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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
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
[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
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
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
[origin of the plague microbe yersinia pestis: structure of the process of speciation].the origin and evolution of the plague microbe yersinia pestis are considered in the context of propositions of modern darwinism. it was shown that the plague pathogen diverged from the pseudotuberculous microbe yersinia pseudotuberculosis o:1b in the mountain steppe landscapes of central asia in the sartan: 22000-15000 years ago. speciation occurred in the tarbagan (marmota sibirica)--flea (oropsylla silantiewi) parasitic system. the structure of the speciation process included six stages: isol ...201622567866
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
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
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
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
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
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
rational design of pathogen-mimicking amphiphilic materials as nanoadjuvants.an opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. this study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. biodegradable amphiphilic polyanhydrides possess the unique ...201122355713
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
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
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
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
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 analysis of genes participating in melibiose fermentation and isocitrate lyase production in yersinia pestis strains of main and non main subspecies].comparative analysis of nucleotide sequences of genes participating in melibiose fermentation and isocitrate lyase production was conducted in 90 natural yersinia pestis strains of main and non main subspecies. it was ascertained that the lack of the ability to utilize disaccharide melibiose in strains of the main subspecies is caused by integration of the insertion sequence is285 at 73 bp from the beginning of the structural gene melb that encodes the transport protein galactoside permease. in ...201122232920
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
virulence plasmid (pyv)-associated expression of phenotypic virulent determinants in pathogenic yersinia species: a convenient method for monitoring the presence of pyv under culture conditions and its application for isolation/detection of yersinia pestis in food.in yersinia pestis, y. pseudotuberculosis, and y. enterocolitica, phenotypic expression of virulence plasmid (pyv: 70-kb)-associated genetic determinants may include low-calcium response (lcr, pinpoint colony, size = 0.36 mm), colony morphology (size = 1.13 mm), crystal violet (cv) binding (dark-violet colony), congo red (cr) uptake (red pinpoint colony, size = 0.36 mm), autoagglutination (aa = cells agglutinate), and hydrophobicity (hp = clumping of cells). y. pseudotuberculosis is chromosomall ...201122567340
[study on genotypes and geographical distribution of 58 strains of yersinia pestis in gansu]. 201022993802
crispr elements in yersinia pestis acquire new repeats by preferential uptake of bacteriophage dna, and provide additional tools for evolutionary studies.the remarkable repetitive elements called crisprs (clustered regularly interspaced short palindromic repeats) consist of repeats interspaced with non-repetitive elements or 'spacers'. crisprs are present in both archaea and bacteria, in association with genes involved in dna recombination and repair. in the yersinia pestis genome, three such elements are found at three distinct loci, one of them being highly polymorphic. the authors have sequenced a total of 109 alleles of the three y. pestis cr ...200528202106
[effect of antibiotics on streptomycin-resistant and dependent strains of pasteurella pestis in the organism; experimental studies]. 195924545108
[streptomycin-resistant and streptomycin-dependent variants of the causative organism of pest]. 201424544058
yersinia pestis resists predation by acanthamoeba castellanii and exhibits prolonged intracellular survival.plague is a flea-borne rodent-associated zoonotic disease caused by yersinia pestis the disease is characterized by epizootics with high rodent mortalities, punctuated by interepizootic periods when the bacterium persists in an unknown reservoir. this study investigates the interaction between y. pestis and the ubiquitous soil free-living amoeba (fla) acanthamoeba castellanii to assess if the bacterium can survive within soil amoebae and whether intracellular mechanisms are conserved between inf ...201728455335
preparing for biological threats: addressing the needs of pregnant women.intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. we review what is known about the maternal and fetal effects of seven biological threats: bacillus anthracis (anthrax); variola virus (smallpox); clostridium botulinum toxin (botulism); burkholderia mallei (glanders) and burkholderia pseudomallei (melioidosis); yersinia pestis (plague); francisella tularensis (tularemia); and rickettsia ...201728398677
evidence of infection with leptospira interrogans and spotted fever group rickettsiae among rodents in an urban area of osaka city, japan.we examined 33 rodents captured in an urban area of osaka city, japan for igg antibodies against seoul virus, severe fever with thrombocytopenia syndrome virus, hepatitis e virus, leptospira interrogans, yersinia pestis, spotted fever, typhus and scrub typhus group rickettsiae. we found that 3 (9.1%) and 1 (3.0%) of the 33 rodents had antibodies against l. interrogans and spotted fever group rickettsiae, respectively. dnas of leptospires were detected from 2 of the 3 seropositive rodents, but dn ...201728529271
a bivalent anthrax-plague vaccine that can protect against two tier-1 bioterror pathogens, bacillus anthracis and yersinia pestis.bioterrorism remains as one of the biggest challenges to global security and public health. since the deadly anthrax attacks of 2001 in the united states, bacillus anthracis and yersinia pestis, the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the cdc as tier-1 biothreat agents. currently, there is no food and drug administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vacci ...201728694806
competition is the basis of the transport mechanism of the nhab na+/h+ exchanger from klebsiella pneumoniae.na+/h+ exchange is essential for survival of all organisms, having a role in the regulation of the intracellular na+ concentration, ph and cell volume. furthermore, na+/h+ exchangers were shown to be involved in the virulence of the bacterium yersinia pestis, indicating they might be potential targets for novel antibiotic treatments. the model system for na+/h+ exchangers is the nhaa transporter from escherichia coli, ecnhaa. therefore, the general transport mechanism of nhaa exchangers is curre ...201728750048
crispr-cas12a-assisted recombineering in bacteria.clustered regularly interspaced short palindromic repeat (crispr)-cas12a (cpf1) has emerged as an effective genome editing tool in many organisms. here, we developed and optimized a crispr-cas12a-assisted recombineering system to facilitate genetic manipulation in bacteria. using this system, point mutations, deletions, insertions, and gene replacements can be easily generated on the chromosome or native plasmids in escherichia coli, yersinia pestis, and mycobacterium smegmatis because crispr-ca ...201728646112
functionalization promotes pathogen-mimicking characteristics of polyanhydride nanoparticle adjuvants.rational design of adjuvants and delivery systems will promote development of next-generation vaccines to control emerging and re-emerging diseases. to accomplish this, understanding the immune-enhancing properties of new adjuvants relative to those induced by natural infections can help with the development of pathogen-mimicking materials that will effectively initiate innate immune signaling cascades. in this work, the surfaces of polyanhydride nanoparticles composed of sebacic acid (sa) and 1 ...201728556563
rationally designed tlr4 ligands for vaccine adjuvant discovery.adjuvant properties of bacterial cell wall components like mpla (monophosphoryl lipid a) are well described and have gained fda approval for use in vaccines such as cervarix. mpla is the product of chemically modified lipooligosaccharide (los), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are fe ...201728487429
disease surveillance of california ground squirrels ( spermophilus beecheyi ) in a drive-through zoo in oregon, usa.rodents and other small wild mammals are often considered to be pests and vectors for disease in zoos that house small populations of valuable threatened and endangered animals. in 2005, three nonhuman primates at a drive-through zoo in oregon, us, acquired tularemia from an unknown source. due to an abundance of california ground squirrels ( spermophilus beecheyi ) on zoo grounds, we instituted serosurveillance of this species from july through september 2008 to determine the prevalence of anti ...201728418764
aggregation-induced-emission materials with different electric charges as an artificial tongue: design, construction, and assembly with various pathogenic bacteria for effective bacterial imaging and discrimination.imaging-based total bacterial count and type identification of bacteria play crucial roles in clinical diagnostics, public health, biological and medical science, and environmental protection. herein, we designed and synthesized a series of tetraphenylethenes (tpes) functionalized with one or two aldehyde, carboxylic acid, and quaternary ammonium groups, which were successfully used as fluorescent materials for rapid and efficient staining of eight kinds of representative bacterial species, incl ...201728809473
responses of juvenile black-tailed prairie dogs ( cynomys ludovicianus ) to a commercially produced oral plague vaccine delivered at two doses.we confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (rcn-f1/v307) expressing yersinia pestis v and f1 antigens. forty-five juvenile black-tailed prairie dogs ( cynomys ludovicianus ) were randomly divided into three treatment groups (n=15 animals/group). animals in the first group received one standard-dose vaccine bait (5×10(7) plaque-forming units [pfu]; std). the second group received a lower-dose bait (1×10(7) pfu; ...201728463626
draft genome sequence of the luminescent strain vibrio campbellii lb102, isolated from a black tiger shrimp (penaeus monodon) broodstock rearing system.we report here the genome sequence of vibrio campbellii lb102, isolated from the broodstock rearing system of a shrimp hatchery in india. sequence analysis revealed the presence of effector toxins of the type iii (yopt, sharing 39% identity with yersinia pestis) and type vi (vgrg-3 and hemolysin coregulated protein of v. cholerae) secretion systems.201728522707
protein abundances can distinguish between naturally-occurring and laboratory strains of yersinia pestis, the causative agent of plague.the rapid pace of bacterial evolution enables organisms to adapt to the laboratory environment with repeated passage and thus diverge from naturally-occurring environmental ("wild") strains. distinguishing wild and laboratory strains is clearly important for biodefense and bioforensics; however, dna sequence data alone has thus far not provided a clear signature, perhaps due to lack of understanding of how diverse genome changes lead to convergent phenotypes, difficulty in detecting certain type ...201728854255
characterization of yersinia pestis interactions with human neutrophils in vitro.yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. the bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and y. pestis have been demonstrated in vivo. in contrast to macrophages, neutrophils have been considered non-permissive to y. pestis intracellular survival. several s ...201728848716
hmsc controls yersinia pestis biofilm formation in response to redox environment.yersinia pestis biofilm formation, controlled by intracellular levels of the second messenger molecule cyclic diguanylate (c-di-gmp), is important for blockage-dependent plague transmission from fleas to mammals. hmscde is a tripartite signaling system that modulates intracellular c-di-gmp levels to regulate biofilm formation in y. pestis. previously, we found that y. pestis biofilm formation is stimulated in reducing environments in an hmscde-dependent manner. however, the mechanism by which hm ...201728848715
induction of type i interferon through a non-canonical toll-like receptor 7 pathway during yersinia pestis infection.yersinia pestis causes bubonic, pneumonic and septicemic plague, diseases that are rapidly lethal to most mammals, including humans. plague develops as a consequence of bacterial neutralization of the host's innate immune response, which permits uncontrolled growth and causes the systemic hyperactivation of the inflammatory response. we previously found that host type i interferon (ifn) signaling is induced during y. pestis infection and contributes to neutrophil depletion and disease. in this w ...201728847850
eight whole-genome assemblies of yersinia pestis subsp. microtus bv. caucasica isolated from the common vole (microtus arvalis) plague focus in dagestan, russia.we here report the draft genome sequences of 8 yersinia pestis subsp. microtus bv. caucasica strains isolated from the east caucasian (previous name, dagestan) mountain focus (no. 39), representing the most ancient branch of the 0.pe2 phylogroup circulating in populations of common voles (microtus arvalis).201728839028
patterns of human plague in uganda, 2008-2016.plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-saharan africa. during 2008-2016, a combination of active surveillance and laboratory testing in the plague-endemic west nile region of uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. although the mortality rate was 7% among suspected cases, it ...201728820134
small-scale die-offs in woodrats support long-term maintenance of plague in the u.s. southwest.our longitudinal study of plague dynamics was conducted in north-central new mexico to identify which species in the community were infected with plague, to determine the spatial and temporal patterns of the dynamics of plague epizootics, and to describe the dynamics of yersinia pestis infection within individual hosts. a total of 3156 fleas collected from 535 small mammals of 8 species were tested for y. pestis dna. nine fleas collected from six southern plains woodrats (neotoma micropus) and f ...201728792853
the feoabc locus of yersinia pestis likely has two promoters causing unique iron regulation.the feoabc ferrous transporter is a wide-spread bacterial system. while the feoabc locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoabc in yersinia pestis appears to be unique. none of the non-iron responsive transcriptional regulators that control expression of feoabc in other bacteria do so in y. pestis. another unique factor is the iron and fur regulation of the y. pestis feoabc locus occurs during microaerobic but not aerobic g ...201728785546
serological and pcr investigation of yersinia pestis in potential reservoir hosts from a plague outbreak focus in zambia.plague is a bacterial zoonotic disease, caused by yersinia pestis. rodents are the natural hosts with fleas as the vehicle of disease transmission. domestic and wild dogs and cats have also been identified as possible disease hosts. in zambia, plague outbreaks have been reported in the southern and eastern regions in the last 20 years. based on these observations, y. pestis could possibly be endemically present in the area.201728754138
paleoproteomics of the dental pulp: the plague paradigm.chemical decomposition and fragmentation may limit the detection of ancient host and microbial dna while some proteins can be detected for extended periods of time. we applied paleoproteomics on 300-year-old dental pulp specimens recovered from 16 individuals in two archeological funeral sites in france, comprising one documented plague site and one documented plague-negative site. the dental pulp paleoproteome of the 16 teeth comprised 439 peptides representative of 30 proteins of human origin ...201728746380
curative treatment of severe gram-negative bacterial infections by a new class of antibiotics targeting lpxc.the infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. it has been suggested that an antibiotic targeting lpxc of the lipid a biosynthetic pathway in gram-negative bacteria is a promising strategy for curing gram-negative bacterial infections. however, experimental proof of this concept is lacking. here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of lpxc, an essential enzyme in the biosynthesis of the lipid a c ...201728743813
integrated sers-based microdroplet platform for the automated immunoassay of f1 antigens in yersinia pestis.the development of surface-enhanced raman scattering (sers)-based microfluidic platforms has attracted significant recent attention in the biological sciences. sers is a highly sensitive detection modality, with microfluidic platforms providing many advantages over microscale methods, including high analytical throughput, facile automation, and reduced sample requirements. accordingly, the integration of sers with microfluidic platforms offers significant utility in chemical and biological exper ...201728737374
an integrated computational-experimental approach reveals yersinia pestis genes essential across a narrow or a broad range of environmental conditions.the world health organization has categorized plague as a re-emerging disease and the potential for yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. environmental temperature is a key signal which regulates virulence of the bacterium. the bacterium normally grows outside the human host at 28 °c. therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °c is central to the develo ...201728732479
structural insights into the yersinia pestis outer membrane protein ail in lipid bilayers.yersinia pestis the causative agent of plague, is highly pathogenic and poses very high risk to public health. the outer membrane protein ail (adhesion invasion locus) is one of the most highly expressed proteins on the cell surface of y. pestis, and a major target for the development of medical countermeasures. ail is essential for microbial virulence and is critical for promoting the survival of y. pestis in serum. structures of ail have been determined by x-ray diffraction and solution nmr sp ...201728726410
identification of risk factors associated with transmission of plague disease in eastern zambia.plague is a fatal, primarily rodent-flea-borne zoonotic disease caused by yersinia pestis. the identification of risk factors of plague was investigated through questionnaire interview and conducting focus group discussion (fgd) in sinda and nyimba of eastern zambia. a total of 104 questionnaires were administered to individual respondents and 20 groups consisting of 181 discussants, which comprised fgd team in this study. the study revealed that trapping, transportation, and preparation of rode ...201728722614
atp binding and hydrolysis disrupts the high-affinity interaction between the heme abc transporter hmuuv and its cognate substrate binding protein.using the energy of atp hydrolysis abc transporters catalyze the trans-membrane transport of molecules. in bacteria they partner with a high affinity substrate binding protein (sbp) to import essential micronutrients. atp binding by type-i abc transporters (importers of amino acids, sugars, peptides, small ions) stabilizes the interaction between the transporter and the sbp, thus allowing transfer of the substrate from the latter to the former. in type-ii abc transporters (importers of trace ele ...201728710276
crystal structure of yersinia pestis virulence factor yfea reveals two polyspecific metal-binding sites.gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (sbps) to transport transition metals through the periplasm. the sbps share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. in yersinia pestis, the causative agent of plague, yfea (ypo2439, y1897), an sbp, is important for full virulence during mammalian infectio ...201728695856
host iron nutritional immunity induced by a live yersinia pestis vaccine strain is associated with immediate protection against plague.prompt and effective elicitation of protective immunity is highly relevant for cases of rapidly deteriorating fatal diseases, such as plague, which is caused by yersinia pestis. here, we assessed the potential of a live vaccine to induce rapid protection against this infection. we demonstrated that the y. pestis ev76 live vaccine protected mice against an immediate lethal challenge, limiting the multiplication of the virulent pathogen and its dissemination into circulation. ex vivo analysis of y ...201728680860
sylvatic plague vaccine partially protects prairie dogs (cynomys spp.) in field trials.sylvatic plague, caused by yersinia pestis, frequently afflicts prairie dogs (cynomys spp.), causing population declines and local extirpations. we tested the effectiveness of bait-delivered sylvatic plague vaccine (spv) in prairie dog colonies on 29 paired placebo and treatment plots (1-59 ha in size; average 16.9 ha) in 7 western states from 2013 to 2015. we compared relative abundance (using catch per unit effort (cpue) as an index) and apparent survival of prairie dogs on 26 of the 29 paired ...201728643091
thermal stability and rheological properties of the "non-stick" caf1 biomaterial.the ability to culture cells in three dimensions has many applications, from drug discovery to wound healing. 3d cell culture methods often require appropriate scaffolds that mimic the cellular environments of different tissue types. the choice of material from which these scaffolds are made is of paramount importance, as its properties will define the manner in which cells interact with the scaffold. caf1 is a protein polymer that is secreted from its host organism, yersinia pestis, to enable e ...201728632140
novel ctl epitopes identified through a y. pestis proteome-wide analysis in the search for vaccine candidates against plague.the causative agent of plague, yersinia pestis, is a highly virulent pathogen and a potential bioweapon. depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. the latter has a high fatality rate. in the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the f1 and lcrv antigens are currently under clinical trials. it is well known tha ...201728606812
pcr incorporation of polyoxometalate modified deoxynucleotide triphosphates and their application in molecular electrochemical sensing of yersinia pestis.redox-labeled nucleotides are of increasing interest for the fabrication of next generation molecular tools and should meet requirements of being thermally stable, sensitive, and compatible with polymerase-mediated incorporation while also being electrochemically discriminable. the synthesis and characterization of keggin and dawson polyoxometalate-deoxynucleotide (pom-dntp) bioconjugates linked through 7-deaza-modified purines is described. the modified pom-dntps were used for polymerase-based ...201728544266
zinc transporters ybtx and znuabc are required for the virulence of yersinia pestis in bubonic and pneumonic plague in mice.a number of bacterial pathogens require the znuabc zinc (zn(2+)) transporter and/or a second zn(2+) transport system to overcome zn(2+) sequestration by mammalian hosts. previously we have shown that in addition to znuabc, yersinia pestis possesses a second zn(2+) transporter that involves components of the yersiniabactin (ybt), siderophore-dependent iron transport system. synthesis of the ybt siderophore and ybtx, a member of the major facilitator superfamily, are both critical components of th ...201728540946
yersinia pestis yopk inhibits bacterial adhesion to host cells by binding to the extracellular matrix adaptor protein matrilin-2.pathogenic yersiniae harbor a type iii secretion system (t3ss) that injects yersinia outer protein (yop) into host cells. yopk has been shown to control yop translocation and prevent inflammasome recognition of the t3ss by the innate immune system. here, we demonstrate that yopk inhibits bacterial adherence to host cells by binding to the extracellular matrix adaptor protein matrilin-2 (matn2). yopk binds to matn2, and deleting amino acids 91 to 124 disrupts binding of yopk to matn2. a yopk null ...201728533472
flea and small mammal species composition in mixed-grass prairies: implications for the maintenance of yersinia pestis.maintenance of sylvatic plague in prairie dogs (cynomis spp.) was once thought unlikely due to high mortality rates; yet more recent findings indicate that low-level enzootic plague may be maintained in susceptible prairie dog populations. another hypothesis for the maintenance of sylvatic plague involves small mammals, other than prairie dogs, as an alternative reservoir in the sylvatic plague system. these hypotheses, however, are not mutually exclusive, as both prairie dogs and small mammals ...201728520514
glutathionylation of yersinia pestis lcrv and its effects on plague pathogenesis.glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. here we show that yersinia pestis lcrv, a secreted protein capping the type iii secretion machine, is glutathionylated at cys(273) and that this modification promotes association with host ribosomal protein s3 (rps3), moderates y. pestis type iii effector transport and killing of macropha ...201728512097
efficacy of a fipronil bait in reducing the number of fleas (oropsylla spp.) infesting wild black-tailed prairie dogs.bubonic plague (yersinia pestis) is a deadly zoonosis with black-tailed prairie dogs (cynomys ludovicianus) as a reservoir host in the united states. systemic insecticides are a promising means of controlling the vectors, oropsylla spp. fleas, infesting these prairie dogs, subsequently disrupting the y. pestis cycle. the objective of this study was to conduct a field trial evaluating the efficacy of a grain rodent bait containing fipronil (0.005%) against fleas infesting prairie dogs. the study ...201728504448
swabbing prairie dog burrows for fleas that transmit yersinia pestis: influences on efficiency.scientists and health-care professionals sometimes use a swabbing technique to collect fleas from rodent burrows, and later test the fleas for yersinia pestis, the causative agent of plague. detection of y. pestis is enhanced when large pools of fleas are available. the following study investigated factors that might affect the rate at which fleas are collected from burrows in colonies of black-tailed prairie dogs (cynomys ludovicianus). data were collected from 13 colonies in new mexico during ...201728486652
identification and characterization of a neutralizing monoclonal antibody that provides complete protection against yersinia pestis.yersinia pestis (y. pestis) has caused an alarming number of deaths throughout recorded human history, and novel prophylactics and therapeutics are necessary given its potential as a bioweapon. only one monoclonal antibody has been identified to date that provides complete protection against y. pestis. here, we describe a second novel murine monoclonal antibody (f2h5) that provided complete protection against y. pestis 141 infection when administered prophylactically to balb/c mice (100 μg intra ...201728486528
detection of yersinia pestis in complex matrices by intact cell immunocapture and targeted mass spectrometry.we describe an immunoaffinity-liquid chromatography-tandem mass spectrometry (immuno-lc-ms/ms) protocol for the direct (i.e., without prior culture), sensitive and specific detection of yersinia pestis in complex matrices. immunoaffinity enables isolation and concentration of intact bacterial cells from food and environmental samples. after protein extraction and digestion, suitable proteotypic peptides corresponding to three y. pestis-specific protein markers (murine toxine, plasminogen activat ...201728478558
[advance on genome research of yersinia pestis bacteriophage].completion of the genome sequences on yersinia pestis bacteriophage offered unprecedented opportunity for researchers to carry out related genomic studies. this review was based on the genomic sequences and provided a genomic perspective in describing the essential features of genome on yersinia pestis bacteriophage. based on the comparative genomics, genetic evolutionary relationship was discussed. description of functions from the gene prediction and protein annotation provided evidence for fu ...201728468083
potential roles of pigs, small ruminants, rodents, and their flea vectors in plague epidemiology in sinda district, eastern zambia.a cross-sectional study was conducted in the eastern part of zambia that previously reported a plague outbreak. the aim of the study was to evaluate the potential role of pigs, goats, and sheep as sero-surveillance hosts for monitoring plague, and to investigate the flea vectors and potential reservoir hosts to establish the current status of plague endemicity in the district. serum samples were collected from 96 rodents, 10 shrews, 245 domestic pigs, 232 goats, and 31 sheep, whereas 106 organs ...201728399281
[dynamics of f1 antibody responses to yersinia pestis infection in rhombomys opimus].objective: to observe the dynamics of antibody response in great gerbils infected with yersinia pestis in experiment. method: a total of 211 great gerbils were captured in the southern margin of plague natural focus of junggar basin of the xinjiang uygur autonomous region in 2011. among them, there were 167 great gerbils without infection of y. pestis and 44 great gerbils infected by y.pestis. y.pestis no. 2504 was employed for this experimental strain, which was strong toxic strain with negativ ...201728395471
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