| capsule anchoring in bacillus anthracis occurs by a transpeptidation reaction that is inhibited by capsidin. | bacillus anthracis, the causative agent of anthrax, is a dangerous biological weapon, as spores derived from drug-resistant strains cause infections for which antibiotic therapy is no longer effective. we sought to develop an anti-infective therapy for anthrax and targeted capd, an enzyme that cleaves poly-gamma-d-glutamate capsule and generates amide bonds with peptidoglycan cross-bridges to deposit capsular material into the envelope of b. anthracis. in agreement with the model that capsule co ... | 2009 | 19017271 |
| the bicarbonate transporter is essential for bacillus anthracis lethality. | in the pathogenic bacterium bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. elevated co2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. we identified a previously uncharacterized abc transporter (bas2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essen ... | 2008 | 19023421 |
| enhancement of the immune responses of mice to bacillus anthracis protective antigen by cia07 combined with alum. | anthrax is an acute zoonotic disease caused by infection with bacillus anthracis. b. anthracis spores are highly resistant to environmental degradation and are used as a biological weapon. in this study, we investigated the adjuvant activity of cia07 to anthrax protective antigen (pa). a/j mice were immunized intraperitoneally once, or twice with a 4-week interval, with recombinant pa alone or combined with alum, cpg1826, or cia07 as adjuvant, and serum anti-pa igg antibody responses were measur ... | 2008 | 19023533 |
| a unique sensor histidine kinase. | | 2009 | 19028898 |
| medical toxicology and public health-update on research and activities at the centers for disease control and prevention and the agency for toxic substances and disease registry. | an extensive review of cdc epidemiological responses to human outbreaks of anthrax from occupational settings between the years of 1950 and 2001 documented a variety of approaches to mitigation and decontamination [2]. these approaches included taking no action, burning contaminated materials, chlorinating water supplies, instituting administrative and engineering controls and ppe, vaccinating potentially exposed individuals, and in 2 instances, fumigating with formaldehyde vapor (now considered ... | 2008 | 19031383 |
| spatial localization of bacteria controls coagulation of human blood by 'quorum acting'. | blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. bacil ... | 2008 | 19031531 |
| mastitis caused by bacillus anthracis in a beef cow. | a mixed-breed beef cow was presented with swelling of the front and hind left quarters of the mammary gland and mild depression. direct examination and culture of the serosanguinous-like milk samples collected from these quarters were consistent with bacillus anthracis infection. | 2008 | 19043486 |
| structural studies of shikimate dehydrogenase from bacillus anthracis complexed with cofactor nadp. | bacillus anthracis has been employed as an agent of bioterrorism, with high mortality, despite anti-microbial treatment, which strongly indicates the need of new drugs to treat anthrax. shikimate pathway is a seven step biosynthetic route which generates chorismic acid from phosphoenol pyruvate and erythrose-4-phosphate. chorismic acid is the major branch point in the synthesis of aromatic amino acids, ubiquinone, and secondary metabolites. the shikimate pathway is essential for many pathologica ... | 2009 | 19043750 |
| label-free dual sensing of dna molecules using gan nanowires. | we demonstrate a rationale for using gan nanowires (gannws) in label-free dna-sensing using dual routes of electrochemical impedance spectroscopy (eis) and photoluminescence (pl) measurements, employing a popular target dna with anthrax lethal factor (lf) sequence. the in situ eis reveals that both high surface area and surface band-bending in the nanowires, providing more binding sites and surface-enhanced charge transfer, respectively, are responsible for the enhanced sensitivity to surface-im ... | 2009 | 19046071 |
| knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in tanzania. | many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-sahara african region. these include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. the current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-d ... | 2008 | 19046464 |
| neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax. | bacillus anthracis infection is associated with severe hemostatic disturbances but their roles and contribution to fatality remain incompletely characterized. we undertook analyses of circulating antithrombin levels during the course of infection using a comparison of lethal and nonlethal murine anthrax models. plasma samples were obtained from dba/2 mice challenged intraperitoneally with the spores of either toxigenic b. anthracis sterne strain or nontoxigenic, avirulent delta sterne strain. we ... | 2008 | 19049643 |
| discrimination between biothreat agents and 'near neighbor' species using a resequencing array. | timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. this study aims to evaluate the potential of resequencing arrays for this purpose. albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify bacillus anthracis, francisella tularensis, yersinia pestis and distinguish them from benign 'near neighbor' species in ... | 2008 | 19049648 |
| the cmg2 elisa for evaluating inhibitors of the binding of anthrax toxin protective antigen to its receptor. | anthrax toxin comprises a protective antigen (pa) of mw 83 kda, a lethal factor (lf) and an edema factor (ef). upon binding to its receptor on cell surfaces, pa(83) is enzymatically cleaved to a 63 kda product (pa(63)), followed by binding of lf or ef, receptor-mediated internalisation of these factors, and production of their toxic effects. the high-affinity binding of pa(83) to its receptor is essential for the intoxication process. to study the interaction between the pa and its receptor, and ... | 2009 | 19049885 |
| comparative genomic study of spo0e family genes and elucidation of the role of spo0e in bacillus anthracis. | the propensity of bacterium to sporulate or retain the vegetative form depends on the amount of phosphorylated spo0a (spo0a(-p)), regulated by spo0e multigene family of phosphatases (spo0e, yisi and ynzd). phylogenetic analysis revealed that spo0e multigene family of phosphatases (smfp) descends in two distinct clades of aerobic (bacillus cluster) and anaerobic (clostridia cluster) sporulating bacteria. high sequence conservation within species gives a notion that these members could have evolve ... | 2009 | 19050850 |
| europium-based fluorescence nanoparticle sensor for rapid and ultrasensitive detection of an anthrax biomarker. | | 2009 | 19053099 |
| characterization of a bacillus anthracis spore coat-surface protein that influences coat-surface morphology. | bacterial spores are encased in a multilayered proteinaceous shell, called the coat. in many bacillus spp., the coat protects against environmental assault and facilitates germination. in bacillus anthracis, the spore is the etiological agent of anthrax, and the functions of the coat likely contribute to virulence. here, we characterize a b. anthracis spore protein, called cotbeta, which is encoded only in the genomes of the bacillus cereus group. we found that cotbeta is synthesized specificall ... | 2008 | 19054101 |
| use of superabsorbent polymer gels for surface decontamination of bacillus anthracis spores. | this study evaluated the inactivation of bacillus anthracis vollum spores dried on a nonporous surface using a superabsorbent polymer (sap) gel containing commercially available liquid decontaminants. | 2009 | 19055629 |
| photocatalytic inactivation of bacillus anthracis by titania nanomaterials. | photocatalytic inactivation of bacillus anthracis was studied by using titania nanomaterials and uva light. experimental data clearly indicated that, time of exposure, quantity of catalyst, intensity of light, particle size and sunlight affected the inactivation. it also demonstrated the pseudo-first order behavior of inactivation kinetics and pointed out the enhanced rate of inactivation in the presence of nano-titania existing as a mixture of anatase and rutile phases. the values of rate const ... | 2009 | 19056174 |
| molecular analysis of the interaction of anthrax adenylyl cyclase toxin, edema factor, with 2'(3')-o-(n-(methyl)anthraniloyl)-substituted purine and pyrimidine nucleotides. | bacillus anthracis causes anthrax disease and exerts its deleterious effects by the release of three exotoxins: lethal factor, protective antigen, and edema factor (ef), a highly active calmodulin-dependent adenylyl cyclase (ac). however, conventional antibiotic treatment is ineffective against either toxemia or antibiotic-resistant strains. thus, more effective drugs for anthrax treatment are needed. previous studies from our laboratory showed that mammalian membranous ac (mac) exhibits broad s ... | 2009 | 19056899 |
| unique gtp-binding pocket and allostery of uridylate kinase from a gram-negative phytopathogenic bacterium. | using x-ray diffraction methodology, we have successfully determined the tertiary structures of the apo- and gtp-bound forms of uridylate kinase (umpk) from the gram-negative plant pathogen xanthomonas campestris with crystals grown under a strong magnetic field. the flexible atp- and ump-binding loops are clearly shown under this situation. x. campestris umpk contains a unique patch of noticeably positive nature from residue r100 to residue r127, allowing it to form a special gtp-binding pocket ... | 2009 | 19059268 |
| [characteristics of the immune response to the lethal toxin of bacillus anthracis]. | we and other authors have recently shown that the pattern of the immune response to components of anthrax, the bacillus anthracis lethal toxin, is complex. in addition to neutralizing antibodies, the antitoxin antibody pool contains antibodies enhancing the toxin lethal action. we mapped the epitopes in the protective antigen that are responsible for the induction of both antibody types. in this study, we obtained new data on the cytotoxicity of the b. anthracis lethal toxin toward the j774 a.1 ... | 2008 | 19060938 |
| mapping of proteomic composition on the surfaces of bacillus spores by atomic force microscopy-based immunolabeling. | atomic force microscopy (afm) provides a unique capability to image high-resolution architecture and structural dynamics of pathogens (e.g., viruses, bacteria, and bacterial spores) at near-molecular resolution in native conditions. further development of atomic force microscopy to enable the correlation of pathogen protein surface structures with specific gene products is essential to understand the mechanisms of the pathogen life cycle. we applied an afm-based immunolabeling technique for the ... | 2009 | 19063625 |
| association of bacillus anthracis capsule with lethal toxin during experimental infection. | bacillus anthracis lethal toxin (lt) was characterized in plasma from infected african green monkeys, rabbits, and guinea pigs. in all cases, during the terminal phase of infection only the protease-activated 63-kda form of protective antigen (pa(63)) and the residual 20-kda fragment (pa(20)) were detected in the plasma. no uncut pa with a molecular mass of 83 kda was detected in plasma from toxemic animals during the terminal stage of infection. pa(63) was largely associated with lethal factor ... | 2009 | 19064632 |
| variable number of tandem repeats (vntr) and its application in bacterial epidemiology. | molecular epidemiology is the using of molecular techniques to study bacterial distribution in human populations. recently molecular epidemiologist benefit from several techniques such as variable number tandem repeat (vntr) typing method to typing bacterial strains. variable number tandem repeat (vntr) typing is a tool for genotyping and provides data in a simple and numeric format based on the number of repetitive sequences. vntr for first time identified in m. tuberculosis as mycobacterial in ... | 2007 | 19070072 |
| the site for the allosteric activator gtp of escherichia coli ump kinase. | ump kinase (umpk), a key bacterial pyrimidine nucleotide biosynthesis enzyme, is utp-inhibited and gtp-activated. we delineate the gtp site of escherichia coli umpk by alanine mutagenesis of r92, h96, r103, w119 or r130, abolishing gtp activation; of s124 and r127, decreasing affinity for gtp; and of n111 and d115, with little detrimental effect. we exclude the correspondence with the modulatory atp site of bacillus anthracis umpk, confirming the functionality of the gtp site found by evrin. mut ... | 2009 | 19071117 |
| complete genome sequence of macrococcus caseolyticus strain jcscs5402, [corrected] reflecting the ancestral genome of the human-pathogenic staphylococci. | we isolated the methicillin-resistant macrococcus caseolyticus strain jcsc5402 from animal meat in a supermarket and determined its whole-genome nucleotide sequence. this is the first report on the genome analysis of a macrococcal species that is evolutionarily closely related to the human pathogens staphylococcus aureus and bacillus anthracis. the essential biological pathways of m. caseolyticus are similar to those of staphylococci. however, the species has a small chromosome (2.1 mb) and lack ... | 2009 | 19074389 |
| the bacillus anthracis protein mprf is required for synthesis of lysylphosphatidylglycerols and for resistance to cationic antimicrobial peptides. | during inhalational anthrax, bacillus anthracis survives and replicates in alveolar macrophages, followed by rapid invasion into the host's bloodstream, where it multiplies to cause heavy bacteremia. b. anthracis must therefore defend itself from host immune functions encountered during both the intracellular and the extracellular stages of anthrax infection. in both of these niches, cationic antimicrobial peptides are an essential component of the host's innate immune response that targets b. a ... | 2009 | 19074395 |
| the spore-specific alanine racemase of bacillus anthracis and its role in suppressing germination during spore development. | spores of bacillus anthracis are enclosed by an exosporium composed of a basal layer and an external hair-like nap. the nap is apparently formed by a single glycoprotein, while the basal layer contains many different structural proteins and several enzymes. one of the enzymes is alr, an alanine racemase capable of converting the spore germinant l-alanine to the germination inhibitor d-alanine. unlike other characterized exosporium proteins, alr is nonuniformly distributed in the exosporium and m ... | 2009 | 19074397 |
| efficient neutralization of antibody-resistant forms of anthrax toxin by a soluble receptor decoy inhibitor. | a soluble receptor decoy inhibitor (rdi), comprised of the extracellular i domain of antxr2, is a candidate anthrax therapeutic. here we show that rdi can effectively neutralize altered forms of the protective antigen toxin subunit that are resistant to 14b7 monoclonal antibody neutralization. these data highlight the potential of rdi to act as an adjunct to existing antibody-based therapies and indicate that inhibitors based on rdi might be useful as a stand-alone treatment against specifically ... | 2009 | 19075066 |
| an essential role for the antiviral endoribonuclease, rnase-l, in antibacterial immunity. | type i ifns were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. accordingly, established mediators of ifn antiviral activity may mediate previously unrecognized antibacterial functions. rnase-l is the terminal component of an rna decay pathway that is an important mediator of ifn-induced antiviral activity. here, we identify a role for rnase-l in the host antibacterial response. rnase-l(-/-) mice exhibited ... | 2008 | 19075243 |
| defensive strategies of bacillus anthracis that promote a fatal disease. | bacillus anthracis is a gram-positive bacterium that causes anthrax. bacterial spores that enter the host germinate into metabolically active bacilli that disseminate throughout the body and replicate to high numbers. two virulence factors are essential for this unrestrained growth. the first is a weakly immunogenic poly gamma-d-glutamic acid capsule that surrounds the bacilli and confers resistance to phagocytosis. the second virulence factor, anthrax toxin, disrupts multiple host functions to ... | 2007 | 19081825 |
| a genetic screen to identify bacteriophage lysins. | lysins are phage-encoded, peptidoglycan (cell wall) hydrolases that accumulate in the bacterial cytoplasm during a lytic infection cycle. late during infection, the lysins undergo holin-mediated translocation across the inner membrane into the peptidoglycan matrix where they cleave cell wall covalent bonds required for wall stability and allow bacterial lysis and progeny phage release. this potent hydrolytic activity is now the foundation of a powerful genetic-based screening process for the ide ... | 2009 | 19082564 |
| how to extend the use of grid-based interaction energy maps from chemistry to biotopics. | many computational tools routinely used in chemistry could successfully be applied to the biosciences since protein-protein and protein-ligand interactions are governed by the laws of chemistry. this paper shows that it is possible to extend the use of existing computational tools from their traditional application field (e.g. chemistry) to culturally-related research areas by the implementation of simple but well-designed utilities. in particular, a computational strategy obtained by combining ... | 2009 | 19085992 |
| investigations and control measures following a case of inhalation anthrax in east london in a drum maker and drummer, october 2008. | the patient is believed to have acquired the infection from making animal hide drums. environmental investigations identified one drum and two pieces of animal skins contaminated with anthrax spores. | 2008 | 19094916 |
| increased african-american involvement in vaccine studies. | | 2009 | 19095169 |
| what is the relevance of lung epithelial cells during the dissemination of spores in inhalational anthrax? | | 2009 | 19098284 |
| a short course of antibiotic treatment is effective in preventing death from experimental inhalational anthrax after discontinuing antibiotics. | postexposure prophylaxis of inhalational anthrax requires prolonged antibiotic therapy or antibiotics and vaccination. the duration of treatment for established anthrax is controversial, because retained spores may germinate and cause disease after antibiotics are discontinued. using rhesus macaques, we determined whether a short course of antibiotic treatment, as opposed to prophylaxis, could effectively treat inhalational anthrax and prevent disease caused by the germination of spores after di ... | 2009 | 19099484 |
| mucosal immunization with attenuated salmonella enterica serovar typhi expressing protective antigen of anthrax toxin (pa83) primes monkeys for accelerated serum antibody responses to parenteral pa83 vaccine. | salmonella enterica serovar typhi vaccine strain cvd 908-htra was genetically engineered for stable plasmid-based expression of protective antigen of anthrax toxin (pa83) fused with the export protein clya (clya-pa83). the priming potential of cvd 908-htra expressing clya-pa83 was assessed in 12 rhesus and 20 cynomolgus macaques that were immunized mucosally (i.e., intranasally) on days 0 and 14. a parenteral booster with purified pa83 plus alum was given to rhesus macaques on days 42 and 225; c ... | 2009 | 19099487 |
| induction of autophagy by anthrax lethal toxin. | autophagy is an evolutionary conserved intracellular process whereby cells break down long-lived proteins and organelles. accumulating evidences suggest increasing physiological significance of autophagy in pathogenesis of infectious diseases. anthrax lethal toxin (lt) exerts its influence on numerous cells and herein, we report a novel effect of lt-induced autophagy on mammalian cells. several autophagy biochemical markers including lc3-ii conversion, increased punctuate distribution of gfp-lc3 ... | 2009 | 19103170 |
| extensive antibody cross-reactivity among infectious gram-negative bacteria revealed by proteome microarray analysis. | antibodies provide a sensitive indicator of proteins displayed by bacteria during sepsis. because signals produced by infection are naturally amplified during the antibody response, host immunity can be used to identify biomarkers for proteins that are present at levels currently below detectable limits. we developed a microarray comprising approximately 70% of the 4066 proteins contained within the yersinia pestis proteome to identify antibody biomarkers distinguishing plague from infections ca ... | 2009 | 19112181 |
| efficacy of a vaccine based on protective antigen and killed spores against experimental inhalational anthrax. | protective antigen (pa)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by pa. addition of formaldehyde-inactivated spores (fis) to pa (pa-fis) elicits total protection against cutaneous anthrax. nevertheless, vaccines that are effective against cutaneous anthrax may not be so ag ... | 2009 | 19114543 |
| [the dirty dozen]. | the term "the dirty dozen" refers to the 12 biological agents such as, for example, the anthrax bacillus or botulinum toxin that could be used as biological weapons. even if their military use is considered unlikely physicians should be familiar with the problematic because these pathogens can also occur naturally or, respectively, cause disease as the consequence of a laboratory accident. it is of decisive importance to make the diagnosis as quickly as possible in order to limit any further spr ... | 2009 | 19115185 |
| the anthrax vaccine and research: reactions from postal workers and public health professionals. | during the 2001 anthrax attacks, public health agencies faced operational and communication decisions about the use of antibiotic prophylaxis and the anthrax vaccine with affected groups, including postal workers. this communication occurred within an evolving situation with incomplete and uncertain data. guidelines for prophylactic antibiotics changed several times, contributing to confusion and mistrust. at the end of 60 days of taking antibiotics, people were offered an additional 40 days' su ... | 2008 | 19117431 |
| inflammasomes: guardians of cytosolic sanctity. | the innate immune system is critical in recognizing bacterial and viral infections to evoke a proper immune response. certain members of the intracellular nucleotide-binding and oligomerization domain (nod)-like receptor (nlr) family detect microbial components in the cytosol and trigger the assembly of large caspase-1-activating complexes termed inflammasomes. autoproteolytic maturation of caspase-1 zymogens within these inflammasomes leads to maturation and secretion of the pro-inflammatory cy ... | 2009 | 19120479 |
| effects of anthrax lethal toxin on human primary keratinocytes. | to investigate the effects of anthrax lethal toxin (letx) on human primary keratinocytes. | 2008 | 19120626 |
| anthrax lethal toxin triggers the formation of a membrane-associated inflammasome complex in murine macrophages. | multiple microbial components trigger the formation of an inflammasome complex that contains pathogen-specific nucleotide oligomerization and binding domain (nod)-like receptors (nlrs), caspase-1, and in some cases the scaffolding protein asc. the nlr protein nalp1b has been linked to anthrax lethal toxin (lt)-mediated cytolysis of murine macrophages. here we demonstrate that in unstimulated j774a.1 macrophages, caspase-1 and nalp1b are membrane associated and part of approximately 200- and appr ... | 2009 | 19124602 |
| molecular modeling as a tool for drug discovery. | with the progression of structural genomics projects, comparative modeling remains an increasingly important method of choice to obtain 3d structure of proteins. it helps to bridge the gap between the available sequence and structure information by providing reliable and accurate protein models. comparative modeling based on more than 30% sequence identity is now approaching its natural template-based limits and further improvements require the development of effective refinement techniques capa ... | 2008 | 19128219 |
| the listeria monocytogenes sortase-b recognizes varied amino acids at position 2 of the sorting motif. | sortases are bacterial enzymes that anchor surface proteins covalently to the peptidoglycan upon cleavage of a motif located at their c-terminal end. motifs recognized by sortases of the class-b (srtb) are defined by the consensus sequence np(q/k)(t/s)(n/g/s)(d/a). evidence supporting this consensus is limited to isdc of staphylococcus aureus and bacillus anthracis, cleaved at motifs npqtn and npktg, respectively. in listeria monocytogenes, strb has two substrates, lmo2185 and lmo2186, containin ... | 2009 | 19129190 |
| detection of anthrax toxin by an ultrasensitive immunoassay using europium nanoparticles. | we developed a europium nanoparticle-based immunoassay (enia) for the sensitive detection of anthrax protective antigen (pa). the enia exhibited a linear dose-dependent pattern within the detection range of 0.01 to 100 ng/ml and was approximately 100-fold more sensitive than enzyme-linked immunosorbent assay (elisa). false-positive results were not observed with serum samples from healthy adults, mouse plasma without pa, or plasma samples collected from mice injected with anthrax lethal factor o ... | 2009 | 19129473 |
| anthrax protective antigen administered by dna vaccination to distinct subcellular locations potentiates humoral and cellular immune responses. | based on the hypothesis that immune outcome can be influenced by the form of antigen administered and its ability to access various antigen-processing pathways, we targeted the 63 kda fragment of protective antigen (pa) of bacillus anthracis to various subcellular locations by dna chimeras bearing a set of signal sequences. these targeting signals, namely, lysosome-associated membrane protein 1 (lamp1), tissue plasminogen activator (tpa) and ubiquitin, encoded various forms of pa viz. lysosomal, ... | 2009 | 19130551 |
| detection of disease outbreaks by the use of oral manifestations. | oral manifestations of diseases caused by bioterrorist agents could be a potential data source for biosurveillance. this study had the objectives of determining the oral manifestations of diseases caused by bioterrorist agents, measuring the prevalence of these manifestations in emergency department reports, and constructing and evaluating a detection algorithm based on them. we developed a software application to detect oral manifestations in free text and identified positive reports over three ... | 2009 | 19131324 |
| role of visible light-activated photocatalyst on the reduction of anthrax spore-induced mortality in mice. | photocatalysis of titanium dioxide (tio(2)) substrates is primarily induced by ultraviolet light irradiation. anion-doped tio(2) substrates were shown to exhibit photocatalytic activities under visible-light illumination, relative environmentally-friendly materials. their anti-spore activity against bacillus anthracis, however, remains to be investigated. we evaluated these visible-light activated photocatalysts on the reduction of anthrax spore-induced pathogenesis. | 2009 | 19132100 |
| conservation in the face of diversity: multistrain analysis of an intracellular bacterium. | with the recent completion of numerous sequenced bacterial genomes, notable advances have been made in understanding the level of conservation between various species. however, relatively little is known about the genomic diversity among strains. we determined the complete genome sequence of the florida strain of anaplasma marginale, and near complete (>96%) sequences for an additional three strains, for comparative analysis with the previously fully sequenced st. maries strain genome. | 2009 | 19134224 |
| rapid, high-throughput, culture-based pcr methods to analyze samples for viable spores of bacillus anthracis and its surrogates. | to rapidly remediate facilities after a biothreat agent release, improved turnaround times are needed for sample analysis. current methods to confirm the presence of a viable biothreat agent are limited by low sample throughput. we have developed a rapid-viability-polymerase chain reaction (rv-pcr) method to determine the presence of viable spores. the method combines high-throughput sample processing with 96-well pcr analysis, which measures a change in real-time, quantitative pcr response aris ... | 2009 | 19141303 |
| bioterrorism for the respiratory physician. | terrorist attacks by definition are designed to cause fear and panic. there is no question that a terrorist attack using biological agents would present a grave threat to stability of the society in which they were released. early recognition of such a bioterrorist attack is crucial to containing the damage they could cause. as many of the most likely bioterrorism agents present with pulmonary disease, respiratory physicians may be crucial in the initial recognition and diagnosis phase, and cert ... | 2009 | 19144044 |
| classification of select category a and b bacteria by fourier transform infrared spectroscopy. | fourier transform infrared (ft-ir) spectroscopy historically is a powerful tool for the taxonomic classification of bacteria by genus, species, and strain when they are grown under carefully controlled conditions. relatively few reports have investigated the determination and classification of pathogens such as the national institute of allergy and infectious diseases (niaid) category a bacillus anthracis spores and cells (ba), yersinia species, francisella tularensis (ft), and category b brucel ... | 2009 | 19146715 |
| caspase- and p53-dependent apoptosis in breast carcinoma cells induced by a synthetic selenadiazole derivative. | selenadiazole derivative is one kind of synthetic organoselenium compounds with potent and broad-spectrum antitumor activity. in this study, we showed that anthrax [1,2-c] [1,2,5] selenadiazolo-6,11-dione (asdo), an novel selenadiazole derivative, induced time- and dose-dependent apoptotic cell death in mcf-7 human breast carcinoma cells, as indicated by accumulation of sub-g1 cell population, dna fragmentation, nuclear condensation, caspase activation and parp cleavage. asdo-induced apoptosis w ... | 2009 | 19146838 |
| stochastic gating and drug-ribosome interactions. | gentamicin is a potent antibiotic that is used in combination therapy for inhalation anthrax disease. the drug is also often used in therapy for methicillin-resistant staphylococcusaureus. gentamicin works by flipping a conformational switch on the ribosome, disrupting the reading head (i.e., 16s ribosomal decoding bases 1492-1493) used for decoding messenger rna. we use explicit solvent all-atom molecular simulation to study the thermodynamics of the ribosomal decoding site and its interaction ... | 2009 | 19146858 |
| antigen-specific human polyclonal antibodies from hyperimmunized cattle. | antigen-specific human polyclonal antibodies (hpabs), produced by hyperimmunization, could be useful for treating many human diseases. however, yields from available transgenic mice and transchromosomic (tc) cattle carrying human immunoglobulin loci are too low for therapeutic applications. we report a tc bovine system that produces large yields of hpabs. tc cattle were generated by transferring a human artificial chromosome vector carrying the entire unrearranged, human immunoglobulin heavy (hi ... | 2009 | 19151699 |
| the structure of rph, an exoribonuclease from bacillus anthracis, at 1.7 a resolution. | maturation of trna precursors into functional trna molecules requires trimming of the primary transcript at both the 5' and 3' ends. cleavage of nucleotides from the 3' stem of trna precursors, releasing nucleotide diphosphates, is accomplished in bacillus by a phosphate-dependent exoribonuclease, rph. the crystal structure of this enzyme from b. anthracis has been solved by molecular replacement to a resolution of 1.7 a and refined to an r factor of 19.3%. there is one molecule in the asymmetri ... | 2009 | 19153445 |
| seasonality of bacillus species isolated from blood cultures and its potential implications. | because they are rarely associated with actual infections, bacillus species are usually defined as contaminants. however, when isolated, they require precise laboratory identification and may influence treatment. | 2009 | 19162377 |
| protective antigen composite nanofibers as a transdermal anthrax vaccine. | anthrax, a disease caused by the gram positive bacteria bacillus anthracis, has become an increasing threat to public health in the last several years, due to its use as an agent of biological warfare. the currently utilized human anthrax vaccine, which confers immunity through the host antibody recognition of protective antigen (pa), requires a three dose regimen and annual booster shots after the initial vaccination to maintain its efficacy. the long term goal of this project is to produce an ... | 2008 | 19162840 |
| an approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigen. | heptameric pores formed by the protective antigen (pa) moiety of anthrax toxin translocate the intracellular effector moieties of the toxin across the endosomal membrane to the cytosol of mammalian cells. we devised a protocol to characterize the effects of individual mutations in a single subunit of heptameric pa prepores (pore precursors) or pores. we prepared monomeric pa containing a test mutation plus an innocuous cys-replacement mutation at a second residue (lys563, located on the external ... | 2009 | 19165720 |
| killed but metabolically active bacillus anthracis vaccines induce broad and protective immunity against anthrax. | bacillus anthracis is the causative agent of anthrax. we have developed a novel whole-bacterial-cell anthrax vaccine utilizing b. anthracis that is killed but metabolically active (kbma). vaccine strains that are asporogenic and nucleotide excision repair deficient were engineered by deleting the spoiie and uvrab genes, rendering b. anthracis extremely sensitive to photochemical inactivation with s-59 psoralen and uv light. we also introduced point mutations into the lef and cya genes, which all ... | 2009 | 19168734 |
| thioamide hydroxypyrothiones supersede amide hydroxypyrothiones in potency against anthrax lethal factor. | anthrax lethal factor (lf) is a critical virulence factor in the pathogenesis of anthrax. a structure-activity relationship (sar) of potential lethal factor inhibitors (lfi) is presented in which the zinc-binding group (zbg), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematically varied. it was found that hydroxypyrothione zbgs generate more potent inhibitors than hydroxypyrone zbgs. furthermore, coupling the hydroxypyrothione to a backbone group via a th ... | 2009 | 19170530 |
| [cutaneous anthrax: seven cases]. | anthrax is an acute infection caused by the gram-positive organism, bacillus anthracis, which rarely affects humans under normal conditions. depending on the mode of contamination, there are three distinct clinical forms: pulmonary, gastrointestinal and cutaneous. this type of infection is still common in the developing countries, a fact that should be borne in mind by examining doctors, and in particular by dermatologists. it is important to recognise the clinical aspects of this disease rarely ... | 2009 | 19171223 |
| the survivability of bacillus anthracis (sterne strain) in processed liquid eggs. | in this study, we investigated the survival and inactivation kinetics of a surrogate strain of bacillus anthracis (sterne strain) in whole egg (we), egg white (ew), sugared egg yolk (ysu), and salted egg yolk (ysa) at low (-20, 0, and 5 degrees c), moderate (15, 20, 25, 30, 35, and 40 degrees c), and high storage temperatures (45, 50, 55, and 60 degrees c). outgrowth of the spores was measured as lag phase duration (lpd). replication of vegetative cells was measured in terms of growth rate (gr) ... | 2009 | 19171252 |
| cytotoxicity of bacterial-derived toxins to immortal lung epithelial and macrophage cells. | health risks associated with inhalation and deposition of biological materials have been a topic of great concern due to highly publicized cases of inhalation anthrax, of new regulations on the release of particulate matter, and to increased concerns on the hazards of indoor air pollution. here, we present an evaluation of the sensitivity of two immortal cell lines (a549, human lung carcinoma epithelia) and nr8383 (rat alveolar macrophages) to a variety of bacterial-derived inhalation hazards an ... | 2010 | 19172232 |
| monitoring anthrax toxin receptor dissociation from the protective antigen by nmr. | the binding of the bacillus anthracis protective antigen (pa) to the host cell receptor is the first step toward the formation of the anthrax toxin, a tripartite set of proteins that include the enzymatic moieties edema factor (ef), and lethal factor (lf). pa is cleaved by a furin-like protease on the cell surface followed by the formation of a donut-shaped heptameric prepore. the prepore undergoes a major structural transition at acidic ph that results in the formation of a membrane spanning po ... | 2009 | 19177347 |
| engineering antibody fragments to fold in the absence of disulfide bonds. | disulfide bonds play a critical role in the stabilization of the immunoglobulin beta-sandwich sandwich. under reducing conditions, such as those that prevail in the cytoplasm, disulfide bonds do not normally form and as a result most antibodies expressed in that compartment (intrabodies) accumulate in a misfolded and inactive state. we have developed a simple method for the quantitative isolation of antibody fragments that retain full activity under reducing conditions from large mutant librarie ... | 2009 | 19177559 |
| antimicrobial effects of interferon-inducible cxc chemokines against bacillus anthracis spores and bacilli. | based on previous studies showing that host chemokines exert antimicrobial activities against bacteria, we sought to determine whether the interferon-inducible glu-leu-arg-negative cxc chemokines cxcl9, cxcl10, and cxcl11 exhibit antimicrobial activities against bacillus anthracis. in vitro analysis demonstrated that all three cxc chemokines exerted direct antimicrobial effects against b. anthracis spores and bacilli including marked reductions in spore and bacillus viability as determined using ... | 2009 | 19179419 |
| anthrax protective antigen delivered by salmonella enterica serovar typhi ty21a protects mice from a lethal anthrax spore challenge. | bacillus anthracis, the etiological agent of anthrax disease, is a proven weapon of bioterrorism. currently, the only licensed vaccine against anthrax in the united states is ava biothrax, which, although efficacious, suffers from several limitations. this vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires a cold chain for storage, and in many cases has been associated with adverse effects. in this study, we modified the b. anthracis protective antige ... | 2009 | 19179420 |
| roles of germination-specific lytic enzymes cwlj and sleb in bacillus anthracis. | the structural characteristics of a spore enable it to withstand stresses that typically kill a vegetative cell. spores remain dormant until small molecule signals induce them to germinate into vegetative bacilli. germination requires degradation of the thick cortical peptidoglycan by germination-specific lytic enzymes (gsles). bacillus anthracis has four putative gsles, based upon sequence similarities with enzymes in other species: sleb, cwlj1, cwlj2, and slel. in this study, the roles of sleb ... | 2009 | 19181808 |
| codon-optimized fluorescent proteins designed for expression in low-gc gram-positive bacteria. | fluorescent proteins have wide applications in biology. however, not all of these proteins are properly expressed in bacteria, especially if the codon usage and genomic gc content of the host organism are not ideal for high expression. in this study, we analyzed the dna sequences of multiple fluorescent protein genes with respect to codons and gc content and compared them to a low-gc gram-positive bacterium, bacillus anthracis. we found high discrepancies for cyan fluorescent protein (cfp), yell ... | 2009 | 19181829 |
| aptamer selection express: a novel method for rapid single-step selection and sensing of aptamers. | here we describe a new dna capture element (dce) sensing system, based on the quenching and dequenching of a double-stranded aptamer. this system shows very good sensitivity and thermal stability. while quenching, dequenching, and separating the dce systems made from different aptamers (all selected by selex), an alternative method to rapidly select aptamers was developed-the aptamer selection express (asexp). this process has been used to select aptamers against different types of targets (baci ... | 2008 | 19183794 |
| differential cell surface properties of vegetative bacillus. | the genus bacillus encompasses a wide range of species which display varying pathogenic abilities. the hydrophobicity of a range of bacillus species was determined to evaluate the correlation between bacterial hydrophobicity and pathogenicity. | 2009 | 19187499 |
| a combined immunomagnetic separation and lateral flow method for a sensitive on-site detection of bacillus anthracis spores--assessment in water and dairy products. | combination of immunomagnetic separation (ims) and lateral flow device (lfd) assays for the development of a sensitive, rapid, on-site methodology that enables concentration and detection of bacillus anthracis spores in complex samples. | 2009 | 19187500 |
| landscape phage as a molecular recognition interface for detection devices. | filamentous phages are thread-shaped bacterial viruses. their outer coat is a tube formed by thousands equal copies of the major coat protein pviii. libraries of random peptides fused to pviii domains were used for selection of phages probes specific for a panel of test antigens and biological threat agents. because the viral carrier in the phage borne bio-selective probes is infective, they can be cloned individually and propagated indefinitely without needs of their chemical synthesis or recon ... | 2008 | 19190724 |
| evaluation of ultrafiltration cartridges for a water sampling apparatus. | to determine the efficiency of various ultrafiltration cartridges (ufc) in concentrating test micro-organisms from drinking water. | 2009 | 19191977 |
| biochemical characterization of alanine racemase--a spore protein produced by bacillus anthracis. | alanine racemase catalyzes the interconversion of l-alanine and d-alanine and plays a crucial role in spore germination and cell wall biosynthesis. in this study, alanine racemase produced by bacillus anthracis was expressed and purified as a monomer in escherichia coli and the importance of lysine 41 in the cofactor binding octapeptide and tyrosine 270 in catalysis was evaluated. the native enzyme exhibited an apparent k(m) of 3 mm for l-alanine, and a v(max) of 295 micromoles/min/mg, with the ... | 2009 | 19192393 |
| expression, purification, crystallization and preliminary x-ray diffraction analysis of dihydrodipicolinate synthase from bacillus anthracis in the presence of pyruvate. | dihydrodipicolinate synthase (dhdps) catalyses the first committed step in the lysine-biosynthesis pathway in bacteria, plants and some fungi. in this study, the expression of dhdps from bacillus anthracis (ba-dhdps) and the purification of the recombinant enzyme in the absence and presence of the substrate pyruvate are described. it is shown that dhdps from b. anthracis purified in the presence of pyruvate yields greater amounts of recombinant enzyme with more than 20-fold greater specific acti ... | 2009 | 19194017 |
| genetic immunization with gpi-anchored anthrax protective antigen raises combined cd1d- and mhc ii-restricted antibody responses by natural killer t cell-mediated help. | studies have demonstrated that lipid rafts ultimately regulate the endocytosis of anthrax toxin via clathrin dependent pathway. interestingly, gpi-anchored protein rich rafts have also been shown to be transported down to the endocytic pathway to reducing late endosomes. taking advantage of this parallelism, we tried translating the anthrax toxin natural intoxication mechanism by administering a dna chimera that encoded protective antigen attached to a mammalian gpi-anchor sequence at its c-term ... | 2009 | 19195490 |
| resistance of athymic nude mice to experimental cutaneous bacillus anthracis infection. | previous studies in a murine cutaneous anthrax model have demonstrated that hairless and haired hrs/j mice are extremely resistant to bacillus anthracis. because these mice are relatively thymus deficient, we used c57bl/6 athymic nude and euthymic mice to evaluate the relationship between t cell deficiency and this heightened resistance. | 2009 | 19199545 |
| evolution of pathogenicity in the bacillus cereus group. | the bacillus cereus group of bacteria comprises soil-dwelling saprophytes but on occasion these bacteria can cause a wide range of diseases in humans, including food poisoning, systemic infections and highly lethal forms of anthrax. while anthrax is almost invariably caused by strains from a single evolutionary lineage, bacillus anthracis, variation in the virulence properties of strains from other lineages has not been fully addressed. using multi-locus sequence data from 667 strains, we recons ... | 2009 | 19200684 |
| a case of pneumonia caused by bacillus anthracis secondary to gastrointestinal anthrax. | we present herein an unusual case of anthrax pneumonia secondary to gastrointestinal infection. in this case, severe abdominal pain occurred during the course of a stent placement procedure. the patient had undergone surgery with the prediagnosis of intestinal ischemia. on the second postoperative day, pneumonia developed and b. anthracis grew as the etiologic agent. pathological examination of small-bowel sections revealed findings in accordance with anthrax. | 2009 | 19201638 |
| involvement of tlr2 in innate response to bacillus anthracis infection. | the involvement of tlr2 receptor in the innate response to infection with bacillus anthracis was investigated. we studied the response to virulent or attenuated vollum strains in either in vitro assays using macrophage cultures, or in an in vivo model comparing the sensitivity of syrian hamster cells (expressing normal tlr2) to chinese hamster cells (lacking functional tlr2) to infection by the various b. anthracis strains. phagocytosis experiments with murine cell cultures or primary macrophage ... | 2009 | 19201824 |
| evidence for a proton-protein symport mechanism in the anthrax toxin channel. | the toxin produced by bacillus anthracis, the causative agent of anthrax, is composed of three proteins: a translocase heptameric channel, (pa(63))(7), formed from protective antigen (pa), which allows the other two proteins, lethal and edema factors (lf and ef), to translocate across a host cell's endosomal membrane, disrupting cellular homeostasis. it has been shown that (pa(63))(7) incorporated into planar phospholipid bilayer membranes forms a channel capable of transporting lf and ef. prote ... | 2009 | 19204186 |
| nicotinamide mononucleotide synthetase is the key enzyme for an alternative route of nad biosynthesis in francisella tularensis. | enzymes involved in the last 2 steps of nicotinamide adenine dinucleotide (nad) cofactor biosynthesis, which catalyze the adenylylation of the nicotinic acid mononucleotide (namn) precursor to nicotinic acid dinucleotide (naad) followed by its amidation to nad, constitute promising drug targets for the development of new antibiotics. these enzymes, namn adenylyltransferase (gene nadd) and nad synthetase (gene nade), respectively, are indispensable and conserved in nearly all bacterial pathogens. ... | 2009 | 19204287 |
| anti-toxin antibodies in prophylaxis and treatment of inhalation anthrax. | the cdc recommend 60 days of oral antibiotics combined with a three-dose series of the anthrax vaccine for prophylaxis after potential exposure to aerosolized bacillus anthracis spores. the anthrax vaccine is currently not licensed for anthrax postexposure prophylaxis and has to be made available under an investigational new drug protocol. postexposure prophylaxis based on antibiotics can be problematic in cases where the use of antibiotics is contraindicated. furthermore, there is a concern tha ... | 2009 | 19207098 |
| pathogenic bacillus anthracis in the progressive gene losses and gains in adaptive evolution. | sequence mutations represent a driving force of adaptive evolution in bacterial pathogens. it is especially evident in reductive genome evolution where bacteria underwent lifestyles shifting from a free-living to a strictly intracellular or host-depending life. it resulted in loss-of-function mutations and/or the acquisition of virulence gene clusters. bacillus anthracis shares a common soil bacterial ancestor with its closely related bacillus species but is the only obligate, causative agent of ... | 2009 | 19208130 |
| identification of bacillus anthracis spore component antigens conserved across diverse bacillus cereus sensu lato strains. | we sought to identify proteins in the bacillus anthracis spore, conserved in other strains of the closely related bacillus cereus group, that elicit an immune response in mammals. two high throughput approaches were used. first, an in silico screening identified 200 conserved putative b. anthracis spore components. a total of 192 of those candidate genes were expressed and purified in vitro, 75 of which reacted with the rabbit immune sera generated against b. anthracis spores. the second approac ... | 2009 | 19208616 |
| phylogeny in aid of the present and novel microbial lineages: diversity in bacillus. | bacillus represents microbes of high economic, medical and biodefense importance. bacillus strain identification based on 16s rrna sequence analyses is invariably limited to species level. secondly, certain discrepancies exist in the segregation of bacillus subtilis strains. in the rdp/ncbi databases, out of a total of 2611 individual 16s rdna sequences belonging to the 175 different species of the genus bacillus, only 1586 have been identified up to species level. 16s rrna sequences of bacillus ... | 2009 | 19212464 |
| dynamics and energetics: a consensus analysis of the impact of calcium on ef-cam protein complex. | we have studied the relationship between dynamical correlations and energetic contributions in an attempt to model the transmission of information inside protein-protein complexes. the complex formed between the edema factor (ef) of bacillus anthracis and calmodulin (cam) was taken as an example, as the formation and stability of the complex depend on the calcium complexation level. the effect of calcium through ef-cam residue network has been investigated with various approaches: 1), the elasti ... | 2009 | 19217845 |
| two small c-type cytochromes affect virulence gene expression in bacillus anthracis. | regulated expression of the genes for anthrax toxin proteins is essential for the virulence of the pathogenic bacterium bacillus anthracis. induction of toxin gene expression depends on several factors, including temperature, bicarbonate levels, and metabolic state of the cell. to identify factors that regulate toxin expression, transposon mutagenesis was performed under non-inducing conditions and mutants were isolated that untimely expressed high levels of toxin. a number of these mutations cl ... | 2009 | 19222757 |
| frequency and domain specificity of toxin-neutralizing paratopes in the human antibody response to anthrax vaccine adsorbed. | protective antigen (pa) is the cell surface recognition unit of the binary anthrax toxin system and the primary immunogenic component in both the current and proposed "next-generation" anthrax vaccines. several studies utilizing animal models have indicated that pa-specific antibodies, acquired by either active or passive immunization, are sufficient to protect against infection with bacillus anthracis. to investigate the human antibody response to anthrax immunization, we have established a lar ... | 2009 | 19223482 |
| immuno-detection of anthrose containing tetrasaccharide in the exosporium of bacillus anthracis and bacillus cereus strains. | bacillus anthracis strains of various origins were analysed with the view to describe intrinsic and persistent structural components of the bacillus collagen-like protein of anthracis glycoprotein associated anthrose containing tetrasaccharide in the exosporium. | 2009 | 19226390 |
| [research and development policy on bioterrorism medical countermeasures in the united states]. | the united states department of health and human services (dhhs) plays a key role in biodefense, which accounts for almost 80% of the u.s. civilian biodefense budget, which itself has amount to over 500 billion yen a year since the 2001 anthrax mailings and has involved programs based on the hspd-10 "biodefense for the 21st century". to promote r&d on medical countermeasures, the dhhs has invested in basic research and ensuring market, and closely communicated with stakeholders to overcome r&d b ... | 2009 | 19227217 |
| structural and chemical basis for glucosamine 6-phosphate binding and activation of the glms ribozyme. | the glms ribozyme is the first naturally occurring catalytic rna that relies on an exogenous, nonnucleotide cofactor for reactivity. from a biochemical perspective, the glms ribozyme derived from bacillus anthracis is the best characterized. however, much of the structural work to date has been done on a variant glms ribozyme, derived from thermoanaerobacter tengcongensis. here we present structures of the b. anthracis glms ribozyme in states before the activating sugar, glucosamine 6-phosphate ... | 2009 | 19228039 |
| the tubulin-like repx protein encoded by the pxo1 plasmid forms polymers in vivo in bacillus anthracis. | bacillus anthracis contains two megaplasmids, pxo1 and pxo2, that are critical for its pathogenesis. stable inheritance of pxo1 in b. anthracis is dependent upon the tubulin/ftsz-like repx protein encoded by this plasmid. previously, we have shown that repx undergoes gtp-dependent polymerization in vitro. however, the polymerization properties and localization pattern of repx in vivo are not known. here, we utilize a repx-green fluorescent protein (gfp) fusion to show that repx forms foci and th ... | 2009 | 19233922 |
| livestock keeper perceptions of four indigenous cattle breeds in tsetse infested areas of ethiopia. | four cattle breeds indigenous to western and south-western ethiopia--abigar, gurage, horro and sheko--were included in a study of the perceptions of smallholder cattle keepers regarding cattle management, production levels and constraints for production. a semi-structured questionnaire was used and 60 cattle keepers from each of the four areas were interviewed. diseases were reported as the main constraint to cattle production by a majority of livestock keepers in all areas except in the sheko a ... | 2009 | 19234873 |