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baulamycins a and b, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in staphylococcus aureus and bacillus anthracis.siderophores are high-affinity iron chelators produced by microorganisms and frequently contribute to the virulence of human pathogens. targeted inhibition of the biosynthesis of siderophores staphyloferrin b of staphylococcus aureus and petrobactin of bacillus anthracis hold considerable potential as a single or combined treatment for methicillin-resistant s. aureus (mrsa) and anthrax infection, respectively. the biosynthetic pathways for both siderophores involve a nonribosomal peptide synthet ...201424401083
inhibitions of the translocation pore of clostridium botulinum c2 toxin by tailored azolopyridinium salts protects human cells from intoxication.c2 toxin from clostridium botulinum represents the prototype of clostridial binary actin adp-ribosylating toxins which destroy the actin-cytoskeleton of mammalian cells and cause severe enteric diseases in humans and animals. after receptor-mediated endocytosis of the c2 toxin complex, the binding/translocation component c2iia forms a heptameric transmembrane pore in membranes of acidified endosomal vesicles. the separate adp-ribosyltransferase component c2i translocates through this c2iia-pore ...201424394545
failure of sterne- and pasteur-like strains of bacillus anthracis to replicate and survive in the urban bluebottle blow fly calliphora vicina under laboratory conditions.this study aimed to elucidate the bacteriological events occurring within the gut of calliphora vicina, selected as the european representative of blow flies held responsible for the spread of anthrax during epidemics in certain parts of the world. green-fluorescent-protein-carrying derivatives of bacillus anthracis were used. these lacked either one of the virulence plasmids pxo1 and pxo2 and were infected, or not infected, with a worm intestine phage (wip4) known to influence the phenotype and ...201424392098
cervical collagen network remodeling in normal pregnancy and disrupted parturition in antxr2 deficient mice.the remodeling of the cervix from a rigid barrier into a compliant structure, which dilates to allow for delivery, is a critical process for a successful pregnancy. changes in the mechanical properties of cervical tissue during remodeling are hypothesized to be related to the types of collagen crosslinks within the tissue. to further understand normal and abnormal cervical remodeling, we quantify the material properties and collagen crosslink density of cervical tissue throughout pregnancy from ...201424390076
molecular determinants for a cardiovascular collapse in anthrax.bacillus anthracis releases two bipartite proteins, lethal toxin and edema factor, that contribute significantly to the progression of anthrax-associated shock. as blocking the anthrax toxins prevents disease, the toxins are considered the main virulence factors of the bacterium. the anthrax bacterium and the anthrax toxins trigger multi-organ failure associated with enhanced vascular permeability, hemorrhage and cardiac dysfunction in animal challenge models. a recent study using mice that eith ...201424389148
(19)f nuclear magnetic resonance and crystallographic studies of 5-fluorotryptophan-labeled anthrax protective antigen and effects of the receptor on stability.the anthrax protective antigen (pa) is an 83 kda protein that is one of three protein components of the anthrax toxin, an ab toxin secreted by bacillus anthracis. pa is capable of undergoing several structural changes, including oligomerization to either a heptameric or octameric structure called the prepore, and at acidic ph a major conformational change to form a membrane-spanning pore. to follow these structural changes at a residue-specific level, we have conducted initial studies in which w ...201424387629
high-level secretory production of recombinant single-chain variable fragment (scfv) in corynebacterium glutamicum.we describe the development of a new secretory production system for the enhanced production of a single-chain variable fragment (scfv) against the anthrax toxin in corynebacterium glutamicum. for efficient secretory production of the antibody fragment, the following components were examined: (1) signal peptides, (2) codon usage of antibody fragment, (3) promoters, (4) 5' untranslated region (5' utr) sequence, and (5) transcriptional terminator. among all the systems examined, the use of a codon ...201424380967
expression and purification of the functional ectodomain of human anthrax toxin receptor 2 in escherichia coli origami b cells with assistance of bacterial trigger factor.the ectodomain of anthrax toxin receptor 2 (antxr2) is composed of a von willebrand factor a (vwa) domain that binds to anthrax toxin protective antigen (pa) and a newly defined immunoglobulin-like (ig) domain, in which the disulfide bonds are required for pa pore formation and for the folding of antxr2. while the vwa domain has been well characterized, the structure and function of the whole ectodomain (vwa-ig) are poorly defined, which is mainly due to the limited production of the soluble rec ...201424380801
identification and validation of specific markers of bacillus anthracis spores by proteomics and genomics approaches.bacillus anthracis is the causative bacteria of anthrax, an acute and often fatal disease in humans. the infectious agent, the spore, represents a real bioterrorism threat and its specific identification is crucial. however, because of the high genomic relatedness within the bacillus cereus group, it is still a real challenge to identify b. anthracis spores confidently. mass spectrometry-based tools represent a powerful approach to the efficient discovery and identification of such protein marke ...201424379445
microbicidal power of alpha radiation in sterilizing germinating bacillus anthracis spores.radioimmunotherapy (rit) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver microbicidal radioactive nuclides to a site of infection. in this study, we investigated the microbicidal properties of an alpha particle-emitting 213bi-labeled monoclonal antibody (mab), ea2-1 (213bi-ea2-1), that binds to the immunodominant antigen on bacillus anthracis spores. our results showed that dormant spores were resistant to 213bi-ea2-1. significant spore killing was ...201424379209
nanoscale structural and mechanical analysis of bacillus anthracis spores inactivated with rapid dry heating.effective killing of bacillus anthracis spores is of paramount importance to antibioterrorism, food safety, environmental protection, and the medical device industry. thus, a deeper understanding of the mechanisms of spore resistance and inactivation is highly desired for developing new strategies or improving the known methods for spore destruction. previous studies have shown that spore inactivation mechanisms differ considerably depending upon the killing agents, such as heat (wet heat, dry h ...201424375142
quantitative anti-pa igg elisa; assessment and comparability with the anthrax toxin neutralization assay in goats.presently, few data exist on the level and duration of anti-protective antigen (pa) igg in vaccinated livestock. various adaptation of enzyme-linked immunosorbent assays (elisas) have been developed in studies to assess immune response following vaccination, albeit mostly in laboratory rodent models. the quantitative anti-anthrax igg elisa in this study describes a method of enumerating the concentration of anti-pa specific igg present in sera of immunized goats, with the aid of an affinity-puri ...201324373579
effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.we evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (ava). ava's originally licensed schedule was 6 subcutaneous (sq) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired.201424373307
anthrax lethal toxin inhibits translation of hypoxia-inducible factor 1α and causes decreased tolerance to hypoxic stress.hypoxia is considered to be a contributor to the pathology associated with administration of anthrax lethal toxin (lt). however, we report here that serum lactate levels in lt-treated mice are reduced, a finding inconsistent with the anaerobic metabolism expected to occur during hypoxia. reduced lactate levels are also observed in the culture supernatants of lt-treated cells. lt inhibits the accumulation of hypoxia-inducible factor (hif)-1α, a subunit of hif-1, the master regulator directing cel ...201424366872
novel role for the ycegh tellurite resistance genes in the pathogenesis of bacillus anthracis.bacillus anthracis, the causative agent of anthrax, relies on multiple virulence factors to subvert the host immune defense. using caenorhabditis elegans as an infection model, we screened approximately 5,000 transposon mutants of b. anthracis sterne for decreased virulence. one of the attenuated mutants resulted in loss of expression of yceg and yceh, the last two genes in a six-gene cluster of tellurite resistance genes. we generated an analogous insertional mutant to confirm the phenotype and ...201424366250
genetic evidence for the involvement of the s-layer protein gene sap and the sporulation genes spo0a, spo0b, and spo0f in phage ap50c infection of bacillus anthracis.in order to better characterize the bacillus anthracis typing phage ap50c, we designed a genetic screen to identify its bacterial receptor. insertions of the transposon mariner or targeted deletions of the structural gene for the s-layer protein sap and the sporulation genes spo0a, spo0b, and spo0f in b. anthracis sterne resulted in phage resistance with concomitant defects in phage adsorption and infectivity. electron microscopy of bacteria incubated with ap50c revealed phage particles associat ...201424363347
daptomycin exerts rapid bactericidal activity against bacillus anthracis without disrupting membrane integrity.to examine whether the novel cyclic lipopeptide antibiotic daptomycin could be used to treat anthrax and to study the mechanisms underlying its bactericidal action against bacillus anthracis.201424362329
allelic-dependent expression of an activating fc receptor on b cells enhances humoral immune responses.b cells are pivotal regulators of acquired immune responses, and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of b cell function can substantially alter immunological responses. the balance of negative and positive signals in maintaining an appropriate b cell activation threshold is critical in b lymphocyte immune tolerance and autoreactivity. fcγriib (cd32b), the only recognized fcγ receptor on b cells, provides immunoglobulin ...201324353158
mechanism of killing of spores of bacillus anthracis in a high-temperature gas environment, and analysis of dna damage generated by various decontamination treatments of spores of bacillus anthracis, bacillus subtilis and bacillus thuringiensis.to determine how hydrated bacillus anthracis spores are killed in a high-temperature gas environment (htge), and how spores of several bacillus species including b. anthracis are killed by uv radiation, dry heat, wet heat and desiccation.201424344920
histopathological effects of anthrax lethal factor on rat liver.bacillus anthracis, the causative agent of anthrax, has become an increasingly important scientific topic due to its potential role in bioterrorism. the lethal toxin (lt) of b. anthracis consists of lethal factor (lf) and a protective antigen (pa). this study investigated whether only lethal factor was efficient as a hepatotoxin in the absence of the pa. to achieve this aim, lf (100 µg/kg body weight, dissolved in sterile distilled water) or distilled water vehicle were intraperitoneally injecte ...201624344743
applications of docking and molecular dynamic studies on the search for new drugs against the biological warfare agents bacillus anthracis and yersinia pestis.the fear of biological warfare agents (bwa) use by terrorists is the major concern of the security agencies and health authorities worldwide today. the non-existence of vaccines or drugs against most bwa and the possibility of genetic modified strains has turned the search for new drugs to a state of urgency. fast in silico techniques are, therefore, perfect tools for this task once they can quickly provide structures of several new lead compounds for further experimental work. here we try to pr ...201324341424
identification of toxin inhibitors using a magnetic nanosensor-based assay.a magnetic nanosensor-based method is described to screen a library of drugs for potential binding to toxins. screening is performed by measuring changes in the magnetic relaxation signal of the nanosensors (bmr nanosensors) in aqueous suspension upon addition of the toxin. the anthrax lethal factor (alf) is selected as a model toxin to test the ability of our bmr nanosensor-based screening method to identify potential inhibitors of the toxin. out of 30 molecules screened, sulindac, naproxen and ...201424339142
bacillus thuringiensis as a surrogate for bacillus anthracis in aerosol research.characterization of candidate surrogate spores prior to experimental use is critical to confirm that the surrogate characteristics are as closely similar as possible to those of the pathogenic agent of interest. this review compares the physical properties inherent to spores of bacillus anthracis (ba) and bacillus thuringiensis (bt) that impact their movement in air and interaction with surfaces, including size, shape, density, surface morphology, structure and hydrophobicity. also evaluated is ...201424338558
arsenic trioxide and other arsenical compounds inhibit the nlrp1, nlrp3, and naip5/nlrc4 inflammasomes.inflammasomes are large cytoplasmic multiprotein complexes that activate caspase-1 in response to diverse intracellular danger signals. inflammasome components termed nucleotide-binding oligomerization domain-like receptor (nlr) proteins act as sensors for pathogen-associated molecular patterns, stress, or danger stimuli. we discovered that arsenicals, including arsenic trioxide and sodium arsenite, inhibited activation of the nlrp1, nlrp3, and naip5/nlrc4 inflammasomes by their respective activ ...201324337744
cross-institute evaluations of inhibitor-resistant pcr reagents for direct testing of aerosol and blood samples containing biological warfare agent dna.rapid pathogen detection is crucial for the timely introduction of therapeutics. two groups (one in the united kingdom and one in the united states) independently evaluated inhibitor-resistant pcr reagents for the direct testing of substrates. in the united kingdom, a multiplexed bacillus anthracis (target) and bacillus subtilis (internal-control) pcr was used to evaluate 4 reagents against 5 pcr inhibitors and down-selected the taqman fast virus 1-step master mix (life technologies inc.). in th ...201424334660
a post-flood co-outbreak of anthrax and enterotoxemia in beef cattle of liaoning province in north-eastern china. 201424333640
surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.establishment of humoral immunity against pathogens is dependent on events that occur in the germinal center and the subsequent induction of high-affinity neutralizing antibodies. quantitative assays that allow monitoring of affinity maturation and duration of antibody responses can provide useful information regarding the efficacy of vaccines and adjuvants. using an anthrax protective antigen (rpa) and alum model antigen/adjuvant system, we describe a methodology for monitoring antigen-specific ...201424316020
synthesis of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazines that have antibacterial activity and also inhibit inorganic pyrophosphatase.inorganic pyrophosphatases are potential targets for the development of novel antibacterial agents. a pyrophosphatase-coupled high-throughput screening assay intended to detect o-succinyl benzoic acid coenzyme a (osb coa) synthetase inhibitors led to the unexpected discovery of a new series of novel inorganic pyrophosphatase inhibitors. lead optimization studies resulted in a series of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazine derivatives that were prepared by an efficient synthetic pathw ...201424315189
eco-genetic structure of bacillus cereus sensu lato populations from different environments in northeastern poland.the bacillus cereus group, which includes entomopathogens and etiologic agents of foodborne illness or anthrax, persists in various environments. the basis of their ecological diversification remains largely undescribed. here we present the genetic structure and phylogeny of 273 soil b. cereus s.l. isolates from diverse habitats in northeastern poland, with samplings acquired from the last european natural forest (białowieża national park), the largest marshes in europe (biebrza national park), ...201324312460
intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (ad5-paopt). a single intramuscular injection of ad5-paopt resulted in rapid and robust humoral and cellular immune responses in fisher 344 rats. animals intramuscularly inoculated with a sing ...201424307239
identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins.clostridium difficile is a major cause of infectious diarrhea worldwide. although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. also, apart from the toxins, proteins exported by c. difficile into the extracellular milieu have been poorly studied. in order to identify novel extracellular factors of c. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and r20291, using liq ...201324303041
introduction of the republic of korea-the united states of america's joint exercise against biothreats in 2013: able response 13.the republic of korea (rok) and the the united states of america (usa) has held joint exercises to respond to biothreats in the korean peninsula since 2011. the exercise was called able response (ar) and it aims to coordinate interministerial procedures inside korea and international procedures in requesting the medical resources urgently between rok and usa, and among rok and the united nations, and nongovernmental organizations. ar13 was a functional exercise with a scenario that presumed a se ...201324298445
risk practices for animal and human anthrax in bangladesh: an exploratory study.from august 2009 to october 2010, international centre for diarrheal disease research, bangladesh and the institute of epidemiology, disease control and research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program.201324298326
comparative evaluation of eleven commercial dna extraction kits for real-time pcr detection of bacillus anthracis spores in spiked dairy samples.spores of bacillus anthracis are highly resistant and can survive conditions used for food preservation. sample size and complexity represent the major hurdles for pathogen detection in food-related settings. eleven commercial dna extraction kits were evaluated for detection of b. anthracis spores by quantitative real-time pcr (qpcr) in dairy products. dna was extracted from serial dilutions of b. anthracis spores in milk powder, cream cheese, whole milk and buttermilk. three kits (qiaamp dna mi ...201424291177
small molecule inhibitors of anthrax lethal factor toxin.this manuscript describes the preparation of new small molecule inhibitors of bacillus anthracis lethal factor. our starting point was the symmetrical, bis-quinolinyl compound 1 (nsc 12155). optimization of one half of this molecule led to new lf inhibitors that were desymmetrized to afford more drug-like compounds.201424290062
development of a simple and rapid method for the specific identification of organism causing anthrax by slide latex agglutination.a specific latex agglutination test (lat) based on anti-pa (protective antigen) antibodies having detection limit of 5 × 10(4) formalin treated bacillus anthracis cells or 110 ng of pa was optimized in this study. the optimized lat could detect anthrax toxin in whole blood as well as in serum from the animal models of anthrax infection. the protocol is a simple and promising method for the specific detection of bacteria causing anthrax under routine laboratory, as well as in field, conditions wi ...201424286182
modified aoac three step method (officialmethod 2008.05): consolidation of fractions b and c.the aoac quantitative three step method (tsm; aoac official method sm 2008.05) is validated for testing the efficacy of liquid sporicides against spores of bacillus subtilis and bacillus anthracis on selected hard, nonporous, and porous surfaces. the tsm uses 5x5x1 mm inoculated coupons (carriers), which are placed in 400 microl liquid sporicidal agent contained in a microcentrifuge tube. following exposure of inoculated carriers to the test chemical and subsequent neutralization, viable spores ...201324282930
fumigation of a laboratory-scale hvac system with hydrogen peroxide for decontamination following a biological contamination incident.to evaluate hydrogen peroxide vapour (h2 o2 ) for its ability to inactivate bacillus spores within a laboratory-scale heating, ventilation and air-conditioning (hvac) duct system.201424279292
immunoproteomically identified gbaa_0345, alkyl hydroperoxide reductase subunit c is a potential target for multivalent anthrax vaccine.anthrax is caused by the spore-forming bacterium bacillus anthracis, which has been used as a weapon for bioterrorism. although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. high rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. to identify novel vaccine candidates, we applied an immunoproteomics approach. using sera from convalescent guinea pigs or from human patients with anthrax ...201424273028
enhanced production of human full-length immunoglobulin g1 in the periplasm of escherichia coli.monoclonal antibodies are currently the most important pharmaceutical proteins, and the economic production of functional immunoglobulin g (igg) is an important issue in biotechnology. recent successes in the development of aglycosylated igg variants that do not require glycosylation for effector functions have increased the use of escherichia coli as an alternative host for economic production of igg, instead of traditional mammalian host expression systems. here, we have developed a new e. col ...201424270917
characterization of the collagen-like exosporium protein, bcla1, of clostridium difficile spores.spores of clostridium difficile are essential for infection, persistence and transmission of c. difficile infections (cdi). proteins of the surface of c. difficile spores are thought to be essential for initiation and persistence of cdi. in this work, we demonstrate that three c. difficile collagen-like exosporium proteins (bcla) encoded in the c. difficile 630 genome are expressed during sporulation and localize to the spore via their n-terminal domains. using polyclonal antibodies against the ...201424269655
investigations on the interactions of λphage-derived peptides against the srta mechanism in bacillus anthracis.bacillus anthracis is a well-known bioweapon pathogen, which coordinates the expression of its virulence factors in response to a specific environmental signal by its protein architecture. absences of sortase signal functioning may fail to assemble the surface linked proteins and so b. anthracis cannot sustain an infection with host cells. targeting the signaling mechanism of b. anthracis can be achieved by inhibition of srta enzyme through λphage-derived plyg. the lysin enzyme plyg is experimen ...201424264995
hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin.anthrax lethal toxin is a classical ab toxin comprised of two components: protective antigen (pa) and lethal factor (lf). here, we show that following assembly and endocytosis, pa forms a channel that translocates lf, not only into the cytosol, but also into the lumen of endosomal intraluminal vesicles (ilvs). these ilvs can fuse and release lf into the cytosol, where lf can proteolyze and disable host targets. we find that lf can persist in ilvs for days, fully sheltered from proteolytic degrad ...201324239351
single, double and quadruple alanine substitutions at oligomeric interfaces identify hydrophobicity as the key determinant of human neutrophil alpha defensin hnp1 function.hnp1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including tyr¹⁶, ile²⁰, leu²⁵, and phe²⁸. previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: i20a-hnp1 and l25a-hnp1, plus the double alanine mutants i20a/l25a-hnp1 and y16a/f28a-hnp1, an ...201324236072
a hierarchical distance sampling approach to estimating mortality rates from opportunistic carcass surveillance data.distance sampling is widely used to estimate the abundance or density of wildlife populations. methods to estimate wildlife mortality rates have developed largely independently from distance sampling, despite the conceptual similarities between estimation of cumulative mortality and the population density of living animals. conventional distance sampling analyses rely on the assumption that animals are distributed uniformly with respect to transects and thus require randomized placement of trans ...201324224079
an unusual mechanism of isopeptide bond formation attaches the collagenlike glycoprotein bcla to the exosporium of bacillus anthracis. 201324222492
nlrp1 is an inflammasome sensor for toxoplasma gondii.the obligate intracellular parasite toxoplasma gondii is able to infect nearly all nucleated cell types of warm-blooded animals. this is achieved through the injection of hundreds of parasite effectors into the host cell cytosol, allowing the parasite to establish a vacuolar niche for growth, replication, and persistence. here we show that toxoplasma infection actives an inflammasome response in mice and rats, an innate immune sensing system designed to survey the host cytosol for foreign compon ...201424218483
modulation of the bacillus anthracis secretome by the immune inhibitor a1 protease.the bacillus anthracis secretome includes protective antigen, lethal factor, and edema factor, which are the components of anthrax toxin, and other proteins with known or potential roles in anthrax disease. immune inhibitor a1 (inha1) is a secreted metalloprotease that is unique to pathogenic members of the bacillus genus and has been associated with cleavage of host proteins during infection. here, we report the effect of inha1 on the b. anthracis secretome. differential in-gel electrophoresis ...201424214942
innate immune protection against infectious diseases by pulmonary administration of a phospholipid-conjugated tlr7 ligand.pulmonary administration of toll-like receptor (tlr) ligands protects hosts from inhaled pathogens. however, systemic side effects induced by tlr stimulation limit clinical development. here, a small-molecule tlr7 ligand conjugated with phospholipid, 1v270 (also designated tmx201), was tested for innate immune activation and its ability to prevent pulmonary infection in mice. we hypothesized that phospholipid conjugation would increase internalization by immune cells and localize the compound in ...201324192551
selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses.pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. one common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. to identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. here we report that 4-bromobenzaldehyde n-( ...201324191014
aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles.aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. when dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1-20μm. there is increasing evidence that nanoparticles around or less than 200nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. in the present st ...201424188959
thermostable single domain antibody-maltose binding protein fusion for bacillus anthracis spore protein bcla detection.we constructed a genetic fusion of a single domain antibody (sdab) with the thermal stable maltose binding protein from the thermophile pyrococcus furiosus (pfumbp). produced in the escherichia coli cytoplasm with high yield, it proved to be a rugged and effective immunoreagent. the sdab-a5 binds bcla, a bacillus anthracis spore protein, with high affinity (k(d) ∼ 50 pm). mbps, including the thermostable pfumbp, have been demonstrated to be excellent folding chaperones, improving production of m ...201424184358
evaluation of sampling methods for bacillus spore-contaminated hvac filters.the objective of this study was to compare an extraction-based sampling method to two vacuum-based sampling methods (vacuum sock and 37mm cassette filter) with regards to their ability to recover bacillus atrophaeus spores (surrogate for bacillus anthracis) from pleated heating, ventilation, and air conditioning (hvac) filters that are typically found in commercial and residential buildings. electrostatic and mechanical hvac filters were tested, both without and after loading with dust to 50% of ...201424184312
evaluation of swabs and transport media for the recovery of yersinia pestis.the government accountability office report investigating the surface sampling methods used during the 2001 mail contamination with bacillus anthracis brought to light certain knowledge gaps that existed regarding environmental sampling with biothreat agents. should a contamination event occur that involves non-spore forming biological select agents, such as yersinia pestis, surface sample collection and processing protocols specific for these organisms will be needed. two y. pestis strains (vir ...201424184311
comparative evaluation of vacuum-based surface sampling methods for collection of bacillus spores.in this study, four commonly-used sampling devices (vacuum socks, 37 mm 0.8 μm mixed cellulose ester (mce) filter cassettes, 37 mm 0.3 μm polytetrafluoroethylene (ptfe) filter cassettes, and 3m™ forensic filters) were comparatively evaluated for their ability to recover surface-associated spores. aerosolized spores (~10(5)cfucm(-2)) of a bacillus anthracis surrogate were allowed to settle onto three material types (concrete, carpet, and upholstery). ten replicate samples were collected using eac ...201324184017
[diagnosis and treatment of anthrax in palpebral localization: report of a case and review of literature]. 201324171070
targeting dxp synthase in human pathogens: enzyme inhibition and antimicrobial activity of butylacetylphosphonate.the unique methylerythritol phosphate pathway for isoprenoid biosynthesis is essential in most bacterial pathogens. the first enzyme in this pathway, 1-deoxy-d-xylulose 5-phosphate (dxp) synthase, catalyzes a distinct thiamin diphosphate (thdp)-dependent reaction to form dxp from d-glyceraldehyde 3-phosphate (d-gap) and pyruvate and represents a potential anti-infective drug target. we have previously demonstrated that the unnatural bisubstrate analog, butylacetylphosphonate (bap), exhibits sele ...201424169798
the designer proline-rich antibacterial peptide a3-apo prevents bacillus anthracis mortality by deactivating bacterial toxins.proline-rich antibacterial peptides protect experimental animals from bacterial challenge even if they are unable to kill the microorganisms in vitro. their major in vivo modes of action are inhibition of bacterial protein folding and immunostimulation. here we investigated whether the proline-rich antibacterial peptide dimer a3-apo was able to inhibit bacillus cereus enterotoxin production in vitro and restrict the proliferation of lethal toxin-induced bacillus anthracis replication in mouse ma ...201424164262
heme oxygenation and the widening paradigm of heme degradation.heme degradation through the action of heme oxygenase (ho) is unusual in that it utilizes heme as both a substrate and cofactor for its own degradation. ho catalyzes the oxygen-dependent degradation of heme to biliverdin with the release of co and "free" iron. the characterization of ho enzymes from humans to bacteria reveals a similar overall structural fold that contributes to the unique reaction manifold. the heme oxygenases share a similar heme-dependent activation of o2 to the ferric hydrop ...201424161941
serological correlate of protection in guinea pigs for a recombinant protective antigen anthrax vaccine produced from bacillus brevis.recombinant protective antigen (rpa) is the active pharmaceutical ingredient of a second generation anthrax vaccine undergoing clinical trials both in korea and the usa. by using the rpa produced from bacillus brevis pnu212 expression system, correlations of serological immune response to anthrax protection efficacy were analyzed in a guinea pig model.201224159510
cationic quaternized aminocalix[4]arenes: cytotoxicity, haemolytic and antibacterial activities.this study reports the characterization of three cationic amphiphillic aminocalix[4]arenes as potential antimicrobial agents in vitro. in cytotoxicity tests on mouse macrophage raw 264.7 cells aminocalix[4]arenes 1 and 3 showed no toxicity up to 200 and 100 μm concentrations, respectively, while 2 was non-toxic only up to 50 μm. with regard to the haemolytic activity on rabbit red blood cells, 1 was not active at concentrations up to 100 μm in contrast to the other two studied macrocycles. compo ...201324157345
circulating lethal toxin decreases the ability of neutrophils to respond to bacillus anthracis.polymorphonuclear leucocytes (pmns) play a protective role during bacillus anthracis infection. however, b. anthracis is able to subvert the pmn response effectively as evidenced by the high mortality rates of anthrax. one major virulence factor produced by b. anthracis, lethal toxin (lt), is necessary for dissemination in the bsl2 model of mouse infection. while human and mouse pmns kill vegetative b. anthracis, short in vitro half-lives of pmns have made it difficult to determine how or if lt ...201424152301
detection of anthrax and other pathogens using a unique liquid array technology.a bead-based liquid hybridization assay, luminex(®) 100™, was used to identify four pathogenic bacteria, bacillus anthracis, clostridium botulinum, francisella tularensis subsp. tularensis, and yersinia pestis, and several close relatives. hybridization between pcr-amplified target sequences and probe sequences (located within the 23s ribosomal rna gene rrl and the genes related to the toxicity of each bacterium) was detected in single-probe or multiple-probe assays, depending on the organism. t ...201424147813
structural and biological studies on bacterial nitric oxide synthase inhibitors.nitric oxide (no) produced by bacterial nos functions as a cytoprotective agent against oxidative stress in staphylococcus aureus, bacillus anthracis, and bacillus subtilis. the screening of several nos-selective inhibitors uncovered two inhibitors with potential antimicrobial properties. these two compounds impede the growth of b. subtilis under oxidative stress, and crystal structures show that each compound exhibits a unique binding mode. both compounds serve as excellent leads for the future ...201324145412
a multiplex bead-based suspension array assay for interrogation of phylogenetically informative single nucleotide polymorphisms for bacillus anthracis.single nucleotide polymorphisms (snps) are abundant in genomes of all species and represent informative dna markers extensively used to analyze phylogenetic relationships between strains. medium to high throughput, open methodologies able to test many snps in a minimum time are therefore in great need. by using the versatile luminex® xtag technology, we developed an efficient multiplexed snp genotyping assay to score 13 phylogenetically informative snps within the genome of bacillus anthracis. t ...201324140576
an unholy disease in the holy land: the history of anthrax between the jordan river and the mediterranean sea (1909-2012).the history of recorded cases of anthrax in human beings and animals from 1909 to 2012 in the area between the jordan river and the mediterranean sea is reviewed. the disease was endemic until the middle of the 20th century, but the incidence decreased thereafter, with only sporadic cases from the 1980s onwards. human cases have not been diagnosed in the region since 1984 and the number of episodes of animal disease has reduced to less than one per year. this decline is mostly due to the disrupt ...201424135549
anthrax of the lower lip.anthrax of the oral cavity and oropharynx is well known, whereas anthrax of the lips is very rare. we present a case of anthrax of the lower lip in a 57-year-old man. the infection was characterized by a wide, black eschar, surrounded by vesicles, crusts, and erythematous-edematous halo, with submandibular and laterocervical lymphadenopathy. the oral cavity, oropharynx, and tonsils were normal. laboratory examinations revealed leukocytosis and increased inflammatory markers. otolaryngologic, gas ...201324120906
zoonoses in rural veterinarians in the central region of argentina.to estimate the frequency of zoonoses in rural veterinarians and to search for risk factors.201324118152
acute infections in intravenous drug users. 201324115713
proteomic analysis of bacillus subtilis strains engineered for improved production of heterologous proteins.the use of bacterial systems for recombinant protein production has advantages of simplicity, time and cost over competing systems. however, widely used bacterial expression systems (e.g. escherichia coli, pseudomonas fluorescens) are not able to secrete soluble proteins directly into the culture medium. this limits yields and increases downstream processing time and costs. in contrast, bacillus spp. secrete native enzymes directly into the culture medium at grams-per-litre quantities, although ...201324115457
b. anthracis associated cardiovascular dysfunction and shock: the potential contribution of both non-toxin and toxin components.the development of cardiovascular dysfunction and shock in patients with invasive bacillus anthracis infection has a particularly poor prognosis. growing evidence indicates that several bacterial components likely play important pathogenic roles in this injury. as with other pathogenic gram-positive bacteria, the b. anthracis cell wall and its peptidoglycan constituent produce a robust inflammatory response with its attendant tissue injury, disseminated intravascular coagulation and shock. howev ...201324107194
inhibition of anthrax lethal factor by curcumin and chemically modified curcumin derivatives.curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric (curcuma longa), has been shown to inhibit the activities of numerous enzymes and signaling molecules involved in cancer, bacterial and viral infections and inflammatory diseases. we have investigated the inhibitory activities of curcumin and chemically modified curcumin (cmc) derivatives toward lethal factor (lf), the proteolytic component of anthrax toxin produced by the bacterium bacillus anthracis. curcumin (co ...201424102525
bacillus cereus sensu lato genomes: basis for identifying anthrax disease strain sources. 201324092785
whole-genome sequences of 94 environmental isolates of bacillus cereus sensu lato.bacillus cereus sensu lato is a species complex that includes the anthrax pathogen bacillus anthracis and other bacterial species of medical, industrial, and ecological importance. their phenotypes of interest are typically linked to large plasmids that are closely related to the anthrax plasmids pxo1 and pxo2. here, we present the draft genome sequences of 94 isolates of b. cereus sensu lato, which were chosen for their plasmid content and environmental origins.201324092776
calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis.the protective antigen component of bacillus anthracis toxins can interact with at least three distinct proteins on the host cell surface, capillary morphogenesis gene 2 (cmg2), tumor endothelial marker 8, and β1-integrin, and, with the assistance of other host proteins, enters targeted cells by receptor-mediated endocytosis. using an antisense-based phenotypic screen, we discovered the role of calpains in this process. we show that functions of a ubiquitous ca(2+)-dependent cysteine protease, c ...201324085852
prophylaxis and treatment of anthrax in pregnant women.to review the safety and pharmacokinetics of antimicrobials recommended for anthrax postexposure prophylaxis and treatment in pregnant women.201324084549
influence of temperature and organic load on chemical disinfection of geobacillus steareothermophilus spores, a surrogate for bacillus anthracis.this study evaluated the influence of temperature and organic load on the effectiveness of domestic bleach (db), surface decontamination foam (sdf), and virkon in inactivating geobacillus stearothermophilus spores, which are a surrogate for bacillus anthracis spores. the spores were suspended in light or heavy organic preparations and the suspension was applied to stainless steel carrier disks. the dried spore inoculum was covered with the disinfectants and the disks were then incubated at vario ...201324082400
bacillus anthracis, virulence factors, pcr, and interpretation of results. 201324067452
a chemically synthesized capture agent enables the selective, sensitive, and robust electrochemical detection of anthrax protective antigen.we report on a robust and sensitive approach for detecting protective antigen (pa) exotoxin from bacillus anthracis in complex media. a peptide-based capture agent against pa was developed by improving a bacteria display-developed peptide into a highly selective biligand through in situ click screening against a large, chemically synthesized peptide library. this biligand was coupled with an electrochemical enzyme-linked immunosorbent assay utilizing nanostructured gold electrodes. the resultant ...201324063758
anthrax toxin receptor 2 promotes human uterine smooth muscle cell viability, migration and contractility.previously we demonstrated anthrax toxin receptor 2 knockout (antxr2(-/-)) mice are fertile but fail to deliver their pups at term. this parturition defect is associated with overaccumulation of extracellular matrix proteins and decreased myometrial cell content in the uterus. myometrial cell loss in antxr2(-/-) uterine tissue prompted us to evaluate if antxr2 is essential for human uterine smooth muscle cell viability and function.201424060446
quantitative models of the dose-response and time course of inhalational anthrax in humans.anthrax poses a community health risk due to accidental or intentional aerosol release. reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. analyses of available data from exposures and infections of humans and non-human primates are often contradictory. we review existing quantitative inhalational anthrax dose-response models in light of criter ...201324058320
a sensitive & specific multiplex pcr assay for simultaneous detection of bacillus anthracis, yersinia pestis, burkholderia pseudomallei & brucella species.bacillus anthracis, yersinia pestis, burkholderia pseudomallei and brucella species are potential biowarfare agents. classical bacteriological methods for their identification are cumbersome, time consuming and of potential risk to the handler.201324056564
the two ccda proteins of bacillus anthracis differentially affect virulence gene expression and sporulation.the cytochrome c maturation system influences the expression of virulence factors in bacillus anthracis. b. anthracis carries two copies of the ccda gene, encoding predicted thiol-disulfide oxidoreductases that contribute to cytochrome c maturation, while the closely related organism bacillus subtilis carries only one copy of ccda. to investigate the roles of the two ccda gene copies in b. anthracis, strains were constructed without each ccda gene, and one strain was constructed without both cop ...201324056109
deletion modification enhances anthrax specific immunity and protective efficacy of a hepatitis b core particle-based anthrax epitope vaccine.protective antigen (pa) is one of the major virulence factors of anthrax and is also the major constituent of the current anthrax vaccine. previously, we found that the 2β2-2β3 loop of pa contains a dominant neutralizing epitope, the sffd. we successfully inserted the 2β2-2β3 loop of pa into the major immunodominant region (mir) of hepatitis b virus core (hbc) protein. the resulting fusion protein, termed hbc-n144-pa-loop2 (hbcl2), can effectively produce anthrax specific protective antibodies i ...201424054942
haem-based sensors: a still growing old superfamily.the haem-based sensors are chimeric multi-domain proteins responsible for the cellular adaptive responses to environmental changes. the signal transduction is mediated by the sensing capability of the haem-binding domain, which transmits a usable signal to the cognate transmitter domain, responsible for providing the adequate answer. four major families of haem-based sensors can be recognized, depending on the nature of the haem-binding domain: (i) the haem-binding pas domain, (ii) the co-sensit ...201324054793
surface display of recombinant proteins on escherichia coli by bcla exosporium of bacillus anthracis.the anchoring motif is one of the most important aspects of cell surface display as well as efficient and stable display of target proteins. thus, there is currently a need for the identification and isolation of novel anchoring motifs.201324053632
overcoming target-mediated quinolone resistance in topoisomerase iv by introducing metal-ion-independent drug-enzyme interactions.quinolones, which target gyrase and topoisomerase iv, are the most widely prescribed antibacterials worldwide. unfortunately, their use is threatened by the increasing prevalence of target-mediated drug resistance. greater than 90% of mutations that confer quinolone resistance act by disrupting enzyme-drug interactions coordinated by a critical water-metal ion bridge. quinazolinediones are quinolone-like drugs but lack the skeletal features necessary to support the bridge interaction. these comp ...201324047414
rapid targeted gene disruption in bacillus anthracis.anthrax is a zoonotic disease recognized to affect herbivores since biblical times and has the widest range of susceptible host species of any known pathogen. the ease with which the bacterium can be weaponized and its recent deliberate use as an agent of terror, have highlighted the importance of gaining a deeper understanding and effective countermeasures for this important pathogen. high quality sequence data has opened the possibility of systematic dissection of how genes distributed on both ...201324047152
bacillus anthracis has two independent bottlenecks that are dependent on the portal of entry in an intranasal model of inhalational infection.bacillus anthracis can cause inhalational anthrax. murine inhalational b. anthracis infections have two portals of entry, the nasal mucosa-associated lymphoid tissue (nalt) and the lumen of the lungs. analysis of the dissemination from these sites is hindered because infections are asynchronous and asymptomatic until the hosts near death. to further understand and compare how b. anthracis disseminates from these two different environments, clonal analysis was employed using a library of equally ...201324042112
hollow-fiber pharmacodynamic studies and mathematical modeling to predict the efficacy of amoxicillin for anthrax postexposure prophylaxis in pregnant women and children.amoxicillin is considered an option for postexposure prophylaxis of bacillus anthracis in pregnant and postpartum women who are breastfeeding and in children because of the potential toxicities of ciprofloxacin and doxycycline to the fetus and child. the amoxicillin regimen that effectively kills b. anthracis and prevents resistance is unknown. fourteen-day dose range and dose fractionation studies were conducted in in vitro pharmacodynamic models to identify the exposure intensity and pharmacod ...201324041894
infectious diseases in poland in 2011.the aim of the study was assessment of the epidemiological situation of infectious and parasitic diseases in poland in 2011 materials and methods: the main source of data to develop the statistical overview was the annual bulletin "infectious diseases in poland in 2011," and "vaccinations in poland in 2011,"/niph-nih, csi, 2011 and information contained in the articles of epidemiological journal in which authors depth discussion of the epidemiological situation of 27 diseases or groups of diseas ...201324040711
evidence of local persistence of human anthrax in the country of georgia associated with environmental and anthropogenic factors.anthrax is a soil-borne disease caused by the bacterium bacillus anthracis and is considered a neglected zoonosis. in the country of georgia, recent reports have indicated an increase in the incidence of human anthrax. identifying sub-national areas of increased risk may help direct appropriate public health control measures. the purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters.201324040426
detection of bacillus anthracis dna in complex soil and air samples using next-generation sequencing.bacillus anthracis is the potentially lethal etiologic agent of anthrax disease, and is a significant concern in the realm of biodefense. one of the cornerstones of an effective biodefense strategy is the ability to detect infectious agents with a high degree of sensitivity and specificity in the context of a complex sample background. the nature of the b. anthracis genome, however, renders specific detection difficult, due to close homology with b. cereus and b. thuringiensis. we therefore elec ...201324039948
effect of delayed anthrax vaccine dose on bacillus anthracis protective antigen igg response and lethal toxin neutralization activity.we describe the bacillus anthracis protective antigen igg antibody response and the b. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (ava, biothrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of ava. overall, 23.6% of subjects showed detectable anti-pa igg before the boost, compared to 99.2% (p<0.0001) 28 days after the boost. geometric mean anti-pa igg concentra ...201324026013
[current situation of endemic status, prevention and control of neglected zoonotic diseases in china].neglected zoonotic diseases not only threaten the health of human, especially to the livestock keepers in poverty-stricken areas but also cause great economic losses to the animal husbandry. this paper reviews the current situation of the endemic status, prevention and control of neglected zoonotic diseases existing in china including rabies, bovine tuberculosis, brucellosis, anthrax, leptospirosis, echinococcosis, cysticercosis, leishmaniasis and fascioliasis, so as to provide the basic informa ...201324024457
beetroot-pigment-derived colorimetric sensor for detection of calcium dipicolinate in bacterial spores.in this proof-of-concept study, we describe the use of the main red beet pigment betanin for the quantification of calcium dipicolinate in bacterial spores, including bacillus anthracis. in the presence of europium(iii) ions, betanin is converted to a water-soluble, non-luminescent orange 1∶1 complex with a stability constant of 1.4 × 10(5) l mol(-1). the addition of calcium dipicolinate, largely found in bacterial spores, changes the color of the aqueous solution of [eu(bn)(+)] from orange to m ...201324019934
anthrax edema factor toxicity is strongly mediated by the n-end rule.anthrax edema factor (ef) is a calmodulin-dependent adenylate cyclase that converts adenosine triphosphate (atp) into 3'-5'-cyclic adenosine monophosphate (camp), contributing to the establishment of bacillus anthracis infections and the resulting pathophysiology. we show that ef adenylate cyclase toxin activity is strongly mediated by the n-end rule, and thus is dependent on the identity of the n-terminal amino acid. ef variants having different n-terminal residues varied by more than 100-fold ...201324015319
cyclodextrin derivatives as anti-infectives.cyclodextrin derivatives can be utilized as anti-infectives with pore-forming proteins as the targets. the highly efficient selection of potent inhibitors was achieved because per-substituted cyclodextrins have the same symmetry as the target pores. inhibitors of several bacterial toxins produced by bacillus anthracis, staphylococcus aureus, clostridium perfringens, clostridium botulinum, and clostridium difficile were identified from a library of ∼200 cd derivatives. it was demonstrated that mu ...201324011515
gastrointestinal anthrax: clinical experience in 5 cases.bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal and cutaneous. the gastrointestinal (gi) anthrax develops after eating contaminated meat. thus, in this paper were report 5 cases of intestinal anthrax.201324009958
anthrax of the lower eyelid.because cutaneous anthrax, caused by bacillus anthracis, is rare in developed countries, sporadic cases of anthrax may easily be overlooked because the diagnosis is often difficult to make. lower eyelid involvement of anthrax is rare in clinical practice. a 40-year-old woman with a history of contact with animals was evaluated and treated for a left lower eyelid lesion with a black eschar on it. a diagnosis of cutaneous anthrax had been made and intravenous penicillin had been given by the depar ...200324009441
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