| use of high-resolution melting and melting temperature-shift assays for specific detection and identification of bacillus anthracis based on single nucleotide discrimination. | single nucleotide polymorphisms (snps) are important diagnostic markers for the detection and differentiation of bacillus anthracis. high-resolution melting (hrm) and melting temperature (tm)-shift methods are two approaches that enable snp detection without the need for expensive labeled probes. we evaluated the potential diagnostic capability of those methods to discriminate b. anthracis from the other members of the b. cereus group. two assays targeting b. anthracis-specific snps in the plcr ... | 2011 | 21906635 |
| a is for anthrax. | | 2011 | 22003137 |
| bacillus anthracis lethal toxin alters regulation of visceral sympathetic nerve discharge. | bacillus anthracis infection is a pathophysiological condition that is complicated by progressive decreases in mean arterial pressure (map). lethal toxin (letx) is central to the pathogenesis of b. anthracis infection and the sympathetic nervous system plays a critical role in physiological regulation to acute stressors. however, the effect of letx on sympathetic nerve discharge (snd), a critical link between central sympathetic neural circuits and map regulation, remains unknown. we determined ... | 2011 | 22114180 |
| methylation-dependent dna restriction in bacillus anthracis. | bacillus anthracis, the causative agent of anthrax, is poorly transformed with dna that is methylated on adenine or cytosine. here we characterize three genetic loci encoding type iv methylation-dependent restriction enzymes that target dna containing c5-methylcytosine (m5c). strains in which these genes were inactivated, either singly or collectively, showed increased transformation by methylated dna. additionally, a triple mutant with an ~30-kb genomic deletion could be transformed by dna obta ... | 2011 | 22178763 |
| Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis. | Bacterial lipoproteins play a crucial role in virulence in some Gram-positive bacteria. However, the role of lipoprotein biosynthesis in Bacillus anthracis is unknown. We created a B. anthracis mutant strain altered in lipoproteins by deleting the lgt gene encoding the enzyme prolipoprotein diacylglyceryl transferase, which attaches the lipid anchor to prolipoproteins. (14) C-palmitate labelling confirmed that the mutant strain lacked lipoproteins, and hydrocarbon partitioning showed it to have ... | 2012 | 22103323 |
| Structure-based redesign of an edema toxin inhibitor. | Edema factor (EF) toxin of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3',5'-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an ... | 2012 | 22154558 |
| occurrence, recognition, and reversion of spontaneous, sporulation-deficient bacillus anthracis mutants that arise during laboratory culture. | bacillus anthracis is a spore-forming, soil-dwelling bacterium. this review describes the occurrence of spontaneous mutations leading to loss of sporulation and the selective pressures that can lead to their enrichment. we also discuss recognition of the associated phenotypes on solid medium, thereby allowing researchers to employ measures that either prevent or favor selection of sporulation-deficient mutants. | 2011 | 22166343 |
| t cell targeting by anthrax toxins: two faces of the same coin. | bacillus anthracis, similar to other bacterial pathogens, has evolved effective immune evasion strategies to prolong its survival in the host, thus ensuring the unchecked spread of the infection. this function is subserved by lethal (lt) and edema (et) toxins, two exotoxins produced by vegetative anthrax bacilli following germination of the spores. the structure of these toxins and the mechanism of cell intoxication are topics covered by other reviews in this issue. here we shall discuss how b. ... | 2011 | 22069732 |
| ten years on from anthrax scare, analysis lags behind sequencing. | | 2011 | 21988965 |
| the munich outbreak of cutaneous cowpox infection: transmission by infected pet rats. | cowpox virus infection of humans is an uncommon, potentially fatal, skin disease. it is largely confined to europe, but is not found in eire, or in the usa, australasia, or the middle or far east. patients having contact with infected cows, cats, or small rodents sporadically contract the disease from these animals. we report here clinical aspects of 8 patients from the munich area who had purchased infected pet rats from a local supplier. pet rats are a novel potential source of local outbreaks ... | 2011 | 22041995 |
| Detection of anthrax lef with DNA-based photonic crystal sensors. | Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. ... | 2011 | 22191936 |
| glycoconjugates prevent b. anthracis toxin-induced cell death through binding while activating macrophages. | bacillus anthracis toxins may be attenuated if macrophages could neutralize toxins upon contact or exposure. glycoconjugate-bearing polymers, which have been shown to bind to bacillus spores, were tested for recognition and binding of protective antigen (pa), lethal factor (lf), and edema factor (ef) toxins. we have demonstrated modulation of macrophage activity following exposure to these toxins. without glycoconjugate (gc) activation, murine macrophages were killed by bacillus toxins. gcs were ... | 2011 | 22134879 |
| Interagency Biological Restoration Demonstration (IBRD): a collaborative approach to biological incident recovery. | Following the terrorist attacks in 2001, much time and effort has been put toward improving catastrophic incident response. But recovery--the period following initial response that focuses on the long-term viability of the affected area--has received less attention. Recognizing the importance of being able to recover an area following a catastrophic incident, the Department of Defense, through its Defense Threat Reduction Agency (DTRA), and the Department of Homeland Security, through its Scienc ... | 2011 | 21882966 |
| Developing a regional recovery framework. | A biological attack would present an unprecedented challenge for local, state, and federal agencies, the military, the private sector, and individuals on many fronts, ranging from vaccination and treatment to prioritization of cleanup actions to waste disposal. To prepare for recovery from this type of incident, the Seattle Urban Area Security Initiative (UASI) partners collaborated with military and federal agencies to develop a regional recovery framework. The goal was to identify key informat ... | 2011 | 21882969 |
| S-layer homology motif is an immunogen and confers protection to mouse model against anthrax. | SLH proteins bear an S-layer homology motif comprised of three S-layer homology (SLH) domains. Several SLH proteins in Bacillus anthracis have been recognized as immunogenic in recent past. We hypothesized that the SLH motif, the most common moiety amongst all the SLH proteins could be responsible for their immunogenicity. To test this hypothesis, we checked the immunogenic capacity of recombinant SLH motif. The rSLH fragment on immunization in mice led to the development of a potent humoral and ... | 2011 | 22178119 |
| a novel splice site mutation in antxr2 (cmg2) gene results in systemic hyalinosis. | systemic hyalinosis is a rare autosomal recessive inheritance disease characterized by accumulation of amorphous, unidentified hyaline material in skin and other organs, which leads to papulonodular skin lesions, gingival hypertrophy, flexion contractures of the joints, and large subcutaneous tumors. it is composed of 2 allelic syndromes, infantile systemic hyalinosis and juvenile hyaline fibromatosis. here we describe a patient with juvenile hyaline fibromatosis confirmed by clinical and histop ... | 2011 | 22042284 |
| Adverse health consequences of US Government responses to the 2001 terrorist attacks. | In response to the attacks on Sept 11, 2001 (9/11), and the related security concerns, the USA and its coalition partners began a war in Afghanistan and subsequently invaded Iraq. The wars caused many deaths of non-combatant civilians, further damaged the health-supporting infrastructure and the environment (already adversely affected by previous wars), forced many people to migrate, led to violations of human rights, and diverted resources away from important health needs. After 9/11 and the an ... | 2011 | 21890059 |
| AOAC SMPR 2010.004. Standard method performance requirements for immunological-based handheld assays (HHAs) for detection of Bacillus anthracis spores in visible powders. | | 2011 | 21919368 |
| Association of the ANTXR2 gene polymorphism and ankylosing spondylitis in Chinese Han. | Objective: Ankylosing spondylitis (AS) is an inflammatory disease of unknown origin. Both genetic and environmental factors are involved. A recent genome-wide association study (GWAS) found anthrax toxin receptor 2 (ANTXR2) to be associated with AS in Caucasians. We aimed to investigate whether the ANTXR2 polymorphism is also associated with AS in a Chinese Shandong Han population. Methods: From 2008 to 2009, we recruited 309 patients with AS and 384 age- and sex-matched controls of Han nation ... | 2011 | 22118297 |
| Thawing of permafrost may disturb historic cattle burial grounds in East Siberia. | Climate warming in the Arctic may increase the risk of zoonoses due to expansion of vector habitats, improved chances of vector survival during winter, and permafrost degradation. Monitoring of soil temperatures at Siberian cryology control stations since 1970 showed correlations between air temperatures and the depth of permafrost layer that thawed during summer season. Between 1900s and 1980s, the temperature of surface layer of permafrost increased by 2-4°C; and a further increase of 3°C is e ... | 2011 | 22114567 |
| [Preparation and characterization of monoclonal antibodies to Bacillus anthracis protective antigen]. | Anthrax is the widespread acute infection disease, affecting animals and humans, refers to the bioterrorist threat agents of category A, because of the high resistance of Bacillus anthracis spores to adverse environmental factors and the ease of receiving them. We obtain a representative panel of 20 monoclonal antibodies against the key component of pathogenic exotoxins, anthrax protective antigen. Quantitative sandwich-ELISA for protective antigen with antibody obtained was developed. Six pairs ... | 2011 | 21899050 |
| Application of nanoparticles for the detection and sorting of pathogenic bacteria by flow-cytometry. | In this paper we will describe a new developed contribution of fluorescence nano-crystal (q-dots) as a fluorescence label for detecting pathogenic bacteria by flow cytometry (FCM) and the use of nano-magnetic particles to improve bacterial sorting by Flow cytometry cell sorting (FACS).FCM or FACS systems are based upon single cell detection by light scatter and Immunofluorescence labeling signals. The common FACS systems are based upon single or dual excitation as excitation source both for ligh ... | 2012 | 22101709 |
| bioterror research. panel endorses anthrax vaccine study in children. | | 2011 | 22053016 |
| Anthrax edema toxin impairs protein clearance in mice. | Anthrax edema toxin (ET) of Bacillus anthracis is composed of the receptor-binding component protective antigen (PA) and of the adenylyl cyclase catalytic moiety, edema factor (EF). Uptake of ET into cells raises intracellular concentrations of the secondary messenger cAMP, thereby impairing or activating host cell functions. We report here on a new consequence of ET action in vivo. We show that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the pr ... | 2011 | 22104108 |
| anthrax lethal and edema toxins fail to directly impair human platelet function. | hemorrhage is a prominent clinical manifestation of systemic anthrax. therefore, we have examined the effects of anthrax lethal and edema toxins on human platelets. we find that anthrax lethal toxin fails to cleave its target, mitogen-activated protein kinase 1, and anthrax edema toxin fails to increase intracellular cyclic adenosine monophosphate. surface expression of toxin receptors tumor endothelial marker 8 and capillary morphogenesis gene 2, as well as coreceptor low density lipoprotein re ... | 2011 | 22158563 |
| comparative analysis of the responses of related pathogenic and environmental bacteria to oxidative stress. | bacillus anthracis, the causative agent of anthrax, is exposed to host-mediated antibacterial activities, such as reactive oxygen species (ros), during the early stages of its disease process. the ability to resist these host-mediated insults is an essential characteristic of a successful pathogen while it is generally assumed that non-pathogenic environmental bacteria succumb to these antimicrobial activities. in order to gain insights into the underlying mechanisms that pathogens use to resist ... | 2011 | 22174384 |
| regulation of anthrax toxin-specific antibody titers by natural killer t cell-derived il-4 and ifnγ. | activation of natural killer-like t cells (nkt) with the cd1d ligand α-gc leads to enhanced production of anthrax toxin protective ag (pa)-neutralizing abs, yet the underlying mechanism for this adjuvant effect is not known. in the current study we examined the role of th1 and th2 type responses in nkt-mediated enhancement of antibody responses to pa. first, the contribution of il-4 and ifnγ to the production of pa-specific toxin-neutralizing abs was examined. by immunizing c57bl/6 controls il-4 ... | 2011 | 21858226 |
| A chelating-bond breaking and re-linking technique for rapid re-immobilization of immune micro-sensors. | With high sensitivity and specificity to antigen, immune micro-sensors can be used in rapid detection of pathogenic microbial. This study proposes and develops a method for rapidly regeneration of antibody on a resonant micro-cantilever sensor. A nitrilotriacetic acid (NTA) derivative is synthesized with cystine and bromoacetic acid, then added with 2-mercaptoethanol to prepare a mixed self-assembled monolayer (SAM) on Au (111) surface of the cantilever. Ni(2+) ions are thereafter chelated on th ... | 2011 | 22048777 |
| Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys. | Bacillus anthracis, the causative agent of anthrax, is recognized as one of the most serious bioterrorism threats. The current human vaccines are based on the protective antigen component of the anthrax toxins. Concern about possible vaccine resistant strains and reliance on a single antigen has prompted the search for additional immunogens. Bacterial capsules, as surface-expressed virulence factors, are well-established components of several licensed vaccines. In a previous study we showed that ... | 2011 | 22172509 |
| optimizing acidified bleach solutions to improve sporicidal efficacy on building materials. | we evaluated whether lowering ph (with acetic acid) and raising free available chlorine (fac) levels in bleach solutions would improve efficacy in inactivating bacillus spores on different materials. we also determined how varying ph and fac levels affected bleach stability. | 2011 | 21981715 |
| Optical microchip array biosensor for multiplexed detection of bio-hazardous agents. | An optical waveguide array biosensor suitable for rapid detection of multiple bio-hazardous agents is presented. SpectroSens™ optical microchip sensors contain multiple spatially-separated waveguide channels with integral high-precision Bragg gratings sensitive to changes in refractive-index; selective surface-functionalisation of discrete sensing channels with different antibodies as bio-recognition elements enables selective multi-analyte biological detection. Interactions between target antig ... | 2011 | 21944924 |
| Use of microwells to investigate the effect of quorum sensing on growth and antigen production in Bacillus anthracis Sterne 34F2. | The aim of this study was to investigate the role of quorum sensing in Bacillus anthracis growth and toxin production. | 2011 | 21895896 |
| mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process. | research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (c), transmembrane (t), and receptor binding (r) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the ph triggered conformational changes required for pore ... | 2011 | 22069710 |
| probing biomolecular interaction forces using an anharmonic acoustic technique for selective detection of bacterial spores. | receptor-based detection of pathogens often suffers from non-specific interactions, and as most detection techniques cannot distinguish between affinities of interactions, false positive responses remain a plaguing reality. here, we report an anharmonic acoustic based method of detection that addresses the inherent weakness of current ligand dependant assays. spores of bacillus subtilis (bacillus anthracis simulant) were immobilized on a thickness-shear mode at-cut quartz crystal functionalized ... | 2011 | 21900001 |
| botulinum toxin: therapeutic agent to cosmetic enhancement to lethal biothreat. | the clinical effects of clostridium botulinum and its extremely potent neurotoxin have been known for two centuries. the disease threat and the clinical uses are now well established. what's changed is the potential for botulinum neurotoxin to be used as a biological threat agent. the recent upsurge of illegal trafficking of reagent-grade toxin could, if bought in large enough quantities, be as serious a threat as other biothreat agents such as anthrax and smallpox, which have received much more ... | 2011 | 22178572 |
| Natural biopolymer for preservation of microorganisms during sampling and storage. | Stability of microbial cultures during sampling and storage is a vital issue in various fields of medicine, biotechnology, food science, and forensics. We have developed a unique bacterial preservation process involving a non-toxic, water-soluble acacia gum polymer that eliminates the need for refrigerated storage of samples. The main goal of this study is to characterize the efficacy of acacia gum polymer for preservation of pathogenic bacteria (Bacillus anthracis and methicillin-resistant Stap ... | 2012 | 22093998 |
| anthrax lethal toxin-induced gene expression changes in mouse lung. | a major virulence factor of bacillus anthracis is the anthrax lethal toxin (letx), a bipartite toxin composed of protective antigen and lethal factor. systemic administration of letx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. in this study, we investigated whether systemic exposure of mice to letx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. we observed enhanced susceptibility of a/j mice to death ... | 2011 | 22039574 |
| Development of a hyena immunology toolbox. | Animals that hunt and scavenge are often exposed to a broad array of pathogens. Theory predicts the immune systems of animals specialized for scavenging should have been molded by selective pressures associated with surviving microbial assaults from their food. Spotted hyenas (Crocuta crocuta) are capable hunters that have recently descended from carrion feeding ancestors. Hyenas have been documented to survive anthrax and rabies infections, and outbreaks of several other viral diseases that dec ... | 2011 | 22173276 |
| cross-reactivity of anthrax and c2 toxin: protective antigen promotes the uptake of botulinum c2i toxin into human endothelial cells. | binary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibit fatal enzymatic activities in eukaryotic cells. anthrax and c2 toxin are the most prominent examples for the ab(7/8) type of toxins. the b subunits bind both host cell receptors and the enzymatic a polypeptides to trigger their internalization and translocation into the host cell cytosol. c2 toxin is composed of an actin adp-ribosyltransferase (c2i) and c2ii binding subunit ... | 2011 | 21850257 |
| bacillus anthracis virulence regulator atxa: oligomeric state, function and co(2) -signalling. | atxa, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of bacillus anthracis. the 475 amino acid sequence of atxa reveals dna binding motifs and regions similar to proteins associated with the phosphoenolpyruvate: carbohydrate phosphotransferase system (pts). we used strains producing native and functional epitope-tagged atxa proteins to examine protein-protein interactions in cell lysates and in solutions of purified protein. ... | 2011 | 21923765 |
| Web interface for brownian dynamics simulation of ion transport and its applications to beta-barrel pores. | Brownian dynamics (BD) based on accurate potential of mean force is an efficient and accurate method for simulating ion transport through wide ion channels. Here, a web-based graphical user interface (GUI) is presented for carrying out grand canonical Monte Carlo (GCMC) BD simulations of channel proteins: http://www.charmm-gui.org/input/gcmcbd. The webserver is designed to help users avoid most of the technical difficulties and issues encountered in setting up and simulating complex pore systems ... | 2012 | 22102176 |
| an in vitro survey on the apoptotic effects of uvb ray in bacillus anthracis. | objectives: bacillus anthracis as the bacterial agent of anthrax, is spread in different geographical zones around the world.the purpose of this survey was to observe eventual apoptotic reactions in total genomic dna of uvb irradiated colonies of bacillus anthracis.materials and methods: the colonies of bacillus anthracis were exposed to uvb ray for 10 minutes; then, the dna molecules of control and irradiated colonies were extracted. finally, the dna samples mixed in loading dye, were run in 1% ... | 2011 | 21977187 |
| impact of spores on the comparative efficacies of five antibiotics for the treatment of bacillus anthracis in an in vitro hollow fiber pharmacodynamic model. | background: bacillus anthracis (ba), the bacterium that causes anthrax, is an agent of bioterrorism. the most effective antimicrobial therapy for ba infections is unknown. methods: an in vitro pharmacodynamic model of ba was used to compare the efficacies of simulated clinically-prescribed regimens of moxifloxacin, linezolid, and meropenem with the "gold standards," doxycycline and ciprofloxacin. treatment outcomes for isogenic spore-forming and non-spore-forming strains of ba were compared. res ... | 2011 | 22155821 |
| consequences and utility of the zinc-dependent metalloprotease activity of anthrax lethal toxin. | anthrax is caused by the gram-positive bacterium bacillus anthracis. the pathogenesis of this disease is dependent on the presence of two binary toxins, edema toxin (edtx) and lethal toxin (letx). letx, the major virulence factor contributing to anthrax, contains the effector moiety lethal factor (lf), a zinc-dependent metalloprotease specific for targeting mitogen-activated protein kinase kinases. this review will focus on the protease-specific activity and function of lf, and will include a di ... | 2010 | 22069624 |
| A Review of Zoonotic Disease Surveillance Supported by the Armed Forces Health Surveillance Center. | The Armed Forces Health Surveillance Center (AFHSC), Division of Global Emerging Infections Surveillance and Response System conducts disease surveillance through a global network of US Department of Defense research laboratories and partnerships with foreign ministries of agriculture, health and livestock development in over 90 countries worldwide. In 2010, AFHSC supported zoonosis survey efforts were organized into four main categories: (i) development of field assays for animal disease survei ... | 2011 | 22128834 |
| The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits. | Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T ... | 2012 | 22020310 |
| Domain flexibility modulates the heterogeneous assembly mechanism of anthrax toxin protective antigen. | The three protein components of anthrax toxin are nontoxic individually, but they form active holotoxin complexes upon assembly. The role of the protective antigen (PA) component of the toxin is to deliver two other enzyme components, lethal factor and edema factor, across the plasma membrane and into the cytoplasm of target cells. PA is produced as a proprotein, which must be proteolytically activated; generally, cell surface activation is mediated by a furin family protease. Activated PA can t ... | 2012 | 22063095 |
| The anthrax attacks 10 years later. | Ten years ago, just weeks after the September 11 attacks, the United States experienced a deliberate act of bioterrorism. Through use of the postal service, anthrax spores were widely disseminated, including to homes, the Senate, and major newsrooms, resulting in morbidity and mortality and effectively disrupting our way of life and revealing our vulnerability. Even though such attacks had been the subject of much writing and had been planned for, detection of and the appropriate response to an ... | 2011 | 21969275 |
| Two cases of infection with Bacillus anthracis, Romania, October 2011. | A cluster of two confirmed cases of anthrax were reported in October 2011 from a small village with a population of 3,400 people, in south-eastern Romania.One was a fatal case of cutaneous and anthrax meningoencephalitis, while the other had cutaneous anthrax. Both cases had been exposed to one Bacillus anthracis-infected cow via consumption of its meat or being involved in its slaughter. | 2011 | 22114977 |
| bioterrorism: preparing the plastic surgeon. | introduction: many medical disciplines, such as emergency medicine, trauma surgery, dermatology, psychiatry, family practice, and dentistry have documented attempts at assessing the level of bioterrorism preparedness in their communities. currently, there is neither such an assessment nor an existing review of potential bioterrorism agents as they relate to plastic surgery. therefore, the purpose of this article is to present plastic surgeons with a review of potential bioterrorism agents. metho ... | 2011 | 22132252 |
| epidemic intelligence service investigations of respiratory illness, 1946-2005. | infectious respiratory pathogens were the suspected cause of 480 outbreaks investigated by the centers for disease control and prevention's epidemic intelligence service officers during 1946-2005. all epidemic-assistance investigation reports and associated articles from scientific journals were reviewed. investigations identified 25 different infectious respiratory pathogens including, most frequently, tuberculosis, influenza, and legionellosis. other bacterial-, viral-, and fungal-related path ... | 2011 | 22135392 |
| Hemodynamic effects of anthrax toxins in the rabbit model and the cardiac pathology induced by lethal toxin. | Anthrax lethal toxin (LeTx) and edema toxin (EdTx) have been shown to alter hemodynamics in the rodent model, while LeTx primarily is reported to induce extensive tissue pathology. However, the rodent model has limitations when used for comparison to higher organisms such as humans. The rabbit model, on the other hand, has gained recognition as a useful model for studying anthrax infection and its pathophysiological effects. In this study, we assessed the hemodynamic effects of lethal toxin (LeT ... | 2011 | 22069736 |
| microchip capillary electrophoresis of multi-locus vntr analysis for genotyping of bacillus anthracis and yersinia pestis in microbial forensic cases. | bacillus anthracis and yersinia pestis are etiological agents of anthrax and plague respectively, and are also considered among the most feared potential bioterrorism agents. these microorganisms show intraspecies genome homogeneity, making strains differentiation difficult, while strains identification and comparison with known genotypes may be crucial for naturally occurring outbreaks vs. bioterrorist events discrimination.here an mlva application for b. anthracis and y. pestis strains differe ... | 2012 | 22139674 |
| Bioterrorism: lessons learned since the anthrax mailings. | In the fall of 2001, Bacillus anthracis spores were spread through letters mailed in the United States. Twenty-two people are known to have been infected, and five of these individuals died. Together with the September 11 attacks, this resulted in a reevaluation of the risks and benefits of life science research with the potential for misuse. In this editorial, we review some of the results of these discussions and their implications for the future. | 2011 | 22027008 |
| Sensitive detection of Bacillus anthracis spores by immunocapture and liquid chromatography-tandem mass spectrometry. | Bacillus anthracis is one of the most dangerous agents of the bioterrorism threat. We present here a sensitive immuno-liquid chromatography-tandem mass spectrometry (immuno-LC-MS/MS) approach to spore detection in complex environmental samples. It is based on the combined specificity and sensitivity of two techniques: immunocapture and targeted mass spectrometry. The immunocapture step, realized directly on the intact spores, is essential for their selective isolation and concentration from com ... | 2011 | 21961787 |
| Transient co-expression of post-transcriptional gene silencing suppressors for increased in planta expression of a recombinant anthrax receptor fusion protein. | Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, de ... | 2011 | 21954339 |
| supercharging protein complexes from aqueous solution disrupts their native conformations. | the effects of aqueous solution supercharging on the solution- and gas-phase structures of two protein complexes were investigated using traveling-wave ion mobility-mass spectrometry (twims-ms). low initial concentrations of m-nitrobenzyl alcohol (m-nba) in the electrospray ionization (esi) solution can effectively increase the charge of concanavalin a dimers and tetramers, but at higher m-nba concentrations, the increases in charge are accompanied by solution-phase dissociation of the dimers an ... | 2011 | 22161509 |
| Anthrax toxin protective antigen-Insights into molecular switching from prepore to pore. | The protective antigen is a key component of the anthrax toxin, as it allows entry of the enzymatic components edema factor and lethal factor into the host cell, through the formation of a membrane spanning pore. This event is absolutely critical for the pathogenesis of anthrax, and although we have yet to understand the mechanism of pore formation, recent developments have provided key insights into how this process may occur. Based on the available data, a model is proposed for the kinetic ste ... | 2012 | 22095644 |
| Fluorescent europium-modified polymer nanoparticles for rapid and sensitive anthrax sensors. | Novel fluorescent polyacrylonitrile nanoparticles were synthesized by microemulsion polymerization and Schiff base modification. By further modification with europium, the polyacrylonitrile nanoparticles could be used as a highly sensitive and rapid sensor for Bacillus anthracis spore detection in aqueous solution. The europium-modified polyacrylonitrile nanoparticles were readily combined with dipicolinic acid as a unique biomarker of B. anthracis, leading to high fluorescence emission. These n ... | 2011 | 21893406 |
| A Decade of Spore-Forming Bacterial Infections Among European Injecting Drug Users: Pronounced Regional Variation. | The recent anthrax outbreak among injecting drug users (IDUs) in Europe has highlighted an ongoing problem with severe illness resulting from spore-forming bacteria in IDUs. We collated the numbers of cases of 4 bacterial illnesses (botulism, tetanus, Clostridium novyi, and anthrax) in European IDUs for 2000 to 2009 and calculated population rates. Six countries reported 367 cases; rates varied from 0.03 to 7.54 per million people.Most cases (92%) were reported from 3 neighboring countries: Irel ... | 2011 | 22095355 |
| Optical and electrochemical responses of an anthrax biomarker based on single-walled carbon nanotubes covalently loaded with terbium complexes. | An effective single-walled carbon nanotube (SWNT) covalently loaded with unsaturated terbium emissive material was designed for specific and rapid (2-3 s) detection of calcium dipicolinate (CaDPA) (detection limit 1 µM). The nanoprobe was successfully assembled onto electrodes and its sensing abilities were investigated through electrochemical measurement. Cyclic voltammetry curves were selectively responsive to calcium dipicolinate compared with benzoic acid, o-phthalic acid and m-phthalic acid ... | 2011 | 22027893 |
| Development of artificial neural network based metamodels for inactivation of anthrax spores in ventilated spaces using computational fluid dynamics. | Linear, quadratic, and artificial neural network (ANN)-based metamodels were developed for predicting the extent of anthrax spore inactivation by chlorine dioxide in a ventilated three-dimensional space over time from computational fluid dynamics model (CFD) simulation data. Dimensionless groups were developed to define the design space of the problem scenario. The Hammersley sequence sampling (HSS) method was used to determine the sampling points for the numerical experiments within the design ... | 2011 | 22010381 |
| Structure determination and interception of biosynthetic intermediates for the plantazolicin class of highly discriminating antibiotics. | The soil-dwelling, plant growth-promoting bacterium Bacillus amyloliquefaciens FZB42 is a prolific producer of complex natural products. Recently, a new FZB42 metabolite, plantazolicin (PZN), has been described as a member of the growing thiazole/oxazole-modified microcin (TOMM) family. TOMMs are biosynthesized from inactive, ribosomal peptides and undergo a series of cyclodehydrations, dehydrogenations, and other modifications to become bioactive natural products. Using high-resolution mass spe ... | 2011 | 21950656 |
| Phase 1 Study of a Recombinant Mutant Protective Antigen of Bacillus anthracis. | A Phase 1 study of a recombinant mutant Protective Antigen (rPA) vaccine was conducted in 186 healthy adults aged 18 to 45 years. Volunteers were randomized to receive one of three formulations of rPA (formalin-treated, alum-adsorbed or both) in 10 or 20 µg dosages each, or the licensed vaccine, AVA. Three injections were given at 2 months intervals and a 4(th) one year after the third. Vaccinees were examined once at 48-72 hours following each injection at the clinic. Adverse reactions were rec ... | 2011 | 22190398 |
| inhibition of the adenylyl cyclase toxin, edema factor, from bacillus anthracis by a series of 18 mono- and bis-(m)ant-substituted nucleoside 5'-triphosphates. | bacillus anthracis causes anthrax disease and exerts its deleterious effects by the release of three exotoxins, i.e. lethal factor, protective antigen and edema factor (ef), a highly active calmodulin-dependent adenylyl cyclase (ac). conventional antibiotic treatment is ineffective against either toxaemia or antibiotic-resistant strains. thus, more effective drugs for anthrax treatment are needed. our previous studies showed that ef is differentially inhibited by various purine and pyrimidine nu ... | 2011 | 21947230 |
| A Receptor-based Switch that Regulates Anthrax Toxin Pore Formation. | Cellular receptors can act as molecular switches, regulating the sensitivity of microbial proteins to conformational changes that promote cellular entry. The activities of these receptor-based switches are only partially understood. In this paper, we sought to understand the mechanism that underlies the activity of the ANTXR2 anthrax toxin receptor-based switch that binds to domains 2 and 4 of the protective antigen (PA) toxin subunit. Receptor-binding restricts structural changes within the hep ... | 2011 | 22174672 |
| Characterization of Genetic Diversity of Bacillus anthracis in France by Using High-Resolution Melting Assays and Multilocus Variable-Number Tandem-Repeat Analysis. | Using high-resolution melting (HRM) analysis, we developed a cost-effective method to genotype a set of 13 phylogenetically informative single-nucleotide polymorphisms (SNPs) within the genome of Bacillus anthracis. SNP discrimination assays were performed in monoplex or duplex and applied to 100 B. anthracis isolates collected in France from 1953 to 2009 and a few reference strains. HRM provided a reliable and cheap alternative to subtype B. anthracis into one of the 12 major sublineages or sub ... | 2011 | 21998431 |
| membrane topology of the bacillus anthracis gerh germinant receptor proteins. | bacillus anthracis spores are the etiologic agent of anthrax. nutrient germinant receptors (ngrs) packaged within the inner membrane of the spore sense the presence of specific stimuli in the environment and trigger the process of germination, quickly returning the bacterium to the metabolically active, vegetative bacillus. this ability to sense the host environment and initiate germination is a required step in the infectious cycle. the ngrs are comprised of three subunits: the a-, b-, and c-ty ... | 2011 | 22178966 |
| mechanism of lethal toxin neutralization by a human monoclonal antibody specific for the pa(20) region of bacillus anthracis protective antigen. | the primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (pa) unit of the binary toxin system. pa-specific antibodies neutralize anthrax toxins and protect against infection. recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the pa monomer. the mechanisms by which ... | 2011 | 22069752 |
| rapid sample preparation method of bacillus spores in powdery and environmental matrices based on filtration separation. | suspicious powders and other samples need to be analyzed frequently for biothreat agents by authorities to assess environmental safety. numerous nucleic acid detection technologies have been developed to detect and identify biowarfare agents in a timely fashion. extracting microbial nucleic acids from a wide variety of powdery and environmental samples to obtain a quality level adequate for these technologies still remains a technical challenge. we aimed to develop a rapid and versatile method t ... | 2011 | 22210204 |
| ultrasensitive detection of protein translocated through toxin pores in droplet-interface bilayers. | many bacterial toxins form proteinaceous pores that facilitate the translocation of soluble effector proteins across cellular membranes. with anthrax toxin this process may be monitored in real time by electrophysiology, where fluctuations in ionic current through these pores inserted in model membranes are used to infer the translocation of individual protein molecules. however, detecting the minute quantities of translocated proteins has been a challenge. here, we describe use of the droplet-i ... | 2011 | 21949363 |
| A 45-year-old farmer with an ulcerative rash, shock, and hemorrhagic meningitis. | | 2011 | 22049028 |
| Reviewing the role of peptide rarity in bacterial toxin immunomics. | In the past decade, renewed efforts have been made toward the development of vaccines against cancers, infectious agents, autoimmune diseases, and allergies. These efforts have led to the accumulation of numerous peptide sequences experimentally validated as epitopes. However, the factors that render a peptide immunogenic and, more generally, the nature of the antigen-antibody recognition process remain unclear. Based on the hypothesis that potential epitopes correspond to rare sequences and/or ... | 2012 | 22202055 |
| An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics. | An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990. | 2011 | 21962024 |
| Antibodies against anthrax: mechanisms of action and clinical applications. | B. anthracis is a bioweapon of primary importance and its pathogenicity depends on its lethal and edema toxins, which belong to the A-B model of bacterial toxins, and on its capsule. These toxins are secreted early in the course of the anthrax disease and for this reason antibiotics must be administered early, in addition to other limitations. Antibodies (Abs) may however neutralize those toxins and target this capsule to improve anthrax treatment, and many Abs have been developed in that perspe ... | 2011 | 22174979 |
| a longitudinal study of uk military personnel offered anthrax vaccination: informed choice, symptom reporting, uptake and pre-vaccination health. | aim: to determine longer term health outcome in a cohort of uk service personnel who received the anthrax vaccination. method: we conducted a three year follow up of uk service personnel all of whom were in the armed forces at the start of the iraq war. 3206 had been offered the anthrax vaccination as part of preparations for the 2003 invasion of iraq. a further 1190 individuals who did not deploy to iraq in 2003 were subsequently offered the vaccination as part of later deployments, and in whom ... | 2011 | 22178523 |
| the role of bacillus anthracis recd2 helicase in dna mismatch repair. | dna mismatch repair (mmr) systems can be classified as either muth-dependent or muth-independent. in bacteria, extensive studies have been conducted with the muth-dependent mmr in escherichia coli and its close relatives. the picture of muth-independent mmr in other bacteria is less clear, as mmr components other than muts and mutl have not been identified in the majority of bacteria. bacillus anthracis is one of the muth-less gram(+) bacteria in the phylum of firmicutes. we used papillation as ... | 2011 | 21940221 |
| challenges in disposing of anthrax waste. | disasters often create large amounts of waste that must be managed as part of both immediate response and long-term recovery. while many federal, state, and local agencies have debris management plans, these plans often do not address chemical, biological, and radiological contamination. the interagency biological restoration demonstration's (ibrd) purpose was to holistically assess all aspects of an anthrax incident and assist in the development of a plan for long-term recovery. in the case of ... | 2011 | 21882972 |
| risk factors associated with anthrax in cattle on smallholdings. | summaryunprecedented high rates of anthrax outbreaks have been observed recently in cattle and humans in bangladesh, with 607 human cases in 2010. by enrolling 15 case and 15 control cattle smallholdings in the spatial zone in july-september 2010, we conducted a case-control study, data of which were analysed by matched-pair analysis and multivariable conditional logistic regression. feeding animals with uprooted and unwashed grass [odds ratio (or) 41·2, 95% confidence interval (ci) 3·7-458·8, p ... | 2011 | 22123521 |
| the effects of anthrax lethal toxin on host barrier function. | the pathological actions of anthrax toxin require the activities of its edema factor (ef) and lethal factor (lf) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (pa). lf is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (mkks), but its activity is not directly lethal to many types of primary and transformed cells in vitro. nevertheless, in vivo treatment of several animal species with the combin ... | 2011 | 22069727 |
| the bacillus anthracis arylamine n-acetyltransferase ((bacan)nat1) that inactivates sulfamethoxazole, reveals unusual structural features compared with the other nat isoenzymes. | arylamine n-acetyltransferases (nats) are xenobiotic-metabolizing enzymes that biotransform arylamine drugs. the bacillus anthracis (bacan)nat1 enzyme affords increased resistance to the antibiotic sulfamethoxazole through its acetylation. we report the structure of (bacan)nat1. unexpectedly, endogenous coenzymea was present in the active site. the structure suggests that, contrary to the other prokaryotic nats, (bacan)nat1 possesses a 14-residue insertion equivalent to the "mammalian insertion" ... | 2011 | 22062153 |
| anthrax and the inflammasome. | anthrax lethal toxin (lt), a major virulence determinant of anthrax disease, induces vascular collapse in mice and rats. lt activates the nlrp1 inflammasome in macrophages and dendritic cells, resulting in caspase-1 activation, il-1β and il-18 maturation and a rapid cell death (pyroptosis). this review presents the current understanding of lt-induced activation of nlrp1 in cells and its consequences for toxin-mediated effects in rodent toxin and spore challenge models. | 2011 | 22207185 |
| unusual epidemic events: a new method of early orientation and differentiation between natural and deliberate epidemics. | to develop a model for quick and accurate evaluation of unusual epidemic events (uee), based on the original model of bioterrorism risk assessment. | 2012 | 22136700 |
| differential role of the interleukin-17 axis and neutrophils in resolution of inhalational anthrax. | the roles of interleukin-17 (il-17) and neutrophils in the lung have been described as those of two intricate but independent players. here we identify neutrophils as the primary il-17-secreting subset of cells in a model of inhalation anthrax using a/j and c57bl/6 mice. with il-17 receptor a knockout (il-17ra(-/-)) mice, we confirmed that il-17a/f signaling is instrumental in the self-recruitment of this population. we also show that the il-17a/f axis is critical for surviving pulmonary infecti ... | 2012 | 22025514 |
| three probable cases of cutaneous anthrax in autonomous province of vojvodina, serbia, june 2011. | | 2012 | 22264812 |
| 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 |
| 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 |
| 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 |
| inhibition of bacterial carbonic anhydrases and zinc proteases: from orphantargets to innovative new antibiotic drugs. | zinc-containing enzymes, such as carbonic anhydrases (cas) and metalloproteases (mps) play critical functions in bacteria, being involved in various steps of their life cycle, which are important for survival, colonization, acquisition of nutrients for growth and proliferation, facilitation of dissemination, invasion and pathogenicity. the development of resistance to many classes of clinically used antibiotics emphasizes the need of new antibacterial drug targets to be explored. there is a weal ... | 2012 | 22214451 |
| protective antigen antibody augments hemodynamic support in anthrax lethal toxin shock in canines. | background. anthrax-associated shock is closely linked to lethal toxin (lt) release and is highly lethal despite conventional hemodynamic support. we investigated whether protective antigen-directed monoclonal antibody (pa-mab) treatment further augments titrated hemodynamic support.methods and results. forty sedated, mechanically ventilated, instrumented canines challenged with anthrax lt were assigned to no treatment (controls), hemodynamic support alone (protocol-titrated fluids and norepinep ... | 2012 | 22223857 |
| bacillus anthracis-derived edema toxin (et) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway. | abstract: background: a common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (pmns) in infected tissues in the face of abundant circulating pmns. a major virulence determinant of anthrax is edema toxin (et), which is formed by the combination of two proteins produced by the organism, edema factor (ef), which is an adenyl cyclase, and protective antigen (pa). since camp, a product of adenyl cyclase, is known to enhance endothelial barrier integri ... | 2012 | 22230035 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| coatings capable of germinating and neutralizing bacillus anthracis endospores. | endospores are formed by various bacterial families, including bacillus and clostridium, in response to environmental stresses as a means to survive conditions inhospitable to vegetative growth. although metabolically inert, the endospore must interact with its environment to determine an optimal time to return to a vegetative state, a process known as germination. germination has been shown to occur in response to a variety of chemical stimuli from specific nutrient germinants including amino a ... | 2012 | 22211260 |
| detecting anthrax in the mail by coherent raman microspectroscopy. | in this report, we show the collection of spatial information through a turbid medium by coherent raman microspectroscopic imaging. in particular, the technique is capable of identifying anthrax endospores inside a sealed paper envelope. | 2012 | 22215594 |