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in vivo characterization of an hfq protein encoded by the bacillus anthracis virulence plasmid pxo1.bacterial hfq proteins post-transcriptionally regulate gene expression, primarily by mediating the interaction between srnas (small rnas) and their target mrnas. the role of hfq-based regulation has been well defined in gram-negative bacteria, but comparatively less is known about the impact of hfq proteins in gram-positive species. the gram-positive pathogen bacillus anthracis (causative agent of anthrax) is distinct in that it expresses three homologs of hfq: hfq1 and hfq2 from the chromosome, ...201728288571
a biologically-based computational approach to drug repurposing for anthrax infection.developing drugs to treat the toxic effects of lethal toxin (lt) and edema toxin (et) produced by b. anthracis is of global interest. we utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. for each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. gene expression profiles of drugs were obtained from the connectivity map an ...201728287432
self-defense against bacillus anthracis toxins: is p-selectin the key? 201728281892
genome sequence of historical bacillus anthracis strain tyrol 4675 isolated from a bovine anthrax case in austria.in 1988, an outbreak of anthrax occurred among cattle in the austrian state of tyrol. since then, austria has been declared anthrax-free. here, we report the draft genome sequence of one of these last outbreak strains, bacillus anthracis tyrol 4675, isolated from a diseased cow.201728280006
heroin-associated anthrax with minimal morbidity.in 2010, during an outbreak of anthrax affecting people who inject drugs, a heroin user aged 37 years presented with soft tissue infection. he subsequently was found to have anthrax. we describe his management and the difficulty in distinguishing anthrax from non-anthrax lesions. his full recovery, despite an overall mortality of 30% for injectional anthrax, demonstrates that some heroin-related anthrax cases can be managed predominately with oral antibiotics and minimal surgical intervention.201728275017
systematic substitutions at blip position 50 result in changes in binding specificity for class a β-lactamases.the production of β-lactamases by bacteria is the most common mechanism of resistance to the widely prescribed β-lactam antibiotics. β-lactamase inhibitory protein (blip) competitively inhibits class a β-lactamases via two binding loops that occlude the active site. it has been shown that blip tyr50 is a specificity determinant in that substitutions at this position result in large differential changes in the relative affinity of blip for class a β-lactamases.201728264645
construction of bacillus thuringiensis simulant strains suitable for environmental release.for a surrogate bacterium to be used in outdoor studies, it is important to consider environmental and human safety, and ease of detection. recently, bacillus thuringiensis, a popular bioinsecticide bacterium, is gaining attention as a surrogate bacterium for its use in biodefense. in this study, we constructed simulant strains of b. thuringiensis with enhanced characteristics for environmental studies. through transposon mutagenesis, pigment genes were inserted into the chromosome, producing ye ...201728258144
re-aerosolization of bacillus thuringiensis spores from concrete and turf.spores of bacillus anthracis deposited on surfaces can become airborne again as a result of air currents and mechanical forces. as such they are a potential source of infection by inhalation. spores of bacillus thuringiensis were used to quantify this phenomenon in a simulation of outdoor conditions. concrete and turf surfaces were inoculated by aerosol to produce high spore densities (greater than 1 x 10(9) cfu m(-2) ) which were then subjected to the passage of air at 10 ms(-1) with and withou ...201728256003
development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: a systematic medicinal chemistry based computational approach.to develop 6 conjugate agents of the moribund antibiotic sulfamethoxazole (smz) joined to 6 individual monoterpenes, followed by protocols of medicinal chemistry as potent antibacterials, against multidrug resistant (mdr) human gruesome pathogenic bacteria.201728254074
the epidemiological investigation and control of an anthrax outbreak in a village in central anatolia, turkey. 201728245722
the poly-γ-d-glutamic acid capsule surrogate of bacillus anthracis capsule induces interferon-gamma production in nk cells through interactions with macrophages.the poly-γ-d-glutamic acid (pga) capsule, a major virulence factor of bacillus anthracis, provides protection of the bacillus from phagocytosis and allows its unimpeded growth in the host. we investigated crosstalk between murine nk cells and macrophages stimulated with pga capsule of bacillus licheniformis, a surrogate of b. anthracis capsule. pga induced interferon-gamma (ifn-γ) production from nk cells cultured with macrophages. this effect was dependent on macrophage-derived il-12 and cell-c ...201728237999
ultrastructural characterization of bacillus anthracis spores: the existence of two spores subpopulations? 201728230516
in vitro and in vivo activity of omadacycline against two biothreat pathogens: bacillus anthracis and yersinia pestis.introduction: the in vitro activity and in vivo efficacy of omadacycline (omc) were evaluated against the causative pathogens of anthrax and plague, bacillus anthracis and yersinia pestis, respectively.methods: minimum inhibitory concentrations (mics) of omc were determined by microbroth dilution according to clsi guidelines for 30 isolates each of y. pestis and b. anthracis the in vivo efficacy of omadacycline was studied at a range of dosages in both a post exposure prophylaxis (pep) murine mo ...201728223382
prioritizing zoonotic diseases in ethiopia using a one health approach.ethiopia has the second largest human population in africa and the largest livestock population on the continent. about 80% of ethiopians are dependent on agriculture and have direct contact with livestock or other domestic animals. as a result, the country is vulnerable to the spread of zoonotic diseases. as the first step of the country's engagement in the global health security agenda, a zoonotic disease prioritization workshop was held to identify significant zoonotic diseases of mutual conc ...201628220151
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
medical allocations to persons with special needs during a bioterrorism event.after the bioterrorism-anthrax attacks of 2001, public health officials were tasked with planning population-wide medicine dispensing. this planning started with assumptions and then evaluations of seasonal immunization clinics. research on the 2009 h1n1 pandemic-vaccination campaign showed that an adequately prepared public health system could have prevented over 16% of flu-associated hospitalizations. the 2011 ice storms revealed difficulties with sheltering medically fragile persons with disa ...201628210421
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
mapping as a tool for predicting the risk of anthrax outbreaks in northern region of ghana.anthrax is a febrile soil-born infectious disease that can affect all warm-blooded animals including man. outbreaks of anthrax have been reported in northern region of ghana but no concerted effort has been made to implement risk-based surveillance systems to document outbreaks so as to implement policies to address the disease. we generated predictive maps using soil ph, temperature and rainfall as predictor variables to identify hotspot areas for the outbreaks.201628149439
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
2014 anthrax epidemic in koubia prefecture, guinea-conakry.anthrax disease is an anthropozoonosis caused by a gram-positive bacterium, bacillus anthracis. our objective was to describe the epidemiological, clinical and therapeutic features of the 2014 epidemic in koubia prefecture. this retrospective study examined all of the anthrax cases reported in fafaya, koubia prefecture. in march and april 2014, there were 39 cases of human anthrax reported, for an incidence of 1.135%. the mean age was 20.9 (± 18.3) with a sex ratio of 2.54 (28/11) in favor of me ...201628073730
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
anthrax of domestic animals in vrbas banate: from traditional beliefs to the first scientific views on the ancient disease.from 1929 to 1941, the vrbas banate was one of nine provinces of the kingdom yugoslavia, and according to historical data, the poorest one, without well-organized and sustainable agriculture production. naturalistic production and poor animal health control in the vrbas banate were the most important risk factors for infectious disease spreading. anthrax was very prevalent infectious disease in domestic animals and humans in that period, but some data on this disease remain scarce. in this paper ...201628038486
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
improving phylogeny reconstruction at the strain level using peptidome datasets.typical bacterial strain differentiation methods are often challenged by high genetic similarity between strains. to address this problem, we introduce a novel in silico peptide fingerprinting method based on conventional wet-lab protocols that enables the identification of potential strain-specific peptides. these can be further investigated using in vitro approaches, laying a foundation for the development of biomarker detection and application-specific methods. this novel method aims at reduc ...201628033346
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
genome sequence of the soviet/russian bacillus anthracis vaccine strain 55-vniivvim.bacillus anthracis strain 55-vniivvim is a live-attenuated nonencapsulated soviet/russian veterinary anthrax vaccine strain. we report here the genome of 55-vniivvim and confirm its phylogenetic placement in the global population structure of b. anthracis.201628007853
draft genome sequence of the nonpathogenic, thermotolerant, and exopolysaccharide-producing bacillus anthracis strain pfab2 from panifala hot water spring in west bengal, india.bacillus anthracis is the causative agent of fatal anthrax in both animals and humans. it is prevalently pathogenic. here, we present a bacillus anthracis pfab2 strain from a relatively unexplored panifala hot water spring in west bengal, india. it is nonpathogenic, exopolysaccharide producing, and thermotolerant in nature.201628007848
rapid detection of bacillus anthracis spores using immunomagnetic separation and amperometry.portable detection and quantitation methods for bacillus anthracis (anthrax) spores in pure culture or in environmental samples are lacking. here, an amperometric immunoassay has been developed utilizing immunomagnetic separation to capture the spores and remove potential interferents from test samples followed by amperometric measurement on a field-portable instrument. antibody-conjugated magnetic beads and antibody-conjugated glucose oxidase were used in a sandwich format for the capture and d ...201627999382
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
evaluation of cutaneous anthrax cases during an outbreak in the east region of turkey.anthrax is a zoonotic infection caused by bacillus anthracis. we aimed to retrospectively evaluate cutaneous anthrax cases that occurred during an outbreak in eastern turkey (hakkari-yüksekova), where people mostly earn their living from animal husbandry.201627966316
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
whole genome snp analysis of bovine b. anthracis strains from switzerland reflects strict regional separation of simmental and swiss brown breeds in the past.bacillus anthracis is an evolutionarily young species that presents an extremely low genetic diversity due to its slow mode of propagation, determined by short replication phases and long sporulation periods. in our ongoing efforts to elucidate phylogenetic relationships between european b. anthracis isolates, the genomes of five strains from switzerland belonging to lineages b.br.cneva and a.br.aust94 were sequenced. comparative analysis with additional, available genomes from both lineages, we ...201627939145
[infantile systemic hyalinosis: a case report and literature review].objective: to investigate the clinical, pathological and gene mutation features of infantile systemic hyalinosis(ish). method: data of a child with ish seen in haikou hospital were retrospectively analyzed for the diagnosis and differential diagnosis of infantile systemic hyalinosis and the relevant reports in literature were reviewed. result: a 1 year and 1 month old boy showed limbs joint stiffness, limited mobility and double knee flexion at his first month of life. at third month, red rashes ...201627938598
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
structure, function and evolution of clostridium botulinum c2 and c3 toxins: insight to poultry and veterinary vaccines.clostridium botulinum group iii strains are able to produce cytotoxins, c2 toxin and c3 exotoxin, along with botulinum neurotoxin types c and d. c2 toxin and c3 exotoxin produced from this organism are the most important members of bacterial adp-ribosyltransferase superfamily. both toxins have distinct pathophysiological functions in the avian and mammalian hosts. the members of this superfamily transfer an adp-ribose moiety of nad+ to specific eukaryotic target proteins. the present review desc ...201627915984
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
development of a filter to prevent infections with spore-forming bacteria in injecting drug users.in heroin injectors, there have been a number of outbreaks caused by spore-forming bacteria, causing serious infections such as anthrax or botulism. these are, most likely, caused by injecting contaminated heroin, and our aim was to develop a filter that efficiently removes these bacteria and is also likely to be acceptable for use by people who inject drugs (i.e. quick, simple and not spoil the hit).201627905935
postexposure prophylaxis after possible anthrax exposure: adherence and adverse events.anthrax postexposure prophylaxis (pep) was recommended to 42 people after a laboratory incident that involved potential aerosolization of bacillus anthracis spores in 2 laboratories at the centers for disease control and prevention in 2014. at least 31 (74%) individuals who initiated pep did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. among the 29 that discontinued the antimicrobial component of pep, most (38%) individuals discontinued pep ...201627898235
vaccination via chloroplast genetics: affordable protein drugs for the prevention and treatment of inherited or infectious human diseases.plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. booster vaccines made in chloroplasts prevent global infectious diseases, such as tuberculosis, malaria, cholera, and polio, and biological threats, such as anthrax and plague. recent advances in this field include commercial-scale production of human therapeutic proteins in fda-approved cgmp facilities, development of tags to deliver protein dru ...201627893966
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
notice to readers: final 2015 reports of nationally notifiable infectious diseases and conditions.the table listed in this report on pages 1307-1321 presents finalized data, as of june 30, 2016, from the national notifiable diseases surveillance system (nndss) for 2015. these data will be published in more detail in the summary of notifiable infectious diseases and conditions - united states, 2015 (1). because no cases were reported in the united states during 2015, the following diseases do not appear in this early release table: anthrax; dengue hemorrhagic fever; diphtheria; eastern equine ...201627880744
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 self-quenching-resistant carbon nanodot powder with multicolored solid-state fluorescence for ultra-fast staining of various representative bacterial species within one minute.in this study, we prepared self-quenching-resistant solid-state fluorescent carbon nanodots (sfcds) without any other solid matrices. the sfcds were prepared using a one-step microwave synthesis method through precise control of the heating power and time. the resulting sfcd powder showed excitation-dependent emission behavior with a maximum fluorescence quantum yield of 40%. the multicolored sfcds were successfully used as fluorescent agents for rapid staining of 14 representative bacterial spe ...201627874136
reanalysis of the anthrax epidemic in rhodesia, 1978-1984.in the mid-1980s, the largest epidemic of anthrax of the last 200 years was documented in a little known series of studies by davies in the central african journal of medicine. this epidemic involved thousands of cattle and 10,738 human cases with 200 fatalities in rhodesia during the counterinsurgency. grossly unusual epidemiological features were noted that, to this day, have not been definitively explained. this study performed a historical reanalysis of the data to reveal an estimated geogra ...201627867766
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
impact of dendrimer terminal group chemistry on blockage of the anthrax toxin channel: a single molecule study.nearly all the cationic molecules tested so far have been shown to reversibly block k⁺ current through the cation-selective pa63 channels of anthrax toxin in a wide nm-mm range of effective concentrations. a significant increase in channel-blocking activity of the cationic compounds was achieved when multiple copies of positively charged ligands were covalently linked to multivalent scaffolds, such as cyclodextrins and dendrimers. even though multivalent binding can be strong when the individual ...201627854272
xenobiotic-metabolizing enzymes in bacillus anthracis: molecular and functional analysis of a truncated arylamine n-acetyltransferase isozyme.the arylamine n-acetyltransferases (nats) are xenobiotic-metabolizing enzymes that play an important role in the detoxification and/or bioactivation of arylamine drugs and xenobiotics. in bacteria, nats may contribute to the resistance against antibiotics such as isoniazid or sulfamides through their acetylation, which makes this enzyme family a possible drug target. bacillus anthracis, a bacterial species of clinical significance, expresses three nat isozymes with distinct structural and enzyma ...201627846346
synthesis and fungicidal activity of 1,1-diaryl tertiary alcohols.a series of 1,1-diaryl tertiary alcohols and some of their dehydration derivatives were designed, synthesized and evaluated for their antifungal activities. some compounds exhibited moderate inhibitory activities against seven plant pathogens at 50μg/ml in vitro, compounds 5g and 7c displayed nearly the same or higher fungicidal activities against some certain plant pathogens compared with the lead compound pyrimorph. a qualitative structure-activity relationship (sar) analysis revealed that the ...201627838182
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
temperature exerts control of bacillus cereus emetic toxin production on post-transcriptional levels.in recent years, the emetic toxin cereulide, produced by bacillus cereus, has gained high relevance in food production and food safety. cereulide is synthesized non-ribosomal by the multi-enzyme complex ces-nrps, which is encoded on a megaplasmid that shares its backbone with the bacillus anthracis px01 toxin plasmid. due to its resistance against heat, proteolysis and extreme ph conditions, the formation of this highly potent depsipeptide toxin is of serious concern in food processing procedure ...201627826288
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
alternative pre-approved and novel therapies for the treatment of anthrax.bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category a bioterror agent. this pathogenic microbe can be transmitted to both animals and humans. clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. to date, anthra ...201627809794
self-oriented monolayer immobilization of ovalbumin and b. cereus antibody molecules on a chemically modified surface of silicon nitride fosters the enhancement of capture of bio-agents.a fast and reliable detection of biological agents in air is of a crucial importance to respond to terrorist attacks. with the aim to efficiently react to such hazards there is the need to develop highly sensitive and specific detection analytical devices for selective and quantitative detection of biological threats such as the presence of bacillus anthracis spores and/or the presence of ricin a toxins. in this study we explored how to achieve an oriented immobilization of antibody molecules on ...201627693720
optimization of physiochemical parameters during bioremediation of synthetic dye by marasmius cladophyllus umas ms8 using statistical approach.in many industrial areas such as in food, pharmaceutical, cosmetic, printing, and textile, the use of synthetic dyes has been integral with products such as azo dye, anthrax, and dyestuffs. as such, these industries produce a lot of waste by-products that could contaminate the environment. bioremediation, therefore, has become an important emerging technology due to its cost-sustainable, effective, natural approach to cleaning up contaminated groundwater and soil via the use of microorganisms. t ...201627803944
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
palladium-triggered chemical rescue of intracellular proteins via genetically encoded allene-caged tyrosine.chemical de-caging has emerged as an attractive strategy for gain-of-function study of proteins via small-molecule reagents. the previously reported chemical de-caging reactions have been largely centered on liberating the side chain of lysine on a given protein. herein, we developed an allene-based caging moiety and the corresponding palladium de-caging reagents for chemical rescue of tyrosine (tyr) activity on intracellular proteins. this bioorthogonal de-caging pair has been successfully appl ...201627797486
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
inhibition of interleukin 1β (il-1β) expression by anthrax lethal toxin (letx) is reversed by histone deacetylase 8 (hdac8) inhibition in murine macrophages. 201627794103
comparative genomics of bacillus anthracis from the wool industry highlights polymorphisms of lineage a.br.vollum.with the advent of affordable next-generation sequencing (ngs) technologies, major progress has been made in the understanding of the population structure and evolution of the b. anthracis species. here we report the use of whole genome sequencing and computer-based comparative analyses to characterize six strains belonging to the a.br.vollum lineage. these strains were isolated in switzerland, in 1981, during iterative cases of anthrax involving workers in a textile plant processing cashmere wo ...201627793731
licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the fda animal rule.the availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. biothrax® (anthrax vaccine adsorbed; ava) is the only licensed anthrax vaccine in the us. areas covered: recent licensed improvements to biothrax vaccine for pre-exposure prophylaxis (prep) have included an intramuscular (im) five-dose schedule (in 2008) and a three-dose im primary seri ...201627792416
aerosol and surface deposition characteristics of two surrogates for bacillus anthracis spores.spores of an acrystalliferous derivative of bacillus thuringiensis subsp. kurstaki, termed btcry-, are morphologically, aerodynamically, and structurally indistinguishable from bacillus anthracis spores. btcry- spores were dispersed in a large, open-ended barn together with spores of bacillus atrophaeus subsp. globigii, a historically used surrogate for bacillus anthracis spore suspensions (2 × 10(12) cfu each of b. atrophaeus subsp. globigii and btcry-) were aerosolized in each of five spray ev ...201627613681
acetalated dextran microparticulate vaccine formulated via coaxial electrospray preserves toxin neutralization and enhances murine survival following inhalational bacillus anthracis exposure.subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (mps) via emulsion techniques results in total igg antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. to address this iss ...201627594343
design and synthesis of fluorescent acyclic nucleoside phosphonates as potent inhibitors of bacterial adenylate cyclases.bordetella pertussis adenylate cyclase toxin (act) and bacillus anthracis edema factor (ef) are key virulence factors with adenylate cyclase (ac) activity that substantially contribute to the pathogenesis of whooping cough and anthrax, respectively. there is an urgent need to develop potent and selective inhibitors of bacterial acs with prospects for the development of potential antibacterial therapeutics and to study their molecular interactions with the target enzymes. novel fluorescent 5-chlo ...201627775243
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
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