli from confined environments, that is, the antarctic concordia station and the international space station, were characterized in terms of virulence and plasmid exchange potentials. no specific virulence feature, such as the production of toxins or unusual antibiotic resistance, was detected. most of th ...	2011	21563959
ultrasensitive detection of botulinum neurotoxins and anthrax lethal factor in biological samples by alissa.	both botulinum neurotoxins (bonts) and anthrax lethal factor, a component of anthrax toxin, exhibit zinc metalloprotease activity. the assay detailed here is capable of quantitatively detecting these proteins by measuring their enzymatic functions with high sensitivity. the detection method encompasses two steps: (1) specific target capture and enrichment and (2) cleavage of a fluorogenic substrate by the immobilized active target, the extent of which is quantitatively determined by differential ...	2011	21567315
examination of bacillus anthracis spores by multiparameter flow cytometry.	the ability to rapidly differentiate bacillus anthracis spores from spores belonging to other bacillus spp. is potentially useful for combating the intentional release of this biothreat agent. furthermore, not all b. anthracis strains are fully virulent and the ability to determine the potential virulence of the endospore is also important. in this chapter, we describe a two-color flow cytometric assay capable of simultaneously identifying b. anthracis spores and the presence of spore-associated ...	2011	21567316
aluminum vaccine adjuvants: are they safe?	aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. there is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. in spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. experimental research, however, clearly shows that a ...	2011	21568886
feasibility of selected prophylactic barriers in arrestance of airborne bacterial vegetative cells and endospores.	background: transmission of infection by airborne agents is a risk for health care personnel, patients, and visitors. this risk is heightened in regions without access to environmental controls and personal protective equipment. the ability of 2 prophylactic barriers (ie, semitransparent netting for insect control) to arrest bioaerosols was assessed for potential use within the malarial zones. methods: barriers (pore sizes of 0.8 mm and 0.25 mm) were challenged with bioaerosols of vegetative cel ...	2011	21570738
identification of an african bacillus anthracis lineage that lacks expression of the spore surface associated anthrose containing oligosaccharide.	the surface of bacillus anthracis endospores exposes a pentasaccharide containing the monosaccharide anthrose which has been considered as vaccine or target for specific detection of the spores. in this study b. anthracis strains isolated from cattle carcasses in african countries where anthrax is endemic were tested for their cross-reactivity with monoclonal antibodies (mabs) specific for anthrose containing oligosaccharides. unexpectedly, none of the isolates collected in chad, cameroon and ma ...	2011	21571994
structure of the slh domains from bacillus anthracis surface array protein.	surface (s)-layers, para-crystalline arrays of protein, are deposited in the envelope of most bacterial species. these surface organelles are retained in the bacterial envelope through the non-covalent association of proteins with cell wall carbohydrates. bacillus anthracis, a gram-positive pathogen, produces s-layers of the protein sap, which uses three consecutive repeats of the surface-layer homology (slh) domain to engage secondary cell wall polysaccharides (scwp). using x-ray crystallograph ...	2011	21572039
gsk-3 activation is important for anthrax edema toxin induced dendritic cell maturation and antxr2 expression in macrophages.	anthrax edema toxin (et) is one of two binary toxins produced by bacillus anthracis that contributes to the virulence of this pathogen. et is an adenylate cyclase that generates high levels of camp causing alterations in multiple host-cell signaling pathways. we previously demonstrated that et increases cell surface expression of the anthrax toxin receptors (antxr) in monocyte-derived cells and promotes dendritic cell (dc) migration towards the lymph node homing chemokine mip-3β. in this work we ...	2011	21576335
bacillus cereus g9241 makes anthrax toxin and capsule like highly virulent b. anthracis ames but behaves like attenuated toxigenic nonencapsulated b. anthracis sterne in rabbits and mice.	bacillus cereus g9241 was isolated from a welder with a pulmonary anthrax-like illness. the organism contains two megaplasmids, pbcxo1 and pbc218. these plasmids are analogous to the b. anthracis ames plasmids pxo1 and pxo2 that encode anthrax toxins and capsule, respectively. here we evaluated the virulence of b. cereus g9241 as well as the contributions of pbcxo1 and pbc218 to virulence. b. cereus g9241 was avirulent in new zealand rabbits after subcutaneous inoculation and attenuated 100-fold ...	2011	21576337
[the development and testing of a molecular biological test system for dna detection of anthrax pathogen by real-time polymerase chain reaction assay].	the paper presents the results of the development and testing of a molecular biological test system for dna detection of anthrax pathogen (bacillus anthracis) by real-time polymerase chain reaction assay. the test system has shown high sensitivity, specificity, and reproducibility of results of analysis, as exemplified by aqueous suspensions of daily agar cultures of bacillus anthracis strains, related and heterologous species of microorganisms, and clinical materials of experimental animals. th ...	2011	21584969
the slh-domain protein bslo is a determinant of bacillus anthracis chain length.	the gram-positive pathogen bacillus anthracis grows in characteristic chains of individual, rod-shaped cells. here, we report the cell-separating activity of bslo, a putative n-acetylglucosaminidase bearing three n-terminal s-layer homology (slh) domains for association with the secondary cell wall polysaccharide (scwp). mutants with an insertional lesion in the bslo gene exhibit exaggerated chain lengths, although individual cell dimensions are unchanged. purified bslo complements this phenotyp ...	2011	21585566
structural analysis of a putative aminoglycoside n-acetyltransferase from bacillus anthracis.	for the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. the most popular are antibiotics such as tetracyclines and fluoroquinolones. while aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax ...	2011	21601576
mutually exclusive distribution of the sap and eag s-layer genes and the lytb/lyta cell wall hydrolase genes in bacillus thuringiensis.	recently, two bacillus thuringiensis strains were reported to synthesize parasporal inclusion bodies made not of the expected crystal (cry) proteins but rather of the surface layer proteins (slp) sap (encoded by sap) and ea1 (encoded by eag), respectively. whether the presence of the sap and eag genes is restricted to these two b. thuringiensis strains or ubiquitous in b. thuringiensis is unknown. we report here the distribution of the sap and eag genes in b. thuringiensis. strains in the bacill ...	2011	21611767
negatively charged liposomes show potent adjuvant activity when simply admixed with protein antigens.	liposomes have been investigated extensively as a vaccine delivery system. herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (ova, pi = 4.7), bacillus anthracis protective antigen protein (pa, pi = 5.6), or cationized ova (cova). mice immunized subcutaneously with ova admixed with different liposomes generated different antibody responses. interestingly, ova admixed with net ...	2011	21615153
anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling.	exposure to anthrax causes life-threatening disease through the action of the toxin produced by the bacillus anthracis bacteria. lethal factor (lf), an anthrax toxin component which causes severe vascular leak and edema, is a protease which specifically degrades map kinase kinases (mkk). we have recently shown that p38 map kinase activation leading to hsp27 phosphorylation augments the endothelial permeability barrier. we now show that treatment of rat pulmonary microvascular endothelial cells ( ...	2011	21618534
reference genes for quantitative, reverse-transcription pcr in bacillus cereus group strains throughout the bacterial life cycle.	quantitative reverse-transcription pcr (rt-qpcr) has become a major tool to better understand the biology and pathogenesis of bacteria. one prerequisite of valid rt-qpcr data is their proper normalization to stably expressed reference genes. to identify and evaluate reference genes suitable for normalization of gene expression data in bacillus cereus group strains, mrna levels of eleven candidate reference genes (rpsu, nifu, udp (udp-n-acetylglucosamine 2-epimerase), bt9727_5154/bc_5475, bt9727_ ...	2011	21620905
assembly of minicellulosomes on the surface of bacillus subtilis.	to cost-efficiently produce biofuels new methods are needed to convert lignocellulosic biomass into fermentable sugars. one promising approach is to degrade biomass using cellulosomes, which are surface displayed multi-cellulase containing complexes present in cellulolytic clostridium and ruminococcus species. in this study we created cellulolytic strains of b. subtilis that display one or more cellulase enzymes. proteins containing the appropriate cell wall sorting signal are covalently anchore ...	2011	21622797
clostridial binary toxins: iota and c2 family portraits.	there are many pathogenic clostridium species with diverse virulence factors that include protein toxins. some of these bacteria, such as c. botulinum, c. difficile, c. perfringens, and c. spiroforme, cause enteric problems in animals as well as humans. these often fatal diseases can partly be attributed to binary protein toxins that follow a classic ab paradigm. within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-adp-ribosylation of globular actin by the a c ...	2011	22919577
rapid field detection assays for bacillus anthracis, brucella spp., francisella tularensis and yersinia pestis.	rapid detection is essential for timely initiation of medical post-exposure prophylactic measures in the event of intentional release of biological threat agents. we compared real-time pcr assay performance between the applied biosystems 7300/7500 and the razor instruments for specific detection of the causative agents of anthrax, brucellosis, tularemia and plague. furthermore, an assay detecting bacillus thuringiensis, a bacillus anthracis surrogate, was developed for field-training purposes. a ...	2011	20132255
inter-α inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection.	human inter-α inhibitor proteins are endogenous human plasma proteins that function as serine protease inhibitors. inter-α inhibitor proteins can block the systemic release of proteases in sepsis and block furin-mediated assembly of protective antigen, an essential stop in the intracellular delivery of the anthrax exotoxins, lethal toxin and edema toxin. inter-α inhibitor proteins administered on hour or up to 24 h after spore challenge with bacillus anthracis sterne strain protected mice from l ...	2011	20523269
the surgical management of injectional anthrax.		2011	20615773
characterizing the native codon usages of a genome: an axis projection approach.	codon usage can provide insights into the nature of the genes in a genome. genes that are "native" to a genome (have not been recently acquired by horizontal transfer) range in codon usage from a low-bias "typical" usage to a more biased "high-expression" usage characteristic of genes encoding abundant proteins. genes that differ from these native codon usages are candidates for foreign genes that have been recently acquired by horizontal gene transfer. in this study, we present a method for cha ...	2011	20679093
characterization of an environmental strain of bacillus thuringiensis from a hot spring in western himalayas.	bacillus anthracis, the etiological agent of anthrax, is responsible for a serious and often fatal disease of mammalian livestock and humans and is an important biological warfare agent. bacillus sp. akg was isolated from a hot spring in western himalayas and species-specific primers targeting gyrb gene identified the strain as b. anthracis within cereus-group. cloning, sequencing, and phylogenetic analysis of the partial gyrb sequence from strain akg indicated a close affiliation with b. anthra ...	2011	20737272
[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
are we prepared for emerging and re-emerging diseases? experience and lessons from epidemics that occurred in tanzania during the last five decades.	this paper reviews preparedness for containing and controlling emerging and re-emerging diseases drawing lessons from disease events that occurred in animal and human populations in the last five decades (1961-2011). a comprehensive analysis based on retrieval and analysis of grey and published literature as well as reported cases was carried out to document type and trend of occurrence of emerging and re-emerging infectious diseases in different parts of tanzania. overall, the majority of disea ...	2011	26591993
anthrax: an update.	anthrax is a zoonotic disease caused by bacillus anthracis. it is potentially fatal and highly contagious disease. herbivores are the natural host. human acquire the disease incidentally by contact with infected animal or animal products. in the 18th century an epidemic destroyed approximately half of the sheep in europe. in 1900 human inhalational anthrax occured sporadically in the united states. in 1979 an outbreak of human anthrax occured in sverdlovsk of soviet union. anthrax continued to r ...	2011	23569822
real-time loop-mediated isothermal amplification assay for rapid and sensitive detection of anthrax spores in spiked soil and talcum powder.	loop-mediated isothermal amplification (lamp) assay is a powerful and innovative gene amplification technique that specifically amplifies the target gene under isothermal conditions with a high degree of sensitivity, rapidity and specificity. the major advantage of the lamp assay is monitoring of amplified products without the requirement of any sophisticated equipment. in the present study a real time lamp assay was employed for rapid and real time detection of bacillus anthracis spores spiked ...	2011	25187140
antibacterial and cytotoxic activities of terminalia stenostachya and terminalia spinosa.	plants that belong to the combretaceae family have long history of use in the traditional medicine systems of africa and asia for treatment of diseases and conditions associated with hiv/aids-opportunistic infections. the objective of this study was to investigate the biological activities of extracts of terminalia stenostachya engl. & diels and terminalia spinosa engl. (combretaceae), to verify the rationale for their use by traditional health practitioners in the treatment of hiv/aids patients ...	2011	25566609
swelling of face. cutaneous anthrax.		2011	23022827
incorporating retrospective clustering into a prospective cusum methodology for anthrax: evaluating the effects of disease expectation.	we analysed livestock anthrax in kazakhstan from 1960-2006, using a prospective cusum to examine the affects of expectation on the detection of spatio-temporal clusters. three methods for deriving baselines were used for cusum; a standard z-score, avg, a spatially-weighted z-score derived from local moran's i, lisa, and a moving-window average, mwa. lisa and avg elicited alarm signals in the second year that did not return below threshold during the 47-year period, while mwa signaled an alarm at ...	2011	22749547
pathogens: a new open access journal serving all those interested in infectious disease.	infection ranks alongside cardiovascular disease as the major cause of human death across the world. word health organization data for 2002 shows that 26% of all deaths, almost 15 million in number, were due to infectious disease with hiv/aids, tb and malaria being the top three responsible infections. a significant proportion of these deaths were due to lower respiratory infections and diarrheal diseases in children. the worldwide morbidity associated with infectious disease is incalculable. wh ...	2011	25436600
the emilin/multimerin family.	elastin microfibrillar interface proteins (emilins) and multimerins (emilin1, emilin2, multimerin1, and multimerin2) constitute a four member family that in addition to the shared c-terminus gc1q domain typical of the gc1q/tnf superfamily members contain a n-terminus unique cysteine-rich emi domain. these glycoproteins are homotrimeric and assemble into high molecular weight multimers. they are predominantly expressed in the extracellular matrix and contribute to several cellular functions in pa ...	2011	22566882
exploiting human memory b cell heterogeneity for improved vaccine efficacy.	the major goal in vaccination is establishment of long-term, prophylactic humoral memory to a pathogen. two major components to long-lived humoral memory are plasma cells for the production of specific immunoglobulin and memory b cells that survey for their specific antigen in the periphery for later affinity maturation, proliferation, and differentiation. the study of human b cell memory has been aided by the discovery of a general marker for b cell memory, expression of cd27; however, new data ...	2011	22566866
[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
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
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