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gnez, a udp-glcnac 2-epimerase, is required for s-layer assembly and vegetative growth of bacillus anthracis.bacillus anthracis, the causative agent of anthrax, forms an s-layer atop its peptidoglycan envelope and displays s-layer proteins and bacillus s-layer-associated (bsl) proteins with specific functions to support cell separation of vegetative bacilli and growth in infected mammalian hosts. s-layer and bsl proteins bind via the s-layer homology (slh) domain to the pyruvylated secondary cell wall polysaccharide (scwp) with the repeat structure [→4)-β-mannac-(1→4)-β-glcnac-(1→6)-α-glcnac-(1→]n, whe ...201424914184
identification of three noncontiguous regions on bacillus anthracis plasmid pxo1 that are important for its maintenance.bacillus anthracis pxo1 minireplicon (mr) plasmid consisting of open reading frames (orfs) gbaa_pxo1_0020 to gbaa_pxo1_0023 is not stably maintained in b. anthracis, whereas the full-size parent pxo1 plasmid (having 181,677 bp and 217 orfs) is extremely stable under the same growth conditions. two genetic tools developed for dna manipulation in b. anthracis (cre-loxp and flp-frt systems) were used to identify pxo1 regions important for plasmid stability. we localized a large segment of pxo1 that ...201424914182
negative impact of laws regarding biosecurity and bioterrorism on real diseases.research on highly pathogenic microorganisms in biosafety level 3 and 4 laboratories is very important for human public health, as it provides opportunities for the development of vaccines and novel therapeutics as well as diagnostic methods to prevent epidemics. however, in recent years, after the anthrax and world trade center attacks in 2001 in the usa, the threat of bioterrorism has grown for both the public and the authorities. as a result, technical and physical containment measures and bi ...201424909400
the genetic diversity of cereulide biosynthesis gene cluster indicates a composite transposon tnces in emetic bacillus weihenstephanensis.cereulide is a cyclic dodecadepsipeptide ionophore, produced via non-ribosomal peptide synthetases (nrps), which in rare cases can lead to human death. early studies had shown that emetic toxin formation belongs to a homogeneous group of bacillus cereus sensu stricto and the genetic determinants of cereulide (a 24-kb gene cluster of ceshptabcd) are located on a 270-kb plasmid related to the bacillus anthracis virulence plasmid pxo1.201424906385
application of r-pfe hyperimmune sera for concurrent detection of bacillus anthracis, yersinia pestis and staphylococcal enterotoxin b.to evaluate the potential of an intergeneric multidomain recombinant chimeric protein for the simultaneous detection of bacillus anthracis, yersinia pestis and staphylococcal enterotoxin b.201424905217
bacillus thuringiensis hd-1 cry- : development of a safe, non-insecticidal simulant for bacillus anthracis.a representative simulant for spores of bacillus anthracis is needed for field testing. bacillus thuringiensis is gaining recognition as a suitable organism. a strain that does not form the insecticidal, parasporal crystals that are characteristic of this species is a more accurate physical representative of b. anthracis spores. we developed noninsecticidal derivatives of two isolates of b. thuringiensis hd-1.201424903218
interactions between bacillus anthracis and plants may promote anthrax transmission.environmental reservoirs are essential in the maintenance and transmission of anthrax but are poorly characterized. the anthrax agent, bacillus anthracis was long considered an obligate pathogen that is dormant and passively transmitted in the environment. however, a growing number of laboratory studies indicate that, like some of its close relatives, b. anthracis has some activity outside of its vertebrate hosts. here we show in the field that b. anthracis has significant interactions with a gr ...201424901846
genotyping of french bacillus anthracis strains based on 31-loci multi locus vntr analysis: epidemiology, marker evaluation, and update of the internet genotype database.bacillus anthracis is known to have low genetic variability. in spite of this lack of diversity, multiple-locus variable-number tandem repeat (vntr) analysis (mlva) and single nucleotide polymorphisms (snps) including the canonical snps assay (cansnp) have proved to be highly effective to differentiate strains. five different mlva schemes based on a collection of 31 vntr loci (mlva8, mlva15, mlva20, mlva25 and mlva31) with increased resolving power have been described.201424901417
structure-activity relationship of semicarbazone ega furnishes photoaffinity inhibitors of anthrax toxin cellular entry.ega, 1, prevents the entry of multiple viruses and bacterial toxins into mammalian cells by inhibiting vesicular trafficking. the cellular target of 1 is unknown, and a structure-activity relationship study was conducted in order to develop a strategy for target identification. a compound with midnanomolar potency was identified (2), and three photoaffinity labels were synthesized (3-5). for this series, the expected photochemistry of the phenyl azide moiety is a more important factor than the i ...201424900841
efficiency and effectiveness of using nonmedical staff during an urgent mass prophylaxis response.using a simulated anthrax scenario, the philadelphia department of public health tested the readiness of a nonmedical closed point-of-dispensing (pod) site to see how rapidly and accurately it could provide medication to its internal population. this closed pod had developed and exercised its mass prophylaxis plan in conjunction with the local health department twice before, and the department was interested in assessing the impact of having no onsite department involvement. two sessions were co ...201424896307
history of biological warfare and bioterrorism.bioterrorism literally means using microorganisms or infected samples to cause terror and panic in populations. bioterrorism had already started 14 centuries before christ, when the hittites sent infected rams to their enemies. however, apart from some rare well-documented events, it is often very difficult for historians and microbiologists to differentiate natural epidemics from alleged biological attacks, because: (i) little information is available for times before the advent of modern micro ...201424894605
exposure to bacillus anthracis capsule results in suppression of human monocyte-derived dendritic cells.the antiphagocytic capsule of bacillus anthracis is a major virulence factor. we hypothesized that it may also mediate virulence through inhibition of the host's immune responses. during an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. we sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (idcs). human monocytes were differentiated into idcs by interleukin-4 (il-4) and granuloc ...201424891109
robert koch (1843-1910) and dermatology on his 171st birthday.robert koch (1843-1910) received the nobel prize in medicine in 1905 for his studies of tuberculosis. he contributed significantly to microbiology, isolating also cholera and anthrax pathogens, and introducing several postulates in this field. in addition, he developed staining methods, as well as culturing and microscopic techniques. many of his achievements have also influenced dermatology. this contribution reviews his life and major achievements on the occasion of the 171st anniversary of hi ...201424887990
evaluation of the relationship between the adenosine triphosphate (atp) bioluminescence assay and the presence of bacillus anthracis spores and vegetative cells.the adenosine triphosphate (atp) bioluminescence assay was utilized in laboratory evaluations to determine the presence and concentration of vegetative and spore forms of bacillus anthracis sterne 34f2.201424879485
combination of biobarcode assay with on-chip capillary electrophoresis for ultrasensitive and multiplex biological agent detection.early diagnosis of biological agents is of paramount importance to prevent the casualties and fatal disease in human during bioterrorism or biological warfare. in this study, we reported an efficient and sensitive multiplex biological agent detection method based on the dna biobarcode assay and the micro-capillary electrophoresis (μce) technology. monoplex as well as multiplex pathogen identification was performed using five targets including bacillus anthracis, francisella tularensis, yersinia ...201424878840
cdc report on the potential exposure to anthrax.the centers for disease control and prevention (cdc) conducted an internal review of an incident that involved an unintentional release of potentially viable anthrax within its roybal campus, in atlanta, georgia. on june 5, 2014, a laboratory scientist in the bioterrorism rapid response and advanced technology (brrat) laboratory prepared extracts from a panel of eight bacterial select agents, including bacillus anthracis (b. anthracis), under biosafety level (bsl) 3 containment conditions. these ...201426418856
draft genome sequence of bacillus cereus strain bcfl2013, a clinical isolate similar to g9241.bacillus cereus strains, such as g9241, causing anthrax-like illnesses have recently been discovered. we report the genome sequence of a clinical strain, b. cereus bcfl2013, which is similar to g9241, recovered from a patient in florida.201424874674
glycan surface antigens from bacillus anthracis as vaccine targets: current status and future perspectives.over recent years great attention has been directed to the discovery of novel antigens from bacillus anthracis, because of the potential of its spores in the development of weapons for mass destruction. substantial effort has been directed to the identification and immunochemical evaluation of glycans that might be used for specific diagnostic detection of the spores or immune-mediated prevention of anthrax. carbohydrate structures found on surfaces of vegetative cells and spores are herein disc ...201424867680
more or less is fine: an undercover work of dkk1 in anthrax toxin uptake. 201424865625
cutaneous anthrax in a school teacher.cutaneous anthrax is an infection of the skin caused by bacillus anthracis. this is a report of a case of cutaneous anthrax attending outpatients of mymensingh medical college hospital in october, 2010. the infected person was a retired school teacher with a very good body build. he reported to handle cow flesh about 4-5 days ago, developed few painless papules over shin of right leg, which gradually became large bullae and blackish eschar developed over the lesion. smears from the lesions were ...201424858169
detection of anthrax protective antigen (pa) using europium labeled anti-pa monoclonal antibody and time-resolved fluorescence.inhalation anthrax is a rare but acute infectious disease following adsorption of bacillus anthracis spores through the lungs. the disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. the early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time pcr. consequently, there may be a significant delay in diagnosis and target ...201424857756
clinical microbiologists facing an anthrax alert.microbiological war and terrorist attacks are made to weaken populations by transmitting pathogenic and epidemic microorganisms. these bacteria or viruses are often difficult to diagnose. anthrax alerts following september 2001 showed that most clinical microbiology laboratories were not adequately prepared, using obsolete diagnostic methods or being too slow to use accurate tools when facing a major threat. following this period, most microbiology laboratories were prepared for bioterrorism ale ...201424845109
identification of stringent response-related and potential serological proteins released from bacillus anthracis overexpressing the rela/spot homolog, rsh bant.rela and spot synthesize ppgpp, a key effector molecule that facilitates the adaptation of bacteria to nutrient starvation and other stresses, known as the stringent response. to investigate the role of rsh bant , a putative rela/spot homolog (encoded by bas4302) in bacillus anthracis, we examined the alteration of the secretome profiles after the overexpression of a functional his-rsh bant protein in the b. anthracis strain sterne at the stationary growth phase. in the ppgpp-deficient e. coli m ...201424838666
anthrax vaccine adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. we applied the noninferiority analysis model to this prospective study comparing the bacillus anthracis protective antigen (pa) igg antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (ava) (biothrax®) administered on schedule or delayed. a total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed ...201424837771
n-acetylglucosamine deacetylases modulate the anchoring of the gamma-glutamyl capsule to the cell wall of bacillus anthracis.bacillus anthracis has a complex cell wall structure composed of a peptidoglycan (pg) layer to which major structures are anchored such as a neutral polysaccharide, an s-layer, and a poly-γ-d-glutamate (pdga) capsule. many of these structures have central roles in the biology of b. anthracis, particularly, in virulence. however, little attention has been devoted to structurally study the pg and how it is modified in the presence of these secondary cell wall components. we present here the fine s ...201424833281
impaired colonic b-cell responses by gastrointestinal bacillus anthracis infection.ingestion of bacillus anthracis spores causes gastrointestinal (gi) anthrax. humoral immune responses, particularly immunoglobulin a (iga)-secreting b-1 cells, play a critical role in the clearance of gi pathogens. here, we investigated whether b. anthracis impacts the function of colonic b-1 cells to establish active infection. gi anthrax led to significant inhibition of immunoglobulins (eg, iga) and increased expression of program death 1 on b-1 cells. furthermore, infection also diminished ty ...201424829464
monitoring endocytic trafficking of anthrax lethal factor by precise and quantitative protein labeling.coupling the genetic code expansion technique with bioorthogonal reactions enables precise control over the conjugation site as well as the choice of fluorescent probes during protein labeling. however, the advantages of this strategy over bulky and rigid fluorescent proteins (fps) remain to be fully explored. here we applied site-specific bioorthogonal labeling on anthrax lethal factor (lf) to visualize its membrane translocation inside live cells. in contrast to the previously reported fp tags ...201424828812
extracellular vesicles produced by the gram-positive bacterium bacillus subtilis are disrupted by the lipopeptide surfactin.previously, extracellular vesicle production in gram-positive bacteria was dismissed due to the absence of an outer membrane, where gram-negative vesicles originate, and the difficulty in envisioning how such a process could occur through the cell wall. however, recent work has shown that gram-positive bacteria produce extracellular vesicles and that the vesicles are biologically active. in this study, we show that bacillus subtilis produces extracellular vesicles similar in size and morphology ...201424826903
improving the anti-toxin abilities of the cmg2-fc fusion protein with the aid of computational design.cmg2-fc is a fusion protein composed of the extracellular domain of capillary morphogenesis protein 2 (cmg2) and the fc region of human immunoglobulin g; cmg2-fc neutralizes anthrax toxin and offers protection against bacillus anthracis challenge. to enhance the efficacy of cmg2-fc against anthrax toxin, we attempted to engineer a cmg2-fc with an improved affinity for pa. using the automatic design algorithm foldx and visual inspection, we devised two cmg2-fc variants that introduce mutations in ...201425101992
a retrospective study on the epidemiology of anthrax, foot and mouth disease, haemorrhagic septicaemia, peste des petits ruminants and rabies in bangladesh, 2010-2012.anthrax, foot and mouth disease (fmd), haemorrhagic septicaemia (hs), peste des petits ruminants (ppr) and rabies are considered to be endemic in bangladesh. this retrospective study was conducted to understand the geographic and seasonal distribution of these major infectious diseases in livestock based on data collected through passive surveillance from 1 january 2010 to 31 december 2012. data analysis for this period revealed 5,937 cases of anthrax, 300,333 of fmd, 13,436 of hs, 247,783 of pp ...201425101836
inactivation of bacterial and viral biothreat agents on metallic copper surfaces.in recent years several studies in laboratory settings and in hospital environments have demonstrated that surfaces of massive metallic copper have intrinsic antibacterial and antiviral properties. microbes are rapidly inactivated by a quick, sharp shock known as contact killing. the underlying mechanism is not yet fully understood; however, in this process the cytoplasmic membrane is severely damaged. pathogenic bacterial and viral high-consequence species able to evade the host immune system a ...201425100640
germination and persistence of bacillus anthracis and bacillus thuringiensis in soil microcosms.decontaminating large, outdoor spaces of bacillus anthracis spores presents significant problems, particularly in soil. proof was sought that the addition of germinant chemicals could cause spores of b. anthracis and bacillus thuringiensis, a commonly used simulant of the threat agent, to convert to the less resistant vegetative form in a microcosm.201425099131
bacterial spore detection and analysis using hyperpolarized (129)xe chemical exchange saturation transfer (hyper-cest) nmr.previously, we reported hyperpolarized (129)xe chemical exchange saturation transfer (hyper-cest) nmr techniques for the ultrasensitive (i.e., 1 picomolar) detection of xenon host molecules known as cryptophane. here, we demonstrate a more general role for hyper-cest nmr as a spectroscopic method for probing nanoporous structures, without the requirement for cryptophane or engineered xenon-binding sites. hyper-cest (129)xe nmr spectroscopy was employed to detect bacillus anthracis and bacillus s ...201425089181
draft genomes of three strains representative of the bacillus anthracis diversity found in france.we report here the draft genomes of three bacillus anthracis strains isolated in france: 08-8_20 (a.br.001/002), 99-100 (a.br.011/009), and 00-82 (b.br cneva). the total lengths of assemblies are 5,440,708 bp, 5,446,472 bp, and 5,436,014 bp for 08-8_20, 99-100, and 00-82, respectively.201425081258
[comparative multilocus vntr- and snp-analysis of bacillus anthracis vaccine strains].comparative vntr- and snp-genotype analysis of four bacillus anthracis strains (three vaccinal and one virulent) was carried out using modern molecular-genetic typing methods. it is established that these strains formed four snp patterns completely corresponding to the vntr-profiles. it was demonstrated that all strains tested except vaccinal b. anthracis sti-1 could not belong by snp-profile to three global genetic lines of the anthrax agent extended in the world.201425080817
selective detection of 1000 b. anthracis spores within 15 minutes using a peptide functionalized sers assay.a surface-enhanced raman spectroscopy (sers) assay has been designed to detect bacillus anthracis spores. the assay consists of silver nanoparticles embedded in a porous glass structure that have been functionalized with atyplpir, a peptide developed to discriminately bind b. anthracis versus other species of bacillus. once bound, acetic acid was used to release the biomarker dipicolinic acid from the spores, which was detected by sers through the addition of silver colloids. this sers assay was ...201425263740
anthrax lethal factor inhibitors as potential countermeasure of the infection.anthrax lethal factor (lf) is a zinc-dependent metalloprotease, one of the virulence factor of anthrax infection. three forms of the anthrax infection have been identified: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). anthrax toxin is composed of protective antigen (pa), lethal factor (lf), and edema factor (ef). protective antigen mediates the entry of lethal factor/edema factor into the cytosol of host cells. lethal factor (lf) ...201425262802
semiquinone-induced maturation of bacillus anthracis ribonucleotide reductase by a superoxide intermediate.ribonucleotide reductases (rnrs) catalyze the conversion of ribonucleotides to deoxyribonucleotides, and represent the only de novo pathway to provide dna building blocks. three different classes of rnr are known, denoted i-iii. class i rnrs are heteromeric proteins built up by α and β subunits and are further divided into different subclasses, partly based on the metal content of the β-subunit. in subclass ib rnr the β-subunit is denoted nrdf, and harbors a manganese-tyrosyl radical cofactor. t ...201425262022
identification of potential drug targets by subtractive genome analysis of bacillus anthracis a0248: an in silico approach.bacillus anthracis is a gram positive, spore forming, rod shaped bacteria which is the etiologic agent of anthrax - cutaneous, pulmonary and gastrointestinal. a recent outbreak of anthrax in a tropical region uncovered natural and in vitro resistance against penicillin, ciprofloxacin, quinolone due to over exposure of the pathogen to these antibiotics. this fact combined with the ongoing threat of using b. anthracis as a biological weapon proves that the identification of new therapeutic targets ...201425254941
environmental airborne contact dermatoses.this chapter is complementary to chapter 4 published in the same series. airborne contact dermatitis (abcd) is considered a prototype in the field of environmental dermatology. it is often underestimated in most textbooks of general dermatology, despite its frequent occurrence in daily life. abcd may be irritant, allergic, phototoxic, or photoallergic. airborne contact urticaria is another example. a particular clinical aspect is the "head and neck dermatitis", which occurs in atopic adult patie ...201425252746
possible use of bacteriophages active against bacillus anthracis and other b. cereus group members in the face of a bioterrorism threat.anthrax is an infectious fatal disease with epidemic potential. nowadays, bioterrorism using bacillus anthracis is a real possibility, and thus society needs an effective weapon to neutralize this threat. the pathogen may be easily transmitted to human populations. it is easy to store, transport, and disseminate and may survive for many decades. recent data strongly support the effectiveness of bacteriophage in treating bacterial diseases. moreover, it is clear that bacteriophages should be cons ...201425247187
investigation of the essentiality of glutamate racemase in mycobacterium smegmatis.the mycobacterial cell wall frequently has been used as a target for drug development, and d-glutamate, synthesized by glutamate racemase (muri), is an important component of peptidoglycan. while the essentiality of the muri gene has been shown in several bacterial species, including escherichia coli, bacillus anthracis, and streptococcus pneumoniae, studies in mycobacteria have not yet provided definitive results. this study aimed to determine whether muri is indeed essential and can serve as a ...201425246478
bacillus anthracis grlav96a topoisomerase iv, a quinolone resistance mutation that does not affect the water-metal ion bridge.the rise in quinolone resistance is threatening the clinical use of this important class of broad-spectrum antibacterials. quinolones kill bacteria by increasing the level of dna strand breaks generated by the type ii topoisomerases gyrase and topoisomerase iv. most commonly, resistance is caused by mutations in the serine and acidic amino acid residues that anchor a water-metal ion bridge that facilitates quinolone-enzyme interactions. although other mutations in gyrase and topoisomerase iv hav ...201425246407
immunogenicity and safety of four different dosing regimens of anthrax vaccine adsorbed for post-exposure prophylaxis for anthrax in adults.strategies to implement post exposure prophylaxis (pep) in case of an anthrax bioterror event are needed. to increase the number of doses of vaccine available we evaluated reducing the amount of vaccine administered at each of the vaccinations, and reducing the number of doses administered.201425239484
genome sequence of bacillus anthracis sti, a sterne-like georgian/soviet vaccine strain.the bacillus anthracis strain sti is a soviet vaccine strain that lacks the pxo2 plasmid. previous data indicate that this isolate forms a new branch within the b. anthracis sub-group originally identified as a. br.008/009.201425237016
spxa2, encoding a regulator of stress resistance in bacillus anthracis, is controlled by sair, a new member of the rrf2 protein family.spx, a member of the arsc (arsenate reductase) protein family, is conserved in gram-positive bacteria, and interacts with rna polymerase to activate transcription in response to toxic oxidants. in bacillus anthracis str. sterne, resistance to oxidative stress requires the activity of two paralogues, spxa1 and spxa2. suppressor mutations were identified in spxa1 mutant cells that conferred resistance to hydrogen peroxide. the mutations generated null alleles of the sair gene and resulted in eleva ...201425231235
phylogenetic and clonality analysis of bacillus pumilus isolates uncovered a highly heterogeneous population of different closely related species and clones.bacillus pumilus is a gram-positive bacterium with a wide range of attributed applications, namely as a plant growth promoting rhizobacteria (pgpr), animal, and human probiotic. however, a rare putative role in human diseases has been reported, namely in food poisoning or as anthrax-like cutaneous infectious agent. this species is difficult to distinguish from its closely related species on the basis of phenotypic or biochemical characteristics and 16s rrna gene sequences. in this study, the phy ...201425230950
combination therapy with antibiotics and anthrax immune globulin intravenous (aigiv) is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.we have evaluated the therapeutic efficacy of aigiv when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by aigiv over standard antibiotic treatment alone in a new zealand white rabbit model of inhalational anthrax.201425226075
[use of gis technologies in development of a cadaster of stationary unfavorable by anthrax points in krasnodar region].development of a cadaster of stationary unfavorable by anthrax points in krasnodar region by using gis technologies.201425051698
phylogeography of bacillus anthracis in the country of georgia shows evidence of population structuring and is dissimilar to other regional genotypes.sequence analyses and subtyping of bacillus anthracis strains from georgia reveal a single distinct lineage (aust94) that is ecologically established. phylogeographic analysis and comparisons to a global collection reveals a clade that is mostly restricted to georgia. within this clade, many groups are found around the country, however at least one subclade is only found in the eastern part. this pattern suggests that dispersal into and out of georgia has been rare and despite historical dispers ...201425047912
construction and characterization of stable, constitutively expressed, chromosomal green and red fluorescent transcriptional fusions in the select agents, bacillus anthracis, yersinia pestis, burkholderia mallei, and burkholderia pseudomallei.here, we constructed stable, chromosomal, constitutively expressed, green and red fluorescent protein (gfp and rfp) as reporters in the select agents, bacillus anthracis, yersinia pestis, burkholderia mallei, and burkholderia pseudomallei. using bioinformatic approaches and other experimental analyses, we identified p0253 and p1 as potent promoters that drive the optimal expression of fluorescent reporters in single copy in b. anthracis and burkholderia spp. as well as their surrogate strains, r ...201425044501
protein- and dna-based anthrax toxin vaccines confer protection in guinea pigs against inhalational challenge with bacillus cereus g9241.in the past decade, several bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. one strain was indistinguishable from b. cereus g9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. the finding that b. cereus g9241 pathogenesis in mice is dependent o ...201425044336
high metal substitution tolerance of anthrax lethal factor and characterization of its active copper-substituted analogue.anthrax lethal factor (lf) is a zinc-dependent metalloendopeptidase and a member of the gluzincin family. the current report demonstrates a high metal substitution tolerance of lf atypical of gluzincins and other zinc-dependent metalloproteases. mn(2+), co(2+), ni(2+), cu(2+) and cd(2+) were found to reactivate the apoprotein of lf to a level either comparable to or significantly higher than that noted for the native zinc enzyme. the most active form of lf was obtained with cu(2+), a surprising ...201425042732
decontamination of a bsl3 laboratory by hydrogen peroxide fumigation using three different surrogates for bacillus anthracis spores.two independent trials investigated the decontamination of a bsl3 laboratory using vaporous hydrogen peroxide and compared the effect on spores of bacillus cereus, bacillus subtilis and bacillus thuringiensis as surrogates for bacillus anthracis spores, while spores of geobacillus stearothermophilus served as control.201425040253
optic atrophy secondary to preseptal cutaneous anthrax: case report.bacillus anthracis, the agent of anthrax, is a nonmotile, aerobic gram-positive rod that can form very resistant spores in economically poor environments. anthrax can manifest as cutaneous, gastrointestinal, or inhalational form. cutaneous anthrax, caused by direct skin contact, presents with eschar, lymphadenopathy, and a febrile illness. the face and eyelids are most commonly involved in cutaneous anthrax. a 45-year-old man was admitted to our clinic with high fever and swelling of the right e ...201427928303
changing patterns of human anthrax in azerbaijan during the post-soviet and preemptive livestock vaccination eras.we assessed spatial and temporal changes in the occurrence of human anthrax in azerbaijan during 1984 through 2010. data on livestock outbreaks, vaccination efforts, and human anthrax incidence during soviet governance, post-soviet governance, preemptive livestock vaccination were analyzed. to evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. results indicated an annual p ...201425032701
tailored cyclodextrin pore blocker protects mammalian cells from clostridium difficile binary toxin cdt.some clostridium difficile strains produce, in addition to toxins a and b, the binary toxin clostridium difficile transferase (cdt), which adp-ribosylates actin and may contribute to the hypervirulence of these strains. the separate binding and translocation component cdtb mediates transport of the enzyme component cdta into mammalian target cells. cdtb binds to its receptor on the cell surface, cdta assembles and cdtb/cdta complexes are internalised. in acidic endosomes, cdtb mediates the deliv ...201425029374
sapronosis: a distinctive type of infectious agent.sapronotic disease agents have evolutionary and epidemiological properties unlike other infectious organisms. their essential saprophagic existence prevents coevolution, and no host-parasite virulence trade-off can evolve. however, the host may evolve defenses. models of pathogens show that sapronoses, lacking a threshold of transmission, cannot regulate host populations, although they can reduce host abundance and even extirpate their hosts. immunocompromised hosts are relatively susceptible to ...201425028088
role of ypeb in cortex hydrolysis during germination of bacillus anthracis spores.the infectious agent of the disease anthrax is the spore of bacillus anthracis. bacterial spores are extremely resistant to environmental stresses, which greatly hinders spore decontamination efforts. the spore cortex, a thick layer of modified peptidoglycan, contributes to spore dormancy and resistance by maintaining the low water content of the spore core. the cortex is degraded by germination-specific lytic enzymes (gsles) during spore germination, rendering the cells vulnerable to common dis ...201425022853
the odd one out: bacillus act bacteriophage cp-51 exhibits unusual properties compared to related spounavirinae w.ph. and bastille.the bacillus act group includes three important pathogenic species of bacillus: anthracis, cereus and thuringiensis. we characterized three virulent bacteriophages, bastille, w.ph. and cp-51, that infect various strains of these three species. we have determined the complete genome sequences of cp-51, w.ph. and bastille, and their physical genome structures. the cp-51 genome sequence could only be obtained using a combination of conventional and second and third next generation sequencing techno ...201425010479
prodrug applications for targeted cancer therapy.prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. to date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug de ...201425004822
molecular characterization of bacillus anthracis directly from patients' eschar and beef in an anthrax outbreak in jiangsu province, china, 2012.an outbreak of anthrax was reported in lianyungang, jiangsu province, china in 2012. laboratory confirmation of cases was made by detection of bacillus anthracis genes rpob, paga, and cap using real-time polymerase chain reaction (pcr); source tracking was conducted by multiple locus variable-number tandem-repeat analysis (mlva) and paga sequencing using dna extracted from case specimens and meat from a suspected slaughtered cow. the genotypes were mlva type 57 and paga genotype i. combined with ...201425002304
serological anthrax surveillance in wild boar (sus scrofa) in ukraine.anthrax, caused by bacillus anthracis, is an acute disease affecting wildlife, livestock, and humans worldwide, although its impact on these populations is underappreciated. in ukraine, surveillance is passive, and anthrax is often detected in livestock. however, wildlife is not subject to surveillance, although anthrax deaths (such as in wild boar, sus scrofa) have been documented. the wild boar is a plentiful and widespread species in ukraine and is frequently hunted. we initiated a screening ...201425072994
anthrax in a backyard domestic dog in ukraine: a case report.anthrax has been reported in domestic and wild dogs throughout much of the world. generally, canids are considered resistant to anthrax, although there are several reports of anthrax deaths in both wild and domestic canid populations. prior to 2012, anthrax had not been reported in dogs in ukraine, despite a long history in livestock and wildlife. an outbreak involving at least one cow and one dog was reported from a backyard setting in southern ukraine in august of 2012. laboratory results and ...201425072993
the necrophagous fly anthrax transmission pathway: empirical and genetic evidence from wildlife epizootics.early studies confirmed bacillus anthracis in emesis and feces of flies under laboratory conditions, but there is little empirical field evidence supporting the roles of flies in anthrax transmission. we collected samples during outbreaks of anthrax affecting livestock and native and exotic wildlife on two ranches in west texas (2009-2010). sampling included animal carcasses, maggots, adult flies feeding on or within several meters of carcasses, and leaves from surrounding vegetation. microbiolo ...201425072988
anthrax and smallpox errors highlight gaps in us biosafety. 201425072062
being prepared: bioterrorism and mass prophylaxis: part i.bioterrorism presents a real and omnipresent risk to public health throughout the world. more than 30 biological agents have been identified as possessing the potential to be deployed in a bioterrorist attack. those that have been determined to be of the greatest concern and possess the greatest potential of use in this arena are known as the category a agents: bacillus anthracis (anthrax); variola major (smallpox); yersinia pestis (plague); francisella tularensis (tularemia); viral hemorrhagic ...201425076398
ecthyma: a potential mimicker of zoonotic infections in a returning traveler.the cutaneous ulcer in a patient with a history of international travel poses a vexing diagnostic dilemma for the clinician. while streptococcus and staphylococcus are common causes of cutaneous ecthyma, the necrotizing ulcer can have a vast differential diagnosis including ulcerating zoonoses.201425449255
bacillus subtilis systems biology: applications of -omics techniques to the study of endospore formation.endospore-forming bacteria, with bacillus subtilis being the prevalent model organism, belong to the phylum firmicutes. although the last common ancestor of all firmicutes is likely to have been an endospore-forming species, not every lineage in the phylum has maintained the ability to produce endospores (hereafter, spores). in 1997, the release of the full genome sequence for b. subtilis strain 168 marked the beginning of the genomic era for the study of spore formation (sporulation). in this o ...201426105826
two-component system cross-regulation integrates bacillus anthracis response to heme and cell envelope stress.two-component signaling systems (tcss) are one of the mechanisms that bacteria employ to sense and adapt to changes in the environment. a prototypical tcs functions as a phosphorelay from a membrane-bound sensor histidine kinase (hk) to a cytoplasmic response regulator (rr) that controls target gene expression. despite significant homology in the signaling domains of hks and rrs, tcss are thought to typically function as linear systems with little to no cross-talk between non-cognate hk-rr pairs ...201424675902
bidirectional effect of wnt signaling antagonist dkk1 on the modulation of anthrax toxin uptake.lrp6, a co-receptor for the morphogen wnt, aids endocytosis of anthrax complexes. here we report that dickkopf1 (dkk1) protein, a secreted lrp6 ligand and antagonist, is also a modulator of anthrax toxin sensitivity. shrna-mediated gene silencing or talen-mediated gene knockout of dkk1 reduced sensitivity of cells to pa-dependent hybrid toxins. however, unlike the solely inhibitory effect on wnt signaling, the effects of dkk1 overexpression on anthrax toxicity were bidirectional, depending on it ...201424671437
asymmetric dimethylarginine levels in patients with cutaneous anthrax: a laboratory analysis.asymmetric dimethylarginine (adma), the main endogenous inhibitor of nitric oxide synthase, is considered to be associated with endothelial dysfunction. high adma levels have been shown to be related with disorders causing vascular inflammation such as hypertension, hypercholesterolemia, atherosclerosis, chronic heart failure, stroke and sepsis. cutaneous anthrax (ca) is a serious infectious disease which may cause vasculitis. the aim of the study was to investigate the serum adma levels in pati ...201424669818
capillary morphogenesis gene 2 inhibits growth of breast cancer cells and is inversely correlated with the disease progression and prognosis.capillary morphogenesis gene 2 (cmg2) also known as anthrax toxin receptor 2 was identified as a gene being up-regulated in capillary morphogenesis. it has been shown to be involved in cell adhesion and motility which are critical functions for cancerous cells to disseminate. the present study aimed to examine the expression of cmg2 in breast cancer and its implication in the disease progression.201424667935
x-ray structures of human furin in complex with competitive inhibitors.furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal bacillus anthracis or the pandemic influenza virus. development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. here we present a novel preparation of human furin and the first crystal structures of this enzyme in complex with noncovalent inhibito ...201424666235
transcriptome analysis identifies bacillus anthracis genes that respond to co2 through an atxa-dependent mechanism.upon infection of a mammalian host, bacillus anthracis responds to host cues, and particularly to elevated temperature (37°c) and bicarbonate/co2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer. this response requires the presence of the pxo1 virulence plasmid-encoded pleiotropic regulator atxa. to better understand the genetic basis of this response, we utilized a controlled in vitro system and next generation seque ...201424661624
role of india's wildlife in the emergence and re-emergence of zoonotic pathogens, risk factors and public health implications.evolving land use practices have led to an increase in interactions at the human/wildlife interface. the presence and poor knowledge of zoonotic pathogens in india's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonoti ...201424983511
communication of γ phage lysin plyg enzymes binding toward srta for inhibition of bacillus anthracis: protein-protein interaction and molecular dynamics study.bacillus anthracis is a pathogenic, gram-positive bacterium which chiefly affects the livestock of animals and humans through acute disease anthrax. all around the globe this bio-threat organism damages millions of lives in every year and also most of the drugs were not responding properly in inhibition against this diseased pathogen. in recent development, phage therapy is considered as alternative solution to treat this serious infectious disease. in this study, we elucidated the binding of γ ...201424978154
moxt toxin of bacillus anthracis exhibits sequence specific ribonuclease activity.moxxt module of bacillus anthracis encodes moxx, a labile protein and moxt, a ribonuclease. however, mechanism of cleavage of rna by moxt has not been explored till date. in the present study, we have demonstrated that moxt is a sequence specific ribonuclease which recognizes uacau sequence in ss rna and cleaves between u and a. moreover, cleavage of rna requires 2' oh group of first residue, i.e. u of uacau rna sequence. an interesting finding which makes it distinct from the other mazf family ...201424973712
hdac8-mediated epigenetic reprogramming plays a key role in resistance to anthrax lethal toxin-induced pyroptosis in macrophages.macrophages pre-exposed to a sublethal dose of anthrax lethal toxin (letx) are refractory to subsequent high cytolytic doses of letx, termed toxin-induced resistance (tir). a small population of tir cells (2-4%) retains tir characteristics for up to 5-6 wk. through studying these long-term tir cells, we found that a high level of histone deacetylase (hdac)8 expression was crucial for tir. knocking down or inhibition of hdac8 by small interfering rnas or the hdac8-specific inhibitor pci-34051, re ...201424973453
vaccines: facing complex problems with the promise of immunology.highly renowned in the vaccines world, stanley a. plotkin has worked at many leading institutions throughout his career, and is emeritus professor of the university of pennsylvania and adjunct professor of the johns hopkins university. in 1991, plotkin joined sanofi pasteur and worked there from 1991 to 1997, and now works as principal of vaxconsult, llc as a consultant to vaccine manufacturers, biotechnology companies and non-profit research organizations. plotkin has served as chairman of the ...201424972860
comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.we have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (mmps), urokinase plasminogen activator (upa) or co-localized mmp/upa activities. c57bl/6j mice were challen ...201424971906
classification and management of animal anthrax outbreaks based on the source of infection.anthrax is a non-contagious infectious disease; it primarily affects herbivores, but all mammals, including humans, can be affected. humans may contract anthrax directly or indirectly from infected animals. veterinary surveillance systems, providing information about animal and human cases, should increase the efficacy of the animal anthrax management in order to protect population. any aspect of the disease should be carefully monitored to implement effective prevention and control strategies. ...201424968920
investigation of antimicrobial activity of photothermal therapeutic gold/copper sulfide core/shell nanoparticles to bacterial spores and cells.au/cus core/shell nanoparticles (nps) were designed as a new type of transducer agent for photothermal therapy (ptt), with attractive features of easy preparation, low cost and small size for targeting. this paper studied for the first time the intrinsic antimicrobial activity of au/cus nps to b. anthracis spores and cells in addition to its ptt effect.201424963345
selected infectious disease disasters for nursing staff training at egyptian eastern border.infectious disease disasters are events that involve a biological agent, disease and that result in mass casualties, such as a bioterrorism attack, an emerging outbreak of infectious disease; all disasters pose a risk of infection transmission. but, infectious disease disasters pose the great-risk to illness or death from an infectious disease. this study raised the awareness and improved knowledge by educational program for military nursing staff on selected infectious disease disasters acquire ...201424961011
lessons for control of heroin-associated anthrax in europe from 2009-2010 outbreak case studies, london, uk.outbreaks of serious infections associated with heroin use in persons who inject drugs (pwids) occur intermittently and require vigilance and rapid reporting of individual cases. here, we give a firsthand account of the cases in london during an outbreak of heroin-associated anthrax during 2009-2010 in the united kingdom. this new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. during 2012-13, additional cases of heroin-associated anthrax ...201424959910
cationic pamam dendrimers as pore-blocking binary toxin inhibitors.dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. here we identified poly(amido amine) (pamam) dendrimers as novel blockers for the pore-forming b components of the binary anthrax toxin (pa63) and clostridium botulinum c2 toxin (c2iia). these pores are essential for delivery of the enzymatic a components of the internalized toxins from endosomes into the cytosol of target cells. we demonstrate that at low μm concentration ...201424954629
response surface modeling for hot, humid air decontamination of materials contaminated with bacillus anthracis ∆sterne and bacillus thuringiensis al hakam spores.response surface methodology using a face-centered cube design was used to describe and predict spore inactivation of bacillus anthracis ∆sterne and bacillus thuringiensis al hakam spores after exposure of six spore-contaminated materials to hot, humid air. for each strain/material pair, an attempt was made to fit a first or second order model. all three independent predictor variables (temperature, relative humidity, and time) were significant in the models except that time was not significant ...201424949256
endospore surface properties of commonly used bacillus anthracis surrogates vary in aqueous solution.the hydrophobic character and electrophoretic mobility (epm) of microorganisms are vital aspects of understanding their interactions with the environment. these properties are fundamental in fate-and-transport, physiological, and virulence studies, and thus integral in surrogate selection. hydrophobic and electrostatic forces are significant contributors to particle and microorganism mobility in the environment. herein, the surface properties of commonly used bacillus anthracis surrogate endospo ...201424817579
raxibacumab: potential role in the treatment of inhalational anthrax.anthrax is a highly contagious and potentially fatal human disease caused by bacillus anthracis, an aerobic, gram-positive, spore-forming rod-shaped bacterium with worldwide distribution as a zoonotic infection in herbivore animals. bioterrorist attacks with inhalational anthrax have prompted the development of more effective treatments. antibodies against anthrax toxin have been shown to decrease mortality in animal studies. raxibacumab is a recombinant human monoclonal antibody developed again ...201424812521
nanopore biosensor for label-free and real-time detection of anthrax lethal factor.we report a label-free real-time nanopore sensing method for the detection of anthrax lethal factor, a component of the anthrax toxin, by using a complementary single-stranded dna as a molecular probe. the method is rapid and sensitive: sub-nanomolar concentrations of the target anthrax lethal factor dna could be detected in ∼1 min. further, our method is selective, which can differentiate the target dna from other single-stranded dna molecules at the single-base resolution. this sequence-specif ...201424806593
factors associated with healthcare worker acceptance of vaccination: a systematic review and meta-analysis.healthcare workers experience occupational risk of infection and may transmit infections to patients. vaccination provides an efficient means of protecting workers and patients, but uptake may be low. we sought to identify factors influencing vaccine acceptance by healthcare workers in order to obtain insights leading to more effective vaccination programs in this population.201424799647
anthrax lethal factor as an immune target in humans and transgenic mice and the impact of hla polymorphism on cd4+ t cell immunity.bacillus anthracis produces a binary toxin composed of protective antigen (pa) and one of two subunits, lethal factor (lf) or edema factor (ef). most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. we characterized cd4+ t cell immunity to lf in a panel of humanized hla-dr and dq transgenic mice and in naturally exposed patien ...201424788397
[anthrax meningoencephalitis: a case following a cutaneous lesion in morocco].anthrax meningoencephalitis is very rare especially following skin location. we report a case of meningoencephalitis secondary to skin lesion. the diagnosis is based on clinical presentation and confirmed by microbiological tests. its evolution remains fatal despite aggressive resuscitation.201424784916
descriptive epidemiology of detected anthrax outbreaks in wild wood bison (bison bison athabascae) in northern canada, 1962-2008.we inventoried and assessed historical anthrax outbreak data from 1962-2008 in wild wood bison (bison bison athabascae) in wood buffalo national park and the slave river lowlands (srl), northwest territories, canada. we compared these results with a 2010 outbreak in the srl. anthrax outbreaks have occurred in 12 of the years between 1962 and 2008 in wild wood bison with 1,515 anthrax deaths detected. the average number of carcasses found each outbreak year was 126 (range 1-363), though local ave ...201424779457
pediatric anthrax clinical management.anthrax is a zoonotic disease caused by bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. because b anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. this document provides clinical guidance f ...201424777226
pediatric anthrax clinical management: executive summary. 201424777221
protective immune response against bacillus anthracis induced by intranasal introduction of a recombinant adenovirus expressing the protective antigen fused to the fc-fragment of igg2a.anthrax is a particularly dangerous infectious disease that affects humans and livestock. it is characterized by intoxication, serosanguineous skin lesions, development of lymph nodes and internal organs, and may manifest itsself in either a cutaneous or septic form. the pathogenic agent is bacillus anthracis, a grampositive, endospore-forming, rod-shaped aerobic bacterium. efficacious vaccines that can rapidly induce a long-term immune response are required to prevent anthrax infection in human ...201424772330
evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin g on injection site adverse events following anthrax vaccine adsorbed (ava) in the cdc ava human clinical trial.anthrax vaccine adsorbed (ava) administered intramuscularly (im) results in fewer adverse events (aes) than subcutaneous (sq) administration. women experience more aes than men. antibody response, female hormones, race, and body mass index (bmi) may contribute to increased frequency of reported injection site aes.201424768633
online monitoring of escherichia coli and bacillus thuringiensis spore inactivation after advanced oxidation treatment.various studies have shown that advanced oxidation processes (aops) such as uv light in combination with hydrogen peroxide is an efficient process for the removal of a large variety of emerging contaminants including microorganisms. the mechanism of destruction in the presence of hydrogen peroxide (h2o2) is the enhanced formation of hydroxyl (·oh) radicals, which have a high oxidation potential. the goal of this study was to utilize in-line advanced oxidation to inactivate microbes, and document ...201424766594
in trans complementation of lethal factor reveal roles in colonization and dissemination in a murine mouse model.lethal factor (lf) is a component of the b. anthracis exotoxin and critical for pathogenesis. the roles of lf in early anthrax pathogenesis, such as colonization and dissemination from the initial site of infection, are poorly understood. in mice models of infection, lf-deficient strains either have altered dissemination patterns or do not colonize, precluding analysis of the role of lf in colonization and dissemination from the portal of entry. previous reports indicate rabbit and guinea pig mo ...201424763227
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