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an aggregate of four anthrax cases during the dry summer of 2011 in epirus, greece.human anthrax is currently a sporadic disease in europe, without significant regional clustering.201626523995
presentation of peptides from bacillus anthracis protective antigen on tobacco mosaic virus as an epitope targeted anthrax vaccine.the current anthrax vaccine requires improvements for rapidly invoking longer-lasting neutralizing antibody responses with fewer doses from a well-defined formulation. designing antigens that target neutralizing antibody epitopes of anthrax protective antigen, a component of anthrax toxin, may offer a solution for achieving a vaccine that can induce strong and long lasting antibody responses with fewer boosters. here we report implementation of a strategy for developing epitope focused virus nan ...201526514421
heat and desiccation are the predominant factors affecting inactivation of bacillus licheniformis and bacillus thuringiensis spores during simulated composting.the suitability of composting for disposal of livestock mortalities due to bacillus anthracis was assessed by measuring viability of surrogate spores from two strains each of bacillus licheniformis and bacillus thuringiensis after a heating cycle modelled on a cattle composting study.201626513540
the exosporium layer of bacterial spores: a connection to the environment and the infected host.much of what we know regarding bacterial spore structure and function has been learned from studies of the genetically well-characterized bacterium bacillus subtilis. molecular aspects of spore structure, assembly, and function are well defined. however, certain bacteria produce spores with an outer spore layer, the exosporium, which is not present on b. subtilis spores. our understanding of the composition and biological functions of the exosporium layer is much more limited than that of other ...201526512126
chlamydiaceae genomics reveals interspecies admixture and the recent evolution of chlamydia abortus infecting lower mammalian species and humans.chlamydiaceae are obligate intracellular bacteria that cause a diversity of severe infections among humans and livestock on a global scale. identification of new species since 1989 and emergence of zoonotic infections, including abortion in women, underscore the need for genome sequencing of multiple strains of each species to advance our knowledge of evolutionary dynamics across chlamydiaceae. here, we genome sequenced isolates from avian, lower mammalian and human hosts. based on core gene phy ...201526507799
methyl iodide fumigation of bacillus anthracis spores.fumigation techniques such as chlorine dioxide, vaporous hydrogen peroxide, and paraformaldehyde previously used to decontaminate items, rooms, and buildings following contamination with bacillus anthracis spores are often incompatible with materials (e.g., porous surfaces, organics, and metals), causing damage or residue. alternative fumigation with methyl bromide is subject to u.s. and international restrictions due to its ozone-depleting properties. methyl iodide, however, does not pose a ris ...201526502561
crossing of the epithelial barriers by bacillus anthracis: the known and the unknown.anthrax, caused by bacillus anthracis, a gram-positive spore-forming bacterium, is initiated by the entry of spores into the host body. there are three types of human infection: cutaneous, inhalational, and gastrointestinal. for each form, b. anthracis spores need to cross the cutaneous, respiratory or digestive epithelial barriers, respectively, as a first obligate step to establish infection. anthrax is a toxi-infection: an association of toxemia and rapidly spreading infection progressing to ...201526500645
phospho-mek1/2 and upar expression determine sensitivity of aml blasts to a urokinase-activated anthrax lethal toxin (pragu2/lf).in this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (aml) cell lines and primary aml blasts using pragu2/lf, a urokinase-activated anthrax lethal toxin. pragu2/lf was cytotoxic to five out of nine aml cell lines. cytotoxicity of pragu2/lf appeared to be nonapoptotic and was associated with mapk activation and urokinase activity because all the pragu2/lf-sensitive cell lines showed both upar expres ...201526500025
probing the s2' subsite of the anthrax toxin lethal factor using novel n-alkylated hydroxamates.the lethal factor (lf) enzyme secreted by bacillus anthracis is a zinc hydrolase that is chiefly responsible for anthrax-related cell death. although many studies of the design of small molecule lf inhibitors have been conducted, no lf inhibitor is yet available as a therapeutic agent. inhibitors with considerable chemical diversity have been developed and investigated; however, the lf s2' subsite has not yet been systematically explored as a potential target for lead optimization. here we prese ...201526492514
whole-building decontamination of bacillus anthracis sterne spores by methyl bromide fumigation.to evaluate the field inactivation of bacillus anthracis sterne spores with methyl bromide (mb) using commercial fumigation techniques.201626492200
an investigation of a cluster of parapoxvirus cases in missouri, feb-may 2006: epidemiologic, clinical and molecular aspects.in the spring of 2006, four human cases of parapoxvirus infections in missouri residents were reported to the centers for disease control and prevention (cdc), two of which were initially diagnosed as cutaneous anthrax. this investigation was conducted to determine the level of recognition of zoonotic parapoxvirus infections and prevention measures, the degree to which veterinarians may be consulted on human infections and what forces were behind this perceived increase in reported infections. i ...201326487314
feasibility of asymmetrical flow field-flow fractionation as a method for detecting protective antigen by direct recognition of size-increased target-captured nanoprobes.asymmetrical flow field-flow fractionation (af4) was evaluated as a potential analytical method for detection of a protective antigen (pa), an anthrax biomarker. the scheme was based on the recognition of altered af4 retention through the generation of the size-increased au nanoparticle probes as a result of pa binding, in which a pa-selective peptide was conjugated on the probe surface. in the visible absorption-based af4 fractograms, the band position shifted to a longer retention time as the ...201526482872
analysis of waste management issues arising from a field study evaluating decontamination of a biological agent from a building.the bio-response operational testing and evaluation (bote) project was a cross-government effort designed to operationally test and evaluate a response to a biological incident (release of bacillus anthracis [ba] spores, the causative agent for anthrax) from initial public health and law enforcement response through environmental remediation. the bote project was designed to address site remediation after the release of a ba simulant, bacillus atrophaeus spp. globigii (bg), within a facility, dr ...201626479121
total synthesis of the posttranslationally modified polyazole peptide antibiotic plantazolicin a.the power of rhodium-carbene methodology in chemistry is demonstrated by the synthesis of a structurally complex polyazole antibiotic. plantazolicin a, a novel soil-bacterium metabolite, comprises a linear array of 10 five-membered rings in two pentacyclic regions that derive from ribosomal peptide synthesis followed by extensive posttranslational modification. the compound possesses potent antimicrobial activity, and is selectively active against the anthrax-causing organism. a conceptually dif ...201526473502
recombinant expression of bacillus anthracis lethal toxin components of indian isolate in escherichia coli and determination of its acute toxicity level in mouse model.bacillus anthracis lethal toxin (letx) is the principle factor responsible for toxaemia and anthrax related death. lethal toxin consist of two proteins viz protective antigen (pa) and lethal factor which combines in a typical fashion similar to other toxins belonging to a-b toxin super family. the amount of letx required to kill a particular organism generally differs among strains owing to their geographical distributions and genetic variation. in the present study, we have cloned pa and lf gen ...201526472254
engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens.many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., bacillus anthracis, francisella tularensis, yersinia pestis, and vaccinia virus) is highly desirable. here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capt ...201626462853
diversity, antimicrobial and antioxidant activities of culturable bacterial endophyte communities in aloe vera.twenty-nine culturable bacterial endophytes were isolated from surface-sterilized tissues (root, stem and leaf) of aloe vera and molecularly characterized to 13 genera: pseudomonas, bacillus, enterobacter, pantoea, chryseobacterium, sphingobacterium, aeromonas, providencia, cedecea, klebsiella, cronobacter, macrococcus and shigella. the dominant genera include bacillus (20.7%), pseudomonas (20.7%) and enterobacter (13.8%). the crude and ethyl acetate fractions of the metabolites of six isolates, ...201526454221
first autochthonous coinfected anthrax in an immunocompetent patient.cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. the clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. anthrax is known to be more common in the middle east and iran is one of the countries in which the zoonotic form of anthrax may still be encountered. we report a case of a 19-years-old male who used to apply venetian ceruse ...201526451148
accelerating the smith-waterman algorithm with interpair pruning and band optimization for the all-pairs comparison of base sequences.the smith-waterman algorithm is known to be a more sensitive approach than heuristic algorithms for local sequence alignment algorithms. despite its sensitivity, a greater time complexity associated with the smith-waterman algorithm prevents its application to the all-pairs comparisons of base sequences, which aids in the construction of accurate phylogenetic trees. the aim of this study is to achieve greater acceleration using the smith-waterman algorithm (by realizing interpair block pruning a ...201526445214
anthrax prophylaxis: recent advances and future directions.anthrax is a serious, potentially fatal disease that can present in four distinct clinical patterns depending on the route of infection (cutaneous, gastrointestinal, pneumonic, or injectional); effective strategies for prophylaxis and therapy are therefore required. this review addresses the complex mechanisms of pathogenesis employed by the bacterium and describes how, as understanding of these has developed over many years, so too have current strategies for vaccination and therapy. it covers ...201526441934
prevalence and distribution of soil-borne zoonotic pathogens in lahore district of pakistan.a multidisciplinary, collaborative project was conducted to determine the prevalence and distribution of soil-borne zoonotic pathogens in lahore district of pakistan and ascertain its public health significance. using a grid-based sampling strategy, soil samples (n = 145) were collected from villages (n = 29, 5 samples/village) and examined for bacillus anthracis, burkholderia mallei/pseudomallei, coxiella burnetii, francisella tularensis, and yersinia pestis using real time pcr assays. chemical ...201526441860
global metabolomic analysis of a mammalian host infected with bacillus anthracis.whereas dna provides the information to design life and proteins provide the materials to construct it, the metabolome can be viewed as the physiology that powers it. as such, metabolomics, the field charged with the study of the dynamic small-molecule fluctuations that occur in response to changing biology, is now being used to study the basis of disease. here, we describe a comprehensive metabolomic analysis of a systemic bacterial infection using bacillus anthracis, the etiological agent of a ...201526438791
parenteral administration of capsule depolymerase envd prevents lethal inhalation anthrax infection.left untreated, inhalation anthrax is usually fatal. vegetative forms of bacillus anthracis survive in blood and tissues during infection due to elaboration of a protective poly-γ-d-glutamic acid (pdga) capsule that permits uncontrolled bacterial growth in vivo, eventually leading to overwhelming bacillosis and death. as a measure to counter threats from multidrug-resistant strains, we are evaluating the prophylactic and therapeutic potential of the pdga depolymerase envd, a stable and potent en ...201526438506
development of a bead-based luminex assay using lipopolysaccharide specific monoclonal antibodies to detect biological threats from brucella species.brucella, a gram-negative bacterium, is classified as a potential bioterrorism agent mainly due to the low dose needed to cause infection and the ability to transmit the bacteria via aerosols. goats/sheep, cattle, pigs, dogs, sheep and rodents are infected by b. melitensis, b. abortus, b. suis, b. canis, b. ovis and b. neotomae, respectively, the six classical brucella species. most human cases are caused by b. melitensis and b. abortus. our aim was to specifically detect brucellae with 'smooth' ...201526438077
human anthrax transmission at the urban-rural interface, georgia.human anthrax has increased dramatically in georgia and was recently linked to the sale of meat in an urban market. we assessed epidemiological trends and risk factors for human anthrax at the urban-rural interface. we reviewed epidemiologic records (2000-2012) that included the place of residence (classified as urban, peri-urban, or rural), age, gender, and self-reported source of infection (handling or processing animal by-products and slaughtering or butchering livestock). to estimate risk, w ...201526438026
enhanced immune response to dna vaccine encoding bacillus anthracis pa-d4 protects mice against anthrax spore challenge.anthrax has long been considered the most probable bioweapon-induced disease. the protective antigen (pa) of bacillus anthracis plays a crucial role in the pathogenesis of anthrax. in the current study, we evaluated the efficiency of a genetic vaccination with the fourth domain (d4) of pa, which is responsible for initial binding of the anthrax toxin to the cellular receptor. the eukaryotic expression vector was designed with the immunoglobulin m (igm) signal sequence encoding for pa-d4, which c ...201526430894
passive immunotherapy protects against enteric invasion and lethal sepsis in a murine model of gastrointestinal anthrax.the principal portal for anthrax infection in natural animal outbreaks is the digestive tract. enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. our group has developed a novel animal model of gastrointestinal (gi) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative bacillus anthracis (sterne strain) administered to a/j mice ( ...201526426050
potential role of autophagy in the bactericidal activity of human pmns for bacillus anthracis.bacillus anthracis, the causative agent of anthrax, is acquired by mammalian hosts from the environment, as quiescent endospores. these endospores must germinate inside host cells, forming vegetative bacilli, before they can express the virulence factors that enable them to evade host defenses and disseminate throughout the body. while the role of macrophages and dendritic cells in this initial interaction has been established, the role of polymorphonuclear leukocytes (pmns) has not been adequat ...201526424808
experimental validation of bacillus anthracis a16r proteogenomics.anthrax, caused by the pathogenic bacterium bacillus anthracis, is a zoonosis that causes serious disease and is of significant concern as a biological warfare agent. validating annotated genes and reannotating misannotated genes are important to understand its biology and mechanisms of pathogenicity. proteomics studies are, to date, the best method for verifying and improving current annotations. to this end, the proteome of b. anthracis a16r was analyzed via one-dimensional gel electrophoresis ...201526423727
a s-layer protein of bacillus anthracis as a building block for functional protein arrays by in vitro self-assembly.s-layer proteins create a cell-surface layer architecture in both bacteria and archaea. because s-layer proteins self-assemble into a native-like s-layer crystalline structure in vitro, they are attractive building blocks in nanotechnology. here, the potential use of the s-layer protein ea1 from bacillus anthracis in constructing a functional nanostructure is investigated, and apply this nanostructure in a proof-of-principle study for serological diagnosis of anthrax. ea1 is genetically fused wi ...201526422821
cdc report on the potential exposure to anthrax.the centers for disease control and prevention (cdc) conducted an internal review of an incident that involved an unintentional release of potentially viable anthrax within its roybal campus, in atlanta, georgia. on june 5, 2014, a laboratory scientist in the bioterrorism rapid response and advanced technology (brrat) laboratory prepared extracts from a panel of eight bacterial select agents, including bacillus anthracis (b. anthracis), under biosafety level (bsl) 3 containment conditions. these ...201426418856
correction: bacillus anthracis diversity and geographic potential across nigeria, cameroon and chad: further support of a novel west african lineage. 201526417945
mass spectrometric detection of bacterial protein toxins and their enzymatic activity.mass spectrometry has recently become a powerful technique for bacterial identification. mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (maldi-tof) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. with some bacteria, such as bacillus anthracis and clostridium botulinum, the health threat posed by these organisms is not the organism its ...201526404376
contractile actin cables induced by bacillus anthracis lethal toxin depend on the histone acetylation machinery.it remains a challenge to decode the molecular basis of the long-term actin cytoskeleton rearrangements that are governed by the reprogramming of gene expression. bacillus anthracis lethal toxin (lt) inhibits mitogen-activated protein kinase (mapk) signaling, thereby modulating gene expression, with major consequences for actin cytoskeleton organization and the loss of endothelial barrier function. using a laser ablation approach, we characterized the contractile and tensile mechanical propertie ...201526403219
impact of gastrointestinal bacillus anthracis infection on hepatic b cells.ingestion of bacillus anthracis results in rapid gastrointestinal (gi) infection, known as gi anthrax. we previously showed that during gi anthrax, there is swift deterioration of intestinal barrier function leading to translocation of gut-associated bacteria into systemic circulation. additionally, we described dysfunction in colonic b cells. in concordance with our previous studies, here, we report early migration of the sterne strain of b. anthracis along with other gut-resident bacteria into ...201526402706
binding domains of bacillus anthracis phage endolysins recognize cell culture age-related features on the bacterial surface.bacteriolytic enzymes often possess a c-terminal binding domain that recognizes specific motifs on the bacterial surface and a catalytic domain that cleaves covalent linkages within the cell wall peptidoglycan. plyph, one such lytic enzyme of bacteriophage origin, has been reported to be highly effective against bacillus anthracis, and can kill up to 99.99% of the viable bacteria. the bactericidal activity of this enzyme, however, appears to be strongly dependent on the age of the bacterial cult ...201626399565
mechanisms of ricin toxin neutralization revealed through engineered homodimeric and heterodimeric camelid antibodies.novel antibody constructs consisting of two or more different camelid heavy-chain only antibodies (vhhs) joined via peptide linkers have proven to have potent toxin-neutralizing activity in vivo against shiga, botulinum, clostridium difficile, anthrax, and ricin toxins. however, the mechanisms by which these so-called bispecific vhh heterodimers promote toxin neutralization remain poorly understood. in the current study we produced a new collection of ricin-specific vhh heterodimers, as well as ...201526396190
decontamination efficacy and skin toxicity of two decontaminants against bacillus anthracis.decontamination of bacterial endospores such as bacillus anthracis has traditionally required the use of harsh or caustic chemicals. the aim of this study was to evaluate the efficacy of a chlorine dioxide decontaminant in killing bacillus anthracis spores in solution and on a human skin simulant (porcine cadaver skin), compared to that of commonly used sodium hypochlorite or soapy water decontamination procedures. in addition, the relative toxicities of these decontaminants were compared in hum ...201526394165
efficacy of single and combined antibiotic treatments of anthrax in rabbits.respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. rabbits are highly susceptible to infection with bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. this study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degre ...201526392505
targeting the membrane-anchored serine protease testisin with a novel engineered anthrax toxin prodrug to kill tumor cells and reduce tumor burden.the membrane-anchored serine proteases are a unique group of trypsin-like serine proteases that are tethered to the cell surface via transmembrane domains or glycosyl-phosphatidylinositol-anchors. overexpressed in tumors, with pro-tumorigenic properties, they are attractive targets for protease-activated prodrug-like anti-tumor therapies. here, we sought to engineer anthrax toxin protective antigen (prag), which is proteolytically activated on the cell surface by the proprotein convertase furin ...201526392335
microbiological laboratory diagnostics of neglected zoonotic diseases (nzds).this review reports on laboratory diagnostic approaches for selected, highly pathogenic neglected zoonotic diseases, i.e. anthrax, bovine tuberculosis, brucellosis, echinococcosis, leishmaniasis, rabies, taenia solium-associated diseases (neuro-/cysticercosis & taeniasis) and trypanosomiasis. diagnostic options, including microscopy, culture, matrix-assisted laser-desorption-ionisation time-of-flight mass spectrometry, molecular approaches and serology are introduced. these procedures are critic ...201726391646
bacillus anthracis lcp genes support vegetative growth, envelope assembly, and spore formation.bacillus anthracis, a spore-forming pathogen, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. surface (s)-layer proteins and b. anthracis s-layer-associated proteins (bsls) function as chain length determinants and are assembled in the envelope by binding to the secondary cell wall polysaccharide (scwp). b. anthracis expresses six different genes encoding lytr-cpsa-psr (lcp) enzymes (lcpb1 to -4, lcpc, and lcpd), which when expressed in staphylococc ...201526391207
nitric oxide as a regulator of b. anthracis pathogenicity.nitric oxide (no) is a key physiological regulator in eukaryotic and prokaryotic organisms. it can cause a variety of biological effects by reacting with its targets or/and indirectly inducing oxidative stress. no can also be produced by bacteria including the pathogenic bacillus anthracis; however, its role in the infectious process only begins to emerge. no incapacitates macrophages by s-nitrosylating the intracellular proteins and protects b. anthracis from oxidative stress. it is also implic ...201526388860
historical evolution of human anthrax from occupational disease to potentially global threat as bioweapon.anthrax is caused by bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. however, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, b. anthracis has been considered the most serious bioterrorism agent for a long time. during the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. several factors may mitigate the consequences ...201526386727
the role of practical advice in bioterrorism news coverage.this study examined the role of crisis advice appearing in us news coverage of the 2001 anthrax attacks. coverage of any crisis can spark public outrage, including fear, speculation, and contradictory or confusing evidence, especially when the stories do not contain practical advice. five coders analyzed 833 news stories from 272 major us newspapers, the associated press, national public radio, and 4 major us television networks. practical advice appeared in only a quarter of the stories, even t ...201526381372
environmental persistence of bacillus anthracis and bacillus subtilis spores.there is a lack of data for how the viability of biological agents may degrade over time in different environments. in this study, experiments were conducted to determine the persistence of bacillus anthracis and bacillus subtilis spores on outdoor materials with and without exposure to simulated sunlight, using ultraviolet (uv)-a/b radiation. spores were inoculated onto glass, wood, concrete, and topsoil and recovered after periods of 2, 14, 28, and 56 days. recovery and inactivation kinetics f ...201526372011
"phylogenetic and evolutionary analysis of functional divergence among gamma glutamyl transpeptidase (ggt) subfamilies".γ-glutamyltranspeptidase (ggt) is a bi-substrate enzyme conserved in all three domains of life. it catalyzes the cleavage and transfer of γ-glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). ggts exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. recently, ggt has been shown to be a virulence factor in microbes like helicobacter pylori and bacillus anthracis. in mammalian cells also, ggt in ...201526370226
investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.hybridomas were created using spleen of mice that were actively immunized with rlfn (recombinant n-terminal domain of lethal factor). later on, separate group of mice were immunized with rlfn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. this led to the identification of one cohort of rlfn-immnized mice that harboured disease-enhancing polyclonal antibodies. at the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. t ...201526364143
peptide probes reveal a hydrophobic steric ratchet in the anthrax toxin protective antigen translocase.anthrax toxin is a tripartite virulence factor produced by bacillus anthracis during infection. under acidic endosomal ph conditions, the toxin's protective antigen (pa) component forms a transmembrane channel in host cells. the pa channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps ...201526363343
development & validation of a quantitative anti-protective antigen igg enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax.anthrax caused by bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. elisa is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. the aims of this study were to develop and evaluate a quantitative elisa for determination of igg antibodies against b. anthracis protective antigen (pa) in human cutaneous anthrax cases.201526354217
a cluster of cns infections due to b. cereus in the setting of acute myeloid leukemia: neuropathology in 5 patients.bacillus cereus typically causes a self-limited foodborne gastrointestinal (gi) illness. severe invasive infection occurs rarely, mainly among immunocompromised hosts. we describe a cluster of b. cereus infections among 5 patients with acute myeloid leukemia and chemotherapy-induced neutropenia. the initial case presented with occipital lobe abscess and was found on biopsy to have organisms consistent with bacillus species. within 1 week, a second patient died of fulminant brain swelling and hem ...201526352989
the makes caterpillars floppy (mcf)-like domain of vibrio vulnificus induces mitochondrion-mediated apoptosis.the multifunctional-autoprocessing repeats-in-toxin (martxvv) toxin of vibrio vulnificus plays a significant role in the pathogenesis of this bacterium through delivery of up to five effector domains to the host cells. previous studies have established that the martxvv toxin is linked to v. vulnificus dependent induction of apoptosis, but the region of the large multifunction protein essential for this activity was not previously identified. recently, we showed that the makes caterpillar floppy- ...201526351282
the poly-γ-d-glutamic acid capsule surrogate of the bacillus anthracis capsule induces nitric oxide production via the platelet activating factor receptor signaling pathway.the poly-γ-d-glutamic acid (pga) capsule, a major virulence factor of bacillus anthracis, confers protection of the bacillus from phagocytosis and allows its unimpeded growth in the host. pga capsules released from b. anthracis are associated with lethal toxin in the blood of experimentally infected animals and enhance the cytotoxic effect of lethal toxin on macrophages. in addition, pga capsule itself activates macrophages and dendritic cells to produce proinflammatory cytokine such as il-1β, i ...201526350415
over-expression, purification, and confirmation of bacillus anthracis transcriptional regulator nprr.quorum sensing (qs) has been recognized as an important biological phenomenon in which bacterial cells communicate and coordinate their gene expression and cellular processes with respect to population density. bacillus anthracis is the etiological agent of fatal pulmonary anthrax infections, and the nprr/nprx qs system may be involved in its pathogenesis. nprr, renamed as aqsr for anthrax quorum sensing regulator, is a transcriptional regulator that may control the expression of genes required ...201626344899
role of the α clamp in the protein translocation mechanism of anthrax toxin.membrane-embedded molecular machines are utilized to move water-soluble proteins across these barriers. anthrax toxin forms one such machine through the self-assembly of its three component proteins--protective antigen (pa), lethal factor, and edema factor. upon endocytosis into host cells, acidification of the endosome induces pa to form a membrane-inserted channel, which unfolds lethal factor and edema factor and translocates them into the host cytosol. translocation is driven by the proton mo ...201526344833
lanthanide induced formation of novel luminescent alginate hydrogels and detection features.responsive photo-luminescent soft matters have led to the design of optical sensors and switches. in this research, two new organic-inorganic type hybrid hydrogels have been fabricated by the self-assembly of sodium alginate and lanthanide elements. the incorporation of europium ions (eu(3+)) (or terbium ions (tb(3+))) was required for the gelation of the dissolved alginate and thermally stable gels were formed. it has been found that red/green emissions derived from lanthanide ions were clearly ...201526344249
a case of cutaneous anthrax presenting with classical lesions. 201526340973
structure of the bacillus anthracis sortase a enzyme bound to its sorting signal: a flexible amino-terminal appendage modulates substrate access.the endospore forming bacterium bacillus anthracis causes lethal anthrax disease in humans and animals. the ability of this pathogen to replicate within macrophages is dependent upon the display of bacterial surface proteins attached to the cell wall by the b. anthracis sortase a ((ba)srta) enzyme. previously, we discovered that the class a (ba)srta sortase contains a unique n-terminal appendage that wraps around the body of the protein to contact the active site of the enzyme. to gain insight i ...201526324714
bacillus anthracis tago is required for vegetative growth and secondary cell wall polysaccharide synthesis.bacillus anthracis elaborates a linear secondary cell wall polysaccharide (scwp) that retains surface (s)-layer and associated proteins via their s-layer homology (slh) domains. the scwp is comprised of trisaccharide repeats [→4)-β-mannac-(1→4)-β-glcnac-(1→6)-α-glcnac-(1→] and tethered via acid-labile phosphodiester bonds to peptidoglycan. earlier work identified udp-glcnac 2-epimerases gney (bas5048) and gnez (bas5117), which act as catalysts of mannac synthesis, as well as a polysaccharide dea ...201526324447
whole genome protein microarrays for serum profiling of immunodominant antigens of bacillus anthracis.a commercial bacillus anthracis (anthrax) whole genome protein microarray has been used to identify immunogenic anthrax proteins (iap) using sera from groups of donors with (a) confirmed b. anthracis naturally acquired cutaneous infection, (b) confirmed b. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the uk anthrax protein vaccine and compared to naïve unexposed controls. anti-iap responses were obs ...201526322022
fighting ebola with novel spore decontamination technologies for the military.recently, global public health organizations such as doctors without borders (msf), the world health organization (who), public health canada, national institutes of health (nih), and the u.s. government developed and deployed field decontamination kits (fdks), a novel, lightweight, compact, reusable decontamination technology to sterilize ebola-contaminated medical devices at remote clinical sites lacking infra-structure in crisis-stricken regions of west africa (medical waste materials are pla ...201526322021
whole genome-sequencing and phylogenetic analysis of a historical collection of bacillus anthracis strains from danish cattle.bacillus anthracis, the causative agent of anthrax, is known as one of the most genetically monomorphic species. canonical single-nucleotide polymorphism (snp) typing and whole-genome sequencing were used to investigate the molecular diversity of eleven b. anthracis strains isolated from cattle in denmark between 1935 and 1988. danish strains were assigned into five cansnp groups or lineages, i.e. a.br.001/002 (n = 4), a.br.ames (n = 2), a.br.008/011 (n = 2), a.br.005/006 (n = 2) and a.br.aust94 ...201526317972
global gene expression by bacillus anthracis during growth in mammalian blood.during the late stages of systemic anthrax, bacillus anthracis grows rapidly in the host bloodstream. to identify potential genes necessary for this observed rapid growth, we defined the transcriptional profile of b. anthracis during in vitro growth in bovine blood. genome-wide transcriptome analysis indicated that b. anthracis undergoes significant changes in its transcriptome profile during growth in blood, including the differential regulation of genes associated both with metabolism and know ...201526316554
rapid detection of bacillus anthracis by γ phage amplification and lateral flow immunochromatography.new, rapid point-of-need diagnostic methods for bacillus anthracis detection can enhance civil and military responses to accidental or deliberate dispersal of anthrax as a biological weapon. current laboratory-based methods for clinical identification of b. anthracis require 12 to 120h, and are confirmed by plaque assay using the well-characterized γ typing phage, which requires an additional minimum of 24h for bacterial culture. to reduce testing time, the natural specificity of γ phage amplifi ...201526310605
investigation of anthrax cases in north-east china, 2010-2014.we determined the genotypes of seven bacillus anthracis strains that were recovered from nine anthrax outbreaks in north-east china from 2010 to 2014, and two approved vaccine strains that are currently in use in china. the causes of these cases were partly due to local farmers being unaware of the presence of anthrax, and butchers with open wounds having direct contact with anthrax-contaminated meat products. the genotype of five of the seven recovered strains was a.br.001/002 sub-lineage, whic ...201526308449
gastrointestinal problems in modern wars: clinical features and possible mechanisms.gastrointestinal problems are common during wars, and they have exerted significant adverse effects on the health of service members involved in warfare. the spectrum of digestive diseases has varied during wars of different eras. at the end of the 20th century, new frontiers of military medical research emerged due to the occurrence of high-tech wars such as the gulf war and the kosovo war, in which ground combat was no longer the primary method of field operations. the risk to the military per ...201526301101
background frequency of bacillus species at the canberra airport: a 12 month study.anthrax, caused by bacillus anthracis, is a naturally occurring disease in australia. whilst mainly limited to livestock in grazing regions of victoria and new south wales, movement of people, stock and vehicles means b. anthracis could be present outside this region. of particular interest is the "background" prevalence of b. anthracis at transport hubs including airports. the aim of this study was to determine the background frequency of b. anthracis and the commonly used hoax agent bacillus t ...201526298416
improved proteomic analysis following trichloroacetic acid extraction of bacillus anthracis spore proteins.proteomic analysis of bacterial samples provides valuable information about cellular responses and functions under different environmental pressures. analysis of cellular proteins is dependent upon efficient extraction from bacterial samples, which can be challenging with increasing complexity and refractory characteristics. while no single method can recover 100% of the bacterial proteins, selected protocols can improve overall protein isolation, peptide recovery, or enrichment for certain clas ...201526295278
cutaneous anthrax: evaluation of 28 cases in the eastern anatolian region of turkey.anthrax is an endemic disease in developing countries. human cases are usually associated with animal products. about 95% of naturally acquired cases are cutaneous anthrax.201626293781
bacillus anthracis diversity and geographic potential across nigeria, cameroon and chad: further support of a novel west african lineage.zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries. anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in nigeria. here we describe the genetic diversity of bacillus anthracis in nigeria and compare it to chad, cameroon and a broader global dataset based on the multiple locus variable number tandem repeat (mlva-25) genetic typing sys ...201526291625
anthrax toxins in context of bacillus anthracis spores and spore germination.the interaction of anthrax toxin or toxin components with b. anthracis spores has been demonstrated. germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. in this review, we will summarize the work performed that has led to our understanding of toxin and spore interactions and discuss the complexities associated with these interactions.201526287244
insights into smad4 loss in pancreatic cancer from inducible restoration of tgf-β signaling.pancreatic ductal adenocarcinoma (pdac) is the fourth-leading cause of cancer death in the united states. the tgf-β signaling protein smad family member 4 is lost in 60% of pdac, and this has been associated with poorer prognosis. however, the mechanisms by which smad4 loss promotes pdac development are not fully understood. we expressed smad4 in human pdac cell lines bxpc3 and cfpac1 by selection of stable clones containing an inducible smad4 tetracycline inducible expression system construct. ...201526284758
intranasal immunization with protective antigen of bacillus anthracis induces a long-term immunological memory response.although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. here, we investigated whether intranasal immunization with recombinant protective antigen (rpa) of bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. intranasal immunization with rpa plus cholera toxin (ct) sustained pa-specific antibody responses for 6 months in lung, nasal was ...201526278659
pore-forming activity of clostridial binary toxins.clostridial binary toxins (clostridium perfringens iota toxin, clostridium difficile transferase, clostridium spiroforme toxin, clostridium botulinum c2 toxin) as bacillus binary toxins, including bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. clostridial binary toxins induce actin cytoskeleton disorganization through mono-adp-ribosylation of globular actin and ar ...201626278641
hfqs in bacillus anthracis: role of protein sequence variation in the structure and function of proteins in the hfq family.hfq proteins in gram-negative bacteria play important roles in bacterial physiology and virulence, mediated by binding of the hfq hexamer to small rnas and/or mrnas to post-transcriptionally regulate gene expression. however, the physiological role of hfqs in gram-positive bacteria is less clear. bacillus anthracis, the causative agent of anthrax, uniquely expresses three distinct hfq proteins, two from the chromosome (hfq1, hfq2) and one from its pxo1 virulence plasmid (hfq3). the protein seque ...201526271475
sulforaphane inhibits multiple inflammasomes through an nrf2-independent mechanism.the inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18. these events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and auto ...201526269198
a method detection limit for bacillus anthracis spores in water using an automated waterborne pathogen concentrator.the method detection limit (mdl, 99% chance of detecting a positive result in a single replicate), as per the united states code of federal regulations, was determined for a protocol using an ultrafiltration based automated waterborne pathogen concentration device. bacillus anthracis sterne strain spores were seeded at low levels into 100 l reagent water samples. suspect colonies were confirmed through morphological, chemical, and genetic tests. samples of 100 l (n=14) of reagent water were seed ...201526268983
microevolution of anthrax from a young ancestor (m.a.y.a.) suggests a soil-borne life cycle of bacillus anthracis.during an anthrax outbreak at the pollino national park (basilicata, italy) in 2004, diseased cattle were buried and from these anthrax-foci bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. recent data suggest that b. anthracis multiplies in soil outside the animal-host body. this notion is supported by the frequent isolation of b. anthracis from soil lacking one or both virulence plasmids. such strains represent an evolutionary dead end, as they are l ...201526266934
reagent-free and portable detection of bacillus anthracis spores using a microfluidic incubator and smartphone microscope.bacillus anthracis is the causative agent of anthrax and can be contracted by humans and herbivorous mammals by inhalation, ingestion, or cutaneous exposure to bacterial spores. due to its stability and disease potential, b. anthracis is a recognized biothreat agent and robust detection and viability methods are needed to identify spores from unknown samples. here we report the use of smartphone-based microscopy (spm) in combination with a simple microfluidic incubation device (mid) to detect 50 ...201526266749
test methods and response surface models for hot, humid air decontamination of materials contaminated with dirty spores of bacillus anthracis ∆sterne and bacillus thuringiensis al hakam.to develop test methods and evaluate survival of bacillus anthracis ∆sterne or bacillus thuringiensis al hakam on materials contaminated with dirty spore preparations after exposure to hot, humid air using response surface modelling.201526258399
electrochemical dna sensor for anthrax toxin activator gene atxa-detection of pcr amplicons.we report the dna probe functionalized electrochemical genosensor for the detection of bacillus anthracis, specific towards the regulatory gene atxa. the dna sensor is fabricated on electrochemically deposited gold nanoparticle on self assembled layer of (3-mercaptopropyl) trimethoxysilane (mpts) on gc electrode. dna hybridization is monitored by differential pulse voltammogram (dpv). the modified gc electrode is characterized by atomic force microscopy (afm), cyclic voltammetry (cv), and electr ...201526257186
anti-infective immunoadhesins from plants.immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. all fda-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as etanercept (enbrel(®) ), which interferes with the binding of tumour necrosis factor (tnf) to the tnf-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. like antibodies, immunoadhesins h ...201526242703
dna persistence in a sink drain environment.biofilms are organized structures composed mainly of cells and extracellular polymeric substances produced by the constituent microorganisms. ubiquitous in nature, biofilms have an innate ability to capture and retain passing material and may therefore act as natural collectors of contaminants or signatures of upstream activities. to determine the persistence and detectability of dna passing through a sink drain environment, bacillus anthracis strain ames35 was cultured (6.35 x 107 cfu/ml), ster ...201526230525
toxins as weapons: a historical review.this review article summarizes the use of toxins as weapons dating from the first world war until today, when there is a high concern of possible terrorist attacks with weapons of mass destruction. all through modern history, military programs and terrorist groups have favored toxins because of their high toxicity. however, difficulties of extraction or synthesis, as well as effective dissemination to cause a large number of casualties, have been the most important drawbacks. special emphasis is ...201426227025
cutaneous anthrax: evaluation of 28 cases in the eastern anatolian region of turkey.anthrax is an endemic disease in developing countries. human cases are usually associated with animal products. about 95% of naturally acquired cases are cutaneous anthrax.201526225872
controlled release of an anthrax toxin-neutralizing antibody from hydrolytically degradable polyethylene glycol hydrogels.in this study, hydrophilic and hydrolytically degradable poly (ethylene glycol) (peg) hydrogels were formed via michael-type addition and employed for sustained delivery of a monoclonal antibody against the protective antigen of anthrax. taking advantage of the peg-induced precipitation of the antibody, burst release from the matrix was avoided. these hydrogels were able to release active antibodies in a controlled manner from 14 days to as long as 56 days in vitro by varying the polymer archite ...201626223817
anthrax toxin receptor 2 gene (antxr2) rs4333130 is associated with ankylosing spondylitis.results of recent published studies on the association between the antxr2 rs4333130 polymorphism and the risk of ankylosing spondylitis (as) have often been conflicting. to make a more precise estimation of the potential relationship, a meta-analysis was performed. we conducted a comprehensive search in the electronic database of pubmed and embase to retrieve relevant articles. nine studies including 14,523 cases and 34,421 controls were finally selected in this meta-analysis. antxr2 rs4333130 w ...201526221317
bacillus anthracis slaq promotes s-layer protein assembly.bacillus anthracis vegetative forms assemble an s-layer comprised of two s-layer proteins, sap and ea1. a hallmark of s-layer proteins are their c-terminal crystallization domains, which assemble into a crystalline lattice once these polypeptides are deposited on the bacterial surface via association between their n-terminal s-layer homology domains and the secondary cell wall polysaccharide. here we show that slaq, encoding a small cytoplasmic protein conserved among pathogenic bacilli elaborat ...201526216847
weissella oryzae dc6-facilitated green synthesis of silver nanoparticles and their antimicrobial potential.nanoparticles and nanomaterials are at the prominent edge of the rapidly developing field of nanotechnology. recently, nanoparticle synthesis using biological resources has been found to be a new area with considerable prospects for development. biological systems are the masters of ambient condition chemistry and are able to synthesize nanoparticles by utilizing metal salts. in the perspective of the current initiative to develop green technologies for the synthesis of nanoparticles, microorgan ...201626212222
structural basis of proline-proline peptide bond specificity of the metalloprotease zmp1 implicated in motility of clostridium difficile.clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. in common with other pathogenic bacteria, c. difficile secretes proteins involved in adhesion, colonization, and dissemination. the recently identified zmp1 is an extracellular metalloprotease showing a unique specificity for pro-pro peptide bonds. the endogenous substrates of zmp1 are two surface proteins implicated in adhesion of c. difficile to surface proteins of human cel ...201526211609
lab-on-a-chip-based pcr-rflp assay for the confirmed detection of short-length feline dna in food.wider availability but lack of legal market trades has given feline meat a high potential for use as an adulterant in common meat and meat products. however, mixing of feline meat or its derivatives in food is a sensitive issue, since it is a taboo in most countries and prohibited in certain religions such as islam and judaism. cat meat also has potential for contamination with of severe acute respiratory syndrome, anthrax and hepatitis, and its consumption might lead to an allergic reaction. we ...201526208950
spatiotemporal clustering analysis and risk assessments of human cutaneous anthrax in china, 2005-2012.to investigate the epidemic characteristics of human cutaneous anthrax (ca) in china, detect the spatiotemporal clusters at the county level for preemptive public health interventions, and evaluate the differences in the epidemiological characteristics within and outside clusters.201526208355
immunization with a recombinant, pseudomonas fluorescens-expressed, mutant form of bacillus anthracis-derived protective antigen protects rabbits from anthrax infection.protective antigen (pa), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (biothrax). human anthrax vaccines approved in the united states and europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of bacillus anthracis. approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection ...201526207820
the poly-γ-d-glutamic acid capsule surrogate of the bacillus anthracis capsule is a novel toll-like receptor 2 agonist.bacillus anthracis is a pathogenic gram-positive bacterium that causes a highly lethal infectious disease, anthrax. the poly-γ-d-glutamic acid (pga) capsule is one of the major virulence factors of b. anthracis, along with exotoxins. pga enables b. anthracis to escape phagocytosis and immune surveillance. our previous study showed that pga activates the human macrophage cell line thp-1 and human dendritic cells, resulting in the production of the proinflammatory cytokine interleukin-1β (il-1β) ( ...201526195551
anthrax pathogenesis.anthrax is caused by the spore-forming, gram-positive bacterium bacillus anthracis. the bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. these are encoded by two large plasmids, the former by pxo1 and the latter by pxo2. the expression of both is controlled by the bicarbonate-responsive transcriptional regulator, atxa. the anthrax toxins are three polypeptides-protective antigen (pa), lethal factor (lf), and edema factor (ef)-that com ...201526195305
acyl carrier protein is a bacterial cytoplasmic target of cationic antimicrobial peptide ll-37.in addition to membrane disruption, the cathelicidin antimicrobial peptide (amp) ll-37 translocates through the bacterial inner membrane to target intracellular molecules. the present study aims to identify an alternate mechanism and a cytoplasmic target of ll-37 in francisella. ll-37 binding proteins from francisella novicida u112 bacterial lysates were precipitated by using biotinylated ll-37 (b-ll-37) and neutravidin-agarose beads. bound proteins were identified by lc-ms/ms, validated and cha ...201526188040
the differential effects of heat-shocking on the viability of spores from bacillus anthracis, bacillus subtilis, and clostridium sporogenes after treatment with peracetic acid- and glutaraldehyde-based disinfectants.this study investigated (1) the susceptibility of bacillus anthracis (ames strain), bacillus subtilis (atcc 19659), and clostridium sporogenes (atcc 3584) spores to commercially available peracetic acid (paa)- and glutaraldehyde (ga)-based disinfectants, (2) the effects that heat-shocking spores after treatment with these disinfectants has on spore recovery, and (3) the timing of heat-shocking after disinfectant treatment that promotes the optimal recovery of spores deposited on carriers. suspen ...201526185111
different roles of n-terminal and c-terminal domains in calmodulin for activation of bacillus anthracis edema factor.bacillus anthracis adenylyl cyclase toxin edema factor (ef) is one component of the anthrax toxin and is essential for establishing anthrax disease. ef activation by the eukaryotic ca2+-sensor calmodulin (cam) leads to massive camp production resulting in edema. camp also inhibits the nicotinamide adenine dinucleotide phosphate (nadph)-oxidase, thus reducing production of reactive oxygen species (ros) used for host defense in activated neutrophils and thereby facilitating bacterial growth. methi ...201526184312
translocation of non-canonical polypeptides into cells using protective antigen.a variety of pathogenic bacteria infect host eukaryotic cells using protein toxins, which enter the cytosol and exert their cytotoxic effects. anthrax lethal toxin, for example, utilizes the membrane-spanning translocase, protective antigen (pa) pore, to deliver the protein toxin lethal factor (lf) from the endosome into the cytosol of cells. previous work has investigated the delivery of natural peptides and enzymatic domains appended to the c-terminus of the pa-binding domain of lethal factor ...201526178180
unlocking the sporicidal potential of ethanol: induced sporicidal activity of ethanol against clostridium difficile and bacillus spores under altered physical and chemical conditions.due to their efficacy and convenience, alcohol-based hand sanitizers have been widely adopted as the primary method of hand hygiene in healthcare settings. however, alcohols lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we hypothesized that sporicidal activity could be induced in alcohols through alteration of physical or chemical conditions that have been shown to degrade or allow penetration of spore coats.201526177038
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