Publications

anthrax toxin lethal factor domain 3 is highly mobile and responsive to ligand binding.	the secreted anthrax toxin consists of three components: the protective antigen (pa), edema factor (ef) and lethal factor (lf). lf, a zinc metalloproteinase, compromises the host immune system primarily by targeting mitogen-activated protein kinase kinases in macrophages. peptide substrates and small-molecule inhibitors bind lf in the space between domains 3 and 4 of the hydrolase. domain 3 is attached on a hinge to domain 2 via residues ile300 and pro385, and can move through an angular arc of ...	2014	25372673
being prepared: bioterrorism and mass prophylaxis: part ii.	although several biological agents have been recognized as presenting a significant threat to public health if used in a bioterrorist attack, those that are of greatest importance are known as the category a agents: bacillus anthracis (anthrax); variola major (smallpox); yersinia pestis (plague); francisella tularensis (tularemia); ribonucleic acid viruses (hemorrhagic fevers); and clostridium botulinum (botulism toxin). in the previous issue, part i of this review focused on the clinical presen ...	2014	25356890
a reaction path study of the catalysis and inhibition of the bacillus anthracis capd γ-glutamyl transpeptidase.	the capd enzyme of bacillus anthracis is a γ-glutamyl transpeptidase from the n-terminal nucleophile hydrolase superfamily that covalently anchors the poly-γ-d-glutamic acid (pdga) capsule to the peptidoglycan. the capsule hinders phagocytosis of b. anthracis by host cells and is essential for virulence. the role capd plays in capsule anchoring and remodeling makes the enzyme a promising target for anthrax medical countermeasures. although the structure of capd is known, and a covalent inhibitor ...	2014	25334088
whole proteome analysis of mouse lymph nodes in cutaneous anthrax.	this study aimed to characterize a soluble proteome of popliteal lymph nodes during lymphadenitis induced by intradermal injection of bacillus anthracis sterne spores in mice using tandem lc-ms/ms and reverse-phase protein microarray with antibodies specific to epitopes of phosphorylated proteins. more than 380 proteins were detected in the normal intra-nodal lymph, while the infectious process resulted in the profound changes in the protein abundances and appearance of 297 unique proteins. thes ...	2014	25329596
[bacillus anthracis].		2014	25327200
antibiofilm activity of biosurfactant producing coral associated bacteria isolated from gulf of mannar.	coral associated bacteria (cab) (n = 22) isolated from the mucus of the coral acropora digitifera were screened for biosurfactants using classical screening methods; hemolysis test, lipase production, oil displacement, drop collapse test and emulsifying activity. six cab (u7, u9, u10, u13, u14, and u16) were found to produce biosurfactants and were identified by 16s ribosomal rna gene sequencing as providencia rettgeri, psychrobacter sp., bacillus flexus, bacillus anthracis, psychrobacter sp., a ...	2014	25320434
preparation and evaluation of human-murine chimeric antibody against protective antigen of bacillus anthracis.	the aim of this research is to develop a human/murine chimeric fab antibody which neutralizes the anthrax toxin, protective antigen (pa). the chimeric fab was constructed using variable regions of murine anti-pa monoclonal antibody in combination with constant regions of human igg. the chimeric pa6-fab was expressed in e. coli. bl21 and evaluated by elisa and co-immunoprecipitation- mass spectra. the potency of pa6-fab to neutralize letx was examined in j774a.1 cell viability in vitro and in fis ...	2014	25318053
polylysine-mediated translocation of the diphtheria toxin catalytic domain through the anthrax protective antigen pore.	the protective antigen (pa) moiety of anthrax toxin forms oligomeric pores in the endosomal membrane, which translocate the effector proteins of the toxin to the cytosol. effector proteins bind to oligomeric pa via their respective n-terminal domains and undergo n- to c-terminal translocation through the pore. earlier we reported that a tract of basic amino acids fused to the n-terminus of an unrelated effector protein (the catalytic domain diphtheria toxin, dta) potentiated that protein to unde ...	2014	25317832
counteracting suppression of cftr and voltage-gated k+ channels by a bacterial pathogenic factor with the natural product tannic acid.	mutations in the cystic fibrosis transmembrane conductance regulator (cftr) cause recurring bacterial infection in cf patients' lungs. however, the severity of cf lung disease correlates poorly with genotype. antibiotic treatment helps dramatically prolong patients' life. the lung disease generally determines prognosis and causes most morbidity and mortality; early control of infections is thus critical. staphylococcus aureus is a main cause of early infection in cf lungs. it secretes sphingomye ...	2014	25313718
terror medicine as part of the medical school curriculum.	terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. calls to teach aspects of the subject in american medical schools surged after the 2001 jetliner and anthrax attacks. although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. this paper suggests a template for incorporating the sub ...	2014	25309891
twenty whole-genome bacillus sp. assemblies.	bacilli are genetically and physiologically diverse, ranging from innocuous to highly pathogenic. here, we present annotated genome assemblies for 20 strains belonging to bacillus anthracis, b. atrophaeus, b. cereus, b. licheniformis, b. macerans, b. megaterium, b. mycoides, and b. subtilis.	2014	25301645
draft genome sequence of strain bf-4, a lysinibacillus-like bacillus isolated during an anthrax outbreak in bavaria.	we report the draft genome sequence of lysinibacillus sp. strain bf-4. strain bf-4 has a notably small genome for a free-living bacillus, with a size of 2.63 mbp. in agreement with phenotypic observations, the genome lacks genes essential for endospore formation.	2014	25301643
bacillus anthracis.		2014	25295335
bacillus anthracis pxo1 plasmid encodes a putative membrane-bound bacteriocin.	evolutionary advantages over cousin cells in bacterial pathogens may decide about the success of a specific cell in its environment. bacteria use a plethora of methods to defend against other cells and many devices to attack their opponents when competing for resources. bacteriocins are antibacterial proteins that are used to eliminate competition. we report the discovery of a putative membrane-bound bacteriocin encoded by the bacillus anthracis pathogenic pxo1 plasmid. we analyze the genomic st ...	2014	25426338
inhibitory effects of nisin-coated multi-walled carbon nanotube sheet on biofilm formation from bacillus anthracis spores.	multi-walled carbon nanotube (mwcnt) sheet was fabricated from a drawable mwcnt forest and then deposited on poly(methyl methacrylate) film. the film was further coated with a natural antimicrobial peptide nisin. we studied the effects of nisin coating on the attachment of bacillus anthracis spores, the germination of attached spores, and the subsequent biofilm formation from attached spores. it was found that the strong adsorptivity and the super hydrophobicity of mwcnts provided an ideal platf ...	2014	25499501
bacillus anthracis genomic dna enhances lethal toxin-induced cytotoxicity through tnf-α production.	bacillus anthracis is the etiological agent of anthrax. lethal toxin (lt) produced by b. anthracis is a well-known key virulence factor for anthrax because of its strong cytotoxic activity. however, little is known about the role of b. anthracis genomic dna (bag) in anthrax pathogenesis.	2014	25472474
composite sampling of a bacillus anthracis surrogate with cellulose sponge surface samplers from a nonporous surface.	a series of experiments was conducted to explore the utility of composite-based collection of surface samples for the detection of a bacillus anthracis surrogate using cellulose sponge samplers on a nonporous stainless steel surface. two composite-based collection approaches were evaluated over a surface area of 3716 cm2 (four separate 929 cm2 areas), larger than the 645 cm2 prescribed by the standard centers for disease control (cdc) and prevention cellulose sponge sampling protocol for use on ...	2014	25470365
virulence plasmids of spore-forming bacteria.	plasmid-encoded virulence factors are important in the pathogenesis of diseases caused by spore-forming bacteria. unlike many other bacteria, the most common virulence factors encoded by plasmids in clostridium and bacillus species are protein toxins. clostridium perfringens causes several histotoxic and enterotoxin diseases in both humans and animals and produces a broad range of toxins, including many pore-forming toxins such as c. perfringens enterotoxin, epsilon-toxin, beta-toxin, and netb. ...	2014	26104459
spore resistance properties.	spores of various bacillus and clostridium species are among the most resistant life forms known. since the spores of some species are causative agents of much food spoilage, food poisoning, and human disease, and the spores of bacillus anthracis are a major bioweapon, there is much interest in the mechanisms of spore resistance and how these spores can be killed. this article will discuss the factors involved in spore resistance to agents such as wet and dry heat, desiccation, uv and γ-radiatio ...	2014	26104355
the design and statistical analysis of animal experiments: introduction to this issue.	animal research has made major contributions to the health and welfare of humans and domestic animals. immunization, first developed against rabies and anthrax by pasteur using dogs, sheep, and rabbits, is now used to control many infectious diseases. the first drug, salvarsan, was developed by ehrlich using rabbits infected with the organism causing syphilis. this was the forerunner of the many drugs developed by the pharmaceutical industry today. the discovery of vitamins using rats has almost ...	2014	25541539
safety, efficacy and utility of methods of transferring adhesive and cohesive escherichia coli cells to microplates to avoid aerosols.	the virtual colony count (vcc) microbiological assay has been utilized for over a decade to measure the antimicrobial activity of peptides such as defensins and ll-37 against biosafety level (bsl)-1 and bsl-2 bacteria including escherichia coli, staphylococcus aureus, bacillus cereus, and enterobacter aerogenes. in addition, a modified pipetting technique was presented in a 2011 study of defensin activity against the bsl-3 pathogen bacillus anthracis. both studies were published in the journal ...	2014	25671086
genomic analysis of three african strains of bacillus anthracis demonstrates that they are part of the clonal expansion of an exclusively pathogenic bacterium.	bacillus anthracis is the causative agent of anthrax and is classified as a 'category a' biological weapon. six complete genomes of b. anthracis (a0248, ames, ames ancestor, cdc684, h0491, and sterne) are currently available. in this report, we add three african strain genomes: sen2col2, sen3 and gmb1. to study the pan-genome of b. anthracis, we used bioinformatics tools, such as cluster of orthologous groups, and performed phylogenetic analysis. we found that the three african strains contained ...	2014	25566394
anthrax as an example of the one health concept.	anthrax is a peracute, acute or subacute multispecies bacterial infection that occurs on many continents. it is one of the oldest infectious diseases known; the biblical fifth and sixth plagues (exodus chapters 7 to 9) that affected first livestock and then humans were probably anthrax. from the earliest historical records until development of an effective vaccine midway through the 20th century, anthrax was one of the foremost causes of uncontrolled mortality in cattle, sheep, goats, horses and ...	2014	25707186
[clustered regularly interspaced short palindromic repeats (crispr) site in bacillus anthracis].	to investigate the polymorphism of clustered regularly interspaced short palindromic repeats (crispr) in bacillu santhracis and the application to molecular typing based on the polymorphism of crispr in b. anthracis.	2014	25752143
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 ...	2014	24102525
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.	2014	24060446
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 ...	2014	24214942
an electrochemiluminescence assay for the detection of bio threat agents in selected food matrices and in the screening of clostridium botulinum outbreak strains associated with type a botulism.	specific screening methods for complex food matrices are needed that enable unambiguous and sensitive detection of bio threat agents (btas) such as bacillus anthracis spores and microbial toxins (e.g. staphylococcal enterotoxin b (seb) and clostridial botulinum neurotoxins (bonts)). the present study describes an image-based 96-well meso scale discovery (msd) electrochemiluminescence (ecl) assay for simultaneous detection of btas in dairy milk products.	2014	23873138
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 ...	2014	24054942
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.	2014	24344920
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.	2014	24373307
retrospective review of the case of cutaneous anthrax-malignant pustule from 1995 in 15-year old girl.	a 15-year-old girl was admitted to our department with cutaneous lesion resembling black eschar. anamnesis revealed that before getting ill she was wearing pullover made of rough sheep's wool and ornaments made of leather like straps. cutaneous anthrax was confirmed by identification of b. anthracis in specimens from weeping ulceration, culture from black eschar, thermoprecipitation test, and bioassay on guinea pig. the girl was treated with crystalline penicillin. she responded well to the ther ...	2014	25848786
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 ...	2014	24366872
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 ...	2014	24366250
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 ...	2014	24363347
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.	2014	24362329
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 ...	2014	24339142
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 ...	2014	24338558
a post-flood co-outbreak of anthrax and enterotoxemia in beef cattle of liaoning province in north-eastern china.		2014	24333640
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 ...	2014	24316020
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 ...	2014	24315189
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 ...	2014	24307239
bacillus anthracis lethal toxin induces cell-type-specific cytotoxicity in human lung cell lines.	inhalational anthrax is caused by the entry of bacillus anthracis spores into the lung. inhaled spores are phagocytosed by alveolar macrophages. bacilli then escape from the macrophage and spread to other cells, initiating a systemic anthrax infection. based on the pathological studies of primate and human inhalational anthrax cases, it appears that lung tissue injury is a lethal consequence of the disease. although the cytotoxicity of anthrax lethal toxin to macrophages is well known, it is not ...	2014	24471528
the regulated synthesis of a bacillus anthracis spore coat protein that affects spore surface properties.	examine the regulation of a spore coat protein and the effects on spore properties.	2014	24460572
special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women.	in august 2012, the centers for disease control and prevention, in partnership with the association of maternal and child health programs, convened a meeting of national subject matter experts to review key clinical elements of anthrax prevention and treatment for pregnant, postpartum, and lactating (p/pp/l) women. national experts in infectious disease, obstetrics, maternal fetal medicine, neonatology, pediatrics, and pharmacy attended the meeting, as did representatives from professional organ ...	2014	24457117
centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.	the centers for disease control and prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. the panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. panelists discussed recent patients with syste ...	2014	24447897
particle concentration dynamics in the ventilation duct after an artificial release: for countering potential bioterrorist attack.	ventilation duct serves as a potential target for bioterrorist attack. understanding the dynamics of aerosolized harmful agents in the ventilation ducts provides the fundamentals for effective control and management, e.g., risk assessment. in this work, new models for predicting the concentration dynamics in the ventilation duct after a particle resuspension (representing the case that harmful agents are dosed when the ventilation is off and subsequently being turned on) or puff injection (repre ...	2014	24447859
investigation of inhalation anthrax case, united states.	inhalation anthrax occurred in a man who vacationed in 4 us states where anthrax is enzootic. despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. although rare, inhalation anthrax can occur naturally in the united states.	2014	24447835
human cutaneous anthrax, georgia 2010-2012.	we assessed the occurrence of human cutaneous anthrax in georgia during 2010--2012 by examining demographic and spatial characteristics of reported cases. reporting increased substantially, as did clustering of cases near urban centers. control efforts, including education about anthrax and livestock vaccination, can be directed at areas of high risk.	2014	24447721
injectional anthrax in heroin users, europe, 2000-2012.		2014	24447525
lethal factor and anti-protective antigen igg levels associated with inhalation anthrax, minnesota, usa.	bacillus anthracis was identified in a 61-year-old man hospitalized in minnesota, usa. cooperation between the hospital and the state health agency enhanced prompt identification of the pathogen. treatment comprising antimicrobial drugs, anthrax immune globulin, and pleural drainage led to full recovery; however, the role of passive immunization in anthrax treatment requires further evaluation.	2014	24447456
recovery and identification of bacterial dna from illicit drugs.	bacterial infections, including bacillus anthracis (anthrax), are a common risk associated with illicit drug use, particularly among injecting drug users. there is, therefore, an urgent need to survey illicit drugs used for injection for the presence of bacteria and provide valuable information to health and forensic authorities. the objectives of this study were to develop a method for the extraction of bacterial dna from illicit drugs and conduct a metagenomic survey of heroin and methamphetam ...	2014	24447454
designing inhibitors of anthrax toxin.	present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates and physical forces that govern their interactions. the 2013 nobel prize in chemistry awarded 'for the development of multiscale models for complex chemical systems' once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial-and-error approach to a minimum. the intentional dissemination of bacillus an ...	2014	24447197
cloning, expression and purification of binding domains of lethal factor and protective antigen of bacillus anthracis in escherichia coli and evaluation of their related murine antibody.	anthrax is common disease between human and animals caused by bacillus anthracis. the cell binding domain of protective antigen (pad4) and the binding domain of lethal factor (lfd1) have high immunogenicity potential and always were considered as a vaccine candidate against anthrax. the aims of this study are cloning and expressing of pad4 and lfd1 in escherichia coli, purification of the recombinant proteins and determination of their immunogenicity through evaluating of the relative produced p ...	2014	24430302
a poly-γ-(d)-glutamic acid depolymerase that degrades the protective capsule of bacillus anthracis.	a mixed culture of pseudomonas fluorescens and pusillimonas noertemanii, obtained by soil enrichment, elaborated an enzyme (envd) which rapidly hydrolysed poly-γ-d-glutamic acid (pdga), the constituent of the anti-phagocytic capsule conferring virulence on bacillus anthracis. the envd gene is carried on the p. noertemanii genome but co-culture is required for the elaboration of pdga depolymerase activity. envd showed strong sequence homology to dienelactone hydrolases from other gram-negative ba ...	2014	24428662
toxin-independent virulence of bacillus anthracis in rabbits.	the accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play a major role in pathogenicity. in the guinea pig (gp) model we have previously shown that deletion of all three toxin components results in a relatively moderate attenuation in virulence, indicating that b. anthracis possesses an additional toxin-independent virulence mechanism. to characterize this toxin-independent mechanism in anthrax disease, we developed a new rabbit model by intra ...	2014	24416317
exoproteome analysis of a novel strain of bacillus cereus implicated in disease resembling cutaneous anthrax.	bacillus cereus belongs to b. cereus sensu lato group, shared by six other related species including bacillus anthracis. b. anthracis is the causative agent for serious illness affecting a wide range of animals as well as humans and is a category a biological and toxin warfare (btw) agent. recent studies indicate that a bacillus species other than b. anthracis can cause anthrax-like disease and role of anthrax virulence plasmids (pxo1 and pxo2) on the pathogenicity of b. cereus has been document ...	2014	24412723
delineating the effect of host environmental signals on a fully virulent strain of bacillus anthracis using an integrated transcriptomics and proteomics approach.	pathogenic bacteria sense the host environment and regulate expression of virulence-related genes. environmental signals like temperature, bicarbonate/co2 and glucose induce toxin production in bacillus anthracis, but the mechanisms by which these signals contribute to virulence and overall physiological adaptation remains elusive. an integrated, systems level investigation using transcriptomics and itraq-based proteomics was done to assess the effect of temperature, bicarbonate/co2 and glucose ...	2014	24406299
human igg fc domain engineering enhances antitoxin neutralizing antibody activity.	the effector activity of antibodies is dependent on engagement with fcγ receptors (fcγrs) and activation of the associated intracellular signaling pathways. preclinical evaluation of therapeutic humanized or chimeric mabs to study the interactions of their fc regions with fcγrs is hampered by substantial structural and functional fcγr diversity among species. in this report, we used mice expressing only human fcγrs to evaluate the contribution of fcγr-mediated pathways to the neutralizing activi ...	2014	24401277
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 ...	2014	24394545
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 ...	2014	24392098
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 ...	2014	24390076
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 ...	2014	24389148
(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 ...	2014	24387629
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 ...	2014	24380967
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 ...	2014	24380801
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 ...	2014	24379445
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 ...	2014	24379209
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 ...	2014	24375142
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.	2014	24279292
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 ...	2014	24273028
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 ...	2014	24270917
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 ...	2014	24269655
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 ...	2014	24264995
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 ...	2014	24291177
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.	2014	24290062
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 ...	2014	24286182
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 ...	2014	24188959
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 ...	2014	24184358
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 ...	2014	24184312
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 ...	2014	24184311
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 ...	2014	24169798
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 ...	2014	24164262
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 ...	2014	24161941
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 ...	2014	24152301
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 ...	2014	24147813
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 ...	2014	24135549
the use of complementary and alternative medicine among dermatology outpatients in eastern turkey.	over the past decade, complementary and alternative medicine (cam) has become increasingly popular around the world.	2014	23836839
the potential impact of an anthrax attack on real estate prices and foreclosures in seattle.	this article provides a methodology for the economic analysis of the potential consequences of a simulated anthrax terrorism attack on real estate within the seattle metropolitan area. we estimate spatially disaggregated impacts on median sales price of residential housing within the seattle metro area following an attack on the central business district (cbd). using a combination of longitudinal panel regression and gis analysis, we find that the median sales price in the cbd could decline by a ...	2014	23682844
structure-based non-canonical amino acid design to covalently crosslink an antibody-antigen complex.	engineering antibodies to utilize non-canonical amino acids (ncaa) should greatly expand the utility of an already important biological reagent. in particular, introducing crosslinking reagents into antibody complementarity determining regions (cdrs) should provide a means to covalently crosslink residues at the antibody-antigen interface. unfortunately, finding the optimum position for crosslinking two proteins is often a matter of iterative guessing, even when the interface is known in atomic ...	2014	23680795
evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.	the aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (a-chmp) for oral vaccine against anthrax. the zeta potential of a-chmp was -29.7 mv, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. the results indicated that a-chmp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. the immunization studies indicated that a-chmp resulted in the induction of potent systemi ...	2014	23452384
validation of potential inhibitors for srta against bacillus anthracis by combined approach of ligand-based and molecular dynamics simulation.	the development of srta inhibitors targeting the biothreat organism namely bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, adme, and molecular dynamics studies. in this study, experimentally reported ba-srta inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the development of enhanced pharmacophoric model. the obtained aaahr hypothesis was a pure theoretical concept that accounts ...	2014	23869520
soil-related bacterial and fungal infections.	a variety of classic and emerging soil-related bacterial and fungal pathogens cause serious human disease that frequently presents in primary care settings. typically, the growth of these microorganisms is favored by particular soil characteristics and may involve complex life cycles including amoebae or animal hosts. specific evolved virulence factors or the ability to grow in diverse, sometimes harsh, microenvironments may promote pathogenesis. infection may occur by direct inoculation or inge ...	2014	22956709
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 ...	2014	26227025
anthrax: a case report.	anthrax is a zoonotic disease caused by a bacterium called bacillus anthracis. in humans, it causes a cutaneous, gastro-intestinal and inhalation form of disease. the in-cutaneous form progresses along with skin necrosis and oedema. since the necroses in the skin are not quite superficial, they can affect the tendon sheaths progressing close to the skin. therefore, in surgical treatment, the closure in the areas where tendons are surfaced must be provided by a flap instead of a graft.the repair ...	2014	25823167
cytotoxicity of the vibrio vulnificus martx toxin effector duf5 is linked to the c2a subdomain.	the multifunctional-autoprocessing repeats-in-toxin (martx) toxins are bacterial protein toxins that serve as delivery platforms for cytotoxic effector domains. the domain of unknown function in position 5 (duf5) effector domain is present in at least six different species' martx toxins and as a hypothetical protein in photorhabdus spp. its presence increases the potency of the vibrio vulnificus martx toxin in mouse virulence studies, indicating duf5 directly contributes to pathogenesis. in this ...	2014	24935440
tabanids: neglected subjects of research, but important vectors of disease agents!	tabanids are nuisance pests for people and livestock because of their painful and irritating bite, persistent biting behavior, and blood ingestion. about 4400 tabanid species have been described; they are seasonally present in all kinds of landscapes, latitudes, and altitudes. high populations have a significant economic impact on outdoor activities, tourism, and livestock production. tabanids are also vectors of animal disease agents, including viruses, bacteria and parasites. however, tabanids ...	2014	24727644
detection of the urban release of a bacillus anthracis simulant by air sampling.	in 2005 and 2009, the pentagon force protection agency (pfpa) staged deliberate releases of a commercially available organic pesticide containing bacillus amyloliquefaciens to evaluate pfpa's biothreat response protocols. in concert with, but independent of, these releases, the department of homeland security sponsored experiments to evaluate the efficacy of commonly employed air and surface sampling techniques for detection of an aerosolized biological agent. high-volume air samplers were place ...	2014	24697146
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 ...	2014	24401083
exoy from pseudomonas aeruginosa is a nucleotidyl cyclase with preference for cgmp and cump formation.	in addition to the well known second messengers camp and cgmp, mammalian cells contain the cyclic pyrimidine nucleotides ccmp and cump. soluble guanylyl cyclase and soluble adenylyl cyclase produce all four cnmps. several bacterial toxins exploit mammalian cyclic nucleotide signaling. the type iii secretion protein exoy from pseudomonas aeruginosa induces severe lung damage and effectively produces cgmp. here, we show that transfection of mammalian cells with exoy or infection with exoy-expressi ...	2014	24971548