Publications

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metal homeostasis in bacteria: the role of arsr-smtb family of transcriptional repressors in combating varying metal concentrations in the environment.bacterial infections cause severe medical problems worldwide, resulting in considerable death and loss of capital. with the ever-increasing rise of antibiotic-resistant bacteria and the lack of development of new antibiotics, research on metal-based antimicrobial therapy has now gained pace. metal ions are essential for survival, but can be highly toxic to organisms if their concentrations are not strictly controlled. through evolution, bacteria have acquired complex metal-management systems tha ...201728512703
identification of beta-lactamases and beta-lactam-related proteins in human pathogenic bacteria using a computational search approach.a systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. in this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. the amino acid sequences for 19 different types of beta-lactamases (act, carb, cifa, cmy, ctx, fox, ges, gob, imp, ind, kpc, len, okp, oxa, oxy, shv, tem, ndm, and vim) were obtained from the arg-annot database and were used to constru ...201728508147
evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.risk of inhalation exposure to viable bacillus anthracis (b. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. while a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. the goal of this study was to determine the best sampler-filter co ...201728506101
lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated.a major difference between two currently licensed anthrax vaccines is presence (united kingdom anthrax vaccine precipitated, avp) or absence (united states anthrax vaccine adsorbed, ava) of quantifiable amounts of the lethal toxin (lt) component lethal factor (lf). the primary immunogen in both vaccine formulations is protective antigen (pa), and lt-neutralizing antibodies directed to pa are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrate ...201728504191
characterization of the dihydroorotase from methanococcus jannaschii.the gene that codes for the putative dihydroorotase in the hyperthermophilic archaeon methanococcus jannaschii was subcloned in pet-21a and expressed in escherichia coli. a purification protocol was devised. the purity of the protein was evaluated by sds-page and the protein was confirmed by sequencing using lc-ms. the calculated molecular mass is 48104 da. sec-ls suggested that the protein is a monomer in solution. icp-ms showed that there are two zn ions per monomer. kinetic analysis of the re ...201728660315
correction: comparison of french and worldwide bacillus anthracis strains favors a recent, post-columbian origin of the predominant north-american clade.[this corrects the article doi: 10.1371/journal.pone.0146216.].201728654701
ser/thr protein kinase prkc-mediated regulation of groel is critical for biofilm formation in bacillus anthracis.prkc is a conserved ser/thr protein kinase encoded in bacillus anthracis genome. prkc is shown to be important for b. anthracis pathogenesis, but little is known about its other functions and phosphorylated substrates. systemic analyses indicate the compelling role of prkc in phosphorylating multiple substrates, including the essential chaperone groel. through mass spectrometry, we identified that prkc phosphorylates groel on six threonine residues that are distributed in three canonical regions ...201728649408
milk-originated bacillus cereus sensu lato strains harbouring bacillus anthracis-like plasmids are genetically and phenotypically diverse.bacillus cereus sensu lato is widely distributed in food products, including raw and processed milk. plasmids often determine bacterial virulence and toxicity, but their role in the evolution of b. cereus sensu lato is only partly known. here, we observed that nearly 8% of b. cereus sensu lato isolates were positive for pxo1-like plasmids and 12% for pxo2-like plasmids in raw and ultra-heat-treated (uht) milk from one dairy plant. however, pxo1-like plasmids were significantly more frequent in r ...201728648290
inactivation of bacillus spores in wash waters using dilute chlorine bleach solutions at different temperatures and ph levels.inactivation of bacillus globigii spores in wash water was studied to simulate chlorine inactivation of bacillus anthracis spores in water generated in during biological clean ups. eight waters were studied, with six containing detergent. chlorine levels were approximately 3,000 mg/l. results across different waters showed decreasing inactivation with increasing ph. inactivation did not appear to be influenced by chemical oxygen demand, suspended solids, turbidity, or dissolved solids. inactivat ...201728646570
in defense of bacillus thuringiensis, the safest and most successful microbial insecticide available to humanity - a response to efsa.the bacillus cereus group contains vertebrate pathogens such as bacillus anthracis and bacillus cereus and the invertebrate pathogen bacillus thuringiensis. microbial biopesticides based on b. thuringiensis (bt) are widely recognized as being among the safest and least environmentally damaging insecticidal products available. nevertheless, a recent food poisoning incident prompted a european food safety authority review which argued that b. thuringiensis poses a health risk equivalent to b. cere ...201728645183
assembly and function of the bacillus anthracis s-layer.bacillus anthracis, the anthrax agent, is a member of the bacillus cereus sensu lato group, which includes invasive pathogens of mammals or insects as well as nonpathogenic environmental strains. the genes for anthrax pathogenesis are located on two large virulence plasmids. similar virulence plasmids have been acquired by other b. cereus strains and enable the pathogenesis of anthrax-like diseases. among the virulence factors of b. anthracis is the s-layer-associated protein bsla, which endows ...201728622090
green tea and epigallocatechin-3-gallate are bactericidal against bacillus anthracis.bacillus anthracis, the etiological agent of anthrax, is listed as a category a biothreat agent by the united states centers for disease control and prevention. the virulence of the organism is due to expression of two exotoxins and capsule, which interfere with host cellular signaling, alter host water homeostasis, and inhibit phagocytosis of the pathogen, respectively. concerns regarding the past and possible future use of b. anthracis as a bioterrorism agent have resulted in an impetus to dev ...201728605495
targeting bacillus anthracis toxicity with a genetically selected inhibitor of the pa/cmg2 protein-protein interaction.the protein-protein interaction between the human cmg2 receptor and the bacillus anthracis protective antigen (pa) is essential for the transport of anthrax lethal and edema toxins into human cells. we used a genetically encoded high throughput screening platform to screen a siclopps library of 3.2 million cyclic hexapeptides for inhibitors of this protein-protein interaction. unusually, the top 3 hits all contained stop codons in the randomized region of the library, resulting in linear rather ...201728596569
requirements for the development of bacillus anthracis spore reference materials used to test detection systems.bacillus anthracis spores have been used as biological weapons and the possibility of their further use requires surveillance systems that can accurately and reliably detect their presence in the environment. these systems must collect samples from a variety of matrices, process the samples, and detect the spores. the processing of the sample may include removal of inhibitors, concentration of the target, and extraction of the target in a form suitable for detection. suitable reference materials ...201727274929
the use of xenosurveillance to detect human bacteria, parasites, and viruses in mosquito bloodmeals.infectious disease surveillance is hindered by several factors, including limited infrastructure and geographic isolation of many resource-poor regions. in addition, the complexities of sample acquisition, processing, and analysis, even in developed regions, can be rate limiting. therefore, new strategies to survey human populations for emerging pathogens are necessary. xenosurveillance is a method that utilizes mosquitoes as sampling devices to search for genetic signatures of pathogens in vert ...201728722623
the fluorocycline tp-271 is efficacious in models of aerosolized bacillus anthracis infection in balb/c mice and cynomolgus macaques.the fluorocycline tp-271 was evaluated in mouse and non-human (nhp) primate models of inhalational anthrax. balb/c mice were exposed by nose-only aerosol to 18 - 88 ld50bacillus anthracis ames spores. when 21 days of once-daily dosing was initiated at 24 hours post-challenge (post-exposure prophylaxis, pep), survival for the 3, 6, 12 and 18 mg/kg tp-271 groups was 90%, 95%, 95%, and 84%, respectively. when 21 days of dosing was initiated at 48 hours post-challenge (treatment, tx) survival for th ...201728784679
correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the av7909 anthrax vaccine candidate.the anthrax vaccine candidate av7909 is being developed as a next generation vaccine for a post-exposure prophylaxis (pep) indication against anthrax. av7909 consists of the anthrax vaccine adsorbed (ava, biothrax®) bulk drug substance adjuvanted with the immunostimulatory oligodeoxynucleotide (odn) compound, cpg 7909. the addition of cpg 7909 to ava enhances both the magnitude and the kinetics of antibody responses in animals and human subjects, making av7909 a suitable next-generation vaccine ...201728774566
bacillus anthracis peptidoglycan integrity is disrupted by the chemokine cxcl10 through the ftse/x complex.the antimicrobial activity of the chemokine cxcl10 against vegetative cells of bacillus anthracis occurs via both bacterial ftse/x-dependent and-independent pathways. previous studies established that the ftse/x-dependent pathway was mediated through interaction of the n-terminal region(s) of cxcl10 with a functional ftse/x complex, while the ftse/x-independent pathway was mediated through the c-terminal α-helix of cxcl10. both pathways result in cell lysis and death of b. anthracis. in other ba ...201728496437
ten genome sequences of human and livestock isolates of bacillus anthracis from the country of georgia.bacillus anthracis causes the acute fatal disease anthrax, is a proven biological weapon, and is endemic in georgia, where human and animal cases are reported annually. here, we present whole-genome sequences of 10 historical b. anthracis strains from georgia.201728495766
high stringency evaluation of the inactivation / exclusion efficacy of a maldi-tof ms chemical extraction method, with filtration of extract through 0.1 µm filters, on bacillus anthracis vollum vegetative cells and spores.a previous report indicated that a formic acid chemical extraction method for the preparation of protein extracts for matrix-assisted laser desorption time-of-flight mass spectrometry (maldi-tof ms) identification, with filtration of extracts through 0.2 μm regenerated cellulose (rc) filters, would not reliably inactivate or exclude bacillus anthracis vollum cells or spores when tested under high stringency conditions. b. anthracis was recovered from 13/36 extracts (3/18 from vegetative cell ext ...201728481931
obiltoxaximab: adding to the treatment arsenal for bacillus anthracis infection.to review the safety and efficacy of obiltoxaximab, a monoclonal antibody indicated for the treatment of bacillus anthracis inhalational anthrax in adult and pediatric patients.201728573869
elucidation of the recognition sequence of sortase b from bacillus anthracis by using a newly developed liquid chromatography-mass spectrometry-based method.sortases are enzymes that are responsible for the attachment of secreted proteins to the cell wall of gram-positive bacteria. hereby, the sortases recognize short, five-residue amino acid sequences present in the target proteins and fuse them to the peptidoglycan layer via a transpeptidation reaction, creating a new peptide bond between the c-terminus of the recognition sequence and the cell wall. the transpeptidation activity of sortases is widely used in protein engineering for modification of ...201728475305
interactions between quinolones and bacillus anthracis gyrase and the basis of drug resistance.gyrase appears to be the primary cellular target for quinolone antibacterials in multiple pathogenic bacteria, including bacillus anthracis, the causative agent of anthrax. given the significance of this type ii topoisomerase as a drug target, it is critical to understand how quinolones interact with gyrase and how specific mutations lead to resistance. however, these important issues have yet to be addressed for a canonical gyrase. therefore, we utilized a mechanistic approach to characterize i ...201728708938
a single nucleotide polymorphism is involved in regulation of growth and spore formation of bacillus anthracis pasteur ii strain.anthrax toxins and capsules, which are encoded by genes located on pxo1 and pxo2, respectively, are major virulence factors of bacillus anthracis. our previous studies demonstrated that exposure to high-temperatures is unable to abolish the pxo1 plasmid of the pasteur ii strain, but the growth of the strain was obviously slower than that of the sterne strain and wild-type virulent strain. to elucidate a potential regulatory mechanism of slowing growth, we employed comparative genome and bioinfor ...201728702375
biochemical characterization of the gtp-sensing protein, cody of bacillus anthracis.the pleiotropism of the gtp-sensing transcriptional regulator cody is evident by the gamut of processes that it regulates in almost all low g+c gram-positive bacteria, including general metabolism, biosynthesis of some amino acids and transport systems, nitrogen uptake, sporulation, biofilm formation, motility and virulence. the role of cody in virulence has been established in bacillus anthracis, the top rated bioterrorism agent. in this study, we investigated the biochemical attributes of this ...201728472295
comparative analysis of the sensitivity of metagenomic sequencing and pcr to detect a biowarfare simulant (bacillus atrophaeus) in soil samples.to evaluate the sensitivity of high-throughput dna sequencing for monitoring biowarfare agents in the environment, we analysed soil samples inoculated with different amounts of bacillus atrophaeus, a surrogate organism for bacillus anthracis. the soil samples considered were a poorly carbonated soil of the silty sand class, and a highly carbonated soil of the silt class. control soil samples and soil samples inoculated with 10, 103, or 105 cfu were processed for dna extraction. about 1% of the d ...201728472119
unexpected relations of historical anthrax strain.in 1998, it was claimed that an 80-year-old glass tube intentionally filled with bacillus anthracis and embedded in a sugar lump as a wwi biological weapon still contained viable spores. today, genome sequencing of three colonies isolated in 1998 and subjected to phylogenetic analysis surprisingly identified a well-known b. anthracis reference strain isolated in the united states in 1981, pointing to accidental laboratory contamination.importance next-generation sequencing and subsequent phyloge ...201728442608
anti-proliferative role of recombinant lethal toxin of bacillus anthracis on primary mammary ductal carcinoma cells revealing its therapeutic potential.bacillus anthracis secretes three secretary proteins; lethal factor (lf), protective antigen (pa) and edema factor (ef). the lf has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (mapk) signaling pathway. evaluation of therapeutic potential of recombinant lf (rlf), recombinant pa (rpa) and lethal toxin (rlf + rpa = letx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells ...201728415766
preparation and characterization of expanded graphite/metal oxides for antimicrobial application.composite materials based on expanded graphite (eg) and metal oxide (mo) particles was prepared by an explosive combustion and blending method. the objective of the study was to develop eg impregnated with metal oxide particulates (ag2o, cuo and zno) and evaluate the level of protection the materials conferred against biological agents. the physical properties of the eg/mo composites were examined using sem, edx and xrd spectroscopy, and the results indicated that the mo particles were incorpora ...201728415384
rapid detection of bacillus anthracis blood stream infections using a novel assay in the genexpert system.background.bacillus anthracis is a tier1 select agent with the potential to quickly cause severe disease. rapid identification of this pathogen may accelerate treatment and reduce mortality in the event of a bioterrorism attack. we developed a rapid and sensitive assay to detect b. anthracis bacteremia using a system that is suitable for point of care testing.methods. a filter-based cartridge that included both sample processing and pcr amplification functions was loaded with all reagents needed ...201728747367
evaluation of lumazine synthase from bacillus anthracis as a presentation platform for polyvalent antigen display.polyvalent antigen display is an effective strategy to enhance the immunogenicity of subunit vaccines by clustering them in an array-like manner on a scaffold system. this strategy results in a higher local density of antigens, increased high avidity interactions with b cells and other antigen presenting cells, and therefore a more effective presentation of vaccine antigens. in the present study, we used lumazine synthase (ls), an icosahedral symmetry capsid derived from bacillus anthracis, as a ...201728736824
tlr sensing of bacterial spore-associated rna triggers host immune responses with detrimental effects.the spores of pathogenic bacteria are involved in host entry and the initial encounter with the host immune system. how bacterial spores interact with host immunity, however, remains poorly understood. here, we show that the spores of bacillus anthracis (ba), the etiologic agent of anthrax, possess an intrinsic ability to induce host immune responses. this immunostimulatory activity is attributable to high amounts of rna present in the spore surface layer. rna-sensing tlrs, tlr7, and tlr13 in mi ...201728400473
deterministic models of inhalational anthrax in new zealand white rabbits.computational models describing bacterial kinetics were developed for inhalational anthrax in new zealand white (nzw) rabbits following inhalation of ames strain b. anthracis. the data used to parameterize the models included bacterial numbers in the airways, lung tissue, draining lymph nodes, and blood. initial bacterial numbers were deposited spore dose. the first model was a single exponential ordinary differential equation (ode) with 3 rate parameters that described mucociliated (physical) c ...201724527843
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