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[genetic analysis of biochemical differences of yersinia pestis strains].literature data and results of our experimental studies on genetic base of biochemical differentiation of yersinia pestis strains of various subspecies and biovars are summarized in the review. data on variability of genes coding biochemical features (sugar and alcohol fermentation, nitrate reduction), the differential development of which are the base of existing phenotypic schemes of y. pestis strains classification, are presented. variability of these genes was shown to have possible use for ...201322830282
inhibition of yersinia pestis dna adenine methyltransferase in vitro by a stibonic acid compound: identification of a potential novel class of antimicrobial agents.multiple antibiotic resistant strains of plague are emerging, driving a need for the development of novel antibiotics effective against yersinia pestis. dna adenine methylation regulates numerous fundamental processes in bacteria and alteration of dna adenine methlytransferase (dam) expression is attenuating for several pathogens, including y. pestis. the lack of a functionally similar enzyme in humans makes dam a suitable target for development of novel therapeutics for plague.201322889062
structural analysis of pla protein from the biological warfare agent yersinia pestis: docking and molecular dynamics of interactions with the mammalian plasminogen system.yersinia pestis protein pla is a plasmid-coded outer membrane protein with aspartic-protease activity. pla exhibits a plasminogen (plg) activator activity (paa) that promotes the cleavage of plg to the active serine-protease form called plasmin. exactly how pla activates plg into plasmin remains unclear. to investigate this event, we performed the interactions between the predicted plg and pla protein structures by rigid-body docking with the hex program and evaluated the complex stability by mo ...201322881127
the future of plague vaccines: hopes raised by a surrogate, live-attenuated recombinant vaccine candidate.yersinia pestis (yp) is the gram-negative etiological agent of plague against which no commercial vaccine exists to prophylactically prevent a potential outbreak due to natural or bio-warfare/terrorism-mediated causes. the us fda only recently approved levofloxacin to combat this deadly pathogen. in the article under review, an attenuated, recombinant salmonella typhimurium δphopq mutant strain producing yp antigens f1, lcrv and f1-v (fusion protein) from either low-copy pbr or high-copy puc vec ...201222873124
yersinia pestis lineages in mongolia.whole genome sequencing allowed the development of a number of high resolution sequence based typing tools for yersinia (y.) pestis. the application of these methods on isolates from most known foci worldwide and in particular from china and the former soviet union has dramatically improved our understanding of the population structure of this species. in the current view, y. pestis including the non or moderate human pathogen y. pestis subspecies microtus emerged from yersinia pseudotuberculosi ...201222363455
comparative genomics of 2009 seasonal plague (yersinia pestis) in new mexico.plague disease caused by the gram-negative bacterium yersinia pestis routinely affects animals and occasionally humans, in the western united states. the strains native to the north american continent are thought to be derived from a single introduction in the late 19(th) century. the degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of north american plague are highly desired. to assay genetic diversity ...201222359605
[eco-geographic landscapes of natural plague foci in china iv. characterization of biovars of yersinia pestis, china]. 201222883275
climate predictors of the spatial distribution of human plague cases in the west nile region of uganda.east africa has been identified as a region where vector-borne and zoonotic diseases are most likely to emerge or re-emerge and where morbidity and mortality from these diseases is significant. understanding when and where humans are most likely to be exposed to vector-borne and zoonotic disease agents in this region can aid in targeting limited prevention and control resources. often, spatial and temporal distributions of vectors and vector-borne disease agents are predictable based on climatic ...201222403328
a toll/interleukin (il)-1 receptor domain protein from yersinia pestis interacts with mammalian il-1/toll-like receptor pathways but does not play a central role in the virulence of y. pestis in a mouse model of bubonic plague.the toll/interleukin (il)-1 receptor (tir) domain is an essential component of eukaryotic innate immune signalling pathways. interaction between tir domains present in toll-like receptors and associated adaptors initiates and propagates an immune signalling cascade. proteins containing tir domains have also been discovered in bacteria. studies have subsequently shown that these proteins are able to modulate mammalian immune signalling pathways dependent on tir interactions and that this may repr ...201222403187
[eco-geographic landscapes of natural plague foci in china iii. biological characteristics of major dfr/mlva-based genotypes of yersinia pestis, china]. 201222883187
sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?plague, a disease caused by yersinia pestis introduced into north america about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. alternative approaches to plague manag ...201222846964
bioluminescence imaging to track bacterial dissemination of yersinia pestis using different routes of infection in mice.plague is caused by yersinia pestis, a bacterium that disseminates inside of the host at remarkably high rates. plague bacilli disrupt normal immune responses in the host allowing for systematic spread that is fatal if left untreated. how y. pestis disseminates from the site of infection to deeper tissues is unknown. dissemination studies for plague are typically performed in mice by determining the bacterial burden in specific organs at various time points. to follow bacterial dissemination dur ...201222827851
serine/threonine acetylation of tgfβ-activated kinase (tak1) by yersinia pestis yopj inhibits innate immune signaling.the gram-negative bacteria yersinia pestis, causative agent of plague, is extremely virulent. one mechanism contributing to y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, yops, directly into immune cells of the infected host. one of these yop proteins, yopj, is proapoptotic and inhibits mammalian nf-κb and map-kinase signal transduction pathways. although the molecular mechanism remained elusive for some time, recent work has shown that yop ...201222802624
evolution and virulence contributions of the autotransporter proteins yapj and yapk of yersinia pestis co92 and their homologs in y. pseudotuberculosis ip32953.yersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogen yersinia pseudotuberculosis. both species have numerous type va autotransporters, most of which appear to be highly conserved. in y. pestis co92, the autotransporter genes yapk and yapj share a high level of sequence identity. by comparing yapk and yapj to three homologous genes in y. pseudotuberculosis ip32953 (yptb0365, yptb3285, and yptb3286), we show that yapk is conserved in y. pseudotuberculosis, whi ...201222802344
yersinia pestis autoagglutination is mediated by hcp-like protein and siderophore yersiniachelin (ych). 201222782775
yersinia pestis transition metal divalent cation transporters. 201222782773
substrates of the plasminogen activator protease of yersinia pestis. 201222782771
biofilm-dependent and biofilm-independent mechanisms of transmission of yersinia pestis by fleas. 201222782769
impact on the host of the yersinia pestis-specific virulence set and the contribution of the pla surface protease. 201222782765
the life stage of yersinia pestis in the flea vector confers increased resistance to phagocytosis and killing by murine polymorphonuclear leukocytes. 201222782759
innate immune responses during infection with yersinia pestis. 201222782758
[standard algorithm of molecular typing of yersinia pestis strains].development of the standard algorithm of molecular typing of yersinia pestis that ensures establishing of subspecies, biovar and focus membership of the studied isolate. determination of the characteristic strain genotypes of plague infectious agent of main and nonmain subspecies from various natural foci of plague of the russian federation and the near abroad.201222830271
yersinia pestis versus yersinia pseudotuberculosis: effects on host macrophages.yersinia pestis, the causative agent of plague, is proved to be a recently emerged clone from y. pseudotuberculosis. however, the diseases they cause and their patterns of transmission are very different. people always focus on the genetic changes between y. pestis and y. pseudotuberculosis to reveal their pathogenic differences, and little is known about host defence differences to these two yersinia. in this study, the effects of y. pestis and y. pseudotuberculosis on macrophages were analysed ...201222882408
pulmonary infection by yersinia pestis rapidly establishes a permissive environment for microbial proliferation.disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. during the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. in a coinfection model of pneumonic plague, it appears that yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. yersinia pseudotube ...201222308352
large is fast, small is tight: determinants of speed and affinity in subunit capture by a periplasmic chaperone.the chaperone/usher pathway assembles surface virulence organelles of gram-negative bacteria, consisting of fibers of linearly polymerized protein subunits. fiber subunits are connected through 'donor strand complementation': each subunit completes the immunoglobulin (ig)-like fold of the neighboring subunit by donating the seventh β-strand in trans. whereas the folding of ig domains is a fast first-order process, folding of ig modules into the fiber conformation is a slow second-order process. ...201222321795
evaluation and modification of off-host flea collection techniques used in northwest uganda: laboratory and field studies.quantifying the abundance of host-seeking fleas is critical for assessing risk of human exposure to flea-borne disease agents, including yersinia pestis, the etiological agent of plague. yet, reliable measures of the efficacy of existing host-seeking flea collection methods are lacking. in this study, we compare the efficacy of passive and active methods for the collection of host-seeking fleas in both the laboratory and human habitations in a plague-endemic region of northwest uganda. in the la ...201222308790
structural and mechanistic studies of pesticin, a bacterial homolog of phage lysozymes.yersinia pestis produces and secretes a toxin named pesticin that kills related bacteria of the same niche. uptake of the bacteriocin is required for activity in the periplasm leading to hydrolysis of peptidoglycan. to understand the uptake mechanism and to investigate the function of pesticin, we combined crystal structures of the wild type enzyme, active site mutants, and a chimera protein with in vivo and in vitro activity assays. wild type pesticin comprises an elongated n-terminal transloca ...201222593569
rapid identification and antibiotic susceptibility testing of yersinia pestis using bioluminescent reporter phage.the rapid identification and antibiotic susceptibility testing of yersinia pestis is paramount for a positive prognosis. we previously engineered a y. pestis-specific 'bioluminescent' reporter phage for the identification of y. pestis. in this study, we generated an improved reporter phage and evaluated the ability of this phage to provide direct and rapid susceptibility testing. compared to the first generation reporter, the second generation reporter exhibited a 100-fold increase in signal str ...201222579583
using comparative genomics for inquiry-based learning to dissect virulence of escherichia coli o157:h7 and yersinia pestis.genomics and bioinformatics are topics of increasing interest in undergraduate biological science curricula. many existing exercises focus on gene annotation and analysis of a single genome. in this paper, we present two educational modules designed to enable students to learn and apply fundamental concepts in comparative genomics using examples related to bacterial pathogenesis. students first examine alignments of genomes of escherichia coli o157:h7 strains isolated from three food-poisoning o ...201222383620
plague in the genomic area.with plague being not only a subject of interest for historians, but still a disease of public health concern in several countries, mainly in africa, there were hopes that analyses of the yersinia pestis genomes would put an end to this deadly epidemic pathogen. genomics revealed that y. pestis isolates evolved from yersinia pseudotuberculosis in central asia some millennia ago, after the acquisition of two y. pestis-specific plasmids balanced genomic reduction parallel with the expansion of ins ...201222369155
the yersinia pestis rcs phosphorelay inhibits biofilm formation by repressing transcription of the diguanylate cyclase gene hmst.yersinia pestis, which causes bubonic plague, forms biofilms in fleas, its insect vectors, as a means to enhance transmission. biofilm development is positively regulated by hmst, encoding a diguanylate cyclase that synthesizes the bacterial second messenger cyclic-di-gmp. biofilm development is negatively regulated by the rcs phosphorelay signal transduction system. in this study, we show that rcs-negative regulation is accomplished by repressing transcription of hmst.201222328676
construction and screening of attenuated δphop/q salmonella typhimurium vectored plague vaccine candidates.preclinical studies evaluating plague vaccine candidates have demonstrated that the f1 and v protein antigens of yersinia pestis confer protection against challenge from virulent strains. live-attenuated δphop/q salmonella typhimurium recombinants were constructed expressing either f1, v antigens, f1 and v antigens, or a f1-v fusion from asd (+) balanced-lethal plasmids. to improve antigen delivery, genes encoding plague antigens were modified in order to localize antigens to specific bacterial ...201222327496
evidence of yersinia pestis dna from fleas in an endemic plague area of zambia.yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. the disease is usually transmitted among wild rodents through a flea vector. the sources and routes of transmission of plague are poorly researched in africa, yet remains a concern in several sub-saharan countries. in zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenan ...201222280795
structural insights into ripc, a putative citrate lyase β subunit from a yersinia pestis virulence operon.yersinia pestis remains a threat, with outbreaks of plague occurring in rural areas and its emergence as a weapon of bioterrorism; thus, an improved understanding of its various pathogenicity pathways is warranted. the rip (required for intracellular proliferation) virulence operon is required for y. pestis survival in interferon-γ-treated macrophages and has been implicated in lowering macrophage-produced nitric oxide levels. ripc, one of three gene products from the rip operon, is annotated as ...201222232161
alexandre yersin's explorations (1892-1894) in french indochina before the discovery of the plague bacillus.alexandre yersin, the great french discoverer of yersinia pestis, was a keen explorer of unknown lands. at the age of 30, a member of the french colonial health service, he set off to fulfil his intimate dream and explore other continents. for almost two years and three long expeditions, he journeyed through widely unknown regions in the province of the french indochina, in southeast asia, territories of vietnam, cambodia and laos. this article presents vignettes from his explorations. during hi ...201223560756
crystallization and preliminary x-ray diffraction analysis of psaa, the adhesive pilin subunit that forms the ph 6 antigen on the surface of yersinia pestis.yersinia pestis has been responsible for a number of high-mortality epidemics throughout human history. like all other bacterial infections, the pathogenesis of y. pestis begins with the attachment of bacteria to the surface of host cells. at least five surface proteins from y. pestis have been shown to interact with host cells. psa, the ph 6 antigen, is one of them and is deployed on the surface of bacteria as thin flexible fibrils that are the result of the polymerization of a single psaa pili ...201223027758
complex network analysis in microbial systems: theory and examples.an essential idea in the area of systems biology is that a good understanding of interactions between components is crucial for developing deep knowledge of the functioning of the system as a whole. network analysis is an approach uniquely suited to uncover patterns and organizing principles in a wide variety of complex systems. in this chapter, we will give a detailed description of central network concepts and their algorithmic implementation, and demonstrate how they may be applied on two bio ...201222639226
rapid detection and antimicrobial resistance gene profiling of yersinia pestis using pyrosequencing technology.when a bioterrorism attack is attempted or perpetrated there is considerable risk for public health and large scale socioeconomic consequences. it is imperative that we possess established assays for the rapid identification of biothreat agents with high sensitivity and specificity to ensure emergency response measures can be deployed appropriately. highly trustworthy information within a relevant timeframe is required to make a rapid and informed decision. obtaining dna sequence data from a sus ...201222634001
comparative genomic analysis of gene variations of two chinese yersinia pestis isolates from vaccine strain ev76.to investigate genomic variations of two chinese yersinia pestis isolates that were isolated from different plague foci obtained from vaccine strain ev76 from the yunnan province of china.201223026524
improvement of disease prediction and modeling through the use of meteorological ensembles: human plague in uganda.climate and weather influence the occurrence, distribution, and incidence of infectious diseases, particularly those caused by vector-borne or zoonotic pathogens. thus, models based on meteorological data have helped predict when and where human cases are most likely to occur. such knowledge aids in targeting limited prevention and control resources and may ultimately reduce the burden of diseases. paradoxically, localities where such models could yield the greatest benefits, such as tropical re ...201223024750
conjugation of y. pestis f1-antigen to gold nanoparticles improves immunogenicity.the efficacy of 15 nm gold nanoparticles (aunp) coated with yersinia pestis f1-antigen, as an immunogen in mice, has been assessed. the nanoparticles were decorated with f1-antigen using n-hydroxysuccinimide and n-(3-dimethylaminopropyl)-n'-ethylcarbodiimide hydrochloride coupling chemistry. mice given aunp-f1 in alhydrogel generated the greatest igg antibody response to f1-antigen when compared with mice given aunp-f1 in pbs or given unconjugated f1-antigen in pbs or alhydrogel. compared with u ...201223000121
[the phylogeography of the yersinia pestis vole strains isolated from the natural foci of caucasian region].57 y pestis bv. caucasica strains were assayed using molecular typing. the results of these assays indicated the presence within this biovar of the three separate clonal clusters and necessity of detachment of the leninakan mountain mesofocus (subfocus) from the structure of transcaucasian-highland focus into self-supporting one, as well as inclusion of a part of the pre-araks low-mountain natural plague focus in the capacity of the subfocus along with pre-sevan mountain and zanzegur-karabakh mo ...201222984768
modern advances against plague.plague has been a scourge of humanity, responsible for the deaths of millions. the etiological agent, yersinia pestis, has evolved relatively recently from an enteropathogen, yersinia pseudotuberculosis. the evolution of the plague pathogen has involved a complex series of genetic acquisitions, deletions, and rearrangements in its transition from an enteric niche to becoming a systemic, flea-vectored pathogen. with the advent of modern molecular biology techniques, we are starting to understand ...201222958531
induction of pulmonary mucosal immune responses with a protein vaccine targeted to the dec-205/cd205 receptor.it is of great interest to develop a pneumonic plague vaccine that would induce combined humoral and cellular immunity in the lung. here we investigate a novel approach based on targeting of dendritic cells using the dec-205/cd205 receptor (dec) via the intranasal route as way to improve mucosal cellular immunity to the vaccine. intranasal administration of yersinia pestis lcrv (v) protein fused to anti-dec antibody together with poly ic as an adjuvant induced high frequencies of ifn-γ secreting ...201222947140
yersinia pestis and approaches to targeting its outer protein h protein-tyrosine phosphatase (yoph).plague is an infectious disease with a high mortality rate that has repeatedly impacted human society. it remains a threat in many parts of the world today. plague is caused by the bacterium, yersinia pestis (y. pestis), which has as one of its required virulence factors, the protein-tyrosine phosphatase, yoph. therefore, yoph represents a potential target for the treatment of y. pestis infection. recent recognition of y. pestis as a possible bioterrorism agent and the fact that it is still the ...201222934808
the effect of low shear force on the virulence potential of yersinia pestis: new aspects that space-like growth conditions and the final frontier can teach us about a formidable pathogen.manned space exploration has created a need to evaluate the effects of space-like stress (sls) on pathogenic and opportunistic microbes. interestingly, several gram-negative enteric pathogens, e.g., salmonella enterica serovar typhimurium, have revealed a transient hyper-virulent phenotype following simulated microgravity (smg) or actual space flight exposures. we have explored the virulence potential of yersinia pestis kim/d27 (yp) following exposure to mechanical low shear forces associated wi ...201222919696
identification of chromosomal genes in yersinia pestis that influence type iii secretion and delivery of yops into target cells.pathogenic yersinia species possess a type iii secretion system, which is required for the delivery of effector yop proteins into target cells during infection. genes encoding the type iii secretion machinery, its substrates, and several regulatory proteins all reside on a 70-kb virulence plasmid. genes encoded in the chromosome of yersiniae are thought to play important roles in bacterial perception of host environments and in the coordinated activation of the type iii secretion pathway. here, ...201222479512
a curve of thresholds governs plague epizootics in central asia.a core concept of infectious disease epidemiology is the abundance threshold, below which an infection is unable to invade or persist. there have been contrasting theoretical predictions regarding the nature of this threshold for vector-borne diseases, but for infections with an invertebrate vector, it is common to assume a threshold defined by the ratio of vector and host abundances. here, we show in contrast, both from field data and model simulations, that for plague (yersinia pestis) in kaza ...201222449078
yersinia pestis ail: multiple roles of a single protein.yersinia pestis is one of the most virulent bacteria identified. it is the causative agent of plague-a systemic disease that has claimed millions of human lives throughout history. y. pestis survival in insect and mammalian host species requires fine-tuning to sense and respond to varying environmental cues. multiple y. pestis attributes participate in this process and contribute to its pathogenicity and highly efficient transmission between hosts. these include factors inherited from its enteri ...201222919692
the nlrp12 inflammasome recognizes yersinia pestis.yersinia pestis, the causative agent of plague, is able to suppress production of inflammatory cytokines il-18 and il-1β, which are generated through caspase-1-activating nucleotide-binding domain and leucine-rich repeat (nlr)-containing inflammasomes. here, we sought to elucidate the role of nlrs and il-18 during plague. lack of il-18 signaling led to increased susceptibility to y. pestis, producing tetra-acylated lipid a, and an attenuated strain producing a y. pseudotuberculosis-like hexa-acy ...201222840842
evolution of a novel lysine decarboxylase in siderophore biosynthesis.structural backbones of iron-scavenging siderophore molecules include polyamines 1,3-diaminopropane and 1,5-diaminopentane (cadaverine). for the cadaverine-based desferroxiamine e siderophore in streptomyces coelicolor, the corresponding biosynthetic gene cluster contains an orf encoded by desa that was suspected of producing the cadaverine (decarboxylated lysine) backbone. however, desa encodes an l-2,4-diaminobutyrate decarboxylase (daba dc) homologue and not any known form of lysine decarboxy ...201222906379
hereditary hemochromatosis restores the virulence of plague vaccine strains.nonpigmented yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. recently, a y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. we used hemojuvelin-knockout (hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented y. pestis. unlike wild-type mice, hjv(-/-) mice developed lethal plague wh ...201222896664
poly-n-acetylglucosamine expression by wild-type yersinia pestis is maximal at mammalian, not flea, temperatures.numerous bacteria, including yersinia pestis, express the poly-n-acetylglucosamine (pnag) surface carbohydrate, a major component of biofilms often associated with a specific appearance of colonies on congo red agar. biofilm formation and pnag synthesis by y. pestis have been reported to be maximal at 21 to 28°c or "flea temperatures," facilitating the regurgitation of y. pestis into a mammalian host during feeding, but production is diminished at 37°c and thus presumed to be decreased during ma ...201222893384
field and clinical applications of advanced bacteriophage-based detection of yersinia pestis. 201222782756
consequences of missense mutations in yersinia pestis: efficient flow of metabolic carbon versus virulence. 201222782743
structure of the cytoplasmic domain of yersinia pestis yscd, an essential component of the type iii secretion system.the yersinia pestis yscd protein is an essential component of the type iii secretion system. yscd consists of an n-terminal cytoplasmic domain (residues 1-121), a transmembrane linker (122-142) and a large periplasmic domain (143-419). both the cytoplasmic and the periplasmic domains are required for the assembly of the type iii secretion system. here, the structure of the yscd cytoplasmic domain solved by sad phasing is presented. although the three-dimensional structure is similar to those of ...201222349221
an encapsulated yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. we previously reported that oral inoculation of a live attenuated yersinia pseudotuberculosis, the recent ancestor of yersinia pestis, provided protection against bubonic plague. however, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined.201222348169
immuno-pcr--a new tool for paleomicrobiology: the plague paradigm.the cause of past plague pandemics was controversial but several research teams used pcr techniques and dental pulp as the primary material to reveal that they were caused by yersinia pestis. however, the degradation of dna limits the ability to detect ancient infections.201222347507
establishment of a swiss webster mouse model of pneumonic plague to meet essential data elements under the animal rule.a recombinant vaccine (rf1v) is being developed for protection against pneumonic plague. this study was performed to address essential data elements to establish a well-characterized swiss webster mouse model for licensing the rf1v vaccine using the fda's animal rule. these elements include the documentation of challenge material characteristics, aerosol exposure parameters, details of the onset and severity of clinical signs, pathophysiological response to disease, and relevance to human diseas ...201222336286
[determination of genetic bases of auxotrophy in yersinia pestis ssp. caucasica strains].based on the results of computer analysis of nucleotide sequences in strains yersinia pestis and y. pseudotuberculosis recorded in the files of ncbi genbank database, differences between genes arga, arog, arof, thih, and thig of strain pestoides f (subspecies caucasica) were found, compared to other strains of plaque agent and pseudotuberculosis microbe. using pcr with calculated primers and the method of sequence analysis, the structure of variable regions of these genes was studied in 96 natur ...201222730764
immune responses to plague infection in wild rattus rattus, in madagascar: a role in foci persistence?plague is endemic within the central highlands of madagascar, where its main reservoir is the black rat, rattus rattus. typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. however, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. immunity against plague a ...201222719908
misidentification of yersinia pestis by automated systems, resulting in delayed diagnoses of human plague infections--oregon and new mexico, 2010-2011.one human plague case was reported in oregon in september 2010 and another in new mexico in may 2011. misidentification of yersinia pestis by automated identification systems contributed to delayed diagnoses for both cases.201222715170
structural basis for activation of an integral membrane protease by lipopolysaccharide.omptins constitute a unique family of outer membrane proteases that are widespread in enterobacteriaceae. the plasminogen activator (pla) of yersinia pestis is an omptin family member that is very important for development of both bubonic and pneumonic plague. the physiological function of pla is to cleave (activate) human plasminogen to form the plasma protease plasmin. uniquely, lipopolysaccharide (lps) is essential for the catalytic activity of all omptins, including pla. why omptins require ...201222645135
vulnerabilities in yersinia pestis caf operon are unveiled by a salmonella vector.during infection, yersinia pestis uses its f1 capsule to enhance survival and cause virulence to mammalian host. since f1 is produced in large quantities and secreted into the host tissues, it also serves as a major immune target. to hold this detrimental effect under proper control, y. pestis expresses the caf operon (encoding the f1 capsule) in a temperature-dependent manner. however, additional properties of the caf operon limit its expression. by overexpressing the caf operon in wild-type sa ...201222558420
a yersinia pestis yscn atpase mutant functions as a live attenuated vaccine against bubonic plague in mice.yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. the bacterium uses the plcr plasmid-encoded type iii secretion system to deliver virulence factors into host cells. delivery requires atp hydrolysis by the yscn atpase encoded by the yscn gene also on plcr. a yscn mutant was constructed in the fully virulent co92 strain containing a nonpolar, in-frame internal deletion within the gene. we demonstrate that co92 with a yscn mutation was not able to secrete the lcr ...201222537022
flea diversity as an element for persistence of plague bacteria in an east african plague focus.plague is a flea-borne rodent-associated zoonotic disease that is caused by yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. how plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. existing hypotheses of how y. pestis is maintained within plague foci t ...201222530057
gene expression analysis of xenopsylla cheopis (siphonaptera: pulicidae) suggests a role for reactive oxygen species in response to yersinia pestis infection.fleas are vectors for a number of pathogens including yersinia pestis, yet factors that govern interactions between fleas and y. pestis are not well understood. examining gene expression changes in infected fleas could reveal pathways that affect y. pestis survival in fleas and subsequent transmission. we used suppression subtractive hybridization to identify genes that are induced in xenopsylla cheopis (rothschild) (siphonaptera: pulicidae) in response to oral or hemocoel infection with y. pest ...201222493856
vespa: software to facilitate genomic annotation of prokaryotic organisms through integration of proteomic and transcriptomic data.the procedural aspects of genome sequencing and assembly have become relatively inexpensive, yet the full, accurate structural annotation of these genomes remains a challenge. next-generation sequencing transcriptomics (rna-seq), global microarrays, and tandem mass spectrometry (ms/ms)-based proteomics have demonstrated immense value to genome curators as individual sources of information, however, integrating these data types to validate and improve structural annotation remains a major challen ...201222480257
ail protein binds ninth type iii fibronectin repeat (9fniii) within central 120-kda region of fibronectin to facilitate cell binding by yersinia pestis.the yersinia pestis adhesin molecule ail interacts with the extracellular matrix protein fibronectin (fn) on host cells to facilitate efficient delivery of cytotoxic yop proteins, a process essential for plague virulence. a number of bacterial pathogens are known to bind to the n-terminal region of fn, comprising type i fn (fni) repeats. using proteolytically generated fn fragments and purified recombinant fn fragments, we demonstrated that ail binds the centrally located 120-kda fragment contai ...201222447929
the natural history and incidence of yersinia pestis and prospects for vaccination.plague is an ancient, serious, infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. this paper discusses the natural history of the bacterium and its evolution into a flea-vectored bacterium able to transmit bubonic plague. it reviews the incidence of plague in the modern world and charts the history of vaccines which have been used to protect against the flea-vectored disease, which erupts as bubonic plague. current approaches to vaccine d ...201222442294
identification by cdna cloning of abundant srnas in a human-avirulent yersinia pestis strain grown under five different growth conditions.srna regulation is supposedly involved in the stress response of a pathogen during infection. yersinia pestis, the etiologic agent of plague, must encounter temperature and microenvironment changes, given its lifestyle. here, we used the cdna cloning approach to discover full-length srna candidates that are highly expressed in y. pestis under five different growth conditions.201222439729
use of a public telephone hotline to detect urban plague cases.current methods for vector-borne disease surveillance are limited by time and cost. to avoid human infections from emerging zoonotic diseases, it is important that the united states develop cost-effective surveillance systems for these diseases. this study examines the methodology used in the surveillance of a plague epizootic involving tree squirrels (sciurus niger) in denver colorado, during the summer of 2007. a call-in centre for the public to report dead squirrels was used to direct animal ...201222429398
yersinia--flea interactions and the evolution of the arthropod-borne transmission route of plague.yersinia pestis, the causative agent of plague, is unique among the enteric group of gram-negative bacteria in relying on a blood-feeding insect for transmission. the yersinia-flea interactions that enable plague transmission cycles have had profound historical consequences as manifested by human plague pandemics. the arthropod-borne transmission route was a radical ecologic change from the food-borne and water-borne transmission route of yersinia pseudotuberculosis, from which y. pestis diverge ...201222406208
yersinia pestis: examining wildlife plague surveillance in china and the usa.plague is a zoonotic disease caused by the bacterium yersinia pestis lehmann and neumann, 1896. although it is essentially a disease of rodents, plague can also be transmitted to people. historically, plague has caused massive morbidity and mortality events in human populations, and has recently been classified as a reemerging disease in many parts of the world. this public health threat has led many countries to set up wild and domestic animal surveillance programs in an attempt to monitor plag ...201222405453
contrasted patterns of selection on mhc-linked microsatellites in natural populations of the malagasy plague reservoir.plague (yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. the black rat (rattus rattus) is the main host involved in the plague focus of the central highlands of madagascar. black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of madagascar) are susceptible. various lines of evidence suggest a role for the major histocompatibility complex (mhc) in pla ...201222403713
role of a new intimin/invasin-like protein in yersinia pestis virulence.a comprehensive tnphoa mutant library was constructed in yersinia pestis kim6 to identify surface proteins involved in y. pestis host cell invasion and bacterial virulence. insertion site analysis of the library repeatedly identified a 9,042-bp chromosomal gene (ypo3944), intimin/invasin-like protein (ilp), similar to the gram-negative intimin/invasin family of surface proteins. deletion mutants of ilp were generated in y. pestis strains kim5(pcd1(+)) pgm(-) (pigmentation negative)/, kim6(pcd1(- ...201222851752
roles of chaperone/usher pathways of yersinia pestis in a murine model of plague and adhesion to host cells.yersinia pestis and many other gram-negative pathogenic bacteria use the chaperone/usher (cu) pathway to assemble virulence-associated surface fibers termed pili or fimbriae. y. pestis has two well-characterized cu pathways: the caf genes coding for the f1 capsule and the psa genes coding for the ph 6 antigen. the y. pestis genome contains additional cu pathways that are capable of assembling pilus fibers, but the roles of these pathways in the pathogenesis of plague are not understood. we const ...201222851745
yersinia pestis intracellular parasitism of macrophages from hosts exhibiting high and low severity of plague.yersinia pestis causes severe disease in natural rodent hosts, but mild to inapparent disease in certain rodent predators such as dogs. y. pestis initiates infection in susceptible hosts by parasitizing and multiplying intracellularly in local macrophages prior to systemic dissemination. thus, we hypothesize that y. pestis disease severity may depend on the degree to which intracellular y. pestis overcomes the initial host macrophage imposed stress.201222848745
use of rich bhi medium instead of synthetic tmh medium for gene regulation study in yersinia pestis.this study is to verify the use of rich bhi medium to substitute synthetic media for gene regulation studies in yersinia pestis.201223228833
hunger for iron: the alternative siderophore iron scavenging systems in highly virulent yersinia.low molecular weight siderophores are used by many living organisms to scavenge scarcely available ferric iron. presence of at least a single siderophore-based iron acquisition system is usually acknowledged as a virulence-associated trait and a pre-requisite to become an efficient and successful pathogen. currently, it is assumed that yersiniabactin (ybt) is the solely functional endogenous siderophore iron uptake system in highly virulent yersinia (yersinia pestis, y. pseudotuberculosis, and y ...201223226687
genetic diversity of yersinia pestis in brazil.plague outbreaks are occasionally reported in brazil. unfortunately, due to great genetic similarity, molecular subtyping of yersinia pestis strains is difficult. analysis of multiple-locus variable number of tandem repeats (vntr), also known as mlva, has been found to be a valuable tool to discriminate among strains. to check for genetic differences, strains obtained from two different ecological complexes in brazil collected during two different epidemiological events, an epizootic in sítio al ...201223079835
dynamics of yersinia pestis and its antibody response in great gerbils (rhombomys opimus) by subcutaneous infection.rhombomys opimus (great gerbil) is a reservoir of yersinia pestis in the natural plague foci of central asia. great gerbils are highly resistant to y. pestis infection. the coevolution of great gerbils and y. pestis is believed to play an important role in the plague epidemics in central asia plague foci. however, the dynamics of y. pestis infection and the corresponding antibody response in great gerbils have not been evaluated. in this report, animal experiments were employed to investigate th ...201223071647
lipopolysaccharide of yersinia pestis, the cause of plague: structure, genetics, biological properties.the present review summarizes data pertaining to the composition and structure of the carbohydrate moiety (core oligosaccharide) and lipid component (lipid a) of the various forms of lipopolysaccharide (lps), one of the major pathogenicity factors ofyersinia pestis, the cause of plague. the review addresses the functions and the biological significance of genes for the biosynthesis of lps, as well as the biological properties of lps in strains from various intraspecies groups ofy. pestis and the ...201223150803
cell-mediated immune response to epitopic map (multiple antigen peptide) construct of lcrv antigen of yersinia pestis in murine model.yersinia pestis is the causative agent of plague. cellular immunity seems to play an important role in defense against this disease. the subunit vaccine based on v (lcr v) antigen has been proved to be immunogenic in animals and in humans. the multiple antigen peptide (map), incorporating all the relevant b and t cell epitopes is highly immunogenic in mice through intranasal route of immunization in plga particles containing cpg-odn as an immunoadjuvant inducing humoral and mucosal immune respon ...201223121976
plague vaccines: current developments and future perspectives.despite many decades of intensive studies of yersinia pestis, the causative agent of plague, there is no safe and efficient vaccine against this devastating disease. a recently developed f1/v subunit vaccine candidate, which relies mainly on humoral immunity, showed promising results in animal studies; however, its efficacy in humans still has to be carefully evaluated. in addition, those developing next-generation plague vaccines need to pay particular attention to the importance of eliciting c ...201226038406
rapid detection and identification of yersinia pestis from food using immunomagnetic separation and pyrosequencing.interest has recently been renewed in the possible use of y. pestis, the causative agent of plague, as a biological weapon by terrorists. the vulnerability of food to intentional contamination coupled with reports of humans having acquired plague through eating infected animals that were not adequately cooked or handling of meat from infected animals makes the possible use of y. pestis in a foodborne bioterrorism attack a reality. rapid, efficient food sample preparation and detection systems th ...201223091729
genome-level transcription data of yersinia pestis analyzed with a new metabolic constraint-based approach.constraint-based computational approaches, such as flux balance analysis (fba), have proven successful in modeling genome-level metabolic behavior for conditions where a set of simple cellular objectives can be clearly articulated. recently, the necessity to expand the current range of constraint-based methods to incorporate high-throughput experimental data has been acknowledged by the proposal of several methods. however, these methods have rarely been used to address cellular metabolic respon ...201223216785
yersinia pestis: new evidence for an old infection.the successful reconstruction of an ancient bacterial genome from archaeological material presents an important methodological advancement for infectious disease research. the reliability of evolutionary histories inferred by the incorporation of ancient data, however, are highly contingent upon the level of genetic diversity represented in modern genomic sequences that are publicly accessible, and the paucity of available complete genomes restricts the level of phylogenetic resolution that can ...201223209603
host stress and immune responses during aerosol challenge of brown norway rats with yersinia pestis.inhalation exposure models are becoming the preferred method for the comparative study of respiratory infectious diseases due to their resemblance to the natural route of infection. to enable precise delivery of pathogen to the lower respiratory tract in a manner that imposes minimal biosafety risk, nose-only exposure systems have been developed. early inhalation exposure technology for infectious disease research grew out of technology used in asthma research where predominantly the collison ne ...201223226684
acquisition of maternal antibodies both from the placenta and by lactation protects mouse offspring from yersinia pestis challenge.artificially passive immunization has been demonstrated to be effective against yersinia pestis infection in animals. however, maternal antibodies' protective efficacy against plague has not yet been demonstrated. here, we evaluated the kinetics, protective efficacy, and transmission modes of maternal antibodies, using mice immunized with plague subunit vaccine sv1 (20 μg of f1 and 10 μg of rv270). the results showed that the rv270- and f1-specific antibodies could be detected in the sera of new ...201222933398
evaluation of the infectiousness to mice of soil contaminated with yersinia pestis-infected blood.plague, an often-fatal zoonotic disease caused by yersinia pestis, is characterized by epizootic and quiescent periods. how y. pestis is maintained during inter-epizootic periods is poorly understood, but soil has been implicated as a potential reservoir. although previous studies have suggested that y. pestis is able to survive in soil for weeks or months, it is unclear whether or not it is infectious to susceptible hosts. here we investigate the potential for y. pestis to infect mice through c ...201222925020
the yersinia virulence effector yopm binds caspase-1 to arrest inflammasome assembly and processing.inflammasome assembly activates caspase-1 and initiates the inflammatory cell death program pyroptosis, which is protective against numerous pathogens. consequently, several pathogens, including the plague causing bacterium yersinia pestis, avoid activating this pathway to enhance their virulence. however, bacterial molecules that directly modulate the inflammasome have yet to be identified. examining the contribution of yersinia type iii secretion effectors to caspase-1 activation, we identifie ...201223245324
toward a molecular pathogenic pathway for yersinia pestis yopm.yopm is one of the six "effector yops" of the human-pathogenic yersinia, but its mechanism has not been defined. after delivery to j774a.1 monocyte-like cells, yopm can rapidly bind and activate the serine/threonine kinases rsk1 and prk2. however, in infected mice, effects of y. pestis yopm have been seen only after 24-48 h post-infection (p.i.). to identify potential direct effects of yopm in-vivo we tested for effects of yopm at 1 h and 16-18 h p.i. in mice infected systemically with 10(6) bac ...201223248776
allosteric mechanism controls traffic in the chaperone/usher pathway.many virulence organelles of gram-negative bacterial pathogens are assembled via the chaperone/usher pathway. the chaperone transports organelle subunits across the periplasm to the outer membrane usher, where they are released and incorporated into growing fibers. here, we elucidate the mechanism of the usher-targeting step in assembly of the yersinia pestis f1 capsule at the atomic level. the usher interacts almost exclusively with the chaperone in the chaperone:subunit complex. in free chaper ...201222981947
kinetics of innate immune response to yersinia pestis after intradermal infection in a mouse model.a hallmark of yersinia pestis infection is a delayed inflammatory response early in infection. in this study, we use an intradermal model of infection to study early innate immune cell recruitment. mice were injected intradermally in the ear with wild-type (wt) or attenuated y. pestis lacking the pyv virulence plasmid (pyv(-)). the inflammatory responses in ear and draining lymph node samples were evaluated by flow cytometry and immunohistochemistry. as measured by flow cytometry, total neutroph ...201222966041
draft genome sequence of yersinia pestis strain 2501, an isolate from the great gerbil plague focus in xinjiang, china.we deciphered the genome of yersinia pestis strain 2501, isolated from the junggar basin, a newly discovered great gerbil plague focus in xinjiang, china. the total length of assembly was 4,597,322 bp, and 4,265 coding sequences were predicted within the genome. it is the first y. pestis genome from this plague focus.201222965078
[ecological-geographic landscapes of natural plague foci in china vii. typing of natural plague foci].to group and characterize natural plague foci in china.201223290901
fur is a repressor of biofilm formation in yersinia pestis.yersinia pestis synthesizes the attached biofilms in the flea proventriculus, which is important for the transmission of this pathogen by fleas. the hmshfrs operons is responsible for the synthesis of exopolysaccharide (the major component of biofilm matrix), which is activated by the signaling molecule 3', 5'-cyclic diguanylic acid (c-di-gmp) synthesized by the only two diguanylate cyclases hmst, and ypo0449 (located in a putative operonypo0450-0448).201223285021
identification of potential drug targets in yersinia pestis using metabolic pathway analysis: mure ligase as a case study.sporadic outbreaks of plague, lack of a vaccine, emergence of multidrug-resistant strains of yersinia pestis, and its potential use in bioterrorism, call for an urgent need to develop new drugs for plague. we have used comparative metabolic pathway analysis to identify 245 drug-target candidate enzymes in y. pestis co92 which are non-homologous to host homo sapiens and likely to be essential for the pathogen's survival. further analysis revealed that 25 of these are potential choke point enzymes ...201223059547
local persistence and extinction of plague in a metapopulation of great gerbil burrows, kazakhstan.speculation on how the bacterium yersinia pestis re-emerges after years of absence in the prebalkhash region in kazakhstan has been ongoing for half a century, but the mechanism is still unclear. one of the theories is that plague persists in its reservoir host (the great gerbil) in so-called hotspots, i.e. small regions in which the conditions remain favourable for plague to persist during times where the conditions in the prebalkhash region as a whole have become unfavourable for plague persis ...201223351373
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