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tnfα and ifnγ but not perforin are critical for cd8 t cell-mediated protection against pulmonary yersinia pestis infection.septic pneumonias resulting from bacterial infections of the lung are a leading cause of human death worldwide. little is known about the capacity of cd8 t cell-mediated immunity to combat these infections and the types of effector functions that may be most effective. pneumonic plague is an acutely lethal septic pneumonia caused by the gram-negative bacterium yersinia pestis. we recently identified a dominant and protective y. pestis antigen, yope69-77, recognized by cd8 t cells in c57bl/6 mice ...201424854422
detection of yersinia pestis in environmental and food samples by intact cell immunocapture and liquid chromatography-tandem mass spectrometry.yersinia pestis is the causative agent of bubonic and pneumonic plague, an acute and often fatal disease in humans. in addition to the risk of natural exposure to plague, there is also the threat of a bioterrorist act, leading to the deliberate spread of the bacteria in the environment or food. we report here an immuno-liquid chromatography-tandem mass spectrometry (immuno-lc-ms/ms) method for the direct (i.e., without prior culture), sensitive, and specific detection of y. pestis in such comple ...201424847944
rapid degradation of hfq-free ryhb in yersinia pestis by pnpase independent of putative ribonucleolytic complexes.the rna chaperone hfq in bacteria stabilizes srnas by protecting them from the attack of ribonucleases. upon release from hfq, srnas are preferably degraded by pnpase. pnpase usually forms multienzyme ribonucleolytic complexes with endoribonuclease e and/or rna helicase rhlb to facilitate the degradation of the structured rna. however, whether pnpase activity on hfq-free srnas is associated with the assembly of rnase e or rhlb has yet to be determined. here we examined the roles of the main endo ...201424818153
mapping the distribution of the main host for plague in a complex landscape in kazakhstan: an object-based approach using spot-5 xs, landsat 7 etm+, srtm and multiple random forests.plague is a zoonotic infectious disease present in great gerbil populations in kazakhstan. infectious disease dynamics are influenced by the spatial distribution of the carriers (hosts) of the disease. the great gerbil, the main host in our study area, lives in burrows, which can be recognized on high resolution satellite imagery. in this study, using earth observation data at various spatial scales, we map the spatial distribution of burrows in a semi-desert landscape. the study area consists o ...201324817838
yersinia pestis requires the 2-component regulatory system ompr-envz to resist innate immunity during the early and late stages of plague.plague is transmitted by fleas or contaminated aerosols. to successfully produce disease, the causal agent (yersinia pestis) must rapidly sense and respond to rapid variations in its environment. here, we investigated the role of 2-component regulatory systems (2css) in plague because the latter are known to be key players in bacterial adaptation to environmental change. along with the previously studied phop-phoq system, ompr-envz was the only one of y. pestis' 23 other 2css required for produc ...201424813471
sylvatic plague in a canadian black-tailed prairie dog (cynomys ludovicianus).in 2010, a black-tailed prairie dog (cynomys ludovicianus) was found dead in grasslands national park, saskatchewan, canada. postmortem gross and histologic findings indicated bacterial septicemia, likely due to yersinia pestis, which was confirmed by molecular analysis. this is the first report of y. pestis in the prairie dog population within canada.201424807359
phylogenetic analysis of entomoparasitic nematodes, potential control agents of flea populations in natural foci of plague.entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. we examined the flea samples from the volga-ural natural focus of plague for their infestation with nematodes. among the six flea species feeding on different rodent hosts (citellus pygmaeus, microtus socialis, and allactaga major), the rate of infestation varied from 0 to 21%. the propaga ...201424804197
caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of nf-κb and mapk signaling.toll-like receptor signaling and subsequent activation of nf-κb- and mapk-dependent genes during infection play an important role in antimicrobial host defense. the yopj protein of pathogenic yersinia species inhibits nf-κb and mapk signaling, resulting in blockade of nf-κb-dependent cytokine production and target cell death. nevertheless, yersinia infection induces inflammatory responses in vivo. moreover, increasing the extent of yopj-dependent cytotoxicity induced by yersinia pestis and yersi ...201424799700
caspase-8 and rip kinases regulate bacteria-induced innate immune responses and cell death.a number of pathogens cause host cell death upon infection, and yersinia pestis, infamous for its role in large pandemics such as the "black death" in medieval europe, induces considerable cytotoxicity. the rapid killing of macrophages induced by y. pestis, dependent upon type iii secretion system effector yersinia outer protein j (yopj), is minimally affected by the absence of caspase-1, caspase-11, fas ligand, and tnf. caspase-8 is known to mediate apoptotic death in response to infection with ...201424799678
yersinia pestis infection in dogs: 62 cases (2003-2011).to describe the epidemiology, clinical signs, and treatment practices in dogs with yersinia pestis infection in new mexico.201424786165
yersinia pestis ail recruitment of c4b-binding protein leads to factor i-mediated inactivation of covalently and noncovalently bound c4b.the outer membrane protein ail of yersinia pestis mediates several virulence functions, including serum resistance. here, we demonstrate that ail binds c4b-binding protein (c4bp), the primary fluid-phase regulator of the classical and lectin pathways. noncovalent binding of c4 and c4b to ail was also observed. c4bp bound to ail can act as a cofactor to the serine protease factor i (fi) in the cleavage of fluid-phase c4b. employing a panel of c4bp alpha-chain mutants, we observed that the absence ...201424765656
yersinia pestis ail recruitment of c4b-binding protein leads to factor i-mediated inactivation of covalently and noncovalently bound c4b.the outer membrane protein ail of yersinia pestis mediates several virulence functions, including serum resistance. here, we demonstrate that ail binds c4b-binding protein (c4bp), the primary fluid-phase regulator of the classical and lectin pathways. non-covalent binding of c4 and c4b to ail was also observed. c4bp bound to ail can act as a cofactor to the serine protease factor i (fi) in the cleavage of fluid-phase c4b. employing a panel of c4bp alpha-chain mutants, we observed that the absenc ...201424760758
plague is a human disease, caused by yersinia pestis. 201424751950
[analysis on the results of etiology and serology of plague in qinghai province from 2001 to 2010].to analyze the results of etiology and serology of plague among human and infected animals in qinghai province from 2001 to 2010.201424746007
[genotyping and its epidemiological significance on yunnan yersinia pestis under fse i enzyme digestion method].to create the fingerprint library of yunnan yersinia pestis by pulse field gel electrophoresis(pfge)with fse i enzyme digestion method and to study its epidemiological significance.201424739561
[application of best subsets regression on the risk classification for spermophilus dauricus focus].to study the risk classification of animal plague in spermophilus dauricus focus, using the best subsets regression (bsr) model.201424739558
the pla protease of yersinia pestis degrades fas ligand to manipulate host cell death and inflammation.pneumonic plague is a deadly respiratory disease caused by yersinia pestis. the bacterial protease pla contributes to disease progression and manipulation of host immunity, but the mechanisms by which this occurs are largely unknown. here we show that pla degrades the apoptotic signaling molecule fas ligand (fasl) to prevent host cell apoptosis and inflammation. wild-type y. pestis, but not a pla mutant (δpla), degrades fasl, which results in decreased downstream caspase-3/7 activation and reduc ...201424721571
remote monitoring of the progression of primary pneumonic plague in brown norway rats in high-capacity, high-containment housing.development of new vaccines, diagnostics, and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. to overcome this experimental gap, the u.s. food and drug administration established the animal rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large-scale clinical trials for diseases ...201424719212
evaluation of imipenem for prophylaxis and therapy of yersinia pestis delivered by aerosol in a mouse model of pneumonic plague.it has been previously shown that mice subjected to an aerosol exposure to yersinia pestis and treated with β-lactam antibiotics after a delay of 42 h died at an accelerated rate compared to controls. it was hypothesized that endotoxin release in antibiotic-treated mice accounted for the accelerated death rate in the mice exposed to aerosol y. pestis. imipenem, a β-lactam antibiotic, binds to penicillin binding protein 2 with the highest affinity and produces rounded cells. the binding of imipen ...201424687492
identification of risk factors for plague in the west nile region of uganda.plague is an often fatal, primarily flea-borne rodent-associated zoonosis caused by yersinia pestis. we sought to identify risk factors for plague by comparing villages with and without a history of human plague cases within a model-defined plague focus in the west nile region of uganda. although rat (rattus rattus) abundance was similar inside huts within case and control villages, contact rates between rats and humans (as measured by reported rat bites) and host-seeking flea loads were higher ...201424686743
deletion of braun lipoprotein and plasminogen-activating protease-encoding genes attenuates yersinia pestis in mouse models of bubonic and pneumonic plague.currently, there is no fda-approved vaccine against yersinia pestis, the causative agent of bubonic and pneumonic plague. since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from y. pestis co92. the δlpp δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic pla ...201424686064
[improvement of typification of natural foci of plague based on ecological-genetic analysis of yersinia pestis].contemporary features of distribution of various subspecies and biovars of plague causative agent by landscape-geographical zones and mountain belts on the territory of russia and other cis countries are examined. the most widely spread in plain and mountain natural foci were noted to be yersinia pestis main subspecies medieval biovar strains. strains of y. pestis non-main subspecies are spread in mountain landscapes of altai, caucasus, tian shan. change of dominating species of rodents consider ...201424605665
direct neutralization of type iii effector translocation by the variable region of a monoclonal antibody to yersinia pestis lcrv.plague is an acute infection caused by the gram-negative bacterium yersinia pestis. antibodies that are protective against plague target lcrv, an essential virulence protein and component of a type iii secretion system of y. pestis. secreted lcrv localizes to the tips of type iii needles on the bacterial surface, and its function is necessary for the translocation of yersinia outer proteins (yops) into the cytosol of host cells infected by y. pestis. translocated yops counteract macrophage funct ...201424599533
editorial: yersinia pestis survives in neutrophils and sends a ps to macrophages: bon appetit! 201424586037
transcriptional regulation mechanism of ter operon by oxyr in yersinia pestis.the aim of this work was to study the transcriptional regulation mechanism of ter operon by oxyr in yersinia pestis. total rnas were extracted from the wild-type (wt) strain and the oxyr null mutant (δoxyr) strain. primer extension assay was employed to detect the promoter activity (the amount of primer extension product) of terz in wt and δoxyr. terz promoter-proximal region was cloned into the prw50 plasmid containing a promoterless lacz gene. the recombinant lacz reporter plasmid was transfor ...201424577613
false positives complicate ancient pathogen identifications using high-throughput shotgun sequencing.identification of historic pathogens is challenging since false positives and negatives are a serious risk. environmental non-pathogenic contaminants are ubiquitous. furthermore, public genetic databases contain limited information regarding these species. high-throughput sequencing may help reliably detect and identify historic pathogens.201424568097
development of yersinia pestis f1 antigen-loaded microspheres vaccine against plague.yersinia pestis f1 antigen-loaded poly(dl-lactide-co-glycolide)/polyethylene glycol (peg) (plga/peg) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. the y. pestis f1 antigen-loaded microspheres (mean particle size 3.8 μm) exhibited a high loading capacity (4.5% w/w), yield (8 ...201424550673
convergent evolution in european and rroma populations reveals pressure exerted by plague on toll-like receptors.recent historical periods in europe have been characterized by severe epidemic events such as plague, smallpox, or influenza that shaped the immune system of modern populations. this study aims to identify signals of convergent evolution of the immune system, based on the peculiar demographic history in which two populations with different genetic ancestry, europeans and rroma (gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, d ...201424550294
[the pathogenic ecology research on plague in qinghai plateau].to study the pathogenic ecology characteristics of plague in qinghai plateau.201324529264
in silico molecular characterization of cysteine protease yopt from yersinia pestis by homology modeling and binding site identification.plague is a major health concern and yersinia pestis plays the central causal role in this disease. yersinia pestis has developed resistance against the commonly available drugs. so, it is now a key concern to find a new drug target. cysteine protease yopt enzyme is an important factor used by yersinia pestis for pathogenesis in its host and it has the anti-phagocytic function of removal of c-termini lipid modification. the 3d structure of cysteine protease yopt of yersinia pestis was determined ...201424526834
construction of an inducible system for the analysis of essential genes in yersinia pestis.yersinia pestis, a gram negative bacterium, causes bubonic and pneumonic plague. emerging antibiotic resistance in clinical isolates is driving a need to develop novel antibiotics to treat infection by this transmissible and highly virulent pathogen. proteins required for viability, so called essential genes, are attractive potential therapeutic targets, however, confirmation of essentiality is problematic. for the first time, we report the development of a system that allows the rapid determina ...201424524852
lung deposition and cellular uptake behavior of pathogen-mimicking nanovaccines in the first 48 hours.pulmonary immunization poses the unique challenge of balancing vaccine efficacy with minimizing inflammation in the respiratory tract. while previous studies have shown that mice immunized intranasally with f1-v-loaded polyanhydride nanoparticles are protected from a lethal challenge with yersinia pestis, little is known about the initial interaction between the nanoparticles and immune cells following intranasal administration. here, the deposition within the lung and internalization by phagocy ...201424520022
biologically active ligands for yersinia outer protein h (yoph): feature based pharmacophore screening, docking and molecular dynamics studies.yersinia pestis, a gram negative bacillus, spreads via lymphatic to lymph nodes and to all organs through the bloodstream, causing plague. yersinia outer protein h (yoph) is one of the important effector proteins, which paralyzes lymphocytes and macrophages by dephosphorylating critical tyrosine kinases and signal transduction molecules. the purpose of the study is to generate a three-dimensional (3d) pharmacophore model by using diverse sets of yoph inhibitors, which would be useful for designi ...201424517834
immunological and clinical response of coyotes (canis latrans) to experimental inoculation with yersinia pestis.multiple publications have reported the use of coyotes (canis latrans) in animal-based surveillance efforts for the detection of yersinia pestis. coyotes are likely exposed via flea bite or oral routes and are presumed to be resistant to the development of clinical disease. these historic data have only been useful for the evaluation of the geographic distribution of y. pestis in the landscape. because the canid immunologic response to y. pestis has not been thoroughly characterized, we conducte ...201324502720
the innate immune response may be important for surviving plague in wild gunnison's prairie dogs.prairie dogs (cynomys spp.) are highly susceptible to yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. a colony of gunnison's prairie dogs (cynomys gunnisoni) in the aubrey valley (av) of northern arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by y. pestis. to examine potential mechanisms accounting for survival in the av colony, we conducted a laboratory y. pestis challenge expe ...201324502719
season and application rates affect vaccine bait consumption by prairie dogs in colorado and utah, usa.plague, a zoonotic disease caused by the bacterium yersinia pestis, causes high rates of mortality in prairie dogs (cynomys spp.). an oral vaccine against plague has been developed for prairie dogs along with a palatable bait to deliver vaccine and a biomarker to track bait consumption. we conducted field trials between september 2009 and september 2012 to develop recommendations for bait distribution to deliver plague vaccine to prairie dogs. the objectives were to evaluate the use of the bioma ...201424484490
a rapid field test for sylvatic plague exposure in wild animals.plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. the most common surveillance method for sylvatic plague is detection of antibodies to yersinia pestis f1 capsular antigen in sentinel animals, such as coyotes (canis latrans). current serologic tests for y. pestis, hemagglutination (ha) test and enzyme-linked immunosorbent assay (elisa), are expensive and labor intensive. to address this need, we developed a complete lateral flow dev ...201424484483
yersinia pestis: one pandemic, two pandemics, three pandemics, more? 201424480150
yersinia pestis and the plague of justinian 541-543 ad: a genomic analysis.yersinia pestis has caused at least three human plague pandemics. the second (black death, 14-17th centuries) and third (19-20th centuries) have been genetically characterised, but there is only a limited understanding of the first pandemic, the plague of justinian (6-8th centuries). to address this gap, we sequenced and analysed draft genomes of y pestis obtained from two individuals who died in the first pandemic.201424480148
epitope recognition of antibodies against a yersinia pestis lipopolysaccharide trisaccharide component.today, the process of selecting carbohydrate antigens as a basis for active vaccination and the generation of antibodies for therapeutic and diagnostic purposes is based on intuition combined with trial and error experiments. in efforts to establish a rational process for glycan epitope selection, we employed glycan array screening, surface plasmon resonance, and saturation transfer difference (std)-nmr to elucidate the interactions between antibodies and glycans representing the yersinia pestis ...201424479563
quantifying interactions of a membrane protein embedded in a lipid nanodisc using fluorescence correlation spectroscopy.using fluorescence correlation spectroscopy, we measured a dissociation constant of 20 nm between egfp-labeled lcrv from yersinia pestis and its cognate membrane-bound protein yopb inserted into a lipid nanodisc. the combination of fluorescence correlation spectroscopy and nanodisc technologies provides a powerful approach to accurately measure binding constants of interactions between membrane bound and soluble proteins in solution. straightforward sample preparation, acquisition, and analysis ...201424461026
[thermodynamic parameters of stabilization in a compact form of the caf1(13-149) subunit from yersinia pestis].with a number of experimental methods (circular dichroism, viscosity, intrinsic fluorescence and fluorescence labelling) the conformational folding-unfolding transitions in a compact monomeric form of the caf1(13-149) subunit were studied under the action of guanidine hydrochloride in the temperature range from 5 to 45 degrees c. it has been shown that transitions always occur between two major states (unfolded and compact). it has made it possible to determine all main thermodynamic functions t ...201424455880
crystallization and preliminary x-ray diffraction analysis of fabg from yersinia pestis.the type ii fatty-acid biosynthesis pathway of bacteria provides enormous potential for antibacterial drug development owing to the structural differences between this and the type i fatty-acid biosynthesis system found in mammals. β-ketoacyl-acp reductase (fabg) is responsible for the reduction of the β-ketoacyl group linked to acyl carrier protein (acp), and is essential for the formation of fatty acids and bacterial survival. here, the cloning, expression, purification, crystallization and di ...201424419628
two-step source tracing strategy of yersinia pestis and its historical epidemiology in a specific region.source tracing of pathogens is critical for the control and prevention of infectious diseases. genome sequencing by high throughput technologies is currently feasible and popular, leading to the burst of deciphered bacterial genome sequences. utilizing the flooding genomic data for source tracing of pathogens in outbreaks is promising, and challenging as well. here, we employed yersinia pestis genomes from a plague outbreak at xinghai county of china in 2009 as an example, to develop a simple tw ...201424416399
yersinia pestis: mechanisms of entry into and resistance to the host cell.during infection, yersinia, a facultative intracellular bacterial species, exhibits the ability to first invade host cells and then counteract phagocytosis by the host cells. during these two distinct stages, invasion or antiphagocytic factors assist bacteria in manipulating host cells to accomplish each of these functions; however, the mechanism through which yersinia regulates these functions during each step remains unclear. here, we discuss those factors that seem to function reversely and g ...201324400226
yfba, a yersinia pestis regulator required for colonization and biofilm formation in the gut of cat fleas.for transmission to new hosts, yersinia pestis, the causative agent of plague, replicates as biofilm in the foregut of fleas that feed on plague-infected animals or humans. y. pestis biofilm formation has been studied in the rat flea; however, little is known about the cat flea, a species that may bridge zoonotic and anthroponotic plague cycles. here, we show that y. pestis infects and replicates as a biofilm in the foregut of cat fleas in a manner requiring hmsfr, two determinants for extracell ...201424391055
kinetics of memory b cell and plasma cell responses in the mice immunized with plague vaccines.in our previous studies, we found that plague vaccines can induce long-term antibody response, but no significant antibody boost was observed when the immunized mice were challenged with virulent yersinia pestis. however, a booster vaccination of subunit vaccine on week 3 after primary immunization elicited a significantly higher antibody titre than a single dose, whereas no significant antibody titre difference was observed between a single dose and two doses of ev76 vaccination. to address the ...201424383627
[a molecular basis of the plague vaccine development].molecular mechanisms of the yersinia pestis pathogenicity and peculiarities of maturation of specific immunity to plague are reviewed. the history and modern state of the plague vaccine development are described. special attention is focused on the prospects in the area of the plague vaccine development. the possible approaches to improvement of vaccine preparations are discussed.201324364139
[morphofunctional evaluation of the state of cells of apud-system biomodel during anti-plague vaccine process].study reaction of cells of apud-system of lymphoid organs and intestine of guinea pigs at the stages of morpho- and immunogenesis in response to administration of yersinia pestis ev research institute of epidemiology and hygiene (rieh) line vaccine strain.201324341215
protein markers for identification of yersinia pestis and their variation related to culture.the detection of high consequence pathogens, such as yersinia pestis, is well established in biodefense laboratories for bioterror situations. laboratory protocols are well established using specified culture media and a growth temperature of 37 °c for expression of specific antigens. direct detection of y. pestis protein markers, without prior culture, depends on their expression. unfortunately protein expression can be impacted by the culture medium which cannot be predicted ahead of time. fur ...201524333237
bioluminescent tracking of colonization and clearance dynamics of plasmid-deficient yersinia pestis strains in a mouse model of septicemic plague.yersinia pestis 201 contains 4 plasmids ppcp1, pmt1, pcd1 and pcry, but little is known about the effects of these plasmids on the dissemination of y. pestis. we developed a plasmid-based luxcdabe bioreporter in y. pestis 201, y. pestis 201-pcd1(+), y. pestis 201-pmt1(+), y. pestis 201-ppcp1(+), y. pestis 201-pcry(+), y. pestis 201-p(-) and yersinia pseudotuberculosis pa36060 strains, and investigated their dissemination by bioluminescence imaging during primary septicemic plague in a mouse mode ...201424333143
[preparation and biological activity analysis of chimeric antibody against capsular f1 antigen of yersinia pestis].to express human-mouse chimeric antibody against yersinia pestis f1 capsular antigen (f1 antigen) and analyze its biological activities.201324321075
[study on the functions of potential new genes of yersinia pestis type three secretion system].to investigate the functional relations between the putative proteins ypcd1.08, ypcd1.09, ypcd1.16 encoded in pcd1 plasmid of yersinia pestis and its type iii secretion system (t3ss).201324304956
understanding the persistence of plague foci in madagascar.plague, a zoonosis caused by yersinia pestis, is still found in africa, asia, and the americas. madagascar reports almost one third of the cases worldwide. y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. the black rat rattus rattus, the m ...201324244760
yersinia pestis survival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages.yersinia pestis, the bacterial agent of plague, is transmitted by fleas. the bite of an infected flea deposits y. pestis into the dermis and triggers recruitment of innate immune cells, including phagocytic pmns. y. pestis can subvert this pmn response and survive at the flea-bite site, disseminate, and persist in the host. although its genome encodes a number of antiphagocytic virulence factors, phagocytosis of y. pestis by pmns has been observed. this study tests the hypotheses that y. pestis, ...201424227798
yersinia pestis biovar microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.yersinia pestis biovar microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. it may be used as live attenuated plague vaccine candidates in terms of its low virulence. however, the microtus strain's protection against plague has yet to be demonstrated in larger mammals. in this study, we evaluated the protective efficacy of the microtus strain 201 as a live attenuated plague vaccine candidate. our results show that this strain is highly attenuated ...201424225642
temperature-dependence of yadbc phenotypes in yersinia pestis.yadb and yadc are putative trimeric autotransporters present only in the plague bacterium yersinia pestis and its evolutionary predecessor, yersinia pseudotuberculosis. previously, yadbc was found to promote invasion of epithelioid cells by y. pestis grown at 37 °c. in this study, we found that yadbc also promotes uptake of 37 °c-grown y. pestis by mouse monocyte/macrophage cells. we tested whether yadbc might be required for lethality of the systemic stage of plague in which the bacteria would ...201424222617
the yersinia pestis type iii secretion system: expression, assembly and role in the evasion of host defenses.yersinia pestis, the etiologic agent of plague, utilizes a type iii secretion system (t3ss) to subvert the defenses of its mammalian hosts. t3sss are complex nanomachines that allow bacterial pathogens to directly inject effector proteins into eukaryotic cells. the y. pestis t3ss is not expressed during transit through the flea vector, but t3ss gene expression is rapidly thermoinduced upon entry into a mammalian host. assembly of the t3s apparatus is a highly coordinated process that requires th ...201324198067
imaging early pathogenesis of bubonic plague: are neutrophils commandeered for lymphatic transport of bacteria?vector-borne infections begin in the dermis when a pathogen is introduced by an arthropod during a blood meal. several barriers separate an invading pathogen from its replicative niche, including phagocytic cells in the dermis that activate immunity by engulfing would-be pathogens and migrating to the lymph node. in addition, neutrophils circulating in the blood are rapidly recruited when the dermal barriers are penetrated. for flea-borne disease, no insect-encoded immune-suppressive molecules h ...201324194541
hmsc, a periplasmic protein, controls biofilm formation via repression of hmsd, a diguanylate cyclase in yersinia pestis.yersinia pestis, the cause of plague, forms a biofilm in the foregut of its flea vector to enhance transmission. biofilm formation in y. pestis is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-gmp). hmst and y3730, the two diguanylate cyclases (dgc) in y. pestis, are responsible for the synthesis of c-di-gmp. y3730, which we name here as hmsd, has little effect on in vitro biofilms, but has a major effect on biofilm formation in the flea. the me ...201424192006
potential corridors and barriers for plague spread in central asia.plague (yersinia pestis infection) is a vector-borne disease which caused millions of human deaths in the middle ages. the hosts of plague are mostly rodents, and the disease is spread by the fleas that feed on them. currently, the disease still circulates amongst sylvatic rodent populations all over the world, including great gerbil (rhombomys opimus) populations in central asia. great gerbils are social desert rodents that live in family groups in burrows, which are visible on satellite images ...201324171709
fpsac: fast phylogenetic scaffolding of ancient contigs.recent progress in ancient dna sequencing technologies and protocols has lead to the sequencing of whole ancient bacterial genomes, as illustrated by the recent sequence of the yersinia pestis strain that caused the black death pandemic. however, sequencing ancient genomes raises specific problems, because of the decay and fragmentation of ancient dna among others, making the scaffolding of ancient contigs challenging.201324068034
duration of plague (yersinia pestis) outbreaks in black-tailed prairie dog (cynomys ludovicianus) colonies of northern colorado.plague, caused by the bacterium yersinia pestis, triggers die-offs in colonies of black-tailed prairie dogs (cynomys ludovicianus), but the time-frame of plague activity is not well understood. we document plague activity in fleas from prairie dogs and their burrows on three prairie dog colonies that suffered die-offs. we demonstrate that y. pestis transmission occurs over periods from several months to over a year in prairie dog populations before observed die-offs.201324057801
plague gives surprises in the first decade of the 21st century in the united states and worldwide.plague is an ancient disease caused by the bacterium yersinia pestis and transmitted by rodent flea bites that continues to surprise us with first-ever events. this review documents plague in human cases in the 1st decade of the 21st century and updates our knowledge of clinical manifestations, transmission during outbreaks, diagnostic testing, antimicrobial treatment, and vaccine development. in the united states, 57 persons were reported to have the disease, of which seven died. worldwide, 21, ...201324043686
determination of srna expressions by rna-seq in yersinia pestis grown in vitro and during infection.small non-coding rnas (srnas) facilitate host-microbe interactions. they have a central function in the post-transcriptional regulation during pathogenic lifestyles. hfq, an rna-binding protein that many srnas act in conjunction with, is required for y. pestis pathogenesis. however, information on how yersinia pestis modulates the expression of srnas during infection is largely unknown.201324040259
[analysis on genotype distributions and epidemiological characteristics of yersinia pestis plague foci in gansu province].to study the genotype distributions and epidemiological characteristics of yersinia pestis in gansu province.201324016429
[molecular typing of yersinia pestis].techniques for differentiating single bacterial isolates into intraspecies clusters corresponding to subspecies, biovars, and natural foci are reviewed. the techniques under consideration are reproducible under different laboratory settings. a version of the intraspecies classification of y. pestis that is in harmony with the international code of nomencláture of bacteria is suggested.201324003506
the effects of modeled microgravity on growth kinetics, antibiotic susceptibility, cold growth, and the virulence potential of a yersinia pestis ymoa-deficient mutant and its isogenic parental strain.previously, we reported that there was no enhancement in the virulence potential (as measured by cell culture infections) of the bacterial pathogen yersinia pestis (yp) following modeled microgravity/clinorotation growth. we have now further characterized the effects of clinorotation (cr) on yp growth kinetics, antibiotic sensitivity, cold growth, and yp's virulence potential in a murine model of infection. surprisingly, none of the aforementioned phenotypes were altered. to better understand wh ...201323988036
[the sensitivity of plague agent from siberian natural focuses of disease to antibacterial preparations in vitro].the comparative analysis was applied concerning antimicrobic action of different groups of antibacterial preparations on the plague agent strains isolated from siberian natural focuses of disease. the analysis was applied to results obtained using such different methods as disco-diffusive technique, serial dilution and hicomb mic test. it is established that freshly isolated cultures of yersinia pestis have high sensitivity to antibacterial preparations of different groups. the results obtained ...201323984554
yersinia pestis subverts the dermal neutrophil response in a mouse model of bubonic plague.the majority of human yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. once in the dermis, y. pestis can evade the host's innate immune response and subsequently disseminate to the draining lymph node (dln). there, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. in this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d. ...201323982068
prophylaxis and therapy of plague.plague has been a scourge of mankind for centuries, and outbreaks continue to the present day. the virulence mechanisms employed by the etiological agent yersinia pestis are reviewed in the context of the available prophylactic and therapeutic strategies for plague. although antibiotics are available, resistance is emerging in this dangerous pathogen. therapeutics used in the clinic are discussed and innovative approaches to the design and development of new therapeutic compounds are reviewed. c ...201323977937
serologic survey of plague in animals, western iran. 201323968721
quinto tiberio angelerio and new measures for controlling plague in 16th-century alghero, sardinia.plague, a zoonotic disease caused by the bacterium yersinia pestis, has been responsible for at least 3 pandemics. during 1582-1583, a plague outbreak devastated the seaport of alghero in sardinia. by analyzing contemporary medical texts and local documentation, we uncovered the pivotal role played by the protomedicus of alghero, quinto tiberio angelerio (1532-1617), in controlling the epidemic. angelerio imposed rules and antiepidemic measures new to the 16th-century sanitary system of sardinia ...201323968598
persistence of black-tailed prairie-dog populations affected by plague in northern colorado, usa.the spatial distribution of prairie dog (cynomys ludovicianus) colonies in north america has changed from large, contiguous populations to small, isolated colonies in metapopulations. one factor responsible for this drastic change in prairie-dog population structure is plague (caused by the bacterium yersinia pestis). we fit stochastic patch occupancy models to 20 years of prairie-dog colony occupancy data from two discrete metapopulations (west and east) in the pawnee national grassland in colo ...201323951717
short report: exposing laboratory-reared fleas to soil and wild flea feces increases transmission of yersinia pestis.laboratory-reared oropsylla montana were exposed to soil and wild-caught oropsylla montana feces for 1 week. fleas from these two treatments and a control group of laboratory-reared fleas were infected with yersinia pestis, the etiological agent of plague. fleas exposed to soil transmitted y. pestis to mice at a significantly greater rate (50.0% of mice were infected) than control fleas (23.3% of mice were infected). although the concentration of y. pestis in fleas did not differ among treatment ...201323939709
proposed reclassification of pasteurella lymphangitidis sneath & stevens 1990 as yersinia pseudotuberculosis.the 16s rrna gene sequences of pasteurella lymphangitidis, yersinia pseudotuberculosis and yersinia pestis were found to be identical and multilocus sequence analysis could not discriminate between the three species. the susceptibility to a y. pseudotuberculosis phage and the presence of the y. pseudotuberculosis-specific invasin gene in p. lymphangitidis indicate that the latter should be reclassified as y. pseudotuberculosis.201323919959
preclinical safety assessment of a recombinant plague vaccine (rf1v).a recombinant vaccine (rf1v) is being developed to protect adults 18 to 55 years of age from fatal pneumonic plague caused by aerosolized yersinia pestis. a comprehensive series of studies was conducted to evaluate the general toxicity and local reactogenicity of the rf1v vaccine prior to first use in humans. toxicity was evaluated in cd-1 mice vaccinated with control material and three dosage concentrations of rf1v with or without alhydrogel(®) by intramuscular (im) injection on study days 1, 2 ...201323908395
seroprevalence of hantavirus and yersinia pestis antibodies in professionals from the plague control program.professionals who handle rodents in the field and in the laboratory are at risk of infection by the microorganis mharbored by these animals.201323904080
fibrinolytic and coagulative activities of yersinia pestis.the outer membrane protease pla belongs to the omptin protease family spread by horizontal gene transfer into gram-negative bacteria that infect animals or plants. pla has adapted to support the life style of the plague bacterium yersinia pestis. pla has a β-barrel fold with 10 membrane-spanning β strands and five surface loops, and the barrel surface contains bound lipopolysaccharide (lps) that is critical for the conformation and the activity of pla. the biological activity of pla is influence ...201323898467
earthquakes and plague during byzantine times: can lessons from the past improve epidemic preparedness.natural disasters have always been followed by a fear of infectious diseases. this raised historical debate about one of the most feared scenarios: the outbreak of bubonic plague caused by yersinia pestis. one such event was recorded in the indian state maharashtra in 1994 after an earthquake. in multidisciplinary historical approach to the evolution of plague, many experts ignore the possibility of natural foci and their activation. this article presents historical records from the byzantine em ...201323883083
mutated and bacteriophage t4 nanoparticle arrayed f1-v immunogens from yersinia pestis as next generation plague vaccines.pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism yersinia pestis poses a serious threat for deliberate use as a bioterror agent. currently, there is no fda approved vaccine against plague. the polymeric bacterial capsular protein f1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response v antigen, has high propensity to aggregate, thus affecting its purification and vaccine ef ...201323853602
plague detection by anti-carbohydrate antibodies. 201323843253
yersinia pestis infection in cats: abcd guidelines on prevention and management.plague, the medieval 'black death', is caused by a gram-negative coccobacillus, yersinia pestis, which also infects cats. as in people, it is transmitted from rodents through flea bites; it occurs in asia, africa and the americas in flea-infested regions, all year round, and where rodent reservoirs are abundant. a poor prognosis is associated with high fever, and the pulmonary and septicaemic forms. antibiotic therapy, flea control and avoidance of rodent contacts have made this infection manage ...201323813820
[the development and implementation of polymerase chain reaction to detect in real-time operation mode yersinia pestis in field material].the article presents the results of development and practical implementation of system of polymerase chain reaction testing in real-time operation mode to detect agent of plague infield material. in laboratory conditions the system demonstrated good results and hence it was applied in conditions of field laboratory of epidemiologic team during planned epizootologic examination of gorno-altaisk hot spot of plague. the sampling consisted of more than 1400 objects. it was demonstrated that high sen ...201323808025
factors associated with flea infestation among the different rodent species in mbulu and karatu districts, northern tanzania.flea infection with the bacterium, yersinia pestis is acquired from reservoirs which include several rodents and other small mammals. in areas that are endemic of plague, reservoirs of y. pestis and various flea vectors are responsible for perpetuating existence of the disease. the objective of this cross sectional study was to investigate the magnitude and factors associated with flea infestation among different rodent species of northern tanzania, where outbreaks of plague have been recently r ...201326591705
evidence of yersinia pestis dna in rodents in plague outbreak foci in mbulu and karatu districts, northern tanzania.human plague remains a public health concern in tanzania despite its quiescence in most foci for years, considering the recurrence nature of the disease. appreciable researches have involved serological screening of rodents, fleas and humans but none has involved molecular detection and hence proving the presence of yersinia pestis in rodents in the most recent affected foci, mbulu and karatu districts in northern tanzania. the objective of the current study was to employ a simple pcr to detect ...201326591703
[relationships of the plague pathogen and vector from different parasitic systems].the specific features of interaction of the strains of the plague microbe of the main subspecies, which circulate in the area of natural foci of mongolia and china, with citellophilus tesquorum sungaris fleas, the major vector of the plague pathogen in a transbaikalian natural focus, as well as with xenopsylla cheopis ones, the classical vector, were revealed. experiments used virulent yersinia pestis strains, such as i-3230 isolated from c.tesquorum in mongolia in 1998 and 2155 isolated from hu ...201323805481
group-theoretic models of the inversion process in bacterial genomes.the variation in genome arrangements among bacterial taxa is largely due to the process of inversion. recent studies indicate that not all inversions are equally probable, suggesting, for instance, that shorter inversions are more frequent than longer, and those that move the terminus of replication are less probable than those that do not. current methods for establishing the inversion distance between two bacterial genomes are unable to incorporate such information. in this paper we suggest a ...201423793228
study of effectiveness of bioluminescent reporter phage assay on y. pseudotuberculosis strains.the method describes the phage-mediated transduction of a bioluminescent phenotype to cultivated y. pseudotuberculosis cells which are subsequently measured using a microplate luminometer. reporter phage assay is rapid detection technique and its efficiency is not affected by presence of contaminating bacteria, no sample preparation is needed and it has the ability to test multiple samples simultaneously in a 96-well microtiter plate format. experiments were performed to develop the rapid detect ...201323787513
na+/h+ antiport is essential for yersinia pestis virulence.na(+)/h(+) antiporters are ubiquitous membrane proteins that play a central role in the ion homeostasis of cells. in this study, we examined the possible role of na(+)/h(+) antiport in yersinia pestis virulence and found that y. pestis strains lacking the major na(+)/h(+) antiporters, nhaa and nhab, are completely attenuated in an in vivo model of plague. the y. pestis derivative strain lacking the nhaa and nhab genes showed markedly decreased survival in blood and blood serum ex vivo. complemen ...201323774602
plague circulation and population genetics of the reservoir rattus rattus: the influence of topographic relief on the distribution of the disease within the madagascan focus.landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. plague (yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in africa. human seroprevalence data for the major plague focus of madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. plague is primarily a disease of rodents. we therefore investigated ...201323755317
live-attenuated yersinia pestis vaccines.plague caused by yersinia pestis is one of the most dangerous infectious diseases. there is no ideal plague vaccine available for human use, but a number of licensed killed whole-cell and live-attenuated vaccines have been available in the past. currently, there are a number of vaccines under development, including live-attenuated, dna and subunit vaccines, among others. this review deals with the development of live-attenuated plague vaccines. traditionally, live-attenuated plague vaccines have ...201323750796
structure of the yersinia pestis tip protein lcrv refined to 1.65 å resolution.the human pathogen yersinia pestis requires the assembly of the type iii secretion system (t3ss) for virulence. the structural component of the t3ss contains an external needle and a tip complex, which is formed by lcrv in y. pestis. the structure of an lcrv triple mutant (k40a/d41a/k42a) in a c273s background has previously been reported to 2.2 å resolution. here, the crystal structure of lcrv without the triple mutation in a c273s background is reported at a higher resolution of 1.65 å. overal ...201323695558
[detection of yersinia pestis srna by digoxigenin-labeled northern blot].with the application of high-throughput sequencing methods, more and more srnas are required to be verified. in this study, we developed the digoxigenin-labeled northern blot method for detection of yersinia pestis srna.201323678576
yersinia pestis dna from skeletal remains from the 6(th) century ad reveals insights into justinianic plague.yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. these include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the black death. previous studies have confirmed that y. pestis caused these two more recent pandemics. however, a highly spirited debate still continues as to whether y ...201323658525
proteolytic processing of the yersinia pestis yapg autotransporter by the omptin protease pla and the contribution of yapg to murine plague pathogenesis.autotransporter protein secretion represents one of the simplest forms of secretion across gram-negative bacterial membranes. once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. to better understand the role of autotransporters in disease, our research focused on the autotransp ...201323657527
[ecological-geographic landscapes of natural plague foci in china viii. typing of natural plague foci].since plague is an important natural focus zoonosis, the typing of natural plague foci becomes one of the elements in understanding the nature and developing related prevention program of the disease. natural foci of plague are composed by four fundamental parts which include eco-geographical landscape (natural plague foci), hosts, vectors and pathogens (yersinia pestis) that comprehensively interact through the large temporal scale of evolution. human activities have had great impact on the foc ...201323648259
cyclic amp receptor protein is a repressor of adenylyl cyclase gene cyaa in yersinia pestis.yersinia pestis is one of the most dangerous pathogens. the cyclic amp receptor protein (crp) is required for the full virulence of y. pestis, and it acts as a transcriptional regulator to control a large regulon, which includes several virulence-associated genes. the regulatory action of crp is triggered only by binding to the small molecule cofactor cyclic amp (camp). camp is synthesized from adenosine triphosphate by the adenylyl cyclase encoded by cyaa. in the present work, the regulation of ...201323647342
early apoptosis of macrophages modulated by injection of yersinia pestis yopk promotes progression of primary pneumonic plague.yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. the bacterial type iii secretion system (t3ss) injects 7 effector proteins into host cells and their combined activities are necessary to establish infection. y. pestis infection of the lungs proceeds as a biphasic inflammatory response believed to be regulated through the control of apoptosis and pyroptosis by a single, w ...201323633954
growth of a pyv-bearing yersinia pestis kim5 in retail raw ground pork.yersinia pestis can cause oropharyngeal plague as a result of consumption or handling of meat from infected animals. thus, food naturally or intentionally contaminated can have a role in the dissemination of oropharyngeal plague. the growth of a conditionally virulent pyv-bearing rifampicin-resistant y. pestis kim5 (rif-y. pestis kim5) in retail raw ground pork (rgp) was studied at temperatures ranging from 4 to 30°c. at 4°c, rif-y. pestis kim5 did not grow but survived. in rgp, rif-y. pestis ki ...201323627929
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