transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in yersinia pestis [corrected].the etiologic agent of bubonic plague, yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. though the closely related enteric pathogen y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in y. pestis has been unclear. in this study we performed transcriptional profiling experiments to identify y. pestis quorum sensing regulated functions. our analysis revealed that acyl-homoserine lactone-based quorum s ...201323620823
optimized methods for biofilm analysis in yersinia pestis. 201323611136
effects of low-temperature flea maintenance on the transmission of yersinia pestis by oropsylla montana.yersinia pestis, the causative agent of plague, is primarily a rodent-associated, flea-borne zoonosis maintained in sylvatic foci throughout western north america. transmission to humans is mediated most commonly by the flea vector oropsylla montana and occurs predominantly in the southwestern united states. with few exceptions, previous studies showed o. montana to be an inefficient vector at transmitting y. pestis at ambient temperatures, particularly when such fleas were fed on susceptible ho ...201323590319
a live attenuated strain of yersinia pestis δyscb provides protection against bubonic and pneumonic plagues in mouse develop a safe and effective live plague vaccine, the δyscb mutant was constructed based on yersinia pestis biovar microtus strain 201 that is avirulent to humans, but virulent to mice. the virulence, immunogenicity and protective efficacy of the δyscb mutant were evaluated in this study. the results showed that the δyscb mutant was severely attenuated, elicited a higher f1-specific antibody titer and provided protective efficacy against bubonic and pneumonic plague in mouse model. the δyscb ...201323588087
counting small rna in pathogenic, we present a modification to single-molecule fluorescence in situ hybridization that enables quantitative detection and analysis of small rna (srna) expressed in bacteria. we show that short (~200 nucleotide) nucleic acid targets can be detected when the background of unbound singly dye-labeled dna oligomers is reduced through hybridization with a set of complementary dna oligomers labeled with a fluorescence quencher. by neutralizing the fluorescence from unbound probes, we were able to s ...201323577771
characterization of residual medium peptides from yersinia pestis we demonstrate that when yersinia pesitis is grown in laboratory media, peptides from the medium remain associated with cellular biomass even after washing and inactivation of the bacteria by different methods. these peptides are characteristic of the type of growth medium and of the manufacturer of the medium, reflecting the specific composition of the medium. we analyzed biomass-associated peptides from cultures of two attenuated strains of yersinia pestis [kim d27 (pgm-) and kim d1 (lcr- ...201323550890
a strain of yersinia pestis with a mutator phenotype from the republic of georgia.we describe here a strain of yersinia pestis, g1670a, which exhibits a baseline mutation rate elevated 250-fold over wild-type y. pestis. the responsible mutation, a c to t substitution in the muts gene, results in the transition of a highly conserved leucine at position 689 to arginine (muts(l689r)). when the mutsl 689r protein of g1670a was expressed in a δmuts derivative of y. pestis strain ev76, mutation rates observed were equivalent to those observed in g1670a, consistent with a causal ass ...201323521061
fibrin facilitates both innate and t cell-mediated defense against yersinia pestis.the gram-negative bacterium yersinia pestis causes plague, a rapidly progressing and often fatal disease. the formation of fibrin at sites of y. pestis infection supports innate host defense against plague, perhaps by providing a nondiffusible spatial cue that promotes the accumulation of inflammatory cells expressing fibrin-binding integrins. this report demonstrates that fibrin is an essential component of t cell-mediated defense against plague but can be dispensable for ab-mediated defense. g ...201323487423
multiple antigen peptide containing b and t cell epitopes of f1 antigen of yersinia pestis showed enhanced th1 immune response in murine model.yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. apart from humoral response, cell-mediated protection plays a major role in combating the disease. fraction 1 capsular antigen (f1-ag) of y. pestis has long been exploited as a vaccine candidate. in this study, f1-multiple antigenic peptide (f1-map or map)-specific cell-mediated and cytokine responses were studied in murine model. map consisting ...201323480362
protecting against plague: towards a next-generation vaccine.the causative organism of plague is the bacterium yersinia pestis. advances in understanding the complex pathogenesis of plague infection have led to the identification of the f1- and v-antigens as key components of a next-generation vaccine for plague, which have the potential to be effective against all forms of the disease. here we review the roles of f1- and v-antigens in the context of the range of virulence mechanisms deployed by y. pestis, in order to develop a greater understanding of th ...201323480179
whole-genome sequencing and comparative analysis of yersinia pestis, the causative agent of a plague outbreak in northern peru.the plague is a zoonotic disease caused by the bacterium yersinia pestis. here, we report the complete genome sequence of the y. pestis strain ins, which was isolated from swollen lymph gland aspirate (bubo aspirate) of an infected patient from a pneumonic outbreak in 2010 in northern peru.201323469360
b and t cell epitope mapping and study the humoral and cell mediated immune response to b-t constructs of yscf antigen of yersinia pestis.yscf antigen, a type iii secretion protein has recently been shown partial protection in murine model. five peptides of yscf antigen were predicted using dnastar and t-cell prediction software. peptides were synthesised and authenticated using competitive, direct binding immunoassay with anti yscf/peptide sera raised in mice. peptide p1 and p2 were found to be b cell epitope while p3 was minor b cell epitope. p4 peptide was a pure t cell epitope based on lymphoproliferative response, cytokines p ...201323465748
probabilistic models for crispr spacer content evolution.the crispr/cas system is known to act as an adaptive and heritable immune system in eubacteria and archaea. immunity is encoded in an array of spacer sequences. each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. even in closely related strains, spacer content is very dynamic and evolves quickly. standard models of nucleotide evolution cannot be applied to quantify its rate of change since processes other than single nucleotide changes determ ...201323442002
application of chromosomal dna and protein targeting for the identification of yersinia pestis.a comprehensive strategy was developed and validated for the identification of pathogens from closely related near neighbors using both chromosomal and protein biomarkers, with emphasis on distinguishing yersinia pestis from the ancestral bacterium yersinia pseudotuberculosis.201323436733
induction of the yersinia pestis phop-phoq regulatory system in the flea and its role in producing a transmissible infection.transmission of yersinia pestis is greatly enhanced after it forms a bacterial biofilm in the foregut of the flea vector that interferes with normal blood feeding. here we report that the ability to produce a normal foregut-blocking infection depends on induction of the y. pestis phop-phoq two-component regulatory system in the flea. y. pestis phop-negative mutants achieved normal infection rates and bacterial loads in the flea midgut but produced a less cohesive biofilm both in vitro and in the ...201323435973
natural history of yersinia pestis pneumonia in aerosol-challenged balb/c mice.after a relatively short untreated interval, pneumonic plague has a mortality approaching 100%. we employed a murine model of aerosol challenge with yersinia pestis to investigate the early course of pneumonic plague in the lung, blood, and spleen. we fit a mathematical model to all data simultaneously. the model fit to the data was acceptable. the number of organisms in the lung at baseline was estimated to be 135 (median) or 1,184 (mean) cfu/g. the doubling time was estimated as 1.5 to 1.7 h. ...201323403418
inheritance of the lysozyme inhibitor ivy was an important evolutionary step by yersinia pestis to avoid the host innate immune response.yersinia pestis (the plague bacillus) and its ancestor, yersinia pseudotuberculosis (which causes self-limited bowel disease), encode putative homologues of the periplasmic lysozyme inhibitor ivy and the membrane-bound lysozyme inhibitor mlic. the involvement of both inhibitors in virulence remains subject to debate.201323402825
reciprocal regulation of ph 6 antigen gene loci by phop and rova in yersinia pestis biovar explore the transcriptional regulation of the psaef and psaabc loci by the rova and phop regulators in yersinia pestis.201323374131
rfal is required for yersinia pestis type iii secretion and virulence.yersinia pestis, the causative agent of plague, uses a type iii secretion system (t3ss) to inject cytotoxic yop proteins directly into the cytosol of mammalian host cells. the t3ss can also be activated in vitro at 37°c in the absence of calcium. the chromosomal gene rfal (waal) was recently identified as a virulence factor required for proper function of the t3ss. rfal functions as a ligase that adds the terminal n-acetylglucosamine to the lipooligosaccharide core of y. pestis. we previously sh ...201323357388
the sycn/yscb chaperone-binding domain of yopn is required for the calcium-dependent regulation of yop secretion by yersinia pestis.numerous gram-negative bacterial pathogens employ type iii secretion systems (t3sss) to inject effector proteins into eukaryotic cells. the activation of the type iii secretion (t3s) process is tightly controlled in all t3sss. in yersinia pestis, the secretion of effector proteins, termed yersinia outer proteins (yops), is regulated by the activity of the yopn/sycn/yscb/tyea complex. yopn is a secreted protein that interacts with the sycn/yscb chaperone via an n-terminal chaperone-binding domain ...201323355975
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
plague outbreak in libya, 2009, unrelated to plague in algeria.after 25 years of no cases of plague, this disease recurred near tobruk, libya, in 2009. an epidemiologic investigation identified 5 confirmed cases. we determined ribotypes, not1 restriction profiles, and is100 and is1541 hybridization patterns of strains isolated during this outbreak. we also analyzed strains isolated during the 2003 plague epidemic in algeria to determine whether there were epidemiologic links between the 2 events. our results demonstrate unambiguously that neighboring but in ...201323347743
yersinia pestis plasminogen activator gene homolog in rat tissues. 201323347636
partial retraction: yadbc of yersinia pestis, a new virulence determinant for bubonic plague. 201323335642
colocalized delivery of adjuvant and antigen using nanolipoprotein particles enhances the immune response to recombinant antigens.subunit antigen-based vaccines can provide a number of important benefits over traditional vaccine candidates, such as overall safety. however, because of the inherently low immunogenicity of these antigens, methods for colocalized delivery of antigen and immunostimulatory molecules (i.e., adjuvants) are needed. here we report a robust nanolipoprotein particle (nlp)-based vaccine delivery platform that facilitates the codelivery of both subunit antigens and adjuvants. ni-chelating nlps (ninlps) ...201323331082
identification and characterization of small rnas in yersinia pestis.yersinia pestis, the etiologic agent of plague, is closely related to yersinia pseudotuberculosis evolutionarily but has a very different mode of infection. the rna-binding regulatory protein, hfq, mediates regulation by small rnas (srnas) and is required for virulence of both y. pestis and y. pseudotuberculosis. moreover, hfq is required for growth of y. pestis, but not y. pseudotuberculosis, at 37°c. together, these observations suggest that srnas play important roles in the virulence and surv ...201323324607
subtyping brazilian yersinia pestis strains by pulsed-field gel electrophoresis.we subtyped brazilian yersinia pestis strains by pulsed-field gel electrophoresis (pfge). this was done with 22 brazilian y. pestis strains: 17 from an outbreak and 5 from endemic routine surveillance. the strains were divided into 2 groups (i and ii), 8 subgroups (a-h) and 19 pfge profiles or pulsotypes. pfge did not separate outbreak from non-outbreak strains, as identical pulsotype patterns were found among outbreak strains and strains obtained from surveillance. however, it was able to detec ...201323315882
inhibitors of the yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.the bacterial protein tyrosine phosphatase yoph is an essential virulence determinant in yersinia pestis and a potential antibacterial drug target. here we report our studies of screening for small molecule inhibitors of yoph using both high throughput and in silico approaches. the identified inhibitors represent a diversity of chemotypes and novel ptyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. we demonstrate that the ...201323294700
[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
pilot study on the use of dna priming immunization to enhance y. pestis lcrv-specific b cell responses elicited by a recombinant lcrv protein vaccine.recent studies indicate that dna immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. however, there is limited information on the mechanism of this effect. in particular, it is not known whether dna immunization can also enhance the development of antigen-specific b cell development. in this report, a pilot study was conducted using plague lcrv immunogen as a model system to determine whether dna immunization is able to enhance lcrv-specifi ...201326344467
autoregulation of phop/phoq and positive regulation of the cyclic amp receptor protein-cyclic amp complex by phop in yersinia pestis.yersinia pestis is one of the most dangerous bacterial pathogens. phop and cyclic amp receptor protein (crp) are global regulators of y. pestis, and they control two distinct regulons that contain multiple virulence-related genes. the phop regulator and its cognate sensor phoq constitute a two-component regulatory system. the regulatory activity of crp is triggered only by binding to its cofactor camp, which is synthesized from atp by adenylyl cyclase (encoded by cyaa). however, the association ...201323264579
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
small oversights that led to the great plague of marseille (1720-1723): lessons from the recent decades, the issue of emerging and re-emerging infectious diseases has become an increasingly important area of concern in public health. today, like centuries ago, infectious diseases confront us with the fear of death and have heavily influenced social behaviors and policy decisions at local, national and international levels. remarkably, an infectious disease such as plague, which is disseminated from one country to another mainly by commercial transportation, remains today, as it w ...201323246639
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
biomolecular interactions of small-molecule inhibitors affecting the yoph protein tyrosine phosphatase.we have developed competitive and direct binding methods to examine small-molecule inhibitors of protein tyrosine phosphatase activity. focusing on the yersinia pestis outer protein h, a potent bacterial protein tyrosine phosphatase, we describe how an understanding of the kinetic interactions involving yersinia pestis outer protein h, peptide substrates, and small-molecule inhibitors of protein tyrosine phosphatase activity can be beneficial for inhibitor screening, and we further translate the ...201323241354
beyond an aflp genome scan towards the identification of immune genes involved in plague resistance in rattus rattus from madagascar.genome scans using amplified fragment length polymorphism (aflp) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. this study follows on from an aflp genome scan in the black rat (rattus rattus), the reservoir of plague (yersinia pestis infection) in madagascar. we successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with ...201323237097
lcrh, a class ii chaperone from the type three secretion system, has a highly flexible native structure.the type three secretion system is a large and complex protein nano-machine that many gram-negative pathogens employ to infect host cells. a key structure of this machine is a proteinaceous pore that inserts into the target membrane and forms a channel for bacterial toxins to flow from bacteria into the host cell. the pore is mainly formed from two large membrane proteins called "translocators." importantly, effective secretion and thus pore formation of the translocators depend on their binding ...201323233673
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
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
lcrv mutants that abolish yersinia type iii injectisome function.lcrv, the type iii needle cap protein of pathogenic yersinia, has been proposed to function as a tether between yscf, the needle protein, and yopb-yopd to constitute the injectisome, a conduit for the translocation of effector proteins into host cells. further, insertion of lcrv-capped needles from a calcium-rich environment into host cells may trigger the low-calcium signal for effector translocation. here, we used a genetic approach to test the hypothesis that the needle cap responds to the lo ...201323222719
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
yopk controls both rate and fidelity of yop translocation.yersinia pestis, the causative agent of plague, utilizes a type iii secretion system (t3ss) to intoxicate host cells. the injection of t3ss substrates must be carefully controlled, and dysregulation leads to altered infection kinetics and early clearance of y. pestis. while the sequence of events leading up to cell contact and initiation of translocation has received much attention, the regulatory events that take place after effector translocation is less understood. here we show that the regul ...201323205707
characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.yersinia pestis causes bubonic and pneumonic plague in humans. the pneumonic infection is the most severe and invariably fatal if untreated. because of its high virulence, ease of delivery and precedent of use in warfare, y. pestis is considered as a potential bioterror agent. no licensed plague vaccine is currently available in the us. laboratory research with virulent strains requires appropriate biocontainment (i.e., biosafety level 3 (bsl-3) for procedures that generate aerosol/droplets) and ...201323195858
multiple antigen peptide consisting of b- and t-cell epitopes of f1 antigen of y. pestis showed enhanced humoral and mucosal immune response in different strains of mice.yersinia pestis is a causative agent of plague. f1 and v antigen based vaccines have shown remarkable protection in experimental animals. in order to develop epitope based immunogen, three b and one t-cell epitopes of f1 antigen with palmitate residue at amino terminal were assembled on a lysine backbone as multiple antigen peptide (map or f1-map). map was characterized by sds-page, immunoblot and immunoreactivity with anti f1 sera. map was entrapped in plga (polylactide-co-glycolide) microparti ...201323174507
[reservation forms of plague infectious agent in tuva natural focus].data characterizing the reservation forms of plague infectious agent in tuva natural focus are presented in the review. yersinia pestis was shown to persist most of the year in citellophilus tesquorum altaicus imago --the main carrier, getting into the animal organism only for a short time. an increased ability to aggregate in autumn and accumulate in clumps of c. tesquorum altaicus females that are more adapted to survive the cold season compared with males promote the persistence of the microo ...201223163049
resistance to plague of mus spretus seg/pas mice requires the combined action of at least four genetic factors.we have previously described seg/pas as the first mouse inbred strain able to survive subcutaneous injection of virulent yersinia pestis, the agent of plague, and we identified yprl1, yprl2 and yprl3 as three quantitative trait loci (qtls) controlling this exceptional phenotype in females from a backcross between seg/pas and c57bl/6 strains. we have now developed congenic strains to further characterize the extent and effect of these genomic regions. in this study, we confirm the importance of t ...201323151488
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
a multi-omic systems approach to elucidating yersinia virulence mechanisms.the underlying mechanisms that lead to dramatic differences between closely related pathogens are not always readily apparent. for example, the genomes of yersinia pestis (yp) the causative agent of plague with a high mortality rate and yersinia pseudotuberculosis (ypt) an enteric pathogen with a modest mortality rate are highly similar with some species specific differences; however the molecular causes of their distinct clinical outcomes remain poorly understood. in this study, a temporal mult ...201323147219
x-ray structure of the yersinia pestis heme transporter hmuuv.hmuuv is a bacterial atp-binding cassette (abc) transporter that catalyzes heme uptake into the cytoplasm of the gram-negative pathogen yersinia pestis. we report the crystal structure of hmuuv at 3.0 å resolution in a nucleotide-free state, which features a heme translocation pathway in an outward-facing conformation, poised to accept a heme from the cognate periplasmic binding protein hmut. a new assay allowed us to determine in vitro rates of hmuuv-catalyzed heme transport into proteoliposome ...201223142986
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
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
a non-invasive in vivo imaging system to study dissemination of bioluminescent yersinia pestis co92 in a mouse model of pneumonic plague.the gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. this method, despite being quantitative, requires sacrificing the infected animals. recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (ivibb) for monitoring microbial dissemination within the host has been employed. yersinia pestis is a gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. in this st ...201323063826
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
plague: history and contemporary analysis.plague has caused ravaging outbreaks, including the justinian plague and the "black death" in the middle ages. the causative agents of these outbreaks have been confirmed using modern molecular tests. the vector of plague during pandemics remains the subject of controversy. nowadays, plague must be suspected in all areas where plague is endemic in rodents when patients present with adenitis or with pneumonia with a bloody expectorate. diagnosis is more difficult in the situation of the reemergen ...201323041039
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
comparative genomic analysis of gene variations of two chinese yersinia pestis isolates from vaccine strain 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
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
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 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
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 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
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
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
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
[eco-geographic landscapes of natural plague foci in china iv. characterization of biovars of yersinia pestis, china]. 201222883275
[eco-geographic landscapes of natural plague foci in china iii. biological characteristics of major dfr/mlva-based genotypes of yersinia pestis, china]. 201222883187
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
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
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
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
amino acid substitutions in lcrv at putative sites of interaction with toll-like receptor 2 do not affect the virulence of yersinia pestis.lcrv, a component of the type iii secretion system (t3ss) translocon in yersinia pestis, has been concerned in suppressing inflammation through toll-like receptor 2 (tlr2) by inducing expression of the anti-inflammatory cytokine interleukin-10 (il-10). previous studies have reported that lcrv aa e33, e34, k42 and/or e204 and e205 were important for interactions with tlr2 in vitro. while, recently there have been conflicting reports doubting this interaction and its importance in vivo. to further ...201622841961
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
[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
[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
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
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