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synthesis and in vitro efficacy studies of silver carbene complexes on biosafety level 3 bacteria.a series of n-heterocyclic carbene silver complexes have been synthesized and tested against the select group of bio-safety level 3 bacteria burkholderia pseudomallei, burkholderia mallei, bacillus anthracis, methicillin-resistant staphylococcus aureus and yersinia pestis. minimal inhibitory concentrations, minimal bactericidal and killing assays demonstrated the exceptional efficacy of the complexes against these potentially weaponizable pathogens.200920160993
protein crystal engineering of ypac-iv using the strategy of excess charge reduction.the class iv adenylyl cyclase from yersinia pestis has been engineered by site-specific mutagenesis to facilitate crystallization at neutral ph. the wild-type enzyme crystallized only below ph 5, consistent with the observation of a carboxyl-carboxylate h bond in a crystal contact in the refined structure 2fjt. based on that unliganded structure at 1.9 a resolution, two different approaches were tested with the goal of producing a higher-ph crystal needed for inhibitor complexation and mechanist ...200920160955
dendritic cell targeted hiv gag protein vaccine provides help to a dna vaccine including mobilization of protective cd8+ t cells.to improve the efficacy of t cell-based vaccination, we pursued the principle that cd4(+) t cells provide help for functional cd8(+) t cell immunity. to do so, we administered hiv gag to mice successively as protein and dna vaccines. to achieve strong cd4(+) t cell immunity, the protein vaccine was targeted selectively to dec-205, a receptor for antigen presentation on dendritic cells. this targeting helped cd8(+) t cell immunity develop to a subsequent dna vaccine and improved protection to int ...201020160099
the yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague.iron acquisition from the host is an important step in the pathogenic process. while yersinia pestis has multiple iron transporters, the yersiniabactin (ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. in this study, we determined that the ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the ybt system for virulence in mouse models of bubonic and pneumonic plague. y. pestis mutants unable ...201020160020
recent findings regarding maintenance of enzootic variants of yersinia pestis in sylvatic reservoirs and their significance in the evolution of epidemic plague.despite the widespread presence of bubonic plague in sylvatic reservoirs throughout the world, the causative agent (yersinia pestis) evolved in its present form within the last 20,000 years from enteropathogenic yersinia pseudotuberculosis. comparison of the genomes from the two species revealed that y. pestis possesses only a few unique plasmid-encoded genes that contribute to acute disease, whereas this organism has lost about 13% of the chromosomal genes that remain active in y. pseudotubercu ...201020158336
study on the movement of rattus rattus and evaluation of the plague dispersion in madagascar.plague affects mainly the rural areas in the central highlands of madagascar. rattus rattus is the main rodent host of yersinia pestis in these localities. since the introduction of plague, endemic foci have continued to expand, and spatiotemporal variability in the distribution of human plague has been observed. to assess the movements of r. rattus and evaluate the risk of dispersion of the disease, a field study at the scale of the habitats (houses, hedges of sisals, and rice fields) in the pl ...201020158335
plague in mongolia.mongolia is a country of central asia that occupies 1,564,116 km(2) and has a population of 2.7 million people. the geography of mongolia is varied and has a continental climate. plague, caused by the bacterium yersinia pestis, is enzootic in wild rodent populations over large rural areas of mongolia. natural plague foci have occurred over 28.3% of mongolia, and 47.1% of these foci are highly active. highly active plague foci exist mainly in the western part of mongolia. a total of 27% of all pl ...201020158334
consumption of baits containing raccoon pox-based plague vaccines protects black-tailed prairie dogs (cynomys ludovicianus).baits containing recombinant raccoon poxvirus (rcn) expressing plague antigens (fraction 1 [f1] and a truncated form of the v protein-v307) were offered for voluntary consumption several times over the course of several months to a group of 16 black-tailed prairie dogs (cynomys ludovicianus). for comparison, another group of prairie dogs (n = 12) was injected subcutaneously (sc) (prime and boost) with 40 microg of f1-v fusion protein absorbed to alum, a vaccine-adjuvant combination demonstrated ...201020158332
rodent and flea abundance fail to predict a plague epizootic in black-tailed prairie dogs.small rodents are purported to be enzootic hosts of yersinia pestis and may serve as sources of infection to prairie dogs or other epizootic hosts by direct or flea-mediated transmission. recent research has shown that small rodent species composition and small rodent flea assemblages are influenced by the presence of prairie dogs, with higher relative abundance of both small rodents and fleas at prairie dog colony sites compared to grasslands without prairie dogs. however, it is unclear if incr ...201020158331
mountain plover responses to plague in montana.plague is a bacterial (yersinia pestis) disease that causes epizootic die-offs in black-tailed prairie dog (cynomys ludovicianus) populations in the north american great plains. through their grazing and burrowing, prairie dogs modify vegetation and landscape structure on their colonies in ways that affect other grassland species. plague epizootics on prairie dog colonies can have indirect effects on species associated with colonies. the mountain plover (charadrius montanus) preferentially nests ...201020158330
enzootic plague reduces black-footed ferret (mustela nigripes) survival in montana.black-footed ferrets (mustela nigripes) require extensive prairie dog colonies (cynomys spp.) to provide habitat and prey. epizootic plague kills both prairie dogs and ferrets and is a major factor limiting recovery of the highly endangered ferret. in addition to epizootics, we hypothesized that enzootic plague, that is, presence of disease-causing yersinia pestis without any noticeable prairie dog die off, may also affect ferret survival. we reduced risk of plague on portions of two ferret rein ...201020158329
vector control improves survival of three species of prairie dogs (cynomys) in areas considered enzootic for plague.plague causes periodic epizootics that decimate populations of prairie dogs (pds) (cynomys), but the means by which the causative bacterium (yersinia pestis) persists between epizootics are poorly understood. plague epizootics in pds might arise as the result of introductions of y. pestis from sources outside pd colonies. however, it remains possible that plague persists in pds during interepizootic periods and is transmitted at low rates among highly susceptible individuals within and between t ...201020158328
disease limits populations: plague and black-tailed prairie dogs.plague is an exotic vector-borne disease caused by the bacterium yersinia pestis that causes mortality rates approaching 100% in black-tailed prairie dogs (cynomys ludovicianus). we mapped the perimeter of the active portions of black-tailed prairie dog colonies annually between 1999 and 2005 at four prairie dog colony complexes in areas with a history of plague, as well as at two complexes that were located outside the distribution of plague at the time of mapping and had therefore never been a ...201020158327
[principles of speciation of the plague causative agent yersinia pestis: gradualism or saltation?].the saltation origin of the causative agent of the plague yersinia pestis from the pseudotuberculosis microbe y. pseudotuberculosis o:1b has been proclaimed in recent investigations on molecular genetics. the speciation process in this case is proposed to be connected with horizontal inclusion of exogenous genetic structures (such as specific plasmids pfra and ppst) into the genome of the ancestral form. the alternative "darwinian" model of the gradual origin of the plague agent is proposed base ...200920146413
[evaluation of the protection efficiency of secretory antibodies in experimental yersinia infection in guinea-pigs immunized with polyvalent vaccine against this infection].the paper presents the results of experiments to elucidate the protection efficiency of secretory antibodies via parenteral and oral inoculation with pathogenic yersinia in guinea pigs immunized with a polyvalent yersiniasis vaccine designed on the basis of the pseudotuberculosis microbial strain that synthesizes the f1 antigen of a plague microbe. immunization of guinea pigs with the polyvalent yersiniasis vaccine protects experimental animals against pseudotuberculosis, intestinal yersiniasis, ...200920146406
comparative analyses of transcriptional profiles in mouse organs using a pneumonic plague model after infection with wild-type yersinia pestis co92 and its braun lipoprotein mutant.we employed murine genechips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (wt) y. pestis co92 and its braun lipoprotein (deltalpp) mutant with reduced virulence. these organs showed differential transcriptional responses to infection with wt y. pestis, but the overall host functional processes affected were similar across all three tissues. gene expression alterations were found in inflammation, cyto ...201020145715
[development of a universal primers pcr-coupled liquid bead array to detect biothreat bacteria].to develop a fast, high-throughput screening method with suspension array technique for simultaneous detection of biothreat bacteria.200920137470
a conserved pmk-1/p38 mapk is required in caenorhabditis elegans tissue-specific immune response to yersinia pestis infection.yersinia pestis has acquired a variety of complex strategies that enable the bacterium to overcome defenses in different hosts and ensure its survival and successful transmission. a full-genome microarray analysis on caenorhabditis elegans infected with y. pestis shows enrichment in genes that are markers of innate immune responses and regulated by a conserved pmk-1/p38 mapk. consistent with a role in regulating expression of immune effectors, inhibition of pmk-1/p38 by mutation or rna interfere ...201020133945
rapid field detection assays for bacillus anthracis, brucella spp., francisella tularensis and yersinia pestis.rapid detection is essential for timely initiation of medical post-exposure prophylactic measures in the event of intentional release of biological threat agents. we compared real-time pcr assay performance between the applied biosystems 7300/7500 and the razor instruments for specific detection of the causative agents of anthrax, brucellosis, tularemia and plague. furthermore, an assay detecting bacillus thuringiensis, a bacillus anthracis surrogate, was developed for field-training purposes. a ...201120132255
the art of bacterial warfare. 201020128224
encapsulation into amphiphilic polyanhydride microparticles stabilizes yersinia pestis antigens.the design of biodegradable polymeric delivery systems based on polyanhydrides that would provide for improved structural integrity of yersinia pestis antigens was the main goal of this study. accordingly, the full-length y. pestis fusion protein (f1-v) or a recombinant y. pestis fusion protein (f1(b2t1)-v10) was encapsulated and released from microparticles based on 1,6-bis(p-carboxyphenoxy)hexane (cph) and sebacic acid (sa) copolymers and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (cpteg) and c ...201020123135
neutrophils are important in early control of lung infection by yersinia pestis.in this paper we evaluate the role of neutrophils in pneumonic plague. splenic neutrophils from naïve balb/c mice were found to reduce numbers of culturable yersinia pestis strain gb in suspension. a murine, balb/c, intranasal model of pneumonic plague was used in conjunction with in vivo neutrophil ablation, using the gr-1 antibody. this treatment reduced neutrophil numbers without affecting other leukocyte numbers. neutrophil ablated mice exhibited increased bacterial colonisation of the lung ...201020114086
proteomic analysis of iron acquisition, metabolic and regulatory responses of yersinia pestis to iron starvation.the gram-negative bacterium yersinia pestis is the causative agent of the bubonic plague. efficient iron acquisition systems are critical to the ability of y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. we used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the y. pestis strain kim6+ at two phy ...201020113483
identification of ciprofloxacin resistance by simpleprobe, high resolution melt and pyrosequencing nucleic acid analysis in biothreat agents: bacillus anthracis, yersinia pestis and francisella tularensis.the potential for genetic modification of biological warfare agents makes rapid identification of antibiotic resistant strains critical for the implementation of suitable infection control measures. the fluorinated quinolone, ciprofloxacin, is an antibiotic effective for treating bacterial infections by inhibiting the enzyme activity of the dna type ii topoisomerases dna gyrase and topoisomerase iv. the genes that encode the subunits of dna gyrase (gyra and gyrb) and topo iv (par c and pare) con ...201020100564
a yersinia pestis guaba mutant is attenuated in virulence and provides protection against plague in a mouse model of infection.there is a need to develop effective countermeasures for yersinia pestis, the etiologic agent of plague and a potential bioterrorism agent. salmonella and shigella spp. deleted in the guaba genes involved in guanine biosynthesis have been shown to be attenuated in vivo. in this study, we sought to determine whether deletion of the guaba operon would render y. pestis auxotrophic for guanine and avirulent; such a strain could serve as a live attenuated plague vaccine candidate. a y. pestis guaba m ...201020096773
analysis of hmsh and its role in plague biofilm formation.the yersinia pestis hms(+) phenotype is a manifestation of biofilm formation that causes adsorption of congo red and haemin at 26 degrees c but not at 37 degrees c. this phenotype is required for blockage of the proventricular valve of the oriental rat flea and plays a role in transmission of bubonic plague from fleas to mammals. genes responsible for this phenotype are located in three separate operons, hmshfrs, hmst and hmsp. hmsh and hmsf are outer membrane (om) proteins, while the other four ...201020093287
yersinia pestis with regulated delayed attenuation as a vaccine candidate to induce protective immunity against plague.two mutant strains of yersinia pestis kim5+, a deltacrp mutant and a mutant with arabinose-dependent regulated delayed-shutoff crp expression (arac p(bad) crp), were constructed, characterized in vitro, and evaluated for virulence, immunogenicity, and protective efficacy in mice. both strains were highly attenuated by the subcutaneous (s.c.) route. the 50% lethal doses (ld(50)s) of the deltacrp and arac p(bad) crp mutants were approximately 1,000,000-fold and 10,000-fold higher than those of y. ...201020086087
comparison of mouse, guinea pig and rabbit models for evaluation of plague subunit vaccine f1+rv270.in this study, a new subunit vaccine that comprised native f1 and recombinant rv270 was evaluated for protective efficacy using mouse, guinea pig and rabbit models in comparison with the live attenuated vaccine ev76. complete protection against challenging with 10(6) colony-forming units (cfu) of virulent yersinia pestis strain 141 was observed for mice immunized with the subunit vaccines and ev76 vaccine. in contrast, the subunit vaccine recipes vii (f1-20 microg+rv270-10 microg) and ix (f1-40 ...201020079562
the smpb-ssra mutant of yersinia pestis functions as a live attenuated vaccine to protect mice against pulmonary plague infection.the bacterial smpb-ssra system is a highly conserved translational quality control mechanism that helps maintain the translational machinery at full capacity. here we present evidence to demonstrate that the smpb-ssra genes are required for pathogenesis of yersinia pestis, the causative agent of plague. we found that disruption of the smpb-ssra genes leads to reduction in secretion of the type iii secretion-related proteins yopb, yopd, and lcrv, which are essential for virulence. consistent with ...201020065026
[study of ability to form biofilms in main and non-main subspecies of yersinia pestis strains].to compare biofilm formation in main and non-main subspecies of yersinia pestis strains as well as in yersinia pseudotuberculosis strains and to study influence of different genes on expression of this characteristic in different subspecies of y. pestis.200920063786
genome sequence of the deep-rooted yersinia pestis strain angola reveals new insights into the evolution and pangenome of the plague bacterium.to gain insights into the origin and genome evolution of the plague bacterium yersinia pestis, we have sequenced the deep-rooted strain angola, a virulent pestoides isolate. its ancient nature makes this atypical isolate of particular importance in understanding the evolution of plague pathogenicity. its chromosome features a unique genetic make-up intermediate between modern y. pestis isolates and its evolutionary ancestor, y. pseudotuberculosis. our genotypic and phenotypic analyses led us to ...201020061468
identification of in vivo-induced conserved sequences from yersinia pestis during experimental plague infection in the rabbit.in an effort to identify the novel virulence determinants of yersinia pestis, we applied the gene "discovery" methodology, in vivo-induced (ivi) antigen technology, to detect genes upregulated during infection in a laboratory rabbit model for bubonic plague. after screening over 70,000 escherichia coli clones of y. pestis dna expression libraries, products from 25 loci were identified as being seroreactive to reductively adsorbed, pooled immune serum. upon sequence analysis of the predicted ivi ...201020055582
[efficacy of levofloxacin, lomefloxacin and moxifloxacin vs. other fluoroquinolones in experimental plague due to fi+ and fi- strains of yersinia pestis in albino mice].activity of levofloxacin, lomefloxacin and moxifloxacin against 20 fi+ and 20 fi- strains of yersinia pestis was studied. it was shown that the strains were highly susceptible to the fluoroquinolones. in the experiments on mice subcutaneously infected with suspension of strains 231 fi+ and 231 fi- of y. pestis in a dose of about 1000 ld50 (10(4) microbial cells) the ed50 of levofloxacin and moxifloxacin was 5.5-14.0 mg/kg independent of the infective culture phenotype and that of lomefloxacin wa ...200920052916
development of multitarget real-time pcr for the rapid, specific, and sensitive detection of yersinia pestis in milk and ground beef.real-time pcr has been used previously to detect yersinia pestis; this study applies this rapid, specific, and sensitive nucleic acid-based method to the detection and quantitation of y. pestis specifically in food. five sets of primers and corresponding taqman dual-labelled fluorogenic hybridization probes for y. pestis were designed and optimized for specificity testing using genomic dna from 71 bacterial strains. four y. pestis -specific primer and probe sets were developed, based on the viru ...201020051199
yersinia pestis or: the dyschromatopsic flea. 200820050418
[genomic polymorphism of the main subspecies of the plague agent strains].genomic fingerprinting analysis of plague agent strains of the main subspecies isolated in natural foci of various types in the russian federation and neighboring countries suggests their genetic polymorphism, while they are similar in phenotypic properties. the strains of the main subspecies, y. pesis subsp. pestis, fall into four genetic variants, each of them being associated with specific carrier species. the conserved genomic fingerprinting profile of each genovariant of y. pesis subsp. pes ...200920050162
[molecular mechanisms of the plague pathogenic agent interaction with invertebrates].microbe russian anti-plague research institute, saratov, russia the literature data and experimental results of the authors on the molecular basis of plague agent interaction with invertebrates are discussed. the details of the plague agent life cycle, its genome organization, and molecular genetic mechanisms of its survival in flea vector and on the nematode cuticule are discussed. the experimental data about the ability to form biofilms at abiotic and biotic surfaces in the yersinia pestis str ...200920050160
the effects of substituted cyclodextrins on the colloidal and conformational stability of selected proteins.the effects of various types of substituted and nonsubstituted cyclodextrins (cds) on the physical and colloidal stability of three different proteins were studied to further ascertain the mechanism by which cyclodextrins stabilize proteins. the three proteins examined in this study are the clostridium difficile toxoid a, yersinia pestis low-calcium-response v or v antigen (lcrv), and fibroblast growth factor 10 (fgf-10). these three pharmaceutically relevant proteins differ in molecular weight, ...201020049940
yersinia ironomics: comparison of iron transporters among yersinia pestis biotypes and its nearest neighbor, yersinia pseudotuberculosis.although yersinia pestis epidemic biovars and yersinia pseudotuberculosis are recently diverged, highly related species, they cause different diseases via disparate transmission routes. since iron transport systems are important for iron acquisition from hosts and for survival in the environment, we have analyzed potential iron transport systems encoded by epidemic and non-epidemic or endemic strains of y. pestis as well as two virulent y. pseudotuberculosis strains. computational biology analys ...201020049509
genomic characterization of the yersinia genus.new dna sequencing technologies have enabled detailed comparative genomic analyses of entire genera of bacterial pathogens. prior to this study, three species of the enterobacterial genus yersinia that cause invasive human diseases (yersinia pestis, yersinia pseudotuberculosis, and yersinia enterocolitica) had been sequenced. however, there were no genomic data on the yersinia species with more limited virulence potential, frequently found in soil and water environments.201020047673
feedback inhibition in the phoq/phop signaling system by a membrane peptide.the phoq/phop signaling system responds to low magnesium and the presence of certain cationic antimicrobial peptides. it regulates genes important for growth under these conditions, as well as additional genes important for virulence in many gram-negative pathogens. phoq is a sensor kinase that phosphorylates and activates the transcription factor phop. since feedback inhibition is a common theme in stress-response circuits, we hypothesized that some members of the phop regulon may play such a r ...200920041203
phosphoglucomutase of yersinia pestis is required for autoaggregation and polymyxin b resistance.yersinia pestis, the causative agent of plague, autoaggregates within a few minutes of cessation of shaking when grown at 28 degrees c. to identify the autoaggregation factor of y. pestis, we performed mariner-based transposon mutagenesis. autoaggregation-defective mutants from three different pools were identified, each with a transposon insertion at a different position within the gene encoding phosphoglucomutase (pgma; y1258). targeted deletion of pgma in y. pestis kim5 also resulted in loss ...201020028810
validation of inverse seasonal peak mortality in medieval plagues, including the black death, in comparison to modern yersinia pestis-variant diseases.recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval black death (and subsequent "plagues") and modern empirical y. pestis plague data, most of which is derived from the indian and chinese plague outbreaks of a.d. 1900+/-15 years. previous works have noted apparent differences in seasonal mortality peaks during black death outbreaks versus peaks of bubonic and pneumonic plagues attributed to y. pestis infection, but have not provided spatiotemporal s ...200920027294
systemic but not local infections elicit immunosuppressive il-10 production by natural killer cells.surviving infection represents a balance between the proinflammatory responses needed to eliminate the pathogen, and anti-inflammatory signals limiting damage to the host. il-10 is a potent immunosuppressive cytokine whose impact is determined by the timing and localization of release. we show that nk cells rapidly express il-10 during acute infection with diverse rapidly disseminating pathogens. the proinflammatory cytokine il-12 was necessary and sufficient for nk cell induction of il-10. nk c ...200920006839
regulatory natural killer cells: new players in the il-10 anti-inflammatory response.natural killer (nk) cells boost immune defense via their cytolytic activity and their capacity to produce interferon-gamma. now perona-wright et al. (2009), in this issue of cell host & microbe, show that nk cells can also dampen immune responses to diverse pathogens via secretion of the anti-inflammatory cytokine interleukin-10. remarkably, this immunosuppressive activity only occurs during systemic infections.200920006835
a rapid multiplex assay for nucleic acid-based diagnostics.we have developed a rapid (under 4 hours), multiplex, nucleic acid assay, adapted to a microsphere array detection platform. we call this assay multiplex oligonucleotide ligation-pcr (mol-pcr). unlike other ligation-based assays that require multiple steps, our protocol consists of a single tube reaction, followed by hybridization to a luminex microsphere array for detection. we demonstrate the ability of this assay to simultaneously detect diverse nucleic acid signatures (e.g., unique sequences ...201020006656
amino acid residues 196-225 of lcrv represent a plague protective epitope.lcrv, a protein that resides at the tip of the type iii secretion needles of yersinia pestis, is the single most important plague protective antigen. earlier work reported monoclonal antibody mab 7.3, which binds a conformational epitope of lcrv and protects experimental animals against lethal plague challenge. by screening monoclonal antibodies directed against lcrv for their ability to protect immunized mice against bubonic plague challenge, we examined here the possibility of additional prote ...201020005318
biogenesis of yersinia pestis psaa in recombinant attenuated salmonella typhimurium vaccine (rasv) strain.yersinia pestis psaa is an adhesin important for the establishment of bacterial infection. psaa synthesis requires the products of the psaefabc genes. here, by prediction analysis, we identified a psaa signal sequence with two signal peptidase (spase) cleavage sites, type-i and type-ii (spase-i and spase-ii). by edman degradation and site-directed mutagenesis, the precise site for one of these spase-i psaa cleavage sites was located between alanine and serine at positions 31 and 32, respectively ...201020002189
[evaluation of the immunoregulatory activity of neutrophilokine fractions in a macrophage model].a procedure was proposed to evaluate the immunoregulatory activity of neutrophilokine fractions on a model of macrophages. it was established that all the fractions studied did not affect the absorptive capacity of these cells in both primary and secondary immune responses. at the same time, the majority of neutrophilokine fractions modulated the killer activity of macrophages: they potentiated or inhibited it. the proposed procedure for evaluating the regulatory effect of individual neutrophilo ...200920000114
experimental infection of the chick embryo with virulent and avirulent pasteurella pestis. 194419970765
yopr impacts type iii needle polymerization in yersinia species.a hallmark of yersinia type iii machines is the presence of needles extending from the bacterial surface. needles perform two functions, serving as the conduits for the transport of effectors into immune cells but also acting as a sensor. the polymerized needle protein, yscf, is thought to perceive threshold levels of environmental calcium ions to trigger secretion. yopr (ysch) is a gene downstream of yscefg, encoding the chaperones and principal building blocks of the needle. here we investigat ...201019968786
inferring host-parasite relationships using stable isotopes: implications for disease transmission and host specificity.identifying the roles of different hosts and vectors is a major challenge in the study of the ecology of diseases caused by multi-host pathogens. intensive field studies suggested that grasshopper mice (onychomys leucogaster) help spread the bacterium that causes plague (yersinia pestis) in prairie dog colonies by sharing fleas with prairie dogs (cynomys ludovicianus); yet conclusive evidence that prairie dog fleas (oropsylla hirsuta) feed on grasshopper mice is lacking. using stable nitrogen is ...200919967881
enhanced matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of bacteriophage major capsid proteins with beta-mercaptoethanol pretreatment.bacteriophage (phage) proteins have been analyzed previously with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms). however, analysis of phage major capsid proteins (mcps) has been limited by the ability to reproducibly generate ions from mcp monomers. while the acidic conditions of maldi-tof ms sample preparation have been shown to aid in disassembly of some phage capsids, many require further treatment to successfully liberate mcp monomers. the findin ...201019967739
wild felids as hosts for human plague, western united states.plague seroprevalence was estimated in populations of pumas and bobcats in the western united states. high levels of exposure in plague-endemic regions indicate the need to consider the ecology and pathobiology of plague in nondomestic felid hosts to better understand the role of these species in disease persistence and transmission.200919961691
bacterial communities associated with flea vectors of plague.the microbial flora associated with fleas may affect their ability to transmit specific pathogens, including yersinia pestis, and also could be used to develop paratransgenesis-based approaches to interfere with transmission. to begin addressing this hypothesis, the microbial flora associated with the relatively efficient y. pestis vectors xenopsylla cheopis (rothschild) (siphonaptera: pulicidae) and oropsyllamontana (baker) (siphonaptera: ceratophyllidae), and the inefficient vector ctenocephal ...200919960708
[study on the natural foci of marmota himalayana plague in sichuan province].to explore the existence of natural foci on marmota himalayana plague in sichuan province and to provide basis for prevention and control of the disease.200919957628
blacmy-2-positive inca/c plasmids from escherichia coli and salmonella enterica are a distinct component of a larger lineage of plasmids.large multidrug resistance plasmids of the a/c incompatibility complex (inca/c) have been found in a diverse group of gram-negative commensal and pathogenic bacteria. we present three completed sequences from inca/c plasmids that originated from escherichia coli (cattle) and salmonella enterica serovar newport (human) and that carry the cephamycinase gene blacmy-2. these large plasmids (148 to 166 kbp) share extensive sequence identity and synteny. the most divergent plasmid, peh4h, has lost sev ...201019949054
synthetic {beta}-(1->6)-linked n-acetylated and nonacetylated oligoglucosamines used to produce conjugate vaccines for bacterial pathogens.vaccines for pathogens usually target strain-specific surface antigens or toxins, and rarely is there broad antigenic specificity extending across multiple species. protective antibodies for bacteria are usually specific for surface or capsular antigens. beta-(1-->6)-poly-n-acetyl-d-glucosamine (pnag) is a surface polysaccharide produced by many pathogens, including staphylococcus aureus, escherichia coli, yersinia pestis, bordetella pertussis, acinetobacter baumannii, and others. protective ant ...201019948836
prospects for new plague vaccines.the potential application of yersinia pestis for bioterrorism emphasizes the urgent need to develop more effective vaccines against airborne infection. the current status of plague vaccines has been reviewed. the present emphasis is on subunit vaccines based on the f1 and lcrv antigens. these provide good protection in animal models but may not protect against f1 strains with modifications to the type iii secretion system. the duration of protection against pneumonic infection is also uncertain. ...200919943765
ectoparasites (sucking lice, fleas and ticks) of small mammals in southeastern kenya.during 1998-2000, at least 14 species (n = 309) of small mammals were live-trapped and examined for ectoparasites in moist forests of the taita and shimba hills and drier savannah habitats of nguruman, southeastern kenya. ectoparasites were recorded from 11 species of mammals. five species of sucking lice [hoplopleura inexpectans johnson, h. intermedia kellogg & ferris, polyplax reclinata (nitzsch), p. waterstoni bedford and schizophthirus graphiuri ferris], six species of fleas (ctenophthalmus ...200919941604
long-term observation of subunit vaccine f1-rv270 against yersinia pestis in mice.long-term protection and antibody response for the subunit vaccine f1-rv270 were determined by using the mouse model. antibodies to f1 and rv270 were still detectable over a period of 518 days. the complete protection against lethal challenge of yersinia pestis could be achieved up to day 518 after primary immunization.201019940042
new multispecific array as a tool for electrochemical impedance spectroscopy-based biosensing.using electrochemical impedance spectroscopy (eis) for biosensing applications typically requires repetitive experiments. to address this need, we have designed a multispecific electrochemical array with eight individually addressable 2mm-diameter gold working electrodes for rapid biosensing data accumulation by eis in the presence of redox agent. the array allows to incorporate multiple negative controls in the course of a single binding experiment, as well as to perform parallel identical expe ...201019939660
yersinia pestis two-component gene regulatory systems promote survival in human neutrophils.human polymorphonuclear leukocytes (pmns, or neutrophils) are the most abundant innate immune cell and kill most invading bacteria through combined activities of reactive oxygen species (ros) and antimicrobial granule constituents. pathogens such as yersinia pestis resist destruction by the innate immune system and are able to survive in macrophages and neutrophils. the specific molecular mechanisms used by y. pestis to survive following phagocytosis by human pmns are incompletely defined. to ga ...201019933831
prevention of bubonic and pneumonic plague using plant-derived vaccines.yersinia pestis, the causative agent of bubonic and pneumonic plague, is an extremely virulent bacterium but there are currently no approved vaccines for protection against this organism. plants represent an economical and safer alternative to fermentation-based expression systems for the production of therapeutic proteins. the recombinant plague vaccine candidates produced in plants are based on the two most immunogenic antigens of y. pestis: the fraction-1 capsular antigen (f1) and the low cal ...201019931370
quantitative anti-f1 and anti-v igg elisas as serological correlates of protection against plague in female swiss webster mice.a recombinant fusion protein composed of yersinia pestis fraction 1 capsule (f1) and virulence-associated v antigen (v) (f1-v) has been developed as the next-generation vaccine against plague. in this study, female swiss webster mice received a single intramuscular vaccination with one of eight doses of the f1-v vaccine and exposed 4 weeks later to either y. pestis co92 or c12 organisms by the subcutaneous or aerosol routes of infection. quantitative anti-f1 and anti-v immunoglobulin g (igg) eli ...201019925906
hamiltonian replica exchange method study of escherichia coli and yersinia pestis hppk.hppk (6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase) catalyzes the transfer of pyrophosphate from atp to hp (6-hydroxymethyl-7,8-dihydropterin). this first reaction in the folate biosynthetic pathway is a potential target for antimicrobial agents. a hamiltonian replica exchange method (hrem) molecular dynamics (md) approach is used, with the goal of improving conformational sampling, whereby multiple copies of the system are run without requiring a large number of system copies. for hppk, ...200919924845
neonatal mucosal immunization with a non-living, non-genetically modified lactococcus lactis vaccine carrier induces systemic and local th1-type immunity and protects against lethal bacterial infection.safe and effective immunization of newborns and infants can significantly reduce childhood mortality, yet conventional vaccines have been largely unsuccessful in stimulating the neonatal immune system. we explored the capacity of a novel mucosal antigen delivery system consisting of non-living, non-genetically modified lactococcus lactis particles, designated as gram-positive enhancer matrix (gem), to induce immune responses in the neonatal setting. yersinia pestis lcrv, used as model protective ...201019924118
cellular fatty acids as chemical markers for differentiation of yersinia pestis and yersinia pseudotuberculosis.gas chromatography (gc) was utilized to investigate the cellular fatty acids (cfas) composition of 141 yersinia pestis isolates from different plague foci of china, and 20 yersinia pseudotuberculosis strains as well.201019912526
detection of yersinia pestis over time in seeded bottled water samples by cultivation on heart infusion agar.the viable persistence of yersinia pestis seeded in bottled spring water was evaluated by performing 2 studies that involved inoculating a total of 21 different test strains into individual 500 ml reservoirs. approximately 2 x 104 cfu/ml of y. pestis was inoculated into each reservoir and held for sampling at 26 degrees c +/- 1 degrees c. in study no. 2, 9 strains (harbin, nepal, unh 1a, unh 1b, ze94, co92, pb6, pb6 dp, and pexu) could no longer be recovered using a plate count assay between 79 ...200919898556
a refrigeration temperature of 4 degrees c does not prevent static growth of yersinia pestis in heart infusion broth.multiple barriers such as inspections, testing, and proper storage conditions are used to minimize the risk of contaminated food. knowledge of which barriers, such as refrigeration, are effective in preventing pathogen growth and persistence, can help direct the focus of efforts during food sampling. in this study, the doubling times were evaluated for 10 strains of yersinia pestis of different genetic background cultured in heart infusion broth (hib) kept at 4 degrees c +/- 1 degrees c under st ...200919898555
immunomodulatory effects of yersinia pestis lipopolysaccharides on human macrophages.in the current study, we investigated the activity of lipopolysaccharide (lps) purified from yersinia pestis grown at either 27 degrees c or 37 degrees c (termed lps-27 and lps-37, respectively). lps-27 containing hexa-acylated lipid a, similar to the lps present in usual gram-negative bacteria, stimulated an inflammatory response in human u937 cells through toll-like receptor 4 (tlr4). lps-37, which did not contain hexa-acylated lipid a, exhibited strong antagonistic activity to the tlr4-mediat ...201019889939
further development of raccoon poxvirus-vectored vaccines against plague (yersinia pestis).in previous studies, we demonstrated protection against plague in mice and prairie dogs using a raccoon pox (rcn) virus-vectored vaccine that expressed the f1 capsular antigen of yersinia pestis. in order to improve vaccine efficacy, we have now constructed additional rcn-plague vaccines containing two different forms of the lcrv (v) gene, including full-length (vfull) and a truncated form (v307). mouse challenge studies with y. pestis strain co92 showed that vaccination with a combination of rc ...200919879228
threshold conditions for the persistence of plague transmission in urban rats.in this article we derive a mathematical expression characterizing the tendency for yersinia pestis, the etiologic agent of plague, to become established in an urban rat population upon introduction, and evaluate this risk for several cities. the expression gives a threshold condition for the persistence of y. pestis transmission in terms of measurable attributes of a local urban rat population: the average flea density and the rat colony size. if the local rat and flea populations exceed this t ...200919878483
effect of fat in ground beef on the growth and virulence plasmid (pyv) stability in yersinia pestis.knowledge of the behavior of yersinia pestis in food may be useful in the event y. pestis is used in a bioterrorism attack on the food supply. however, there are no reports on the growth of plasmid-bearing (pyv) virulent y. pestis in food. the growth of a conditionally virulent pyv-bearing y. pestis kim5 in sterile raw ground beef with 7, 15 and 25% fat content was studied at 0, 4, 10 and 25 degrees c. the y. pestis kim5 did not grow but survived in raw ground beef at 0 and 4 degrees c. in raw g ...201019875186
the enzymic hydrolysis of phloridzin.1. considering previously published data on the velocity of hydrolysis of glucosides by acids, it is shown that phloridzin, judged from the standpoint of the velocity coefficient and the critical increment for hydrolysis, resembles the gamma-fructosides (sucrose, raffinose and melezitose) more closely than it does the normal glucosides (salicin, arbutin, maltose, etc.). 2. previous work on the enzymic hydrolysis of phloridzin shows that it is not hydrolysed by emulsin, but that it is hydrolysed ...193019872565
observations on the infection of chick embryos with bacterium tularense, brucella, and pasteurella pestis.1. comparison of the infections of chick embryos by the chorio-allantoic route indicates that bacterium tularense and brucella suis, abortus, and melitensis exhibit varying degrees of facultative intracellular parasitism. pasteurella pestis is adapted to rapid proliferation and spread in the intercellular fluids. 2. in the early stages of infection bacterium tularense has a marked affinity for growth within ectodermal epithelial cells. brucella suis and brucella abortus differ in their selectivi ...194119871129
studies on the bacteriophage of d'herelle : vi. on the virulence of the overgrowth in the lysed cultures of bacillus pestis caviae (m. t. ii).resistants isolated from the overgrowth of cultures of b. pestis caviae (m. t. ii) lysed by various strains of specific bacteriophage proved to be avirulent when administered to mice by feeding, or by intraperitoneal injection. these cultures remained resistant to the action of bacteriophage so long as they were carried on agar. when transferred to broth, however, one group of resistants, namely, those isolated by means of "weak" phages, became susceptible to lysis after five to seven daily pass ...192619869210
microbic virulence and host susceptibility in paratyphoid-enteritidis infection of white mice : xi. seasonal variation in the susceptibility of different strains of mice to per os infection with the type ii bacillus of mouse typhoid (bacillus pestis caviae). further studies.four unrelated strains of mice were tested over a period of 1 year for their seasonal variation in susceptibility to per os feeding with a culture of bacillus pestis caviae of known virulence. certain consistent fluctuations, determined to be in general agreement with those already recorded in a previous paper, were found and described.192619869113
microbic virulence and host susceptibility in paratyphoid-enteritidis infection of white mice : x. the relative susceptibility of different strains of mice to per os infection with the type ii bacillus of mouse typhoid (bacillus pestis cavlae). further studies.four separate strains of mice have been tested for their relative susceptibility to per os infection with the type ii bacillus of mouse typhoid (bacillus pestis caviae), 300 to 600 individuals of each strain having been employed in the course of 12 months. in confirmation of a previous paper, clear-cut differences in the susceptibility of these strains have been shown to exist. in general, the colored strains were distinctly less resistant than the albino strains.192619869112
microbic virulence and host susceptibility in paratyphoid-enteritidis infection of white mice : ix. the relationship of dosage to mortality rate, survival time, and cage population.epidemics of mouse typhoid set up among the rockefeller institute strain of mice were studied over a period of 6 months. during this time the relationship of cage number of mouse typhoid bacilli to mortality, total population, and survival time was determined. a single virulence titration of the epidemic strain was made, and at the end of the experiment all survivors were examined for evidence of infection. the following conclusions may be drawn for the data here presented. 1. the available dosa ...192619869111
studies on the bacteriophage of d'herelle : iv. concerning the oneness of the bacteriophage.lytic filtrates, active against bacillus dysenterioe shiga, bacillus coli, bacillus pestis cavioe, and staphylococcus respectively, proved to be differently affected by changes in hydrogen ion concentration. anti-staphylococcus lysin was the least resistant of the four, showing deterioration in 3 hours at 7 degrees c. beyond the zone of hydrogen ion concentration limited by c(h) = 6.3 x 10(-5) and c(h) = 1.6 x 10(-9). under the same conditions, the zone of resistance of anti-coli filtrate lay be ...192519869092
microbic virulence and host susceptibility in paratyphoid-enteritidis infection of white mice : vii. seasonal variation in the susceptibility of different strains of mice to per os infection with the type ii bacillus of mouse typhoid (bacillus pestis caviae).seasonal variations are described in the response of five strains of mice to inoculation with the type ii bacillus of mouse typhoid (bacillus pestis caviae). there occurred in the case of all strains a high peak of mortality during the spring, a lower death rate during the summer, and a subsequent autumn rise in the number of deaths.192519868982
microbic virulence and host susceptibility in paratyphoid-enteritidis infection of white mice : vi. the relative susceptibility of different strains of mice to per os infection with the type ii bacillus of mouse typhoid (bacillus pestis caviae).five separate strains of mice have been tested for their relative susceptibility to per os infection with the type ii bacillus of mouse typhoid (bacillus pestis caviae), more than 500 individuals of each strain having been employed in the course of 12 months. clear-cut differences in the susceptibility of these strains to the infection have been shown to exist.192519868981
the virulence of an epidemic strain of bacillus pestis caviae.ever since pasteur's demonstration of the modifying effect of animal passage on the virulence of bacteria, this device has been regarded as of great importance in intensifying infective capacity. it is not often, however, that extensive parallel tests have been made of the power of a microorganism to produce infection in a species of animal which is its natural habitat and under conditions in which the normal as well as artificial portal of entry is employed, and the potency of the microorganism ...192319868759
microbic virulence and host susceptibility in mouse typhoid infection.mice bred at the rockefeller institute vary in their susceptibility to mouse typhoid infection caused by a certain strain of bacillus pestis caviae. this graded variation may be roughly analyzed as follows: in any series infected per os with a fixed dose, 20 to 30 per cent show no sign of infection, no positive blood cultures, and no agglutinins; 5 or 10 per cent present symptoms of disease, positive blood cultures, and then recover with or without homologous agglutinins; 70 or 80 per cent devel ...192319868724
the intestinal flora in mouse typhoid infection.the normal flora of laboratory mice at the rockefeller institute, fed on a bread and milk diet, was determined. bacillus acidophilus and bacillus bifidus outnumber the bacillus coli, bacillus acidi lactici, and bacillus coli communior group about twenty-five to one. white and yellow cocci which may or may not liquefy gelatin are occasionally noted; spirochetal and vibrio forms and yeasts are usually seen in stained preparations. this flora does not change when mice are artificially infected per ...192319868710
experiments on normal and immune mice with a bacillus of mouse typhoid.if live cultures of a mouse strain of bacillus pestis caviae are injected intrapleurally or intraperitoneally into normal mice, there occurs an initial lag in the rate of bacterial multiplication lasting a few hours, followed by a rapid and continued acceleration of growth until the death of the animal. if live cultures of this organism are given per os to normal mice, there occurs an incubation period of 5 to 6 days, after which the animal usually develops symptoms of disease and succumbs. a sm ...192219868658
experimental epidemiology : ii. effect of the addition of healthy mice to a population suffering from mouse typhoid.1. a kind of mouse village was set up into which was introduced a small number of mice fed on a culture of so called mouse typhoid (bacillus pestis cavice of the bacillus paratyphosus b group) bacillus. the spread of the infection so induced to the cages, or "homes," of the other mice was left to accident through the attendant who fed the animals and cleaned the cages. that this means was likely to be sufficient was deduced from the epidemic reported by lynch. a spot map was kept throughout the ...192219868657
immunological distinctions of two strains of the mouse typhoid group isolated during two spontaneous outbreaks among the same stock.two strains of the paratyphoid b-enteritidis group causing separate epidemics of mouse typhoid among 2,500 to 4,000 cancer breeding mice are found to be antigenically different. mouse typhoid i, isolated from the first outbreak, is related but not identical with two strains of enteritidis, while mouse typhoid ii is related to but not identical with the human paratyphoid b strains. in a separate paper in this series, webster has identified mouse typhoid ii strain with bacillus pestis caviae smith ...192219868651
tetraacylated lipopolysaccharide of yersinia pestis can inhibit multiple toll-like receptor-mediated signaling pathways in human dendritic cells.yersinia pestis, the causative agent of plague, showed a temperature-dependent change in lipid a composition, with a reduced degree of acylation when bacteria were grown at 37 degrees c (tetraacylated) versus ambient temperature (hexaacylated).200919863438
fine-scale identification of the most likely source of a human plague infection.we describe an analytic approach to provide fine-scale discrimination among multiple infection source hypotheses. this approach uses mutation-rate data for rapidly evolving multiple locus variable-number tandem repeat loci in probabilistic models to identify the most likely source. we illustrate the utility of this approach using data from a north american human plague investigation.200919861057
absence of inflammation and pneumonia during infection with nonpigmented yersinia pestis reveals a new role for the pgm locus in pathogenesis.yersinia pestis causes primary pneumonic plague in many mammalian species, including humans, mice, and rats. virulent y. pestis strains undergo frequent spontaneous deletion of a 102-kb chromosomal dna fragment, known as the pigmentation (pgm) locus, when grown in laboratory media, yet this locus is present in every virulent isolate. the pgm locus encodes, within a high-pathogenicity island, siderophore biosynthesis genes that are required for growth in the mammalian host when inoculated by peri ...201019841077
effect of mara-like proteins on antibiotic resistance and virulence in yersinia pestis.mara, an arac/xyls transcriptional regulator in escherichia coli, affects drug susceptibility and virulence. two mara-like proteins have been found in yersinia pestis: mara47 and mara48. deletion or overexpression of these proteins in the attenuated kim 1001 deltapgm strain led to a change in multidrug susceptibility (including susceptibility to clinically relevant drugs). additionally, lung colonization by the mara47 or mara48 deletion mutant was decreased about 10-fold in a pneumonic plague mo ...201019841071
plague.killed whole cell vaccines for plague were first produced as long ago as the late 1890s and modified versions of these are still used, with evidence that they are efficacious against bubonic plague. renewed efforts with modern technology have yielded new candidate vaccines which are less reactogenic, can be produced in a conventional pharmaceutical manufacturing plant and are protective against the life-threatening pneumonic form of the disease. this paper reviews the progress towards an improve ...200919837288
amino acid and structural variability of yersinia pestis lcrv protein.the lcrv protein is a multifunctional virulence factor and protective antigen of the plague bacterium and is generally conserved between the epidemic strains of yersinia pestis. we investigated the diversity in the lcrv sequences among non-epidemic y. pestis strains which have a limited virulence in selected animal models and for humans. sequencing of lcrv genes from 19 y. pestis strains belonging to different phylogenetic groups (subspecies) showed that the lcrv proteins possess four major vari ...201019835996
dual-function antibodies to yersinia pestis lcrv required for pulmonary clearance of plague.yersinia pestis causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. antibodies to the protective antigen lcrv are thought to neutralize its essential function in the type iii secretion system (ttss) and by themselves are capable of inducing immunity to plague in mouse models. to develop multivalent lcrv antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (mabs) to lcrv that could prevent its function in the ttss. ...200919828767
diagnostic bioluminescent phage for detection of yersinia pestis.yersinia pestis is the etiological agent of the plague. because of the disease's inherent communicability, rapid clinical course, and high mortality, it is critical that an outbreak, whether it is natural or deliberate, be detected and diagnosed quickly. the objective of this research was to generate a recombinant luxab ("light")-tagged reporter phage that can detect y. pestis by rapidly and specifically conferring a bioluminescent signal response to these cells. the bacterial luxab reporter gen ...200919828743
[natural foci of plague in india: epizootological characteristics].in the first half of the 20th century, india was responsible for the incidence of plague in both asia and the world. the early 21st century was marked by two new epidemic outbreaks of plague (in 2002 and 2004) in this country. the major characteristics of plagues in india, activation of which is a cause of new epidemic outbreaks and necessitates a continuous epizootological monitoring, are analyzed. historical experience shows that lower focus on surveillance of natural foci of plaque, dissemina ...200919827520
application of fluorescent nanocrystals (q-dots) for the detection of pathogenic bacteria by flow-cytometry.fluorescent semiconductor nanocrystals (q-dots) benefit from practical features such as high fluorescence intensity, broad excitation band and emission diameter dependency. these unique spectroscopic characterizations make q-dots excellent candidates for new fluorescent labels in multi-chromatic analysis, such as flow-cytometry (fcm). in this work we shall present new possibilities of multi-labeling and multiplex analysis of pathogenic bacteria, by flow-cytometry (fcm) analysis and new specific ...201019826932
bacillus anthracis, francisella tularensis and yersinia pestis. the most important bacterial warfare agents - review.there are three most important bacterial causative agents of serious infections that could be misused for warfare purposes: bacillus anthracis (the causative agent of anthrax) is the most frequently mentioned one; however, fracisella tularensis (causing tularemia) and yersinia pestis (the causative agent of plague) are further bacterial agents enlisted by centers for disease control and prevention into the category a of potential biological weapons. this review intends to summarize basic informa ...200919826916
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