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bacterial effector nanoparticles as breast cancer therapeutics.bacterial pathogens trigger cell death by a variety of mechanisms, including injection of effector proteins. effector proteins have great potential as anticancer agents because they efficiently subvert a variety of eukaryotic signaling pathways involved in cancer development, drug resistance, and metastasis. in breast cancer, mapk and nfκb pathways are known to be dysregulated. yopj, an effector from yersinia pestis, downregulates mapk and nfκb pathways to induce cell death in specific cell type ...201626800341
eighteenth century yersinia pestis genomes reveal the long-term persistence of an historical plague focus.the 14th-18th century pandemic of yersinia pestis caused devastating disease outbreaks in europe for almost 400 years. the reasons for plague's persistence and abrupt disappearance in europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in europe itself, or successive disease introductions from other locations. here we present five y. pestis genomes from one of the last european outbreaks of plague, from 1722 in marseille, france. the lineage id ...201626795402
whole genome multilocus sequence typing as an epidemiologic tool for yersinia pestis.human plague is a severe and often fatal zoonotic disease caused by yersinia pestis. for public health investigations of human cases, nonintensive whole genome molecular typing tools, capable of defining epidemiologic relationships, are advantageous. whole genome multilocus sequence typing (wgmlst) is a recently developed methodology that simplifies genomic analyses by transforming millions of base pairs of sequence into character data for each gene. we sequenced 13 us y. pestis isolates with kn ...201626778487
recombinant murine toxin from yersinia pestis shows high toxicity and β-adrenergic blocking activity in mice.yersinia pestis murine toxin (ymt) encoded on pmt1 is a 61-kda protein, a member of the phospholipase d superfamily, which is found in all the domains of life. it is considered to be an intracellular protein required for the survival of y. pestis in the midgut of the flea, but the exact role of ymt in the pathogenesis of y. pestis has not been clarified. purified ymt is highly toxic to mice and rats, but the exact mechanism of the animals' death is unclear. here, we prepared a recombinant ymt in ...201626774329
detections of yersinia pestis east of the known distribution of active plague in the united states.we examined fleas collected from black-tailed prairie dog (cynomys ludovicianus) burrows from 2009 through 2011 in five national park units east of the known distribution of active plague across the northern great plains for the presence of yersinia pestis. across all national park units, oropsylla tuberculata and oropsylla hirsuta were the most common fleas collected from prairie dog burrows, 42.4% and 56.9%, respectively, of the 3964 fleas collected from burrow swabbing. using a nested pcr ass ...201626771845
genotyping yersinia pestis in historical plague: evidence for long-term persistence of y. pestis in europe from the 14th to the 17th century.ancient dna (adna) recovered from plague victims of the second plague pandemic (14th to 17th century), excavated from two different burial sites in germany, and spanning a time period of more than 300 years, was characterized using single nucleotide polymorphism (snp) analysis. of 30 tested skeletons 8 were positive for yersinia pestis-specific nucleic acid, as determined by qpcr targeting the pla gene. in one individual (mp-19-ii), the pla copy number in dna extracted from tooth pulp was as hig ...201626760973
survival protein a is essential for virulence in yersinia pestis.plague is a highly pathogenic disease caused by the bacterium yersinia pestis. there is currently no vaccine available for prophylaxis and antibiotic resistant strains have been isolated, thus there is a need for the development of new countermeasures to treat this disease. survival protein a (sura) is a chaperone that has been linked to virulence in several species of bacteria, including the close relative yersinia pseudotuberculosis. in this study, we aimed to evaluate the role of sura in viru ...201626724738
modeling the ecologic niche of plague in sylvan and domestic animal hosts to delineate sources of human exposure in the western united states.plague has been established in the western united states (us) since 1900 following the west coast introduction of commensal rodents infected with yersinia pestis via early industrial shipping. over the last century, plague ecology has transitioned through cycles of widespread human transmission, urban domestic transmission among commensal rodents, and ultimately settled into the predominantly sylvan foci that remain today where it is maintained alternatively by enzootic and epizootic transmissio ...201526713244
the hmst 3' untranslated region mediates c-di-gmp metabolism and biofilm formation in yersinia pestis.yersinia pestis, the cause of plague, forms a biofilm in the proventriculus of its flea vector to enhance transmission. biofilm formation in y. pestis is regulated by the intracellular levels of cyclic diguanylate (c-di-gmp). in this study, we investigated the role of the 3' untranslated region (3'utr) in hmst mrna, a transcript that encodes a diguanylate cyclase that stimulates biofilm formation in y. pestis by synthesizing the second messenger c-di-gmp. deletion of the 3'utr increased the half ...201626711808
pneumonic plague: the darker side of yersinia pestis.inhalation of the bacterium yersinia pestis results in primary pneumonic plague. pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of y. pestis as a biological weapon. importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of y. p ...201626698952
novel engineered cationic antimicrobial peptides display broad-spectrum activity against francisella tularensis, yersinia pestis and burkholderia pseudomallei.broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. engineered cationic antimicrobial peptides (ecaps) display activity against a number of bacterial pathogens including multi-drug-resistant strains. two lead ecaps, wlbu2 and wr12, were compared with human cathelicidin (ll-37) against three highly pathogenic bacteria: francisella tularensis, yersinia pesti ...201626673248
[application of pulsed field gel electrophoresis for molecular typing of causative agents of especially dangerous infections].the macro-restriction analysis of the microorganism dna with the use of gel electrophoresis in pulsed field (pfge typing, pulse electrophoresis) is applied in molecular biology to study the clonal structure and typing of causative agents of infectious diseases. determining the degree of the relationship and definition of epidemiological interrelations of studied isolates, as well as studying the evolutionary history of pathogens, is performed by comparing dna restriction patterns. this review pr ...201526665739
[optimization of labeling and localizing bacterial membrane and nucleus with fm4-64 and hoechst dyes].to observe cell membrane and nucleus in bacteria for subcellular localization.201526665605
nqrm (duf539) protein is required for maturation of bacterial na+-translocating nadh:quinone oxidoreductase.na(+)-translocating nadh:quinone oxidoreductase (na(+)-nqr) catalyzes electron transfer from nadh to ubiquinone in the bacterial respiratory chain, coupled with na(+) translocation across the membrane. na(+)-nqr maturation involves covalent attachment of flavin mononucleotide (fmn) residues, catalyzed by flavin transferase encoded by the nqr-associated apbe gene. analysis of complete bacterial genomes has revealed another putative gene (duf539, here renamed nqrm) that usually follows the apbe ge ...201626644436
nineteen whole-genome assemblies of yersinia pestis subsp. microtus, including representatives of biovars caucasica, talassica, hissarica, altaica, xilingolensis, and ulegeica.the etiologic agent of plague, yersinia pestis, includes two subspecies, of which y. pestis subsp. microtus contains the strains that cause only occasional diseases in humans that are not accompanied by human-to-human transmission. here, we report the draft genome sequences of 19 y. pestis strains (across 6 biovars of y. pestis subsp. microtus).201526634751
plague in a pediatric patient: case report and use of polymerase chain reaction as a diagnostic aid.we report a case of bubonic plaque in a 7-year-old patient who presented with a core temperature of 107°f, seizures, vomiting, altered mental status, and septic shock. this case highlights the utility of polymerase chain reaction (pcr) as a diagnostic aid for rapid presumptive identification of yersinia pestis as well as the importance of correlating pcr results with clinical data. we discuss the various manifestations of plague as they relate to infection control, postexposure prophylaxis, anti ...201426625461
investigation of yersinia pestis laboratory adaptation through a combined genomics and proteomics approach.the bacterial pathogen yersinia pestis, the cause of plague in humans and animals, normally has a sylvatic lifestyle, cycling between fleas and mammals. in contrast, laboratory-grown y. pestis experiences a more constant environment and conditions that it would not normally encounter. the transition from the natural environment to the laboratory results in a vastly different set of selective pressures, and represents what could be considered domestication. understanding the kinds of adaptations ...201526599979
high-throughput screening (hts) by nmr guided identification of novel agents targeting the protein docking domain of yoph.recently we described a novel approach, named high-throughput screening (hts) by nmr that allows the identification, from large combinatorial peptide libraries, of potent and selective peptide mimetics against a given target. here, we deployed the "hts by nmr" approach for the design of novel peptoid sequences targeting the n-terminal domain of yersinia outer protein h (yoph-nt), a bacterial toxin essential for the virulence of yersinia pestis. we aimed at disrupting the protein-protein interact ...201626592695
factors associated with flea infestation among the different rodent species in mbulu and karatu districts, northern tanzania.flea infection with the bacterium, yersinia pestis is acquired from reservoirs which include several rodents and other small mammals. in areas that are endemic of plague, reservoirs of y. pestis and various flea vectors are responsible for perpetuating existence of the disease. the objective of this cross sectional study was to investigate the magnitude and factors associated with flea infestation among different rodent species of northern tanzania, where outbreaks of plague have been recently r ...201326591705
evidence of yersinia pestis dna in rodents in plague outbreak foci in mbulu and karatu districts, northern tanzania.human plague remains a public health concern in tanzania despite its quiescence in most foci for years, considering the recurrence nature of the disease. appreciable researches have involved serological screening of rodents, fleas and humans but none has involved molecular detection and hence proving the presence of yersinia pestis in rodents in the most recent affected foci, mbulu and karatu districts in northern tanzania. the objective of the current study was to employ a simple pcr to detect ...201326591703
molecular survey of bartonella species and yersinia pestis in rodent fleas (siphonaptera) from chihuahua, mexico.rodent fleas from northwestern chihuahua, mexico, were analyzed for the presence of bartonella and yersinia pestis. in total, 760 fleas belonging to 10 species were tested with multiplex polymerase chain reaction analysis targeting the glta (338-bp) and pla genes (478-bp) of bartonella and y. pestis, respectively. although none was positive for y. pestis, 307 fleas were infected with bartonella spp., resulting in an overall prevalence of 40.4%. a logistic regression analysis indicated that the p ...201626576933
inhibition of pseudomonas aeruginosa exsa dna-binding activity by n-hydroxybenzimidazoles.the pseudomonas aeruginosa type iii secretion system (t3ss) is a primary virulence determinant and a potential target for antivirulence drugs. one candidate target is exsa, a member of the arac family of dna-binding proteins required for expression of the t3ss. a previous study identified small molecules based on an n-hydroxybenzimidazole scaffold that inhibit the dna-binding activity of several arac proteins, including exsa. in this study, we further characterized a panel of n-hydroxybenzimidaz ...201626574012
the origin of a killer revealed by bronze age yersinia genomes.bubonic plaque is caused by yersinia pestis, a deadly pathogen that left deep scars in human history. rasmussen et al. (2015) have now retrieved y. pestis genomes from 2,800- to 5,000-year-old human teeth, shedding new light on origins of the strain that brought black death to europe 670 years ago.201526567502
isothermal solid-phase amplification system for detection of yersinia pestis.dna amplification is required for most molecular diagnostic applications, but conventional polymerase chain reaction (pcr) has disadvantages for field testing. isothermal amplification techniques are being developed to respond to this problem. one of them is the recombinase polymerase amplification (rpa) that operates at isothermal conditions without sacrificing specificity and sensitivity in easy-to-use formats. in this work, rpa was used for the optical detection of solid-phase amplification o ...201626563112
inactivation of peroxiredoxin 6 by the pla protease of yersinia pestis.pneumonic plague represents the most severe form of disease caused by yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. the y. pestis outer membrane pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by pla in the lungs is not known. in this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/o ...201526553463
structural characterisation of fabg from yersinia pestis, a key component of bacterial fatty acid synthesis.ketoacyl-acyl carrier protein reductases (fabg) are ubiquitously expressed enzymes that catalyse the reduction of acyl carrier protein (acp) linked thioesters within the bacterial type ii fatty acid synthesis (fasii) pathway. the products of these enzymes, saturated and unsaturated fatty acids, are essential components of the bacterial cell envelope. the fasii reductase enoyl-acp reductase (fabi) has been the focus of numerous drug discovery efforts, some of which have led to clinical trials, ye ...201526539719
role of tellurite resistance operon in filamentous growth of yersinia pestis in macrophages.yersinia pestis initiates infection by parasitism of host macrophages. in response to macrophage infections, intracellular y. pestis can assume a filamentous cellular morphology which may mediate resistance to host cell innate immune responses. we previously observed the expression of y. pestis tellurite resistance proteins terd and tere from the terzabcde operon during macrophage infections. others have observed a filamentous response associated with expression of tellurite resistance operon in ...201526536670
comparative proteomic studies of yersinia pestis strains isolated from natural foci in the republic of georgia.yersinia pestis, the causative agent of plague, is a highly virulent bacterium responsible for millions of human deaths throughout history. in the last decade, two natural plague foci have been described in the republic of georgia from which dozens of y. pestis strains have been isolated. analyses indicate that there are genetic differences between these strains, but it is not known if these differences are also reflected in protein expression. we chose four strains of y. pestis (1390, 1853, 294 ...201526528469
viability of yersinia pestis subcultures in agar stabs.since its identification as the causative agent of plague in 1894, thousands of yersinia pestis strains have been isolated and stored. here, we report the ability of y. pestis to survive up to 47 years in agar stabs, in rubber-stoppered tubes, under refrigeration (+4 to +10°c), although overall subculture recovery rates were poor and inversely related to the length of time stored. genetic characterization of virulence gene presence among these subcultures was suggestive of significant variation ...201626524218
a review of methods for subtyping yersinia pestis: from phenotypes to whole genome sequencing.numerous subtyping methods have been applied to yersinia pestis with varying success. here, we review the various subtyping methods that have been applied to y. pestis and their capacity for answering questions regarding the population genetics, phylogeography, and molecular epidemiology of this important human pathogen. methods are evaluated in terms of expense, difficulty, transferability among laboratories, discriminatory power, usefulness for different study questions, and current applicabil ...201626518910
early divergent strains of yersinia pestis in eurasia 5,000 years ago.the bacteria yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. how and when it originated remains contentious. here, we report the oldest direct evidence of yersinia pestis identified by ancient dna in human teeth from asia and europe dating from 2,800 to 5,000 years ago. by sequencing the genomes, we find that these ancient plague strains are basal to all known yersinia pestis. we find the origins of the yersinia pestis ...201526496604
yersinia pestis requires host rab1b for survival in macrophages.yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. during infection of macrophages y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. however, the mechanisms used by y. pestis to subvert killing by the macrophage are unknown. host rab gtpases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macr ...201526495854
virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from yersinia pestis.in the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (dhfr) as a means of a novel drug therapy against plague. potential inhibitors of dhfr from yersinia pestis (ypdhfr) were selected by virtual screening and subjected to docking, molecular dynamics (md) simulations, and poisson-boltzmann surface area method, in order to evaluate their interactions in the active sites of ypdhfr and human dhfr (hssdhfr). the results suggested selectivity for three compound ...201626494420
development of a taqman array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including ebola virus.acute febrile illness (afi) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. we developed a real-time pcr-based taqman array card (tac) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 afi-associated organisms, including 15 viruses (chikungunya, crime ...201526491176
bacterial pathogens activate plasminogen to breach tissue barriers and escape from innate immunity.both coagulation and fibrinolysis are tightly connected with the innate immune system. infection and inflammation cause profound alterations in the otherwise well-controlled balance between coagulation and fibrinolysis. many pathogenic bacteria directly exploit the host's hemostatic system to increase their virulence. here, we review the capacity of bacteria to activate plasminogen. the resulting proteolytic activity allows them to breach tissue barriers and evade innate immune defense, thus pro ...201626485450
flea-associated bacterial communities across an environmental transect in a plague-endemic region of uganda.the vast majority of human plague cases currently occur in sub-saharan africa. the primary route of transmission of yersinia pestis, the causative agent of plague, is via flea bites. non-pathogenic flea-associated bacteria may interact with y. pestis within fleas and it is important to understand what factors govern flea-associated bacterial assemblages. six species of fleas were collected from nine rodent species from ten ugandan villages between october 2010 and march 2011. a total of 660,345 ...201526485147
dissociation of tissue destruction and bacterial expansion during bubonic plague.activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease pla, which activates plasmin and inactivates fibrinolysis inhibitors. pla is encoded by the ppla plasmid. following intradermal inoculation, y. pestis has the capacity to multiply in and cause destruction of the lymph node (ln) drainin ...201526484539
complete protection against pneumonic and bubonic plague after a single oral vaccination.no efficient vaccine against plague is currently available. we previously showed that a genetically attenuated yersinia pseudotuberculosis producing the yersinia pestis f1 antigen was an efficient live oral vaccine against pneumonic plague. this candidate vaccine however failed to confer full protection against bubonic plague and did not produce f1 stably.201526473734
structural characterisation of the beta-ketoacyl-acyl carrier protein synthases, fabf and fabh, of yersinia pestis.yersinia pestis, the causative agent of bubonic, pneumonic, and septicaemic plague, remains a major public health threat, with outbreaks of disease occurring in china, madagascar, and peru in the last five years. the existence of multidrug resistant y. pestis and the potential of this bacterium as a bioterrorism agent illustrates the need for new antimicrobials. the β-ketoacyl-acyl carrier protein synthases, fabb, fabf, and fabh, catalyse the elongation of fatty acids as part of the type ii fatt ...201526469877
spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague.during pneumonic plague, the bacterium yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. this lesion development and persistence are poorly understood. here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (rna-seq) analysis to identify transcriptional differences between lesion microenvironments. we show that cellular pathways involved in leukocyte migration an ...201526463167
engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens.many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., bacillus anthracis, francisella tularensis, yersinia pestis, and vaccinia virus) is highly desirable. here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capt ...201626462853
nuclear magnetic resonance characterization of the type iii secretion system tip chaperone protein pcrg of pseudomonas aeruginosa.lung infection with pseudomonas aeruginosa is the leading cause of death among cystic fibrosis patients. to initiate infection, p. aeruginosa assembles a protein nanomachine, the type iii secretion system (t3ss), to inject bacterial proteins directly into target host cells. an important regulator of the p. aeruginosa t3ss is the chaperone protein pcrg, which forms a complex with the tip protein, pcrv. in addition to its role as a chaperone to the tip protein, pcrg also regulates protein secretio ...201526451841
reconstruction of an ancestral yersinia pestis genome and comparison with an ancient sequence.we propose the computational reconstruction of a whole bacterial ancestral genome at the nucleotide scale, and its validation by a sequence of ancient dna. this rare possibility is offered by an ancient sequence of the late middle ages plague agent. it has been hypothesized to be ancestral to extant yersinia pestis strains based on the pattern of nucleotide substitutions. but the dynamics of indels, duplications, insertion sequences and rearrangements has impacted all genomes much more than the ...201526450112
intramuscular immunization of mice with a live-attenuated triple mutant of yersinia pestis co92 induces robust humoral and cell-mediated immunity to completely protect animals against pneumonic plague.earlier, we showed that the δlpp δmsbb δail triple mutant of yersinia pestis co92 with deleted genes encoding braun lipoprotein (lpp), an acyltransferase (msbb), and the attachment invasion locus (ail), respectively, was avirulent in a mouse model of pneumonic plague. in this study, we further evaluated the immunogenic potential of the δlpp δmsbb δail triple mutant and its derivative by different routes of vaccination. mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) r ...201526446423
autotransporter proteins.this review focuses on the function of the escherichia coli and salmonella autotransporters for which a considerable amount of literature is available. members of the serine protease autotransporters of the enterobacteriaceae (spates) family are proteins from e. coli and shigella spp., which, like the neisseria and haemophilus influenzae iga1 proteases and hap, possess a consensus serine protease motif. the largest subfamily of autotransporters is defined by the aida conserved domain cog3468 and ...200526443517
yersinia pestis and yersinia pseudotuberculosis infection: a regulatory rna perspective.yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. an ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. one idea is that c ...201526441890
prevalence and distribution of soil-borne zoonotic pathogens in lahore district of pakistan.a multidisciplinary, collaborative project was conducted to determine the prevalence and distribution of soil-borne zoonotic pathogens in lahore district of pakistan and ascertain its public health significance. using a grid-based sampling strategy, soil samples (n = 145) were collected from villages (n = 29, 5 samples/village) and examined for bacillus anthracis, burkholderia mallei/pseudomallei, coxiella burnetii, francisella tularensis, and yersinia pestis using real time pcr assays. chemical ...201526441860
impact of the pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.many pathogens usurp the host hemostatic system during infection to promote pathogenesis. yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (a2ap). it is not known, however, if pla inactivates a2ap in vivo; the role of a2ap during respiratory y. pestis infection is not known either. here, we show that ...201526438794
the pla gene, encoding plasminogen activator, is not specific to yersinia pestis.here we present evidence to show that the pla gene, previously thought to be specific to yersinia pestis, occurs in some strains of citrobacter koseri and escherichia coli. this means that detection of this gene on its own can no longer be taken as evidence of detection of y. pestis.201526438258
development of a bead-based luminex assay using lipopolysaccharide specific monoclonal antibodies to detect biological threats from brucella species.brucella, a gram-negative bacterium, is classified as a potential bioterrorism agent mainly due to the low dose needed to cause infection and the ability to transmit the bacteria via aerosols. goats/sheep, cattle, pigs, dogs, sheep and rodents are infected by b. melitensis, b. abortus, b. suis, b. canis, b. ovis and b. neotomae, respectively, the six classical brucella species. most human cases are caused by b. melitensis and b. abortus. our aim was to specifically detect brucellae with 'smooth' ...201526438077
homology analysis and cross-immunogenicity of ompa from pathogenic yersinia enterocolitica, yersinia pseudotuberculosis and yersinia pestis.the outer membrane protein a (ompa) is one of the intra-species conserved proteins with immunogenicity widely found in the family of enterobacteriaceae. here we first confirmed ompa is conserved in the three pathogenic yersinia: yersinia pestis, yersinia pseudotuberculosis and pathogenic yersinia enterocolitica, with high homology at the nucleotide level and at the amino acid sequence level. the identity of ompa sequences for 262 y. pestis strains, 134 y. pseudotuberculosis strains and 219 patho ...201526435220
molecualr cloning of the capsular antigen f1 of yersinia pestis in pbad/giii plasmid.yersinia pestis which is the causative agent of pneumonic plague and distributed in all continents has led to many deaths during the history. because of its high mortality rate, it must be diagnosed and treated at the earliest time post infection and therefore, rapid diagnostic tests are required. in the present study, we cloned the coding sequence of f1 capsular antigen of the bacteria in the pbad/giii plasmid for later expression and purification of the protein to produce poly and monoclonal a ...201726430461
[analysis of the nucleotide sequence of a cryptic plasmid from yersinia pestis strains in the central caucasian high-mountain plague focus].an analysis of a 5.4-kbp cryptic plasmid detected in the course of whole-genome sequencing of the yersinia pestis medieval biovar isolated in the russian central caucasian high-mountain plague focus was performed. the identification of the nucleotide sequence of this cryptic plasmid and its structural and functional analysis revealed that it contained eight open reading frames, among which the following genes were identified: the rep gene of a replication protein, the virb6 gene of a type-iv sec ...201526410928
a new clade of african body and head lice infected by bartonella quintana and yersinia pestis-democratic republic of the congo.the human body louse is known as a vector for the transmission of three serious diseases-specifically, epidemic typhus, trench fever, and relapsing fever caused by rickettsia prowazekii, bartonella quintana, and borrelia recurrentis, respectively-that have killed millions of people. it is also suspected in the transmission of a fourth pathogen, yersinia pestis, which is the etiologic agent of plague. to date, human lice belonging to the genus pediculus have been classified into three mitochondri ...201526392158
an update on the hazards and risks of forensic anthropology, part ii: field and laboratory considerations.this paper focuses on potential hazards and risks to forensic anthropologists while working in the field and laboratory in north america. much has changed since galloway and snodgrass published their seminal article addressing these issues. the increased number of forensic practitioners combined with new information about potential hazards calls for an updated review of these pathogens and chemicals. discussion of pathogen hazards (brucella, borrelia burgdorferi, yersinia pestis, clostridium tet ...201626389711
genome assemblies for 11 yersinia pestis strains isolated in the caucasus region.yersinia pestis, the causative agent of plague, is endemic to the caucasus region but few reference strain genome sequences from that region are available. here, we present the improved draft or finished assembled genomes from 11 strains isolated in the nation of georgia and surrounding countries.201526383663
finished genome assembly of yersinia pestis ev76d and kim 10v.here, we sequenced the completed genome of yersinia pestis ev76d and kim 10v, two genomes used as references in assay development, to improved high-quality draft status.201526383662
yersinia pestis uses the ail outer membrane protein to recruit vitronectin.yersinia pestis, the agent of plague, requires the ail (attachment invasion locus) outer membrane protein to survive in the blood and tissues of its mammalian hosts. ail is important for both attachment to host cells and for resistance to complement-dependent bacteriolysis. previous studies have shown that ail interacts with components of the extracellular matrix, including fibronectin, laminin and heparan sulfate proteoglycans, and with the complement inhibitor c4b-binding protein. here, we dem ...201526377177
burrowing owls, pulex irritans, and plague.western burrowing owls (athene cunicularia hypugaea) are small, ground-dwelling owls of western north america that frequent prairie dog (cynomys spp.) towns and other grasslands. because they rely on rodent prey and occupy burrows once or concurrently inhabited by fossorial mammals, the owls often harbor fleas. we examined the potential role of fleas found on burrowing owls in plague dynamics by evaluating prevalence of yersinia pestis in fleas collected from burrowing owls and in owl blood. dur ...201526367482
role of the yersinia yopj protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes.polymorphonuclear leukocytes, in addition to their direct bactericidal activities, produce cytokines involved in the activation and regulation of the innate and adaptive immune response to infection. in this study we evaluated the cytokine response of human pmns following incubation with the pathogenic yersinia species. yersinia pestis strains with the pcd1 virulence plasmid, which encodes cytotoxic yop proteins that are translocated into host cells, stimulated little or no cytokine production c ...201626361732
[on the origin of yersinia pestis, a causative agent of the plague: a concept of population-genetic macroevolution in transitive environment].an ecological scenario is proposed for the origin of causative agent of the plague (the bacterium yersenia pestis) from the clone of pseudotuberculous microbe of the first serotype y. pseudotuberculosis o:1b. disclosed are the conditions of gradual intrusion of psychrophile saprozoonosis ancestor into the blood of the primary host, mongolian tarbagan marmot marmota sibirica. as an inductor of speciation acted the sartan cooling that occurred in the end of late pleistocene under conditions of ari ...201526353398
a lysr-type transcriptional regulator, rovm, senses nutritional cues suggesting that it is involved in metabolic adaptation of yersinia pestis to the flea gut.yersinia pestis has evolved as a clonal variant of yersinia pseudotuberculosis to cause flea-borne biofilm-mediated transmission of the bubonic plague. the lysr-type transcriptional regulator, rovm, is highly induced only during y. pestis infection of the flea host. rovm homologs in other pathogens regulate biofilm formation, nutrient sensing, and virulence; including in y. pseudotuberculosis, where rovm represses the major virulence factor, rova. here the role that rovm plays during flea infect ...201526348850
intrinsic plasmids influence micf-mediated translational repression of ompf in yersinia pestis.yersinia pestis, which is the causative agent of plague, has acquired exceptional pathogenicity potential during its evolution from y. pseudotuberculosis. two laterally acquired plasmids, namely, pmt1 and ppcp1, are specific to y. pestis and are critical for pathogenesis and flea transmission. small regulatory rnas (srnas) commonly function as regulators of gene expression in bacteria. micf, is a paradigmatic srna that acts as a post-transcriptional repressor through imperfect base pairing with ...201526347736
a recombinant raccoon poxvirus vaccine expressing both yersinia pestis f1 and truncated v antigens protects animals against lethal plague.in previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rrcn) expressing yersinia pestis antigens (f1 and v307-a truncated version of the v protein) provided superior protection against plague challenge compared to individual single antigen constructs. to reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (spv) control program for prairie dogs, a dual antigen construct is more ...201426344891
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
molecular docking based screening of neem-derived compounds with the ns1 protein of influenza virus.different strains of influenza virus are affecting a large number of people worldwide to combat with influenza virus destruction, numerous synthetic antiviral medicines are available for influenza virus in the market. but still there was a need for the development of drug which will target all the strains of influenza virus. for this purpose conserved residues within the influenza virus ns1 protein have been found by aligning all the available sequences of existing strains from the national cent ...201526339153
preliminary survey of ectoparasites and associated pathogens from norway rats in new york city.the norway rat (rattus norvegicus) is a reservoir of many zoonotic pathogens and lives in close proximity to humans in urban environments. human infection with rodent-borne disease occurs either directly through contact with a rat or its excreta, or indirectly via arthropod vectors such as fleas and ticks. here, we report on the diversity and abundance of ectoparasitic arthropod species and associated pathogenic bacteria from 133 norway rats trapped over a 10-mo period in manhattan, new york, ny ...201526336309
the role of early-phase transmission in the spread of yersinia pestis.early-phase transmission (ept) of yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. we review evidence demonstrating ept and current knowledge on its biological and biomechanical processes. we discuss the importance of ept in the epizootic spread of y. pestis and its role in the maintenance of plague bacteria in nature. we further address the role of ept in the epidemiology of plague.201526336267
the perfect burrow, but for what? identifying local habitat conditions promoting the presence of the host and vector species in the kazakh plague system.the wildlife plague system in the pre-balkhash desert of kazakhstan has been a subject of study for many years. much progress has been made in generating a method of predicting outbreaks of the disease (infection by the gram negative bacterium yersinia pestis) but existing methods are not yet accurate enough to inform public health planning. the present study aimed to identify characteristics of individual mammalian host (rhombomys opimus) burrows related to and potentially predictive of the pre ...201526325073
use of insecticide delivery tubes for controlling rodent-associated fleas in a plague endemic region of west nile, uganda.plague is a primarily flea-borne rodent-associated zoonosis that is often fatal in humans. our study focused on the plague-endemic west nile region of uganda where affordable means for the prevention of human plague are currently lacking. traditional hut construction and food storage practices hinder rodent exclusion efforts, and emphasize the need for an inexpensive but effective host-targeted approach for controlling fleas within the domestic environment. here we demonstrate the ability of an ...201426309315
crp-mediated carbon catabolite regulation of yersinia pestis biofilm formation is enhanced by the carbon storage regulator protein, csra.the natural transmission of yersinia pestis is reliant upon biofilm blockage of the flea vector. however, the environmentally-responsive adaptive regulators which facilitate y. pestis biofilm production in accordance with the flea midgut milieu are not well understood. we seek to establish the impact of available carbon source metabolism and storage upon y. pestis biofilm production. our findings demonstrate that y. pestis biofilm production is subject to carbon catabolite regulation in which th ...201526305456
redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of yoph: virulence factor of yersinia pestis.yoph is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing yersinia sp. bacteria. inactivation of yoph activity would lead to the loss of bacterial pathogenicity. we have studied the inhibitory properties of aurintricarboxylic acid (ata) against yoph phosphatase and found that at nanomolar concentrations ata reversibly decreases the activity of yoph. computational docking studies indicated that in all binding poses ata bi ...201526286963
the lcrg tip chaperone protein of the yersinia pestis type iii secretion system is partially folded.the type iii secretion system (t3ss) is essential in the pathogenesis of yersinia pestis, the causative agent of plague. a small protein, lcrg, functions as a chaperone to the tip protein lcrv, and the lcrg-lcrv interaction is important in regulating protein secretion through the t3ss. the atomic structure of the lcrg family is currently unknown. however, because of its predicted helical propensity, many have suggested that the lcrg family forms a coiled-coil structure. here, we show by nmr and ...201526259880
characterization of a cynomolgus macaque model of pneumonic plague for evaluation of vaccine efficacy.the efficacy of a recombinant plague vaccine (rf1v) was evaluated in cynomolgus macaques (cms) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of yersinia pestis strain colorado 92. cms were vaccinated with a range of rf1v doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. the humoral immune response following vaccination was evaluated with anti-rf1, anti-rv, and anti-rf1 ...201526224691
plague in egypt: disease biology, history and contemporary analysis: a minireview.plague is a zoonotic disease with a high mortality rate in humans. unfortunately, it is still endemic in some parts of the world. also, natural foci of the disease are still found in some countries. thus, there may be a risk of global plague re-emergence. this work reviews plague biology, history of major outbreaks, and threats of disease re-emergence in egypt. based on the suspected presence of potential natural foci in the country, the global climate change, and the threat posed by some neighb ...201526199744
map of f1 and v antigens from yersinia pestis astride innate and adaptive immune response.yersinia pestis, a causative agent of plague, has a plethora of armors to fight against major components of innate immunity and survive within host cells. dendritic cells and macrophages are important antigen presenting cells for effective immune response. this report is focused on the changes in dc activation and tlr2 and tlr4 expression on macrophages induced by map of f1 and v antigens of y. pestis. f1 and v maps bear potential synthetic t and b cell epitopes from f1 and v protein respectivel ...201526188288
label-free fab and fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.a unified approach to affinity screening for fab and fc interactions of an antibody for its antigen and fcγr receptor has been developed. an antigen array is used for the fab affinity and cross-reactivity screening and protein a/g proxy is the fcγr receptor. the affinities are derived using a simple 1:1 binding model with a consistent error analysis. the association and dissociation kinetics are measured over optimised times for accurate determination. the fab/fc affinities are derived for ten a ...201526187320
[maldi-tof ms analysis for yersinia pestis, vibrio cholera, and francisella tularensis identification].numerous studies showed that a new technology for the clinical microbiology laboratories, matrix-assisted laser desorption ionization--time of flight mass spectrometry (maldi-tof ms), allows fast, accurate, and effective identification of most clinically relevant microorganisms to be implemented. in the present review, we discuss applications of this approach for identification and typing of extremely dangerous pathogens--yersinia pestis, vibrio cholera, and francisella tularensis, including the ...201526182660
resistance to innate immunity contributes to colonization of the insect gut by yersinia pestis.yersinia pestis, the causative agent of bubonic and pneumonic plague, is typically a zoonotic vector-borne disease of wild rodents. bacterial biofilm formation in the proventriculus of the flea contributes to chronic infection of fleas and facilitates efficient disease transmission. however prior to biofilm formation, ingested bacteria must survive within the flea midgut, and yet little is known about vector-pathogen interactions that are required for flea gut colonization. here we establish a d ...201526177454
gene loss dominates as a source of genetic variation within clonal pathogenic bacterial species.some of the most dangerous pathogens such as mycobacterium tuberculosis and yersinia pestis evolve clonally. this means that little or no recombination occurs between strains belonging to these species. paradoxically, although different members of these species show extreme sequence similarity of orthologous genes, some show considerable intraspecies phenotypic variation, the source of which remains elusive. to examine the possible sources of phenotypic variation within clonal pathogenic bacteri ...201526163675
evaluation of the role of the opggh operon in yersinia pseudotuberculosis and its deletion during the emergence of yersinia pestis.the opggh operon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (opgs) from udp-glucose, using acyl carrier protein (acp) as a cofactor. opgs are required for motility, biofilm formation, and virulence in various bacteria. opgh also sequesters ftsz in order to regulate cell size according to nutrient availability. yersinia pestis (the agent of flea-borne plague) lost the opggh operon during its emergence from the enteropathogen yersinia pseudotuberculosis. when ex ...201526150539
fibrinolytic and procoagulant activities of yersinia pestis and salmonella enterica.pla of the plague bacterium yersinia pestis and pgte of the enteropathogen salmonella enterica are surface-exposed, transmembrane β-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, and both proteases are established virulence factors. pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and α2-antiplasmin, inactivation of the thrombin-activable fibrinolysi ...201526149012
backbone structure of yersinia pestis ail determined in micelles by nmr-restrained simulated annealing with implicit membrane solvation.the outer membrane protein ail (attachment invasion locus) is a virulence factor of yersinia pestis that mediates cell invasion, cell attachment and complement resistance. here we describe its three-dimensional backbone structure determined in decyl-phosphocholine (depc) micelles by nmr spectroscopy. the nmr structure was calculated using the membrane function of the implicit solvation potential, eefxpot, which we have developed to facilitate nmr structure calculations in a physically realistic ...201526143069
a new cellular target for yersinia pestis. 201526124192
early emergence of yersinia pestis as a severe respiratory pathogen.yersinia pestis causes the fatal respiratory disease pneumonic plague. y. pestis recently evolved from the gastrointestinal pathogen y. pseudotuberculosis; however, it is not known at what point y. pestis gained the ability to induce a fulminant pneumonia. here we show that the acquisition of a single gene encoding the protease pla was sufficient for the most ancestral, deeply rooted strains of y. pestis to cause pneumonic plague, indicating that y. pestis was primed to infect the lungs at a ver ...201526123398
surface plasmon resonance imaging of pathogens: the yersinia pestis paradigm.yersinia pestis, causing deadly plague, is classified as a group a bioterrorism bacterium. some recent dna-based methods were used for detection of bioterrorism agents.201526105071
application of pyrosequencing® in food biodefense.the perpetration of a bioterrorism attack poses a significant risk for public health with potential socioeconomic consequences. it is imperative that we possess reliable assays for the rapid and accurate identification of biothreat agents to make rapid risk-informed decisions on emergency response. the development of advanced methodologies for the detection of biothreat agents has been evolving rapidly since the release of the anthrax spores in the mail in 2001, and recent advances in detection ...201526103911
cd8α(-) dendritic cells induce antigen-specific t follicular helper cells generating efficient humoral immune responses.recent studies on t follicular helper (tfh) cells have significantly advanced our understanding of t cell-dependent b cell responses. however, little is known about the early stage of tfh cell commitment by dendritic cells (dcs), particularly by the conventional cd8α(+) and cd8α(-) dc subsets. we show that cd8α(-) dcs localized at the interfollicular zone play a pivotal role in the induction of antigen-specific tfh cells by upregulating the expression of icosl and ox40l through the non-canonical ...201526095362
[establishment and evaluation of identification method for yersinia pestis and yersinia pseudotuberculosis].to establish a gene identification method of yersinia pestis and yersinia pseudotuberculosis for plague surveillance.201526080641
mesaconase activity of class i fumarase contributes to mesaconate utilization by burkholderia xenovorans.pseudomonas aeruginosa, yersinia pestis, and many other bacteria are able to utilize the c5-dicarboxylic acid itaconate (methylenesuccinate). itaconate degradation starts with its activation to itaconyl coenzyme a (itaconyl-coa), which is further hydrated to (s)-citramalyl-coa, and citramalyl-coa is finally cleaved into acetyl-coa and pyruvate. the xenobiotic-degrading betaproteobacterium burkholderia xenovorans possesses a p. aeruginosa-like itaconate degradation gene cluster and is able to gro ...201526070669
diverse genotypes of yersinia pestis caused plague in madagascar in 2007.yersinia pestis is the causative agent of human plague and is endemic in various african, asian and american countries. in madagascar, the disease represents a significant public health problem with hundreds of human cases a year. unfortunately, poor infrastructure makes outbreak investigations challenging.201526069964
[genotyping of yersinia pestis by multiple-locus variable number tandem repeat analysis and its epidemiological characteristics in gansu province]. 201526065103
identification of highly pathogenic microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry: results of an interlaboratory ring trial.in the case of a release of highly pathogenic bacteria (hpb), there is an urgent need for rapid, accurate, and reliable diagnostics. maldi-tof mass spectrometry is a rapid, accurate, and relatively inexpensive technique that is becoming increasingly important in microbiological diagnostics to complement classical microbiology, pcr, and genotyping of hpb. in the present study, the results of a joint exercise with 11 partner institutions from nine european countries are presented. in this exercise ...201526063856
curing both virulent mega-plasmids from bacillus anthracis wild-type strain a16 simultaneously using plasmid incompatibility.plasmid-cured derivative strains of bacillus anthracis are frequently used in laboratory studies. plasmid incompatibility, which does not increase the risk of chromosomal mutation, is a useful method for plasmid curing. however, in bacteria containing multiple plasmids, it often requires the sequential introduction of multiple, specific incompatibility plasmids. this lengthy process renders the traditional plasmid incompatibility method inefficient and mutation-prone. in this study, we successfu ...201526059513
development and validation of an arthropod maceration protocol for zoonotic pathogen detection in mosquitoes and fleas.arthropod-borne diseases remain a pressing international public health concern. while progress has been made in the rapid detection of arthropod-borne pathogens via quantitative real-time (qpcr), or even hand-held detection devices, a simple and robust maceration and nucleic acid extraction method is necessary to implement biosurveillance capabilities. in this study, a comparison of maceration techniques using five types of beads followed by nucleic acid extraction and detection were tested usin ...201526047188
monitoring biothreat agents (francisella tularensis, bacillus anthracis and yersinia pestis) with a portable real-time pcr instrument.in the event of suspected releases or natural outbreaks of contagious pathogens, rapid identification of the infectious agent is essential for appropriate medical intervention and disease containment. the purpose of this study was to compare the performance of a novel portable real-time pcr thermocycler, pikoreal™, to the standard real-time pcr thermocycler, applied biosystems® 7300 (abi 7300), for the detection of three high-risk biothreat bacterial pathogens: francisella tularensis, bacillus a ...201526043838
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
[analysis of diversity and identification of the genovariants of plague agent strains from mongolian foci].the genetic diversity of yersinia pestis strains from the mongolian natural plague foci has been investigated. a total of 32 strains isolated from western, eastern, and central aimaks, as well as from the territory of the gobi region, have been studied. twenty-four strains belong to the main y. pestis subspecies, while eight belong to other subspecies. there is only one strain of biovar medievalis (genovariant 2.med1) among the strains of the main subspecies, while the rest of the subspecies bel ...201526027368
total biosynthesis and diverse applications of the nonribosomal peptide-polyketide siderophore yersiniabactin.yersiniabactin (ybt) is a mixed nonribosomal peptide-polyketide natural product natively produced by the pathogen yersinia pestis. the compound enables iron scavenging capabilities upon host infection and is biosynthesized by a nonribosomal peptide synthetase featuring a polyketide synthase module. this pathway has been engineered for expression and biosynthesis using escherichia coli as a heterologous host. in the current work, the biosynthetic process for ybt formation was improved through the ...201526025901
stress-caused anergy of leukocytes towards staphylococcal enterotoxin b and exposure transcriptome signatures.leucocytes from soldiers exposed to battlefield-like stress (rasp: rangers assessment and selection program) were exposed in vitro to staphylococcal enterotoxin b (seb). we assayed seb-induced regulation of gene expression, both in the presence and absence of severe stress, to generate two sets of gene profiles. one set of transcripts and micrornas were specific to post-rasp seb exposure, and another set were signatures of seb exposure common to both the pre- and post-rasp leucocytes. pathways a ...201726020283
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