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green tea and epigallocatechin-3-gallate are bactericidal against bacillus anthracis.bacillus anthracis, the etiological agent of anthrax, is listed as a category a biothreat agent by the united states centers for disease control and prevention. the virulence of the organism is due to expression of two exotoxins and capsule, which interfere with host cellular signaling, alter host water homeostasis, and inhibit phagocytosis of the pathogen, respectively. concerns regarding the past and possible future use of b. anthracis as a bioterrorism agent have resulted in an impetus to dev ...201728605495
the pag gene of pxo1 is involved in capsule biosynthesis of bacillus anthracis pasteur ii strain.the poly-γ-d-glutamic acid capsule and anthrax toxins are major virulence factors of bacillus anthracis. genes responsible for capsule biosynthesis are located on pxo2, whereas genes encoding the toxins, which are composed of edema factors, lethal factors, and protective antigens (pa), are located on pxo1. in this study, we found that the pag null mutation not only eliminated the production of the protective antigen, it also eliminated the ability of the b. anthracis pasteur ii strain to form ca ...201728603695
functional analysis of bas2108-2109 two component system: evidence for protease regulation in bacillus anthracis.bacillus anthracis (ba) is a major bioterrorism concern which has evolved complex regulatory mechanisms for its virulence factors. secreted proteases play an imperative role in the pathogenesis of ba, however their regulation remains elusive. two component systems (tcs) are often employed by bacteria to sense and adapt to the environmental perturbations. in several pathogens, tcs are commonly associated with the regulation of virulence factors including proteases. the genome of ba encodes 41 tcs ...201728602714
targeting bacillus anthracis toxicity with a genetically selected inhibitor of the pa/cmg2 protein-protein interaction.the protein-protein interaction between the human cmg2 receptor and the bacillus anthracis protective antigen (pa) is essential for the transport of anthrax lethal and edema toxins into human cells. we used a genetically encoded high throughput screening platform to screen a siclopps library of 3.2 million cyclic hexapeptides for inhibitors of this protein-protein interaction. unusually, the top 3 hits all contained stop codons in the randomized region of the library, resulting in linear rather ...201728596569
evaluation of commercial-off-the-shelf materials for the preservation of bacillus anthracis vegetative cells for forensic analysis.environmental surface sampling is crucial in determining the zones of contamination and overall threat assessment. viability retention of sampled material is central to such assessments. a systematic study was completed to determine viability of vegetative cells under nonpermissive storage conditions. despite major gains in nucleic acid sequencing technologies, initial positive identification of threats must be made through direct culture of the sampled material using classical microbiological m ...201728585764
recombinant protein expression, crystallization, and biophysical studies of a bacillus-conserved nucleotide pyrophosphorylase, bcmazg.to overcome safety restrictions and regulations when studying genes and proteins from true pathogens, their homologues can be studied. bacillus anthracis is an obligate pathogen that causes fatal inhalational anthrax. bacillus cereus is considered a useful model for studying b. anthracis due to its close evolutionary relationship. the gene cluster ba1554 - ba1558 of b. anthracis is highly conserved with the bc1531- bc1535 cluster in b. cereus, as well as with the bt1364-bt1368 cluster in bacillu ...201728570540
draft genome sequences of bacillus cereus e41 and bacillus anthracis f34 isolated from algerian salt lakes.two strains of bacillus, b. cereus e41 and b. anthracis f34, were isolated from a salt lake in aïn m'lila-oum el bouaghi, eastern algeria, and ain baida-ouargla, southern algeria, respectively. their genomes display genes for the production of several bioactive secondary metabolites, including polyhydroxyalkanoate, iron siderophores, lipopeptides, and bacteriocins.201728522726
metal homeostasis in bacteria: the role of arsr-smtb family of transcriptional repressors in combating varying metal concentrations in the environment.bacterial infections cause severe medical problems worldwide, resulting in considerable death and loss of capital. with the ever-increasing rise of antibiotic-resistant bacteria and the lack of development of new antibiotics, research on metal-based antimicrobial therapy has now gained pace. metal ions are essential for survival, but can be highly toxic to organisms if their concentrations are not strictly controlled. through evolution, bacteria have acquired complex metal-management systems tha ...201728512703
identification of beta-lactamases and beta-lactam-related proteins in human pathogenic bacteria using a computational search approach.a systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. in this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. the amino acid sequences for 19 different types of beta-lactamases (act, carb, cifa, cmy, ctx, fox, ges, gob, imp, ind, kpc, len, okp, oxa, oxy, shv, tem, ndm, and vim) were obtained from the arg-annot database and were used to constru ...201728508147
evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.risk of inhalation exposure to viable bacillus anthracis (b. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. while a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. the goal of this study was to determine the best sampler-filter co ...201728506101
lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated.a major difference between two currently licensed anthrax vaccines is presence (united kingdom anthrax vaccine precipitated, avp) or absence (united states anthrax vaccine adsorbed, ava) of quantifiable amounts of the lethal toxin (lt) component lethal factor (lf). the primary immunogen in both vaccine formulations is protective antigen (pa), and lt-neutralizing antibodies directed to pa are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrate ...201728504191
bacillus anthracis peptidoglycan integrity is disrupted by the chemokine cxcl10 through the ftse/x complex.the antimicrobial activity of the chemokine cxcl10 against vegetative cells of bacillus anthracis occurs via both bacterial ftse/x-dependent and-independent pathways. previous studies established that the ftse/x-dependent pathway was mediated through interaction of the n-terminal region(s) of cxcl10 with a functional ftse/x complex, while the ftse/x-independent pathway was mediated through the c-terminal α-helix of cxcl10. both pathways result in cell lysis and death of b. anthracis. in other ba ...201728496437
ten genome sequences of human and livestock isolates of bacillus anthracis from the country of georgia.bacillus anthracis causes the acute fatal disease anthrax, is a proven biological weapon, and is endemic in georgia, where human and animal cases are reported annually. here, we present whole-genome sequences of 10 historical b. anthracis strains from georgia.201728495766
high stringency evaluation of the inactivation / exclusion efficacy of a maldi-tof ms chemical extraction method, with filtration of extract through 0.1 µm filters, on bacillus anthracis vollum vegetative cells and spores.a previous report indicated that a formic acid chemical extraction method for the preparation of protein extracts for matrix-assisted laser desorption time-of-flight mass spectrometry (maldi-tof ms) identification, with filtration of extracts through 0.2 μm regenerated cellulose (rc) filters, would not reliably inactivate or exclude bacillus anthracis vollum cells or spores when tested under high stringency conditions. b. anthracis was recovered from 13/36 extracts (3/18 from vegetative cell ext ...201728481931
elucidation of the recognition sequence of sortase b from bacillus anthracis by using a newly developed liquid chromatography-mass spectrometry-based method.sortases are enzymes that are responsible for the attachment of secreted proteins to the cell wall of gram-positive bacteria. hereby, the sortases recognize short, five-residue amino acid sequences present in the target proteins and fuse them to the peptidoglycan layer via a transpeptidation reaction, creating a new peptide bond between the c-terminus of the recognition sequence and the cell wall. the transpeptidation activity of sortases is widely used in protein engineering for modification of ...201728475305
biochemical characterization of the gtp-sensing protein, cody of bacillus anthracis.the pleiotropism of the gtp-sensing transcriptional regulator cody is evident by the gamut of processes that it regulates in almost all low g+c gram-positive bacteria, including general metabolism, biosynthesis of some amino acids and transport systems, nitrogen uptake, sporulation, biofilm formation, motility and virulence. the role of cody in virulence has been established in bacillus anthracis, the top rated bioterrorism agent. in this study, we investigated the biochemical attributes of this ...201728472295
comparative analysis of the sensitivity of metagenomic sequencing and pcr to detect a biowarfare simulant (bacillus atrophaeus) in soil samples.to evaluate the sensitivity of high-throughput dna sequencing for monitoring biowarfare agents in the environment, we analysed soil samples inoculated with different amounts of bacillus atrophaeus, a surrogate organism for bacillus anthracis. the soil samples considered were a poorly carbonated soil of the silty sand class, and a highly carbonated soil of the silt class. control soil samples and soil samples inoculated with 10, 103, or 105 cfu were processed for dna extraction. about 1% of the d ...201728472119
unexpected relations of historical anthrax strain.in 1998, it was claimed that an 80-year-old glass tube intentionally filled with bacillus anthracis and embedded in a sugar lump as a wwi biological weapon still contained viable spores. today, genome sequencing of three colonies isolated in 1998 and subjected to phylogenetic analysis surprisingly identified a well-known b. anthracis reference strain isolated in the united states in 1981, pointing to accidental laboratory contamination.importance next-generation sequencing and subsequent phyloge ...201728442608
bacillus anthracis edema toxin increases fractional free water and sodium reabsorption in an isolated perfused rat kidney model.bacillus anthracis edema toxin (et) consists of protective antigen (pa), necessary for host cell toxin uptake, and edema factor (ef), the toxic moiety which increases host cell cyclic amp (camp). since vasopressin stimulates renal water and sodium reabsorption via increased tubular cell camp levels, we hypothesized the et would also do so. to test this hypothesis, we employed an isolated perfused rat kidney model. kidneys were isolated and perfused with modified krebs-henseleit buffer. perfusate ...201728438974
draft genome sequence of bacillus cereus la2007, a human-pathogenic isolate harboring anthrax-like plasmids.we present the genome sequence of bacillus cereus la2007, a strain isolated in 2007 from a fatal pneumonia case in louisiana. sequence-based genome analysis revealed that la2007 carries a plasmid highly similar to bacillus anthracis pxo1, including the genes responsible for the production and regulation of anthrax toxin.201728428293
response to letter on immunoassays for field screening of bacillus anthracis and ricin. 201728426247
immunoassays for field screening of bacillus anthracis and ricin. 201728418740
anthrax cases associated with animal-hair shaving brushes.during the first world war, anthrax cases in the united states and england increased greatly and seemed to be associated with use of new shaving brushes. further investigation revealed that the source material and origin of shaving brushes had changed during the war. cheap brushes of imported horsehair were being made to look like the preferred badger-hair brushes. unfortunately, some of these brushes were not effectively disinfected and brought with them a nasty stowaway: bacillus anthracis. a ...201728418302
anti-proliferative role of recombinant lethal toxin of bacillus anthracis on primary mammary ductal carcinoma cells revealing its therapeutic potential.bacillus anthracis secretes three secretary proteins; lethal factor (lf), protective antigen (pa) and edema factor (ef). the lf has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (mapk) signaling pathway. evaluation of therapeutic potential of recombinant lf (rlf), recombinant pa (rpa) and lethal toxin (rlf + rpa = letx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells ...201728415766
preparation and characterization of expanded graphite/metal oxides for antimicrobial application.composite materials based on expanded graphite (eg) and metal oxide (mo) particles was prepared by an explosive combustion and blending method. the objective of the study was to develop eg impregnated with metal oxide particulates (ag2o, cuo and zno) and evaluate the level of protection the materials conferred against biological agents. the physical properties of the eg/mo composites were examined using sem, edx and xrd spectroscopy, and the results indicated that the mo particles were incorpora ...201728415384
tlr sensing of bacterial spore-associated rna triggers host immune responses with detrimental effects.the spores of pathogenic bacteria are involved in host entry and the initial encounter with the host immune system. how bacterial spores interact with host immunity, however, remains poorly understood. here, we show that the spores of bacillus anthracis (ba), the etiologic agent of anthrax, possess an intrinsic ability to induce host immune responses. this immunostimulatory activity is attributable to high amounts of rna present in the spore surface layer. rna-sensing tlrs, tlr7, and tlr13 in mi ...201728400473
infantile systemic hyalinosis complicated with right atrial thrombus and pericardial effusion in an infant.infantile systemic hyalinosis (ish) is a rare multisystem fatal autosomal recessive disorder that involves widespread deposition of hyaline on connective tissues and certain internal organs. the major manifestations include painful articular contractures, hyperpigmentation, subcutaneous nodules, gingival hypertrophy, failure to thrive secondary to protein-losing enteropathy, and osteolytic bone lesions. in this paper, we report a 12-month-old girl with ish presenting with recurrent diarrhea, fai ...201725458638
multiplex pcr for species-level identification of bacillus anthracis and detection of pxo1, pxo2, and related plasmids.the bacillus anthracis virulence plasmids pxo1 and pxo2 have critical implications for biosafety and select agent status. the proper identification and characterization of b. anthracis and its plasmid profile is important to the biodefense research community. multiplex pcr was used to simultaneously detect a b. anthracis-specific chromosomal mutation, 4 targets distributed across pxo1, 3 targets distributed across pxo2, and highly conserved regions of the 16s gene, allowing an internal positive ...201725813976
deterministic models of inhalational anthrax in new zealand white rabbits.computational models describing bacterial kinetics were developed for inhalational anthrax in new zealand white (nzw) rabbits following inhalation of ames strain b. anthracis. the data used to parameterize the models included bacterial numbers in the airways, lung tissue, draining lymph nodes, and blood. initial bacterial numbers were deposited spore dose. the first model was a single exponential ordinary differential equation (ode) with 3 rate parameters that described mucociliated (physical) c ...201724527843
protein catalyzed capture agents with tailored performance for in vitro and in vivo applications.we report on peptide-based ligands matured through the protein catalyzed capture (pcc) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. a vascular endothelial growth factor (vegf) binding peptide and a peptide against the protective antigen (pa) protein of bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click c ...201727539157
development of an acid-resistant salmonella typhi ty21a attenuated vector for improved oral vaccine delivery.the licensed oral, live-attenuated bacterial vaccine for typhoid fever, salmonella enterica serovar typhi strain ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. however, ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with ty21a in an enteric-coated capsule (ecc). several ...201727673328
detection probability models for bacteria, and how to obtain them from heterogeneous spiking data. an application to bacillus anthracis.efficient and correct evaluation of sampling results with respect to hypotheses about the concentration or distribution of bacteria generally requires knowledge about the performance of the detection method. to assess the sensitivity of the detection method an experiment is usually performed where the target matrix is spiked (i.e. artificially contaminated) with different concentrations of the bacteria, followed by analyses of the samples using the pre-enrichment method and the analytical detect ...201727764712
genotypic heterogeneity of emetic toxin producing bacillus cereus isolates from china.emetic toxin-producing bacillus cereus (emetic b. cereus) is the third member of b. cereus group whose toxins are encoded by megaplasmids, beside anthrax and insecticidal toxins of b. anthracis and b. thuringiensis, respectively. a total of 18 emetic isolates collected from food poisoning events, clinical and non-random food samples in zhejiang province of china, were analyzed by plasmid screening, pulse field gel electrophoresis, multilocus sequence typing, and toxic gene identification to inve ...201727744366
cutaneous anthrax. 201727742398
killing the spores of bacillus species by molecular iodine.to determine the responses of spores of bacillus subtilis and bacillus anthracis surrogate bacillus thuringiensis al hakam to i2 treatment.201727696602
facile ratiometric fluorapatite nanoprobes for rapid and sensitive bacterial spore biomarker detection.since bacterial spores, such as bacillus anthracis spores, are extremely hazardous to human beings and animals, efforts have focused on the development of bacterial spore detector with rapid response and high selectivity and sensitivity. therefore, we reported a facile one-step chelating-reagent-assisted hydrothermal synthesis of lanthanide-doped fluorapatite (fa) nanoprobes for detecting the biomarker of bacterial spores. in fa synthesis, ethylenediaminetetraacetic acid (edta) can serve not onl ...201727686603
functional characterization of phopr two component system and its implication in regulating phosphate homeostasis in bacillus anthracis.recent report on importance of phosphate starvation (ps) in bacillus anthracis (ba) pathogenesis warrants further investigation of the underlying regulatory mechanism. potential role of phopr two component system (tcs) in phosphate homeostasis and virulence of several pathogens necessitates the study of annotated phopr in ba.201727667172
s-nitrosylation of peroxiredoxin 1 contributes to viability of lung epithelial cells during bacillus anthracis infection.using bacillus anthracis as a model gram-positive bacterium, we investigated the effects of host protein s-nitrosylation during bacterial infection. b. anthracis possesses a bacterial nitric oxide synthase (bnos) that is important for its virulence and survival. however, the role of s-nitrosylation of host cell proteins during b. anthracis infection has not been determined.201727612662
genes required for bacillus anthracis secondary cell wall polysaccharide synthesis.the secondary cell wall polysaccharide (scwp) is thought to be essential for vegetative growth and surface (s)-layer assembly in bacillus anthracis; however, the genetic determinants for the assembly of its trisaccharide repeat structure are not known. here, we report that wpaa (bas0847) and wpab (bas5274) share features with membrane proteins involved in the assembly of o-antigen lipopolysaccharide in gram-negative bacteria and propose that wpaa and wpab contribute to the assembly of the scwp i ...201727795328
antibody-based immunotherapy to treat and prevent infection with hypervirulent klebsiella pneumoniae.hypervirulent klebsiella pneumoniae (hvkp) strains are predicted to become a major threat in asia if antibiotic resistance continues to spread. anticapsular antibodies (abs) were developed because disseminated infections caused by hvkp are associated with significant morbidity and mortality, even with antibiotic-sensitive strains. k1-serotype polysaccharide capsules (k1-cps) are expressed by the majority of hvkp strains. in this study, k1-cps-specific igg abs were generated by conjugation of k1- ...201727795303
a dual purpose universal influenza vaccine candidate confers protective immunity against anthrax.preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. however, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. we designed an influenza antigen consisting of three tandem m2e repeats plus ha2, in ...201727775159
in vitro evaluation of the effect of linezolid and levofloxacin on bacillus anthracis toxin production, spore formation and cell growth.owing to its ability to form spores and toxins, bacillus anthracis is considered a bioterror agent. although current therapeutic strategies can be effective, treatment does not prevent sporulation and toxin production.201727798209
rapid snp detection and genotyping of bacterial pathogens by pyrosequencing.bacterial identification and typing are fixtures of microbiology laboratories and are vital aspects of our response mechanisms in the event of foodborne outbreaks and bioterrorist events. whole genome sequencing (wgs) is leading the way in terms of expanding our ability to identify and characterize bacteria through the identification of subtle differences between genomes (e.g. single nucleotide polymorphisms (snps) and insertions/deletions). modern high-throughput technologies such as pyrosequen ...201727822867
validation of high throughput screening of human sera for detection of anti-pa igg by enzyme-linked immunosorbent assay (elisa) as an emergency response to an anthrax incident.to improve surge testing capability for a response to a release of bacillus anthracis, the cdc anti-protective antigen (pa) igg enzyme-linked immunosorbent assay (elisa) was re-designed into a high throughput screening format. the following assay performance parameters were evaluated: goodness of fit (measured as the mean reference standard r(2)), accuracy (measured as percent error), precision (measured as coefficient of variance (cv)), lower limit of detection (llod), lower limit of quantifica ...201727814939
stability of domain 4 of the anthrax toxin protective antigen and the effect of the vwa domain of cmg2 on stability.the major immunogenic component of the current anthrax vaccine, anthrax vaccine adsorbed (ava) is protective antigen (pa). we have shown recently that the thermodynamic stability of pa can be significantly improved by binding to the von-willebrand factor a (vwa) domain of capillary morphogenesis protein 2 (cmg2), and improvements in thermodynamic stability may improve storage and long-term stability of pa for use as a vaccine. in order to understand the origin of this increase in stability, we h ...201727874231
a "dock and lock" approach to preparation of targeted liposomes.we developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. this strategy is based on "dock and lock" interactions between two mutated fragments of human rnase i, a 1-15 aa fragment with the r4c amino acid substitution (cys-tag), and a 21-127-aa fragment with the v118c substitution, (ad-c). upon binding to each other, cys-tag and ad-c spontaneously form a disulfide bond between the complementary 4c and 118c residues. therefore, any ...201727837532
avoiding pandemic fears in the subway and conquering the platypus.metagenomics is increasingly used not just to show patterns of microbial diversity but also as a culture-independent method to detect individual organisms of intense clinical, epidemiological, conservation, forensic, or regulatory interest. a widely reported metagenomic study of the new york subway suggested that the pathogens yersinia pestis and bacillus anthracis were part of the "normal subway microbiome." in their article in msystems, hsu and collaborators (msystems 1(3):e00018-16, 2016, htt ...201727832215
bletilla striata: medicinal uses, phytochemistry and pharmacological activities.bletilla striata (thunb.) reichb. f. (orchidaceae), also known as hyacinth orchid and baiji (simplified chinese: ), not only has been widely used for the treatment of hematemesis, hemoptysis, and traumatic bleeding due to the efficacy of arresting bleeding with astringent action, but also has been applied topically to overcome ulcers, sores, swellings, and chapped skin due to the efficacy of dispersing swelling and promoting tissue regeneration. additional medical applications include the treatm ...201727865796
tid: standalone software for mining putative drug targets from bacterial proteome.tid is a standalone application, which relies on basic assumption that a protein must be essential for pathogens survival and non-homologous with host to qualify as putative target. with an input bacterial proteome, tid removes paralogous proteins, picks essential ones, and excludes proteins homologous with host organisms. the targets illustrate non-homology with at least 40 out of 84 gut microbes, considered safe for human. tid classifies proposed targets as known, novel and virulent. users can ...201727856224
recombinant anthrax protective antigen: observation of aggregation phenomena by tem reveals specific effects of sterols.negatively stained transmission electron microscope images are presented that depict the aggregation of recombinant anthrax protective antigen (rpa83 monomer and the pa63 prepore oligomer) under varying in vitro biochemical conditions. heat treatment (50°c) of rpa83 produced clumped fibrils, but following heating the pa63 prepore formed disordered aggregates. freeze-thaw treatment of the pa63 prepore generated linear flexuous aggregates of the heptameric oligomers. aqueous suspensions of cholest ...201727883989
identification of a substrate-selective exosite within the metalloproteinase anthrax lethal factor.the metalloproteinase anthrax lethal factor (lf) is secreted by bacillus anthracis to promote disease virulence through disruption of host signaling pathways. lf is a highly specific protease, exclusively cleaving mitogen-activated protein kinase kinases (mkks) and rodent nlrp1b (nacht leucine-rich repeat and pyrin domain-containing protein 1b). how lf achieves such restricted substrate specificity is not understood. previous studies have suggested the existence of an exosite interaction between ...201727909054
animal-to-human dose translation of obiltoxaximab for treatment of inhalational anthrax under the us fda animal rule.obiltoxaximab, a monoclonal antibody against protective antigen (pa), is approved for treatment of inhalational anthrax under the us food and drug administration's (fda) animal rule. the human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected new zealand white rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum pa levels in infected animals. in humans, at 1 ...201727925405
histopathology of vaccine-preventable diseases.the widespread use of vaccines has been one of the most important medical advances in the last century, saving trillions of dollars and millions of lives. despite local eradication of some infections, travellers returning from affected areas may cause outbreaks through reintroduction of pathogens to individuals who are unable to receive vaccines for medical reasons or who have declined vaccination for non-medical reasons. infections that would otherwise be uncommonly encountered by anatomical pa ...201727960239
a mathematical model of anthrax transmission in animal populations.a general mathematical model of anthrax (caused by bacillus anthracis) transmission is formulated that includes live animals, infected carcasses and spores in the environment. the basic reproduction number [formula: see text] is calculated, and existence of a unique endemic equilibrium is established for [formula: see text] above the threshold value 1. using data from the literature, elasticity indices for [formula: see text] and type reproduction numbers are computed to quantify anthrax control ...201728035484
role of the recognition helix of response regulator walr from bacillus anthracis in dna binding and specificity.walrk two-component system of bacillus anthracis potentially regulates multiple genes spanning diverse cellular functions. its constituent response regulator (rr), walr belongs to the ompr/phob family which possesses a winged helix-turn-helix motif for dna binding. an in silico knowledge based model of walr c-terminal dna binding domain in complex with its ftse promoter region binding motif was used to identify specific residues of the recognition helix important for dna binding. the model was v ...201727988294
modeling tool for decision support during early days of an anthrax event.health officials lack field-implementable tools for forecasting the effects that a large-scale release of bacillus anthracis spores would have on public health and hospitals. we created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examine ...201727983505
analysis of anthrax immune globulin intravenous with antimicrobial treatment in injection drug users, scotland, 2009-2010.we studied anthrax immune globulin intravenous (aig-iv) use from a 2009-2010 outbreak of bacillus anthracis soft tissue infection in injection drug users in scotland, uk, and we compared findings from 15 aig-iv recipients with findings from 28 nonrecipients. death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). however, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received aig-iv, 7 ( ...201727983504
epidemiology of human anthrax in china, 1955-2014.using national surveillance data for 120,111 human anthrax cases recorded during 1955-2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in china. after 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. the case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. cases occurred throughout the year, peaking in august. geographic distribution decreased overall from west ...201727983489
transcriptional classification and functional characterization of human airway macrophage and dendritic cell subsets.the respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. we set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. six subsets of ...201728031342
characterization of yersinia species by protein profiling using automated microfluidic capillary electrophoresis.yersinia pestis is a biological agent of high risk to national security due to its ability to be easily disseminated and transmitted among humans. if y. pestis was to be utilized in a deliberate disease outbreak it would be essential to rapidly and accurately identify the agent. current identification methods for yersinia species are limited by their reliance on cultivation, the time taken to achieve results and/or the use of protocols that are not amenable for field use. faster identification m ...201728019002
deletion of a putative nlpc/p60 endopeptidase bas1812 affects germination, long-term survival and endospore formation in bacillus anthracis.bacillus anthracis, an aetiologic agent of the zoonotic disease anthrax, encodes a putative nlpc/p60 endopeptidase bas1812. it harbours a signal peptide, three bacterial sh3 domains and an nlpc/p60 family domain. previous studies showed that bas1812 is immunogenic in infected hosts and is a potential biomarker for anthrax treatment. to date, however, little information is known about its function and involvement in anthrax pathogenesis. here we describe the phenotypic effect of bas1812 deletion ...201728008818
notes from the field: compliance with postexposure prophylaxis for exposure to bacillus anthracis among u.s. military personnel - south korea, may 2015. 201728056004
expression, purification, and biophysical characterization of a secreted anthrax decoy fusion protein in nicotiana benthamiana.anthrax toxin receptor-mediated drug development for blocking anthrax toxin action has received much attention in recent decades. in this study, we produced a secreted anthrax decoy fusion protein comprised of a portion of the human capillary morphogenesis gene-2 (cmg2) protein fused via a linker to the fragment crystallizable (fc) domain of human immunoglobulin g1 in nicotiana benthamiana plants using a transient expression system. using the cauliflower mosaic virus (camv) 35s promoter and co-e ...201728054967
optical screening for rapid antimicrobial susceptibility testing and for observation of phenotypic diversity among strains of the genetically clonal species bacillus anthracis.during high-impact events involving bacillus anthracis, such as the amerithrax incident of 2001 or the anthrax outbreaks in russia and sweden in 2016, critical decisions to reduce morbidity and mortality include rapid selection and distribution of effective antimicrobial agents for treatment and postexposure prophylaxis. detection of antimicrobial resistance currently relies on a conventional broth microdilution method that requires a 16- to 20-h incubation time for b. anthracis advances in high ...201728053211
influence of ppcps on the performance of intermittently operated slow sand filters for household water purification.removal of pharmaceuticals and personal care products (ppcps) from drinking water is usually enhanced by advanced oxidation which is not affordable in low income countries. slow sand filtration has been found to be capable of removing anti-inflammatory compounds, and its low maintenance costs and easy operation make it an attractive technology for treating drinking water in many parts of the world. in addition, slow sand filters can be used at both large and household scales. the biofilm (i.e. s ...201728041695
bacterial virulence factors: secreted for survival.virulence is described as an ability of an organism to infect the host and cause a disease. virulence factors are the molecules that assist the bacterium colonize the host at the cellular level. these factors are either secretory, membrane associated or cytosolic in nature. the cytosolic factors facilitate the bacterium to undergo quick adaptive-metabolic, physiological and morphological shifts. the membrane associated virulence factors aid the bacterium in adhesion and evasion of the host cell. ...201728148975
systemic granulomatous and haemorrhagic syndrome in new zealand dairy cattle.cases were obtained through passive surveillance reporting by veterinary pathologists, via the ministry for primary industries exotic pest and disease hotline. they included ill or dead cows that had evidence of frank haemorrhage, petechial haemorrhages on mucous membranes, wasting or dermatitis of unknown cause, and were reported between 2009-2014. affected cows (n=16) were from nine seasonally calving dairy farms, aged ≥3 years, and were predominantly in their mid-to-late non-lactating period. ...201728147208
cdc's evolving approach to emergency response.the centers for disease control and prevention (cdc) transformed its approach to preparing for and responding to public health emergencies following the anthrax attacks of 2001. the office of public health preparedness and response, an organizational home for emergency response at cdc, was established, and 4 programs were created or greatly expanded after the anthrax attacks: (1) an emergency management program, including an emergency operations center; (2) increased support of state and local h ...201728146366
model systems for pulmonary infectious diseases: paradigms of anthrax and tuberculosis.robert koch utilized animal model systems to put forward his postulates while discovering the etiological agents of anthrax and tuberculosis, bacillus anthracis and mycobacterium tuberculosis, respectively. after more than 130 years, we have achieved limited success towards understanding these two pestilences, which have propagated as scourge against humans. b. anthracis and m. tuberculosis are diverse organisms, which share a common evolutionary path in tropics. they adapt unique strategies to ...201728137237
targeted delivery of an adp-ribosylating bacterial toxin into cancer cells.the actin cytoskeleton is an attractive target for bacterial toxins. the adp-ribosyltransferase tccc3 from the insect bacterial pathogen photorhabdus luminescence modifies actin to force its aggregation. we intended to transport the catalytic part of this toxin preferentially into cancer cells using a toxin transporter (protective antigen, pa) which was redirected to epidermal growth factor receptors (egfr) or to human egf receptors 2 (her2), which are overexpressed in several cancer cells. prot ...201728128281
modeling rabbit responses to single and multiple aerosol exposures of bacillus anthracis spores.survival models are developed to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of bacillus anthracis spores. hazard function models were developed for a multiple-dose data set to predict the probability of death through specifying functions of dose response and the time between exposure and the time-to-death (ttd). among the models developed, the best-fitting survival model (baseline model) is an exponential dose-response m ...201728121020
stability and pre-formulation development of a plant-produced anthrax vaccine candidate.second generation anthrax vaccines focus on the use of recombinant protective antigen (rpa) to elicit a strong, toxin neutralizing antibody responses in immunized subjects. the main difference between the rpa vaccines compared to the current licensed vaccine, anthrax vaccine absorbed (ava), is the rpa vaccines are highly purified preparations of only rpa. these second generation rpa vaccines strive to elicit strong immune responses with substantially fewer doses than ava while provoking less sid ...201728117174
resuspension of biological particles from indoor surfaces: effects of humidity and air swirl.human exposure to airborne particles can lead to adverse health outcomes such as respiratory and allergic symptoms. understanding the transport mechanism of respirable particles in occupied spaces is a first step towards assessing inhalation exposure. several studies have contributed to the current knowledge of particle resuspension from indoor surfaces; however, few published studies are available on resuspension of biological particles from indoor surfaces. the objective of this study is to in ...201728117152
modeling the ecological niche of bacillus anthracis to map anthrax risk in kyrgyzstan.anthrax, caused by the environmental bacterium bacillus anthracis, is an important zoonosis nearly worldwide. in central asia, anthrax represents a major veterinary and public health concern. in the republic of kyrgyzstan, ongoing anthrax outbreaks have been reported in humans associated with handling infected livestock and contaminated animal by-products such as meat or hides. the current anthrax situation has prompted calls for improved insights into the epidemiology, ecology, and spatial dist ...201728115677
secondary structure preferences of the anthrax toxin protective antigen translocase.in order for many proteins to move across hydrophobic membrane bilayers, they must be unfolded and translocated by a membrane-embedded channel. these translocase channels interact with the substrate proteins they translocate via hydrophobic pore loops and cleft structures called clamps. the molecular basis for how clamps facilitate unfolding and translocation is poorly understood. anthrax toxin is composed of three proteins, a translocase channel-forming subunit, called protective antigen (pa), ...201728115202
isolation, characterization and antimicrobial activities of polyacetylene glycosides from coreopsis tinctoria nutt.polyacetylene glycosides, (6z, 12e)-tetradecadiene-8,10-diyne-1-ol-3(r)-o-β-d-glucopyranoside (trivially named coreoside e) and (6z, 12e)-tetradecadiene-8,10-diyne-1-ol-3(r)-o-β-l-arabinopyranosyl-(1 → 2)-β-d-glucopyranoside (trivially named coreoside f), were isolated from buds of coreopsis tinctoria nutt., together with one known compound, coreoside b. their chemical structures were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivities. coreoside e exhi ...201728104231
diagnosis implications of the whole genome sequencing in a large lebanese family with hyaline fibromatosis syndrome.hyaline fibromatosis syndrome (hfs) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (jhf) and infantile systemic hyalinosis (ish). these two variants are secondary to mutations in the anthrax toxin receptor 2 gene (antxr2) located on chromosome 4q21. the main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the ...201728103792
soluble p-selectin rescues mice from anthrax lethal toxin-induced mortality through psgl-1 pathway-mediated correction of hemostasis.as one of the virulence factors of bacillus anthracis, lethal toxin (lt) induces various pathogenic responses including the suppression of the coagulation system. in this study, we observed that lt markedly increased the circulating soluble p-selectin (sp-sel) levels and microparticle (mp) count in wild-type but not p-selectin (p-sel, selp(-/-)) or p-sel ligand-1 (psgl-1, selplg(-/-)) knockout mice. because sp-sel induces a hypercoagulable state through psgl-1 pathway to generate tissue factor-p ...201728102766
a single black ulcer in a child with acute lymphocytic leukemia.ecthyma gangrenosum is an uncommon dermatological manifestation characterized by round, indurated ulcers with a central necrotic black eschar and surrounding erythema. this report describes the case of a 5-year-old girl, affected by acute lymphocytic leukemia, presenting with a black eschar on her right thigh. such lesions should always be correctly identified to avoid potentially fatal bacteraemia. furthermore, because of its similar clinical presentation, cutaneous anthrax must be ruled out.201728099607
genetic source tracking of an anthrax outbreak in shaanxi province, china.anthrax is an acute zoonotic infectious disease caused by the bacterium known as bacillus anthracis. from 26 july to 8 august 2015, an outbreak with 20 suspected cutaneous anthrax cases was reported in ganquan county, shaanxi province in china. the genetic source tracking analysis of the anthrax outbreak was performed by molecular epidemiological methods in this study.201728093076
antxr2 knock-out does not result in the development of hypertension in rats.our recent genetic study as well as robust evidences reported by previous genome-wide association studies (gwass) have indicated that the single nucleotide polymorphism rs16998073, located near gene anthrax toxin receptor 2 (antxr2), was significantly associated with hypertension in asians and europeans. the aim of the present study was to determine whether antxr2 is the causal gene of hypertension at the 4q21 locus using an antxr2 knock-out model.201728077422
a serious case of anthrax associated with compartment syndrome.compartment syndrome linked to skin anthrax is a rare complication that may develop and it should be noted that the disease may progress in spite of medical drug treatment. our case was a farmer who was exposed after slaughtering a dead animal, a time delay for treatment hided this history and then developed compartment syndrome. in anthrax cases with delayed treatment and aggressive progression, circulation in the extremities should be carefully noted. we believe that the cases with compartment ...201728076996
evaluation of clinical and serological findings for diagnosis of cutaneous anthrax infection after an outbreak.anthrax, caused by the bacterium bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. we aimed to evaluate clinical findings and risk factors of patients with cutaneous anthrax infection and report anti-lethal factor (lf) igg and anti-protective antigen (pa) igg titers in the serologic diagnosis of disease.201728076993
gene expression control by bacillus anthracis purine riboswitches.in all kingdoms of life, cellular replication relies on the presence of nucleosides and nucleotides, the building blocks of nucleic acids and the main source of energy. in bacteria, the availability of metabolites sometimes directly regulates the expression of enzymes and proteins involved in purine salvage, biosynthesis and uptake through riboswitches. riboswitches are located in bacterial mrnas and can control gene expression by conformational changes in response to ligand binding. we have est ...201728209633
corrigendum: in vivo dynamics of active edema and lethal factors during anthrax. 201728198803
dynamic phenylalanine clamp interactions define single-channel polypeptide translocation through the anthrax toxin protective antigen channel.anthrax toxin is an intracellularly acting toxin where sufficient detail is known about the structure of its channel, allowing for molecular investigations of translocation. the toxin is composed of three proteins, protective antigen (pa), lethal factor (lf), and edema factor (ef). the toxin's translocon, pa, translocates the large enzymes, lf and ef, across the endosomal membrane into the host cell's cytosol. polypeptide clamps located throughout the pa channel catalyze the translocation of lf ...201728192089
evaluation of immunoassays and general biological indicator tests for field screening of bacillus anthracis and ricin.there is little published data on the performance of biological indicator tests and immunoassays that could be used by first responders to determine if a suspicious powder contains a potential biothreat agent. we evaluated a range of biological indicator tests, including 3 protein tests, 2 atp tests, 1 dna test, and 1 ftir spectroscopy instrument for their ability to screen suspicious powders for bacillus anthracis (b. anthracis) spores and ricin. we also evaluated 12 immunoassays (mostly latera ...201728192054
evaluation of pcr systems for field screening of bacillus anthracis.there is little published data on the performance of hand-portable polymerase chain reaction (pcr) systems that can be used by first responders to determine if a suspicious powder contains a potential biothreat agent. we evaluated 5 commercially available hand-portable pcr instruments for detection of bacillus anthracis. we used a cost-effective, statistically based test plan to evaluate systems at performance levels ranging from 0.85-0.95 lower confidence bound (lcb) of the probability of detec ...201728192050
comparison of sampling methods to recover germinated bacillus anthracis and bacillus thuringiensis endospores from surface coupons.in an attempt to devise decontamination methods that are both effective and minimally detrimental to the environment, we evaluated germination induction as an enhancement to strategies for bacillus anthracis spore decontamination. to determine an optimal method for the recovery of germinating spores from different matrices, it was critical to ensure that the sampling procedures did not negatively impact the viability of the germinating spores possibly confounding the results and downstream analy ...201728191745
full sequence amino acid scanning of θ-defensin rtd-1 yields a potent anthrax lethal factor protease inhibitor.θ-defensin rtd-1 is a noncompetitive inhibitor of anthrax lethal factor (lf) protease (ic50 = 390 ± 20 nm, ki = 365 ± 20 nm) and a weak inhibitor of other mammalian metalloproteases such as tnfα converting enzyme (tace) (ki = 4.45 ± 0.48 μm). using full sequence amino acid scanning in combination with a highly efficient "one-pot" cyclization-folding approach, we obtained an rtd-1-based peptide that was around 10 times more active than wild-type rtd-1 in inhibiting lf protease (ic50 = 43 ± 3 nm, ...201728151653
comparisons of the humoral and cellular immunity induced by live a16r attenuated spore and ava-like anthrax vaccine in mice.the live attenuated anthrax vaccine and anthrax vaccine adsorbed (ava) are two main types of anthrax vaccines currently used in human. however, the immunoprotective mechanisms are not fully understood. in this study, we compared humoral and cellular immunity induced by live a16r spore vaccine and a16r strain derived ava-like vaccine in mice peripheral blood, spleen and bone marrow. both a16r spores and ava-like vaccines induced a sustained igg antibody response with igg1/igg2b subtype dominance. ...201728215694
molecular tiling on the surface of a bacterial spore - the exosporium of the bacillus anthracis/cereus/thuringiensis group.bacteria of the genera bacillus and clostridium form highly resistant spores, which in the case of some pathogens act as the infectious agents. an exosporium forms the outermost layer of some spores; it plays roles in protection, adhesion, dissemination, host targeting in pathogens and germination control. the exosporium of the bacillus cereus group, including the anthrax pathogen, contains a 2d-crystalline basal layer, overlaid by a hairy nap. bcla and related proteins form the hairy nap, and r ...201728214340
dynamics of bacterial class bacilli in the deepest valley lake of kashmir-the manasbal lake.in recognition of the importance of bacteria as ecological indicators of the aquatic systems a comprehensive and systematic analysis was carried out on manasbal lake, the deepest spring fed valley lake of kashmir. the main objective envisaged was to analyze bacterial community composition (bcc) and for this purpose systematic and regular sampling of waters from ten different sampling stations, predetermined in the lake according to differences in degree of human interference and also as zones of ...201728087491
bacteriophage t4 as a nanoparticle platform to display and deliver pathogen antigens: construction of an effective anthrax vaccine.protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. however, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. the bacteriophage t4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. therefore, it offers a strong promise as a novel antigen delivery system. currently ba ...201728374254
what is the predictive value of animal models for vaccine efficacy in humans? the importance of bridging studies and species-independent correlates of protection.animal models have played a pivotal role in all stages of vaccine development. their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). this article will cover key questions regarding bridging animal studies to efficacy trials in humans. examples include human papillomavirus (hpv) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (vlps) p ...201728348035
sublingual targeting of sting with 3'3'-cgamp promotes systemic and mucosal immunity against anthrax toxins.anthrax is caused by bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. the current human anthrax vaccine, anthrax vaccine adsorbed (ava), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. bacterial enterotoxins, which stimulate production of the cyclic nucleotide camp are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. we investigated wh ...201728343781
a novel live attenuated anthrax spore vaccine based on an acapsular bacillus anthracis sterne strain with mutations in the htra, lef and cya genes.we recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htra (high temperature requirement a) gene in the bacillus anthracis sterne veterinary vaccine strain. this vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental sterne strain. here, we report the evaluation of additional mutations in the lef and cya genes, encodi ...201728342664
digital triplex dna assay based on plasmonic nanocrystals.a new analytical method has been developed to detect three kinds of dna simultaneously based on magnetic beads and color-encoded plasmonic nanocrystals. magnetic beads modified with capture dna are employed to collect the specific target dna, and color-encoded plasmonic nanocrystals are applied to signal the target through dna hybridization. as a proof of concept, three types of representative metal nanocrystals of gold nanoparticle (aunp), gold nanorod (aunr), and gold/silver nanoparticle (au/a ...201728331957
penicillin-susceptible, oxidase-negative, nonhemolytic, nonmotile bacillus megaterium in disguise of bacillus anthracis.bacillus anthracis is a bacterial pathogen of major concern. the spores of this bacteria can survive harsh environmental conditions for extended periods and are well recognized as a potential bioterror weapon with significant implications. accurate and timely identification of this bacillus species in the diagnostic laboratory is essential for disease and public health management. biosafety level 3 measures and ciprofloxacin treatment were instituted when b. anthracis was suspected from a patien ...201728331641
the berkeleylactones, antibiotic macrolides from fungal coculture.a carefully timed coculture fermentation of penicillium fuscum and p. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones a-h (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide a26771b (5), patulin, and citrinin. there was no evidence of the production of the berkeleylactones or a26771b (5) by either fungus when grown as axenic cultures. the structures were deduced from analyses of spectral data, and the absolute configurations of compounds 1 and 9 ...201728326781
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