| direct proteolytic cleavage of nlrp1b is necessary and sufficient for inflammasome activation by anthrax lethal factor. | inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the caspase-1 (casp1) protease. activated casp1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (nlr) or aim2-like receptor (alr) protein families. certain nlrs and alrs have been shown to function as direct re ... | 2013 | 23818853 |
| delivery of antibody mimics into mammalian cells via anthrax toxin protective antigen. | antibody mimics have significant scientific and therapeutic utility for the disruption of protein-protein interactions inside cells; however, their delivery to the cell cytosol remains a major challenge. here we show that protective antigen (pa), a component of anthrax toxin, efficiently transports commonly used antibody mimics to the cytosol of mammalian cells when conjugated to the n-terminal domain of lf (lfn). in contrast, a cell-penetrating peptide (cpp) was not able to deliver any of these ... | 2014 | 25250705 |
| sulforaphane inhibits multiple inflammasomes through an nrf2-independent mechanism. | the inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18. these events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and auto ... | 2015 | 26269198 |
| translocation of non-canonical polypeptides into cells using protective antigen. | a variety of pathogenic bacteria infect host eukaryotic cells using protein toxins, which enter the cytosol and exert their cytotoxic effects. anthrax lethal toxin, for example, utilizes the membrane-spanning translocase, protective antigen (pa) pore, to deliver the protein toxin lethal factor (lf) from the endosome into the cytosol of cells. previous work has investigated the delivery of natural peptides and enzymatic domains appended to the c-terminus of the pa-binding domain of lethal factor ... | 2015 | 26178180 |
| the cyclopentenone prostaglandin 15d-pgj2 inhibits the nlrp1 and nlrp3 inflammasomes. | inflammasomes are cytosolic protein complexes that respond to diverse danger signals by activating caspase-1. the sensor components of the inflammasome, often proteins of the nucleotide-binding oligomerization domain-like receptor (nlr) family, detect stress, danger stimuli, and pathogen-associated molecular patterns. we report that the eicosanoid 15-deoxy-δ(12,14)-pgj2 (15d-pgj2) and related cyclopentenone pgs inhibit caspase-1 activation by the nlr family leucine-rich repeat protein (nlrp)1 an ... | 2015 | 25681332 |
| high-sensitivity maldi-tof ms quantification of anthrax lethal toxin for diagnostics and evaluation of medical countermeasures. | inhalation anthrax has a rapid progression and high fatality rate. pathology and death from inhalation of bacillus anthracis spores are attributed to the actions of secreted protein toxins. protective antigen (pa) binds and imports the catalytic component lethal factor (lf), a zinc endoprotease, and edema factor (ef), an adenylyl cyclase, into susceptible cells. pa-lf is termed lethal toxin (ltx) and pa-ef, edema toxin. as the universal transporter for both toxins, pa is an important target for ... | 2015 | 25673244 |
| tumor targeting and drug delivery by anthrax toxin. | anthrax toxin is a potent tripartite protein toxin from bacillus anthracis. it is one of the two virulence factors and causes the disease anthrax. the receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associate ... | 2016 | 27376328 |
| overcoming target-mediated quinolone resistance in topoisomerase iv by introducing metal-ion-independent drug-enzyme interactions. | quinolones, which target gyrase and topoisomerase iv, are the most widely prescribed antibacterials worldwide. unfortunately, their use is threatened by the increasing prevalence of target-mediated drug resistance. greater than 90% of mutations that confer quinolone resistance act by disrupting enzyme-drug interactions coordinated by a critical water-metal ion bridge. quinazolinediones are quinolone-like drugs but lack the skeletal features necessary to support the bridge interaction. these comp ... | 2013 | 24047414 |
| novel strategies for enhanced removal of persistent bacillus anthracis surrogates and clostridium difficile spores from skin. | removing spores of clostridium difficile and bacillus anthracis from skin is challenging because they are resistant to commonly used antimicrobials and soap and water washing provides only modest efficacy. we hypothesized that hygiene interventions incorporating a sporicidal electrochemically generated hypochlorous acid solution (vashe(®)) would reduce the burden of spores on skin. | 2013 | 23844234 |
| topoisomerase iv-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance. | although quinolones are the most commonly prescribed antibacterials, their use is threatened by an increasing prevalence of resistance. the most common causes of quinolone resistance are mutations of a specific serine or acidic residue in the a subunit of gyrase or topoisomerase iv. these amino acids are proposed to serve as a critical enzyme-quinolone interaction site by anchoring a water-metal ion bridge that coordinates drug binding. to probe the role of the proposed water-metal ion bridge, w ... | 2013 | 23460203 |
| anti-inflammatory and anti-superbacterial activity of polyphenols isolated from black raspberry. | the fruit of the black raspberry (rubus coreanus miquel) has been employed in traditional medicine, and recent studies have demonstrated its measureable biological activities. however, the root of the black raspberry has not been studied. therefore, in this study, we evaluated the anti-inflammatory and antibacterial properties of the root and unripe fruit polyphenols of the black raspberry. both polyphenols proved to have anti-inflammatory activity as evidenced by the decreased nitric oxide (no) ... | 2013 | 23440625 |
| anthracimycin activity against contemporary methicillin-resistant staphylococcus aureus. | anthracimycin is a recently discovered novel marine-derived compound with activity against bacillus anthracis. we tested anthracimycin against an expanded panel of staphylococcus aureus strains in vitro and in vivo. all strains of s. aureus tested, including methicillin-susceptible, methicillin-resistant (mrsa) and vancomycin-resistant strains of s. aureus, were susceptible to anthracimycin at mic values of ⩽0.25 mg l(-1). although its postantibiotic effects were minimal, anthracimycin exhibited ... | 2014 | 24736856 |
| storage effects on sample integrity of environmental surface sampling specimens with bacillus anthracis spores. | the effect of packaging, shipping temperatures and storage times on recovery of bacillus anthracis. sterne spores from swabs was investigated. macrofoam swabs were pre-moistened, inoculated with bacillus anthracis spores, and packaged in primary containment or secondary containment before storage at -15°c, 5°c, 21°c, or 35°c for 0-7 days. swabs were processed according to validated centers for disease control/laboratory response network culture protocols, and the percent recovery relative to a r ... | 2013 | 27213119 |
| repurposing cryptosporidium inosine 5'-monophosphate dehydrogenase inhibitors as potential antibacterial agents. | inosine 5'-monophosphate dehydrogenase (impdh) catalyzes the pivotal step in guanine nucleotide biosynthesis. impdh is a target for immunosuppressive, antiviral, and anticancer drugs, but, as of yet, has not been exploited for antimicrobial therapy. we have previously reported potent inhibitors of impdh from the protozoan parasite cryptosporidium parvum (cpimpdh). many pathogenic bacteria, including bacillus anthracis, staphylococcus aureus, and listeria monocytogenes, contain impdhs that should ... | 2014 | 25147601 |
| substrate specificity and kinetic characterization of peptidoglycan o-acetyltransferase b from neisseria gonorrhoeae. | the o-acetylation of the essential cell wall polymer peptidoglycan is a major virulence factor identified in many bacteria, both gram-positive and gram-negative, including staphylococcus aureus, bacillus anthracis, neisseria gonorrhoeae, and neisseria meningitidis. with gram-negative bacteria, the translocation of acetyl groups from the cytoplasm is performed by an integral membrane protein, pata, for its transfer to peptidoglycan by o-acetyltransferase patb, whereas a single bimodal membrane pr ... | 2014 | 24795044 |
| bacillus anthracis overcomes an amino acid auxotrophy by cleaving host serum proteins. | bacteria sustain an infection by acquiring nutrients from the host to support replication. the host sequesters these nutrients as a growth-restricting strategy, a concept termed "nutritional immunity." historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. we emplo ... | 2015 | 25962917 |
| genomic characterization of the bacillus cereus sensu lato species: backdrop to the evolution of bacillus anthracis. | the key genes required for bacillus anthracis to cause anthrax have been acquired recently by horizontal gene transfer. to understand the genetic background for the evolution of b. anthracis virulence, we obtained high-redundancy genome sequences of 45 strains of the bacillus cereus sensu lato (s.l.) species that were chosen for their genetic diversity within the species based on the existing multilocus sequence typing scheme. from the resulting data, we called more than 324,000 new genes repres ... | 2012 | 22645259 |
| sortase-conjugation generates a capsule vaccine that protects guinea pigs against bacillus anthracis. | capsules protect bacteria against phagocytic clearance. capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. linking capsular material to a carrier protein stimulates its presentation to the immune system. for many conjugate vaccines this is achieved by a process of random chemical cross-linking. here we describe a new technology, designated sortase-conjugation, which g ... | 2012 | 22449424 |
| activation of the classical complement pathway by bacillus anthracis is the primary mechanism for spore phagocytosis and involves the spore surface protein bcla. | interactions between spores of bacillus anthracis and macrophages are critical for the development of anthrax infections, as spores are thought to use macrophages as vehicles to disseminate in the host. in this study, we report a novel mechanism for phagocytosis of b. anthracis spores. murine macrophage-like cell line raw264.7, bone marrow-derived macrophages, and primary peritoneal macrophages from mice were used. the results indicated that activation of the classical complement pathway (ccp) w ... | 2012 | 22442442 |
| identification of the immunogenic spore and vegetative proteins of bacillus anthracis vaccine strain a16r. | immunoproteomics was used to screen the immunogenic spore and vegetative proteins of bacillus anthracis vaccine strain a16r. the spore and vegetative proteins were separated by 2d gel electrophoresis and transferred to polyvinylidene difluoride membranes, and then western blotting was performed with rabbit immune serum against b.anthracis live spores. immunogenic spots were cut and digested by trypsin. matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed to ... | 2013 | 23516421 |
| revisiting the concept of targeting only bacillus anthracis toxins as a treatment for anthrax. | protective antigen (pa)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. the bacillus anthracis toxins lethal toxin (lethal factor [lf] plus pa) and edema toxin (edema factor [ef] plus pa) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. since the toxins reach high toxemia levels at the bacteremic stages of the disease, the cdc's recommenda ... | 2016 | 27270276 |
| bacillus anthracis spore surface protein bcla mediates complement factor h binding to spores and promotes spore persistence. | spores of bacillus anthracis, the causative agent of anthrax, are known to persist in the host lungs for prolonged periods of time, however the underlying mechanism is poorly understood. in this study, we demonstrated that bcla, a major surface protein of b. anthracis spores, mediated direct binding of complement factor h (cfh) to spores. the surface bound cfh retained its regulatory cofactor activity resulting in c3 degradation and inhibition of downstream complement activation. by comparing re ... | 2016 | 27304426 |
| bioshock: biotechnology and bioterrorism. | in the recent past, the threat of a global bioterrorist attack has increased dramatically. in addition to the already existing microorganisms and techniques, the recent explosion in biotechnology has considerably added to the arsenal of the bioterrorist. molecular technologies are now available which can be used by committed bioterrorist groups to manipulate and modify microorganisms so as to make them increasingly infectious, virulent or treatment resistant for causing maximum casualties. infec ... | 2009 | 27408292 |
| functional and structural analysis of the siderophore synthetase asbb through reconstitution of the petrobactin biosynthetic pathway from bacillus anthracis. | petrobactin, a mixed catechol-carboxylate siderophore, is required for full virulence of bacillus anthracis, the causative agent of anthrax. the asbabcdef operon encodes the biosynthetic machinery for this secondary metabolite. here, we show that the function of five gene products encoded by the asb operon is necessary and sufficient for conversion of endogenous precursors to petrobactin using an in vitro system. in this pathway, the siderophore synthetase asbb catalyzes formation of amide bonds ... | 2012 | 22408253 |
| menaquinone analogs inhibit growth of bacterial pathogens. | gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. we initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. menadione, 1,4-naphthoquinone, and coenzymes q1 to q3 but not menaquinone, phylloquinone, or coenzyme q10 inhibited the growth and to a greater extent exotoxin production of staphylococcus aureus, ... | 2013 | 23959313 |
| clostridial binary toxins: iota and c2 family portraits. | there are many pathogenic clostridium species with diverse virulence factors that include protein toxins. some of these bacteria, such as c. botulinum, c. difficile, c. perfringens, and c. spiroforme, cause enteric problems in animals as well as humans. these often fatal diseases can partly be attributed to binary protein toxins that follow a classic ab paradigm. within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-adp-ribosylation of globular actin by the a c ... | 2011 | 22919577 |
| pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor. | antibiotic treatment may fail to protect individuals, if not started early enough, after infection with bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. stable and easily stored inhibitors of the edema factor toxin (ef), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. the toxin's basic activity is to convert atp to camp, and it is thus in principle a simple phosphatase, which means that many ... | 2012 | 23202316 |
| identification of novel and cross-species seroreactive proteins from bacillus anthracis using a ligation-independent cloning-based, sos-inducible expression system. | the current standard for bacillus anthracis vaccination is the anthrax vaccine adsorbed (ava, biothrax). while effective, the licensed vaccine schedule requires five intramuscular injections in the priming series and yearly boosters to sustain protection. one potential approach to maintain or improve the protection afforded by an anthrax vaccine, but requiring fewer doses, is through the use of purified proteins to enhance an antibody response, which could be used on their own or in combination ... | 2012 | 22975444 |
| molecular motions as a drug target: mechanistic simulations of anthrax toxin edema factor function led to the discovery of novel allosteric inhibitors. | edema factor (ef) is a component of bacillus anthracis toxin essential for virulence. its adenylyl cyclase activity is induced by complexation with the ubiquitous eukaryotic cellular protein, calmodulin (cam). ef and its complexes with cam, nucleotides and/or ions, have been extensively characterized by x-ray crystallography. those structural data allowed molecular simulations analysis of various aspects of ef action mechanism, including the delineation of ef and cam domains through their associ ... | 2012 | 23012649 |
| binding of regulatory subunits of cyclic amp-dependent protein kinase to cyclic cmp agarose. | the bacterial adenylyl cyclase toxins cyaa from bordetella pertussis and edema factor from bacillus anthracis as well as soluble guanylyl cyclase α(1)β(1) synthesize the cyclic pyrimidine nucleotide ccmp. these data raise the question to which effector proteins ccmp binds. recently, we reported that ccmp activates the regulatory subunits riα and riiα of camp-dependent protein kinase. in this study, we used two ccmp agarose matrices as novel tools in combination with immunoblotting and mass spect ... | 2012 | 22808067 |
| bacillus anthracis edema factor substrate specificity: evidence for new modes of action. | since the isolation of bacillus anthracis exotoxins in the 1960s, the detrimental activity of edema factor (ef) was considered as adenylyl cyclase activity only. yet the catalytic site of ef was recently shown to accomplish cyclization of cytidine 5'-triphosphate, uridine 5'-triphosphate and inosine 5'-triphosphate, in addition to adenosine 5'-triphosphate. this review discusses the broad ef substrate specificity and possible implications of intracellular accumulation of cyclic cytidine 3':5'-mo ... | 2012 | 22852066 |
| cellular and physiological effects of anthrax exotoxin and its relevance to disease. | bacillus anthracis, the causative agent of anthrax, secretes a tri-partite exotoxin that exerts pleiotropic effects on the host. the purification of the exotoxin components, protective antigen, lethal factor, and edema factor allowed the rapid characterization of their physiologic effects on the host. as molecular biology matured, interest focused on the molecular mechanisms and cellular alterations induced by intoxication. only recently have researchers begun to connect molecular and cellular k ... | 2012 | 22919667 |
| cytoskeleton as an emerging target of anthrax toxins. | bacillus anthracis, the agent of anthrax, has gained virulence through its exotoxins produced by vegetative bacilli and is composed of three components forming lethal toxin (lt) and edema toxin (et). so far, little is known about the effects of these toxins on the eukaryotic cytoskeleton. here, we provide an overview on the general effects of toxin upon the cytoskeleton architecture. thus, we shall discuss how anthrax toxins interact with their receptors and may disrupt the interface between ext ... | 2012 | 22474568 |
| mechanisms of nk cell-macrophage bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins. | nk cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. bacillus anthracis spores can efficiently drive ifn-γ production by nk cells. the present study provides insights into the mechanisms of cytokine and cellular signaling that underlie the process of nk-cell activation by b. anthracis and the bacterial strategies to subvert and evade this response. infection with non-toxigenic encapsulated b. anthracis i ... | 2012 | 22253596 |
| nucleotidyl cyclase activity of particulate guanylyl cyclase a: comparison with particulate guanylyl cyclases e and f, soluble guanylyl cyclase and bacterial adenylyl cyclases cyaa and edema factor. | guanylyl cyclases (gcs) regulate many physiological processes by catalyzing the synthesis of the second messenger cgmp. the gc family consists of seven particulate gcs (pgcs) and a nitric oxide-activated soluble gc (sgc). rat sgc α1β1 possesses much broader substrate specificity than previously assumed. moreover, the exotoxins cyaa from bordetella pertussis and edema factor (ef) from bacillus anthracis possess nucleotidyl cyclase (nc) activity. pgc-a is a natriuretic peptide-activated homodimer ... | 2013 | 23922959 |
| increased camp in monocytes augments notch signaling mechanisms by elevating rbp-j and transducin-like enhancer of split (tle). | in cells of the innate immune system, pathological increases in intracellular camp attenuate immune responses and contribute to infections by bacteria such as bacillus anthracis. in this work, camp from b. anthracis edema toxin (et) is found to activate the notch signaling pathway in both mouse macrophages and human monocytes. et as well as a cell-permeable activator of pka induce notch target genes (hes1, hey1, il2ra, and il7r) and are able to significantly enhance the induction of these notch ... | 2013 | 23775085 |
| exoy from pseudomonas aeruginosa is a nucleotidyl cyclase with preference for cgmp and cump formation. | in addition to the well known second messengers camp and cgmp, mammalian cells contain the cyclic pyrimidine nucleotides ccmp and cump. soluble guanylyl cyclase and soluble adenylyl cyclase produce all four cnmps. several bacterial toxins exploit mammalian cyclic nucleotide signaling. the type iii secretion protein exoy from pseudomonas aeruginosa induces severe lung damage and effectively produces cgmp. here, we show that transfection of mammalian cells with exoy or infection with exoy-expressi ... | 2014 | 24971548 |
| different roles of n-terminal and c-terminal domains in calmodulin for activation of bacillus anthracis edema factor. | bacillus anthracis adenylyl cyclase toxin edema factor (ef) is one component of the anthrax toxin and is essential for establishing anthrax disease. ef activation by the eukaryotic ca2+-sensor calmodulin (cam) leads to massive camp production resulting in edema. camp also inhibits the nicotinamide adenine dinucleotide phosphate (nadph)-oxidase, thus reducing production of reactive oxygen species (ros) used for host defense in activated neutrophils and thereby facilitating bacterial growth. methi ... | 2015 | 26184312 |
| effects of 39 compounds on calmodulin-regulated adenylyl cyclases ac1 and bacillus anthracis edema factor. | adenylyl cyclases (acs) catalyze the conversion of atp into the second messenger camp. membranous ac1 (ac1) is involved in processes of memory and learning and in muscle pain. the ac toxin edema factor (ef) of bacillus anthracis is involved in the development of anthrax. both acs are stimulated by the eukaryotic ca(2+)-sensor calmodulin (cam). the cam-ac interaction could constitute a potential target to enhance or impair the ac activity of ac1 and ef to intervene in above (patho)physiological m ... | 2015 | 25946093 |
| a simple luminescent adenylate-cyclase functional assay for evaluation of bacillus anthracis edema factor activity. | edema factor (ef), the toxic sub-unit of the bacillus anthracis edema toxin (et) is a calmodulin-dependent adenylate cyclase whose detrimental activity in the infected host results in severe edema. ef is therefore a major virulence factor of b. anthracis. we describe a simple, rapid and reliable functional adenylate-cyclase assay based on inhibition of a luciferase-mediated luminescence reaction. the assay exploits the efficient adenylate cyclase-mediated depletion of adenosine tri-phosphate (at ... | 2016 | 27548219 |
| dismantling the taboo against vaccines in pregnancy. | vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. prejudice in health professionals add to fears of women and their families. both these feelings are not supported by even the smallest scientific data. harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human pa ... | 2016 | 27338346 |
| structural basis for latency and function of immune inhibitor a metallopeptidase, a modulator of the bacillus anthracis secretome. | immune inhibitor a(inha)-type metallopeptidases are potential virulence factors secreted by members of the bacillus cereus group. two paralogs from anthrax-causing bacillus anthracis (bainha1 and bainha2) were shown to degrade host tissue proteins with broad substrate specificity. analysis of their activation mechanism and the crystal structure of a zymogenic bainha2 variant revealed a ∼750-residue four-domain structure featuring a pro-peptide, a catalytic domain, a domain reminiscent of viral e ... | 2016 | 26745529 |
| standoff detection of biological agents using laser induced fluorescence-a comparison of 294 nm and 355 nm excitation wavelengths. | standoff detection measuring the fluorescence spectra of seven different biological agents excited by 294 nm as well as 355 nm wavelength laser pulses has been undertaken. the biological warfare agent simulants were released in a semi-closed aerosol chamber at 210 m standoff distance and excited by light at either of the two wavelengths using the same instrument. significant differences in several of the agents' fluorescence response were seen at the two wavelengths. the anthrax simulants' fluor ... | 2012 | 23162732 |
| detection of the urban release of a bacillus anthracis simulant by air sampling. | in 2005 and 2009, the pentagon force protection agency (pfpa) staged deliberate releases of a commercially available organic pesticide containing bacillus amyloliquefaciens to evaluate pfpa's biothreat response protocols. in concert with, but independent of, these releases, the department of homeland security sponsored experiments to evaluate the efficacy of commonly employed air and surface sampling techniques for detection of an aerosolized biological agent. high-volume air samplers were place ... | 2014 | 24697146 |
| anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria. | a variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (mapk) signaling pathways, including bacillus anthracis. anthrax lethal toxin (lt) has specific proteolytic activity against the upstream regulators of mapks, the mapk kinases (mkks). using a murine model of intoxication, we show that lt causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. this pathology correlates w ... | 2012 | 22438953 |
| baulamycins a and b, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in staphylococcus aureus and bacillus anthracis. | siderophores are high-affinity iron chelators produced by microorganisms and frequently contribute to the virulence of human pathogens. targeted inhibition of the biosynthesis of siderophores staphyloferrin b of staphylococcus aureus and petrobactin of bacillus anthracis hold considerable potential as a single or combined treatment for methicillin-resistant s. aureus (mrsa) and anthrax infection, respectively. the biosynthetic pathways for both siderophores involve a nonribosomal peptide synthet ... | 2014 | 24401083 |
| θ-defensins: cyclic peptides with endless potential. | θ-defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. human θ-defensin genes contain a premature stop codon that prevents effective translation of ... | 2012 | 22700960 |
| innate immune protection against infectious diseases by pulmonary administration of a phospholipid-conjugated tlr7 ligand. | pulmonary administration of toll-like receptor (tlr) ligands protects hosts from inhaled pathogens. however, systemic side effects induced by tlr stimulation limit clinical development. here, a small-molecule tlr7 ligand conjugated with phospholipid, 1v270 (also designated tmx201), was tested for innate immune activation and its ability to prevent pulmonary infection in mice. we hypothesized that phospholipid conjugation would increase internalization by immune cells and localize the compound in ... | 2013 | 24192551 |
| functional and evolutionary analyses identify proteolysis as a general mechanism for nlrp1 inflammasome activation. | inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the caspase-1 protease. human nlrp1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. recently, specific variants of mouse and rat nlrp1 were found to be activated upon n-terminal cleavage by the anthrax lethal factor protease. however, agonists for other nlrp1 variants, including human nlrp1, are not known, ... | 2016 | 27926929 |
| spatiotemporal clustering analysis and risk assessments of human cutaneous anthrax in china, 2005-2012. | to investigate the epidemic characteristics of human cutaneous anthrax (ca) in china, detect the spatiotemporal clusters at the county level for preemptive public health interventions, and evaluate the differences in the epidemiological characteristics within and outside clusters. | 2015 | 26208355 |
| advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant. | subunit vaccines against anthrax based on recombinant protective antigen (pa) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. this study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant advax or the innate immune adjuvant murabutide alone or together could enhance pa immunogenicity by comparison to an alum adjuvant. a single immunization with pa plus advax adju ... | 2014 | 24554695 |
| toxin-based therapeutic approaches. | protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. in parallel, many research groups turned to explore the pharmaceut ... | 2010 | 22069564 |
| dna vaccines: roles against diseases. | vaccination is the most successful application of immunological principles to human health. vaccine efficacy needs to be reviewed from time to time and its safety is an overriding consideration. dna vaccines offer simple yet effective means of inducing broad-based immunity. these vaccines work by allowing the expression of the microbial antigen inside host cells that take up the plasmid. these vaccines function by generating the desired antigen inside the cells, with the advantage that this may ... | 2013 | 24432284 |
| neglected zoonotic diseases-the long and winding road to advocacy. | years of advocacy for the neglected tropical diseases (ntds) have focused the world's attention on these diseases of the poor, resulting most recently in the 2012 "london declaration" and the recent world health assembly resolution wha66.12 on ntds in may 2013. control of the endemic neglected zoonotic diseases (nzds) would benefit from a similar campaign, which needs the support of a global community. | 2014 | 24901769 |
| prioritization of zoonotic diseases in kenya, 2015. | zoonotic diseases have varying public health burden and socio-economic impact across time and geographical settings making their prioritization for prevention and control important at the national level. we conducted systematic prioritization of zoonotic diseases and developed a ranked list of these diseases that would guide allocation of resources to enhance their surveillance, prevention, and control. | 2016 | 27557120 |
| identification and validation of a linear protective neutralizing epitope in the β-pore domain of alpha toxin. | the plethora of virulence factors associated with staphylococcus aureus make this bacterium an attractive candidate for a molecularly-designed epitope-focused vaccine. this approach, which necessitates the identification of neutralizing epitopes for incorporation into a vaccine construct, is being evaluated for pathogens where conventional approaches have failed to elicit protective humoral responses, like hiv-1 and malaria, but may also hold promise for pathogens like s. aureus, where the elici ... | 2015 | 25635901 |
| effect of pain management on immunization efficacy in mice. | immunization with complete freund adjuvant (cfa) or incomplete freund adjuvant (ifa) is commonly viewed as painful, yet rodents may not receive analgesics due to concerns that these drugs affect the desired immune responses. here we tested the hypothesis that pain associated with immunization with cfa or ifa in mice can be relieved without compromising the effectiveness of the immune response. after subcutaneous immunization in the leg with antigen in cfa or ifa, mice were assessed for signs of ... | 0 | 23043810 |
| maximal adjuvant activity of nasally delivered il-1α requires adjuvant-responsive cd11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production. | il-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. we vaccinated il-1r1 bone marrow (bm) chimeric mice to determine whether il-1r1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered il-1α as determined by the acute induction of cytokine responses and induction of bacillus anthracis lethal factor (lf)-specific adaptive immunity. cytokine and chemokine responses ind ... | 2012 | 22345651 |
| combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays. | monoclonal antibodies (mabs) are potential therapeutic agents against bacillus anthracis toxins, since there is no current treatment to counteract the detrimental effects of toxemia. in hopes of isolating new protective mabs to the toxin component lethal factor (lf), we used a strain of mice (c57bl/6) that had not been used in previous studies, generating mabs to lf. six lf-binding mabs were obtained, representing 3 igg isotypes and one igm. one mab (20c1) provided protection from lethal toxin ( ... | 2013 | 23509144 |
| epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax. | anthrax represents a formidable bioterrorism threat for which new, optimized vaccines are required. we previously demonstrated that epitope-focused multiple antigenic peptides or a recombinant protein in freund's adjuvant can elicit ab against the loop neutralizing determinant (lnd), a cryptic linear neutralizing epitope in the 2ß2-2ß3 loop of protective antigen from bacillus anthracis, which mediated protection of rabbits from inhalation challenge with b. anthracis ames strain. however, demonst ... | 2014 | 25454087 |
| recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax. | we previously showed that a multiple antigenic peptide (map) vaccine displaying amino acids (aa) 304 to 319 from the 2β2-2β3 loop of protective antigen was capable of protecting rabbits from an aerosolized spore challenge with bacillus anthracis ames strain. antibodies to this sequence, referred to as the loop-neutralizing determinant (lnd), are highly potent at neutralizing lethal toxin yet are virtually absent in rabbit and human protective antigen (pa) antiserum. while the map vaccine was pro ... | 2013 | 23283638 |
| stochastic humoral immunity to bacillus anthracis protective antigen: identification of anti-peptide igg correlating with seroconversion to lethal toxin neutralization. | a substantial fraction of individuals vaccinated against anthrax have low to immeasurable levels of serum lethal toxin (letx)-neutralizing activity. the only known correlate of protection against bacillus anthracis in the currently licensed vaccine is magnitude of the igg response to protective antigen (pa); however, some individuals producing high serum levels of anti-pa igg fail to neutralize letx in vitro. this suggests that non-protective humoral responses to pa may be immunodominant in some ... | 2013 | 23415781 |
| historical data analysis of hospital discharges related to the amerithrax attack in florida. | interrupted time-series analysis (itsa) can be used to identify, quantify, and evaluate the magnitude and direction of an event on the basis of time-series data. this study evaluates the impact of the bioterrorist anthrax attacks ("amerithrax") on hospital inpatient discharges in the metropolitan statistical area of palm beach, broward, and miami-dade counties in the fourth quarter of 2001. three statistical methods-standardized incidence ratio (sir), segmented regression, and an autoregressive ... | 2016 | 27843420 |
| bithionol blocks pathogenicity of bacterial toxins, ricin, and zika virus. | diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. this approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and con ... | 2016 | 27686742 |
| a preliminary study on the insect fauna of al-baha province, saudi arabia, with descriptions of two new species. | a preliminary study was carried out on the insect fauna of al-baha province, south-western part of saudi arabia. a total number of 582 species and subspecies (few identified only to the genus level) belonging to 129 families and representing 17 orders were recorded. two of these species are described as new, namely: monomorium sarawatensis sharaf & aldawood, sp. n. [formicidae, hymenoptera] and anthrax alruqibi el-hawagry sp. n. [bombyliidae, diptera]. another eight species are recorded for the ... | 2013 | 23794807 |
| seasonal patterns of hormones, macroparasites, and microparasites in wild african ungulates: the interplay among stress, reproduction, and disease. | sex hormones, reproductive status, and pathogen load all affect stress. together with stress, these factors can modulate the immune system and affect disease incidence. thus, it is important to concurrently measure these factors, along with their seasonal fluctuations, to better understand their complex interactions. using steroid hormone metabolites from fecal samples, we examined seasonal correlations among zebra and springbok stress, reproduction, gastrointestinal (gi) parasite infections, an ... | 2015 | 25875647 |
| division of labour and terminal differentiation in a novel bacillus thuringiensis strain. | a major challenge in bacterial developmental biology has been to understand the mechanisms underlying cell fate decisions. some differentiated cell types display cooperative behaviour. cooperation is one of the greatest mysteries of evolutionary biology and microbes have been considered as an excellent system for experimentally testing evolution theories. bacillus thuringiensis (bt) is a spore-forming bacterium, which is genetically closely related to b. anthracis, the agent of anthrax, and to b ... | 2014 | 25083932 |
| a novel multiplex pcr discriminates bacillus anthracis and its genetically related strains from other bacillus cereus group species. | anthrax is an important zoonotic disease worldwide that is caused by bacillus anthracis, a spore-forming pathogenic bacterium. a rapid and sensitive method to detect b. anthracis is important for anthrax risk management and control in animal cases to address public health issues. however, it has recently become difficult to identify b. anthracis by using previously reported molecular-based methods because of the emergence of b. cereus, which causes severe extra-intestinal infection, as well as t ... | 2015 | 25774512 |
| transcriptional response of bovine monocyte-derived macrophages after the infection with different argentinean mycobacterium bovis isolates. | infection of bovines with mycobacterium bovis causes important financial hardship in many countries presenting also a risk for humans. m. bovis is known to be adapted to survive and thrive within the intramacrophage environment. in spite of its relevance, at present the information about macrophage expression patterns is scarce, particularly regarding the bovine host. in this study, transcriptomic analysis was used to detect genes differentially expressed in macrophages derived from peripheral b ... | 2013 | 23484118 |
| effects of over-expression of tlr2 in transgenic goats on pathogen clearance and role of up-regulation of lysozyme secretion and infiltration of inflammatory cells. | toll-like receptor 2 (tlr2) is important to host recognition of invading gram-positive microbes. in goats, these microbes can cause serious mastitis, anthrax, tetanus, and other problems. transgenic goats constitutively over-expressing tlr2 in many tissues serve as a suitable model for the study of the role of tlr2 over-expression in bacterial clearance. | 2012 | 23082910 |
| draft genome sequences of two south african bacillus anthracis strains. | bacillus anthracis is a gram-positive bacterium that causes anthrax, mainly in herbivores through exotoxins and capsule produced on plasmids, pxo1 and pxo2. this paper compares the whole-genome sequences of two b. anthracis strains from an endemic region and a sporadic outbreak in south africa. sequencing was done using next-generation sequencing technologies. | 2015 | 26586878 |
| nlrp1 is an inflammasome sensor for toxoplasma gondii. | the obligate intracellular parasite toxoplasma gondii is able to infect nearly all nucleated cell types of warm-blooded animals. this is achieved through the injection of hundreds of parasite effectors into the host cell cytosol, allowing the parasite to establish a vacuolar niche for growth, replication, and persistence. here we show that toxoplasma infection actives an inflammasome response in mice and rats, an innate immune sensing system designed to survey the host cytosol for foreign compon ... | 2014 | 24218483 |
| in vitro antibacterial activity of rhodanine derivatives against pathogenic clinical isolates. | bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. therefore, new bacterial targets and new antimicrobials are unmet medical needs. rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. however, their potential use as antibacterials has not been fully examined. in this study, we determined the spectrum of activity of seven rhodanine derivative ... | 2016 | 27711156 |
| immobilization and orientation-dependent activity of a naturally occurring antimicrobial peptide. | a naturally occurring antimicrobial peptide, smap-29, was synthesized with an n-terminal or c-terminal cysteine, termed c_smap and smap_c, respectively, for site-directed immobilization to superparamagnetic beads. immobilized smap orientation-dependent activity was probed against multiple bacteria of clinical interest including acinetobacter baumannii, pseudomonas aeruginosa, bacillus anthracis sterne and staphylococcus aureus. a kinetic microplate assay was employed to reveal both concentration ... | 2015 | 26018607 |
| targeting intracellular bacteria with an extended cationic amphiphilic polyproline helix. | an extended cationic and amphiphilic polyproline helix (caph) is described with a dual mode of action: effective cell penetration of human macrophages, and potent antimicrobial activity in vitro against both gram-positive and negative pathogens, including acinetobacter baumannii, escherichia coli o157 and bacillus anthracis. this dual action was successfully combined to clear pathogenic bacteria (brucella and salmonella) residing within macrophages. | 2015 | 25925008 |
| evaluation of ambulance decontamination using gaseous chlorine dioxide. | we evaluated gaseous chlorine dioxide (clo2) decontamination of an ambulance using a variety of bacterial biological agents. | 2013 | 23734992 |
| cytotoxicity of the vibrio vulnificus martx toxin effector duf5 is linked to the c2a subdomain. | the multifunctional-autoprocessing repeats-in-toxin (martx) toxins are bacterial protein toxins that serve as delivery platforms for cytotoxic effector domains. the domain of unknown function in position 5 (duf5) effector domain is present in at least six different species' martx toxins and as a hypothetical protein in photorhabdus spp. its presence increases the potency of the vibrio vulnificus martx toxin in mouse virulence studies, indicating duf5 directly contributes to pathogenesis. in this ... | 2014 | 24935440 |
| tabanids: neglected subjects of research, but important vectors of disease agents! | tabanids are nuisance pests for people and livestock because of their painful and irritating bite, persistent biting behavior, and blood ingestion. about 4400 tabanid species have been described; they are seasonally present in all kinds of landscapes, latitudes, and altitudes. high populations have a significant economic impact on outdoor activities, tourism, and livestock production. tabanids are also vectors of animal disease agents, including viruses, bacteria and parasites. however, tabanids ... | 2014 | 24727644 |
| highly potent silver-organoalkoxysilane antimicrobial porous nanomembrane. | we used a simple electrospinning technique to fabricate a highly potent silver-organoalkoxysilane antimicrobial composite from agno3-polyvinylpyrrolidone (pvp)/3-aminopropyltrimethoxysilane (aptms)/tetraethoxysilane (teos) solution. spectroscopic and microscopic analyses of the composite showed that the fibers contain an organoalkoxysilane 'skeleton,' 0.18 molecules/nm2 surface amino groups, and highly dispersed and uniformly distributed silver nanoparticles (5 nm in size). incorporation of orga ... | 2013 | 23574791 |
| diversity, antimicrobial and antioxidant activities of culturable bacterial endophyte communities in aloe vera. | twenty-nine culturable bacterial endophytes were isolated from surface-sterilized tissues (root, stem and leaf) of aloe vera and molecularly characterized to 13 genera: pseudomonas, bacillus, enterobacter, pantoea, chryseobacterium, sphingobacterium, aeromonas, providencia, cedecea, klebsiella, cronobacter, macrococcus and shigella. the dominant genera include bacillus (20.7%), pseudomonas (20.7%) and enterobacter (13.8%). the crude and ethyl acetate fractions of the metabolites of six isolates, ... | 2015 | 26454221 |
| dynamics of bacterial class bacilli in the deepest valley lake of kashmir-the manasbal lake. | in recognition of the importance of bacteria as ecological indicators of the aquatic systems a comprehensive and systematic analysis was carried out on manasbal lake, the deepest spring fed valley lake of kashmir. the main objective envisaged was to analyze bacterial community composition (bcc) and for this purpose systematic and regular sampling of waters from ten different sampling stations, predetermined in the lake according to differences in degree of human interference and also as zones of ... | 2017 | 28087491 |
| [screening and antibacterial function of bacillus amyloliquefaciens x030]. | we isolated 339 bacillus strains from 72 soil samples all over the country, then purified their antimicrobial compounds and studied the antibacterial activity, to enrich bacillus resources and explore their second metabolites. | 2015 | 26762026 |
| structural and functional insight into an unexpectedly selective n-methyltransferase involved in plantazolicin biosynthesis. | plantazolicin (pzn), a polyheterocyclic, n(α),n(α)-dimethylarginine-containing antibiotic, harbors remarkably specific bactericidal activity toward strains of bacillus anthracis, the causative agent of anthrax. previous studies demonstrated that genetic deletion of the s-adenosyl-l-methionine-dependent methyltransferase from the pzn biosynthetic gene cluster results in the formation of desmethylpzn, which is devoid of antibiotic activity. here we describe the in vitro reconstitution, mutational ... | 2013 | 23878226 |
| total synthesis of the ribosomally synthesized linear azole-containing peptide plantazolicin a from bacillus amyloliquefaciens. | | 2013 | 23761292 |
| bacteriophage t4 as a nanoparticle platform to display and deliver pathogen antigens: construction of an effective anthrax vaccine. | protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. however, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. the bacteriophage t4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. therefore, it offers a strong promise as a novel antigen delivery system. currently ba ... | 2017 | 28374254 |
| what is the predictive value of animal models for vaccine efficacy in humans? the importance of bridging studies and species-independent correlates of protection. | animal models have played a pivotal role in all stages of vaccine development. their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). this article will cover key questions regarding bridging animal studies to efficacy trials in humans. examples include human papillomavirus (hpv) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (vlps) p ... | 2017 | 28348035 |
| sublingual targeting of sting with 3'3'-cgamp promotes systemic and mucosal immunity against anthrax toxins. | anthrax is caused by bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. the current human anthrax vaccine, anthrax vaccine adsorbed (ava), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. bacterial enterotoxins, which stimulate production of the cyclic nucleotide camp are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. we investigated wh ... | 2017 | 28343781 |
| a novel live attenuated anthrax spore vaccine based on an acapsular bacillus anthracis sterne strain with mutations in the htra, lef and cya genes. | we recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htra (high temperature requirement a) gene in the bacillus anthracis sterne veterinary vaccine strain. this vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental sterne strain. here, we report the evaluation of additional mutations in the lef and cya genes, encodi ... | 2017 | 28342664 |
| digital triplex dna assay based on plasmonic nanocrystals. | a new analytical method has been developed to detect three kinds of dna simultaneously based on magnetic beads and color-encoded plasmonic nanocrystals. magnetic beads modified with capture dna are employed to collect the specific target dna, and color-encoded plasmonic nanocrystals are applied to signal the target through dna hybridization. as a proof of concept, three types of representative metal nanocrystals of gold nanoparticle (aunp), gold nanorod (aunr), and gold/silver nanoparticle (au/a ... | 2017 | 28331957 |
| penicillin-susceptible, oxidase-negative, nonhemolytic, nonmotile bacillus megaterium in disguise of bacillus anthracis. | bacillus anthracis is a bacterial pathogen of major concern. the spores of this bacteria can survive harsh environmental conditions for extended periods and are well recognized as a potential bioterror weapon with significant implications. accurate and timely identification of this bacillus species in the diagnostic laboratory is essential for disease and public health management. biosafety level 3 measures and ciprofloxacin treatment were instituted when b. anthracis was suspected from a patien ... | 2017 | 28331641 |
| the berkeleylactones, antibiotic macrolides from fungal coculture. | a carefully timed coculture fermentation of penicillium fuscum and p. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones a-h (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide a26771b (5), patulin, and citrinin. there was no evidence of the production of the berkeleylactones or a26771b (5) by either fungus when grown as axenic cultures. the structures were deduced from analyses of spectral data, and the absolute configurations of compounds 1 and 9 ... | 2017 | 28326781 |
| dual lanthanide-doped complexes: the development of a time-resolved ratiometric fluorescent probe for anthrax biomarker and a paper-based visual sensor. | in this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (tb: terbium, and eu: europium)-doped complexes (tb/dpa@sio2-eu/gmp) has been designed for detecting anthrax biomarker (dipicolinic acid, dpa), a unique and major component of anthrax spores. in such complexes-based probe, tb/dpa@sio2 can serve as a stable reference signal with green fluorescence and eu/gmp act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing dpa. ad ... | 2017 | 28324858 |
| combined virtual screening, mmpbsa, molecular docking and dynamics studies against deadly anthrax: an in silico effort to inhibit bacillus anthracis nucleoside hydrolase. | anthrax is a deadly disease caused by bacillus anthracis, a dangerous biological warfare agent employed for both military and terrorist purposes. a critical selective target for chemotherapy against this disease is nucleoside hydrolase (nh), an enzyme still not found in mammals. in the current study, we have performed molecular docking and dynamics studies, aiming to propose the new potent inhibitors of b. anthracis nh among national cancer institute (nci) diversity set. we also analyzed the pri ... | 2017 | 28300596 |
| poly(3-hydroxybutyrate) fuels the tricarboxylic acid cycle and de novo lipid biosynthesis during bacillus anthracis sporulation. | numerous bacteria accumulate poly(3-hydroxybutyrate) (phb) as an intracellular reservoir of carbon and energy in response to imbalanced nutritional conditions. in bacillus spp., where phb biosynthesis precedes the formation of the dormant cell type called the spore (sporulation), the direct link between phb accumulation and efficiency of sporulation was observed in multiple studies. although the idea of phb as an intracellular carbon and energy source fueling sporulation was proposed several dec ... | 2017 | 28299860 |
| modeling and simulation in dose determination for biodefense products approved under the fda animal rule. | development of effective medical countermeasures for biodefense is vital to united states biopreparedness and response in the age of terrorism, both foreign and domestic. a traditional drug development pathway toward approval is not possible for most biodefense-related indications, creating the need for alternative development pathways such as the fda's animal rule. under this unique regulatory mechanism, fda-approval is based on adequate and well-controlled animal studies when it is neither eth ... | 2017 | 28299529 |
| relevance of the alternate conductance states of anthrax toxin channel. | | 2017 | 28298532 |
| reply to yamini and nestorovich: alternate clamped states of the anthrax toxin protective antigen channel. | | 2017 | 28298531 |
| a four-gene operon in bacillus cereus produces two rare spore-decorating sugars. | bacterial glycan structures on cell surfaces are critical for cell-cell recognition and adhesion and in host-pathogen interactions. accordingly, unraveling the sugar composition of bacterial cell surfaces can shed light on bacterial growth and pathogenesis. here, we found that two rare sugars with a 3-c-methyl-6-deoxy-hexose structure were linked to spore glycan in bacillus cereus atcc 14579 and atcc 10876. moreover, we identified a four-gene operon in b. cereus atcc 14579 that encodes proteins ... | 2017 | 28298443 |
| time to worry about anthrax again. | | 2017 | 28296844 |
| the detection and quantification of bacillus thuringiensis spores from soil and swabs using quantitative pcr as a model system for routine diagnostics of bacillus anthracis. | to optimize the dna isolation for the routine detection and quantification of bacillary spores in soil and swabs. the procedure is primarily intended for diagnostics of bacillus anthracis spores, but due to its high pathogenicity b. thuringiensis served as its surrogate organism. | 2017 | 28294483 |