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posttranscriptional regulation of the yersinia pestis cyclic amp receptor protein crp and impact on virulence.the cyclic amp receptor protein (crp) is a transcriptional regulator that controls the expression of numerous bacterial genes, usually in response to environmental conditions and particularly by sensing the availability of carbon. in the plague pathogen yersinia pestis, crp regulates the expression of multiple virulence factors, including components of the type iii secretion system and the plasminogen activator protease pla. the regulation of crp itself, however, is distinctly different from tha ...201424520064
lung deposition and cellular uptake behavior of pathogen-mimicking nanovaccines in the first 48 hours.pulmonary immunization poses the unique challenge of balancing vaccine efficacy with minimizing inflammation in the respiratory tract. while previous studies have shown that mice immunized intranasally with f1-v-loaded polyanhydride nanoparticles are protected from a lethal challenge with yersinia pestis, little is known about the initial interaction between the nanoparticles and immune cells following intranasal administration. here, the deposition within the lung and internalization by phagocy ...201424520022
biologically active ligands for yersinia outer protein h (yoph): feature based pharmacophore screening, docking and molecular dynamics studies.yersinia pestis, a gram negative bacillus, spreads via lymphatic to lymph nodes and to all organs through the bloodstream, causing plague. yersinia outer protein h (yoph) is one of the important effector proteins, which paralyzes lymphocytes and macrophages by dephosphorylating critical tyrosine kinases and signal transduction molecules. the purpose of the study is to generate a three-dimensional (3d) pharmacophore model by using diverse sets of yoph inhibitors, which would be useful for designi ...201424517834
immunological and clinical response of coyotes (canis latrans) to experimental inoculation with yersinia pestis.multiple publications have reported the use of coyotes (canis latrans) in animal-based surveillance efforts for the detection of yersinia pestis. coyotes are likely exposed via flea bite or oral routes and are presumed to be resistant to the development of clinical disease. these historic data have only been useful for the evaluation of the geographic distribution of y. pestis in the landscape. because the canid immunologic response to y. pestis has not been thoroughly characterized, we conducte ...201324502720
the innate immune response may be important for surviving plague in wild gunnison's prairie dogs.prairie dogs (cynomys spp.) are highly susceptible to yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. a colony of gunnison's prairie dogs (cynomys gunnisoni) in the aubrey valley (av) of northern arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by y. pestis. to examine potential mechanisms accounting for survival in the av colony, we conducted a laboratory y. pestis challenge expe ...201324502719
a recombinant bivalent fusion protein rve confers active and passive protection against yersinia enterocolitica infection in mice.in the present study, a bivalent chimeric protein rve comprising immunologically active domains of yersinia pestis lcrv and yope was assessed for its prophylactic abilities against yersinia enterocolitica o:8 infection in murine model. mice immunized with rve elicited significantly higher antibody titers with substantial contribution from the rv component (3:1 ratio). robust and significant resistance to y. enterocolitica infection with 100% survival (p<0.001) was seen in rve vaccinated mice whe ...201424486353
season and application rates affect vaccine bait consumption by prairie dogs in colorado and utah, usa.plague, a zoonotic disease caused by the bacterium yersinia pestis, causes high rates of mortality in prairie dogs (cynomys spp.). an oral vaccine against plague has been developed for prairie dogs along with a palatable bait to deliver vaccine and a biomarker to track bait consumption. we conducted field trials between september 2009 and september 2012 to develop recommendations for bait distribution to deliver plague vaccine to prairie dogs. the objectives were to evaluate the use of the bioma ...201424484490
a rapid field test for sylvatic plague exposure in wild animals.plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. the most common surveillance method for sylvatic plague is detection of antibodies to yersinia pestis f1 capsular antigen in sentinel animals, such as coyotes (canis latrans). current serologic tests for y. pestis, hemagglutination (ha) test and enzyme-linked immunosorbent assay (elisa), are expensive and labor intensive. to address this need, we developed a complete lateral flow dev ...201424484483
yersinia pestis: one pandemic, two pandemics, three pandemics, more? 201424480150
yersinia pestis and the plague of justinian 541-543 ad: a genomic analysis.yersinia pestis has caused at least three human plague pandemics. the second (black death, 14-17th centuries) and third (19-20th centuries) have been genetically characterised, but there is only a limited understanding of the first pandemic, the plague of justinian (6-8th centuries). to address this gap, we sequenced and analysed draft genomes of y pestis obtained from two individuals who died in the first pandemic.201424480148
epitope recognition of antibodies against a yersinia pestis lipopolysaccharide trisaccharide component.today, the process of selecting carbohydrate antigens as a basis for active vaccination and the generation of antibodies for therapeutic and diagnostic purposes is based on intuition combined with trial and error experiments. in efforts to establish a rational process for glycan epitope selection, we employed glycan array screening, surface plasmon resonance, and saturation transfer difference (std)-nmr to elucidate the interactions between antibodies and glycans representing the yersinia pestis ...201424479563
[bioterrorism and pathogenic microorganisms].in recent years the use of pathogenic microorganisms in acts of bioterrorism has been the subject of major concern in many countries. this paper presents a possible application of viruses and bacteria for warfare and terrorist purposes, as well as a laboratory diagnosis to identify those agents. the viruses of smallpox (orthopoxvirus), of hemorrhagic fever and those belonging to filovirus have been highlighted, inter alia, as agents of human infection with bioterrorist intent. among the bacteria ...201324473660
quantifying interactions of a membrane protein embedded in a lipid nanodisc using fluorescence correlation spectroscopy.using fluorescence correlation spectroscopy, we measured a dissociation constant of 20 nm between egfp-labeled lcrv from yersinia pestis and its cognate membrane-bound protein yopb inserted into a lipid nanodisc. the combination of fluorescence correlation spectroscopy and nanodisc technologies provides a powerful approach to accurately measure binding constants of interactions between membrane bound and soluble proteins in solution. straightforward sample preparation, acquisition, and analysis ...201424461026
[thermodynamic parameters of stabilization in a compact form of the caf1(13-149) subunit from yersinia pestis].with a number of experimental methods (circular dichroism, viscosity, intrinsic fluorescence and fluorescence labelling) the conformational folding-unfolding transitions in a compact monomeric form of the caf1(13-149) subunit were studied under the action of guanidine hydrochloride in the temperature range from 5 to 45 degrees c. it has been shown that transitions always occur between two major states (unfolded and compact). it has made it possible to determine all main thermodynamic functions t ...201424455880
metabolic network analysis-based identification of antimicrobial drug targets in category a bioterrorism agents.the 2001 anthrax mail attacks in the united states demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three category a-designated bioterrorism agents ...201424454817
the origin of behçet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection.it is recognised that the genetic profiles that give rise to chronic inflammatory diseases, under the influence of environmental agents, might have been implicated in the host defence mechanism against lethal infections in the past. behçet's disease (bd) is an immune-mediated inflammatory disease, expressed as vasculitis, triggered by environmental factors in genetically susceptible individuals. we carried out a review of published data to draw up an evolutionary adaptation model, as author's pe ...201724447390
reverse line blot macroarray for simultaneous detection and characterization of four biological warfare agents.the need for a rapid detection and characterization of biowarfare (bw) agents cannot be over emphasized. with diverse array of potential bw pathogen available presently, rapid identification of the pathogen is crucial, so that specific therapy and control measures can be initiated. we have developed a multiplex polymerase chain reaction based reverse line blot macroarray to simultaneously detect four pathogens of bw importance viz. bacillus anthracis, yersinia pestis, brucella melitensis and bur ...201324426077
crystallization and preliminary x-ray diffraction analysis of fabg from yersinia pestis.the type ii fatty-acid biosynthesis pathway of bacteria provides enormous potential for antibacterial drug development owing to the structural differences between this and the type i fatty-acid biosynthesis system found in mammals. β-ketoacyl-acp reductase (fabg) is responsible for the reduction of the β-ketoacyl group linked to acyl carrier protein (acp), and is essential for the formation of fatty acids and bacterial survival. here, the cloning, expression, purification, crystallization and di ...201424419628
two-step source tracing strategy of yersinia pestis and its historical epidemiology in a specific region.source tracing of pathogens is critical for the control and prevention of infectious diseases. genome sequencing by high throughput technologies is currently feasible and popular, leading to the burst of deciphered bacterial genome sequences. utilizing the flooding genomic data for source tracing of pathogens in outbreaks is promising, and challenging as well. here, we employed yersinia pestis genomes from a plague outbreak at xinghai county of china in 2009 as an example, to develop a simple tw ...201424416399
yersinia pestis: mechanisms of entry into and resistance to the host cell.during infection, yersinia, a facultative intracellular bacterial species, exhibits the ability to first invade host cells and then counteract phagocytosis by the host cells. during these two distinct stages, invasion or antiphagocytic factors assist bacteria in manipulating host cells to accomplish each of these functions; however, the mechanism through which yersinia regulates these functions during each step remains unclear. here, we discuss those factors that seem to function reversely and g ...201324400226
yfba, a yersinia pestis regulator required for colonization and biofilm formation in the gut of cat fleas.for transmission to new hosts, yersinia pestis, the causative agent of plague, replicates as biofilm in the foregut of fleas that feed on plague-infected animals or humans. y. pestis biofilm formation has been studied in the rat flea; however, little is known about the cat flea, a species that may bridge zoonotic and anthroponotic plague cycles. here, we show that y. pestis infects and replicates as a biofilm in the foregut of cat fleas in a manner requiring hmsfr, two determinants for extracell ...201424391055
ail proteins of yersinia pestis and y. pseudotuberculosis have different cell binding and invasion activities.the yersinia pestis adhesin ail mediates host cell binding and facilitates delivery of cytotoxic yop proteins. ail from y. pestis and y. pseudotuberculosis is identical except for one or two amino acids at positions 43 and 126 depending on the y. pseudotuberculosis strain. ail from y. pseudotuberculosis strain ypiii has been reported to lack host cell binding ability, thus we sought to determine which amino acid difference(s) are responsible for the difference in cell adhesion. y. pseudotubercul ...201324386237
kinetics of memory b cell and plasma cell responses in the mice immunized with plague vaccines.in our previous studies, we found that plague vaccines can induce long-term antibody response, but no significant antibody boost was observed when the immunized mice were challenged with virulent yersinia pestis. however, a booster vaccination of subunit vaccine on week 3 after primary immunization elicited a significantly higher antibody titre than a single dose, whereas no significant antibody titre difference was observed between a single dose and two doses of ev76 vaccination. to address the ...201424383627
rational considerations about development of live attenuated yersinia pestis vaccines.the risk of plague as a bioweapon has prompted increasing research efforts to develop plague vaccines due to its extreme virulence and the ease of its transmission. subunit vaccines that contain f1 and lcrv antigens of y. pestis have been tested for safety and immunogenicity, but doubts have been raised about whether subunit vaccines that engender antibody responses will protect against pneumonic plague, which requires both humeral and cellular immune responses for protection. the live, attenuat ...201424372254
[a molecular basis of the plague vaccine development].molecular mechanisms of the yersinia pestis pathogenicity and peculiarities of maturation of specific immunity to plague are reviewed. the history and modern state of the plague vaccine development are described. special attention is focused on the prospects in the area of the plague vaccine development. the possible approaches to improvement of vaccine preparations are discussed.201324364139
yopp-expressing variant of y. pestis activates a potent innate immune response affording cross-protection against yersiniosis and tularemia [corrected].plague, initiated by yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. the existence of antibiotic-resistant y. pestis strains emphasizes the need for the development of novel countermeasures against plague. we previously reported the generation of a recombinant y. pestis strain (kim53δj+p) that over-expresses y. enterocolitica yopp. when this strain was administered subcutaneously to mice, it elicited a fast and effective protective i ...201324358292
applications of docking and molecular dynamic studies on the search for new drugs against the biological warfare agents bacillus anthracis and yersinia pestis.the fear of biological warfare agents (bwa) use by terrorists is the major concern of the security agencies and health authorities worldwide today. the non-existence of vaccines or drugs against most bwa and the possibility of genetic modified strains has turned the search for new drugs to a state of urgency. fast in silico techniques are, therefore, perfect tools for this task once they can quickly provide structures of several new lead compounds for further experimental work. here we try to pr ...201324341424
[morphofunctional evaluation of the state of cells of apud-system biomodel during anti-plague vaccine process].study reaction of cells of apud-system of lymphoid organs and intestine of guinea pigs at the stages of morpho- and immunogenesis in response to administration of yersinia pestis ev research institute of epidemiology and hygiene (rieh) line vaccine strain.201324341215
protein markers for identification of yersinia pestis and their variation related to culture.the detection of high consequence pathogens, such as yersinia pestis, is well established in biodefense laboratories for bioterror situations. laboratory protocols are well established using specified culture media and a growth temperature of 37 °c for expression of specific antigens. direct detection of y. pestis protein markers, without prior culture, depends on their expression. unfortunately protein expression can be impacted by the culture medium which cannot be predicted ahead of time. fur ...201524333237
bioluminescent tracking of colonization and clearance dynamics of plasmid-deficient yersinia pestis strains in a mouse model of septicemic plague.yersinia pestis 201 contains 4 plasmids ppcp1, pmt1, pcd1 and pcry, but little is known about the effects of these plasmids on the dissemination of y. pestis. we developed a plasmid-based luxcdabe bioreporter in y. pestis 201, y. pestis 201-pcd1(+), y. pestis 201-pmt1(+), y. pestis 201-ppcp1(+), y. pestis 201-pcry(+), y. pestis 201-p(-) and yersinia pseudotuberculosis pa36060 strains, and investigated their dissemination by bioluminescence imaging during primary septicemic plague in a mouse mode ...201424333143
[preparation and biological activity analysis of chimeric antibody against capsular f1 antigen of yersinia pestis].to express human-mouse chimeric antibody against yersinia pestis f1 capsular antigen (f1 antigen) and analyze its biological activities.201324321075
the exoribonuclease polynucleotide phosphorylase influences the virulence and stress responses of yersiniae and many other pathogens.microbes are incessantly challenged by both biotic and abiotic stressors threatening their existence. therefore, bacterial pathogens must possess mechanisms to successfully subvert host immune defenses as well as overcome the stress associated with host-cell encounters. to achieve this, bacterial pathogens typically experience a genetic re-programming whereby anti-host/stress factors become expressed and eventually translated into effector proteins. in that vein, the bacterial host-cell induced ...201324312901
[study on the functions of potential new genes of yersinia pestis type three secretion system].to investigate the functional relations between the putative proteins ypcd1.08, ypcd1.09, ypcd1.16 encoded in pcd1 plasmid of yersinia pestis and its type iii secretion system (t3ss).201324304956
a type iii secretion system inhibitor targets yopd while revealing differential regulation of secretion in calcium-blind mutants of yersinia pestis.numerous gram-negative pathogens rely upon type iii secretion (t3s) systems to cause disease. several small-molecule inhibitors of the type iii secretion systems have been identified; however, few targets of these inhibitors have been elucidated. here we report that 2,2'-thiobis-(4-methylphenol) (compound d), inhibits type iii secretion in yersinia pestis, yersinia pseudotuberculosis, and pseudomonas aeruginosa. yopd, a protein involved in the formation of the translocon and regulatory processes ...201424247143
understanding the persistence of plague foci in madagascar.plague, a zoonosis caused by yersinia pestis, is still found in africa, asia, and the americas. madagascar reports almost one third of the cases worldwide. y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. the black rat rattus rattus, the m ...201324244760
yersinia pestis survival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages.yersinia pestis, the bacterial agent of plague, is transmitted by fleas. the bite of an infected flea deposits y. pestis into the dermis and triggers recruitment of innate immune cells, including phagocytic pmns. y. pestis can subvert this pmn response and survive at the flea-bite site, disseminate, and persist in the host. although its genome encodes a number of antiphagocytic virulence factors, phagocytosis of y. pestis by pmns has been observed. this study tests the hypotheses that y. pestis, ...201424227798
yersinia pestis biovar microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.yersinia pestis biovar microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. it may be used as live attenuated plague vaccine candidates in terms of its low virulence. however, the microtus strain's protection against plague has yet to be demonstrated in larger mammals. in this study, we evaluated the protective efficacy of the microtus strain 201 as a live attenuated plague vaccine candidate. our results show that this strain is highly attenuated ...201424225642
temperature-dependence of yadbc phenotypes in yersinia pestis.yadb and yadc are putative trimeric autotransporters present only in the plague bacterium yersinia pestis and its evolutionary predecessor, yersinia pseudotuberculosis. previously, yadbc was found to promote invasion of epithelioid cells by y. pestis grown at 37 °c. in this study, we found that yadbc also promotes uptake of 37 °c-grown y. pestis by mouse monocyte/macrophage cells. we tested whether yadbc might be required for lethality of the systemic stage of plague in which the bacteria would ...201424222617
customizable pcr-microplate array for differential identification of multiple pathogens.customizable pcr-microplate arrays were developed for the rapid identification of salmonella typhimurium, salmonella saintpaul, salmonella typhi, shigella dysenteriae, escherichia coli o157:h7, francisella tularensis subsp. tularensis, francisella tularensis subsp. novicida, vibrio cholerae, vibrio parahaemolyticus, yersinia pestis, and yersinia pseudotuberculosis. previously, we identified highly specific primers targeting each of these pathogens. here, we report the development of customizable ...201324215700
the yersinia pestis type iii secretion system: expression, assembly and role in the evasion of host defenses.yersinia pestis, the etiologic agent of plague, utilizes a type iii secretion system (t3ss) to subvert the defenses of its mammalian hosts. t3sss are complex nanomachines that allow bacterial pathogens to directly inject effector proteins into eukaryotic cells. the y. pestis t3ss is not expressed during transit through the flea vector, but t3ss gene expression is rapidly thermoinduced upon entry into a mammalian host. assembly of the t3s apparatus is a highly coordinated process that requires th ...201324198067
[transcriptional regulation of dps by oxyr protein in yersinia pestis].to study the transcriptional regulation mechanism of dps by oxyr in yersinia pestis.201324195375
imaging early pathogenesis of bubonic plague: are neutrophils commandeered for lymphatic transport of bacteria?vector-borne infections begin in the dermis when a pathogen is introduced by an arthropod during a blood meal. several barriers separate an invading pathogen from its replicative niche, including phagocytic cells in the dermis that activate immunity by engulfing would-be pathogens and migrating to the lymph node. in addition, neutrophils circulating in the blood are rapidly recruited when the dermal barriers are penetrated. for flea-borne disease, no insect-encoded immune-suppressive molecules h ...201324194541
hmsc, a periplasmic protein, controls biofilm formation via repression of hmsd, a diguanylate cyclase in yersinia pestis.yersinia pestis, the cause of plague, forms a biofilm in the foregut of its flea vector to enhance transmission. biofilm formation in y. pestis is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-gmp). hmst and y3730, the two diguanylate cyclases (dgc) in y. pestis, are responsible for the synthesis of c-di-gmp. y3730, which we name here as hmsd, has little effect on in vitro biofilms, but has a major effect on biofilm formation in the flea. the me ...201424192006
evaluation of swabs and transport media for the recovery of yersinia pestis.the government accountability office report investigating the surface sampling methods used during the 2001 mail contamination with bacillus anthracis brought to light certain knowledge gaps that existed regarding environmental sampling with biothreat agents. should a contamination event occur that involves non-spore forming biological select agents, such as yersinia pestis, surface sample collection and processing protocols specific for these organisms will be needed. two y. pestis strains (vir ...201424184311
potential corridors and barriers for plague spread in central asia.plague (yersinia pestis infection) is a vector-borne disease which caused millions of human deaths in the middle ages. the hosts of plague are mostly rodents, and the disease is spread by the fleas that feed on them. currently, the disease still circulates amongst sylvatic rodent populations all over the world, including great gerbil (rhombomys opimus) populations in central asia. great gerbils are social desert rodents that live in family groups in burrows, which are visible on satellite images ...201324171709
targeting dxp synthase in human pathogens: enzyme inhibition and antimicrobial activity of butylacetylphosphonate.the unique methylerythritol phosphate pathway for isoprenoid biosynthesis is essential in most bacterial pathogens. the first enzyme in this pathway, 1-deoxy-d-xylulose 5-phosphate (dxp) synthase, catalyzes a distinct thiamin diphosphate (thdp)-dependent reaction to form dxp from d-glyceraldehyde 3-phosphate (d-gap) and pyruvate and represents a potential anti-infective drug target. we have previously demonstrated that the unnatural bisubstrate analog, butylacetylphosphonate (bap), exhibits sele ...201424169798
managing iron supply during the infection cycle of a flea borne pathogen, bartonella henselae.bartonella are hemotropic bacteria responsible for emerging zoonoses. most bartonella species appear to share a natural cycle that involves an arthropod transmission, followed by exploitation of a mammalian host in which they cause long-lasting intra-erythrocytic bacteremia. persistence in erythrocytes is considered an adaptation to transmission by bloodsucking arthropod vectors and a strategy to obtain heme required for bartonella growth. bartonella genomes do not encode for siderophore biosynt ...201324151576
detection of anthrax and other pathogens using a unique liquid array technology.a bead-based liquid hybridization assay, luminex(®) 100™, was used to identify four pathogenic bacteria, bacillus anthracis, clostridium botulinum, francisella tularensis subsp. tularensis, and yersinia pestis, and several close relatives. hybridization between pcr-amplified target sequences and probe sequences (located within the 23s ribosomal rna gene rrl and the genes related to the toxicity of each bacterium) was detected in single-probe or multiple-probe assays, depending on the organism. t ...201424147813
exsa and lcrf recognize similar consensus binding sites, but differences in their oligomeric state influence interactions with promoter dna.exsa activates type iii secretion system (t3ss) gene expression in pseudomonas aeruginosa and is a member of the arac family of transcriptional regulators. arac proteins contain two helix-turn-helix (hth) dna binding motifs. one helix from each hth motif inserts into the major groove of the dna to make base-specific contacts with the promoter region. the amino acids that comprise the hth motifs of exsa are nearly identical to those in lcrf/virf, the activators of t3ss gene expression in the path ...201324142246
homology analysis of pathogenic yersinia species yersinia enterocolitica, yersinia pseudotuberculosis, and yersinia pestis based on multilocus sequence typing.we developed a multilocus sequence typing (mlst) scheme and used it to study the population structure and evolutionary relationships of three pathogenic yersinia species. mlst of these three yersinia species showed a complex of two clusters, one composed of yersinia pseudotuberculosis and yersinia pestis and the other composed of yersinia enterocolitica. within the first cluster, the predominant y. pestis sequence type 90 (st90) was linked to y. pseudotuberculosis st43 by one locus difference, a ...201424131695
an alternative outer membrane secretion mechanism for an autotransporter protein lacking a c-terminal stable core.autotransporter (at) proteins are a broad class of virulence factors from gram-negative pathogens. at outer membrane (om) secretion appears simple in many regards, yet the mechanism that enables transport of the central at 'passenger' across the om remains unclear. om secretion efficiency for two at passengers is enhanced by approximately 20 kda stable core at the c-terminus of the passenger, but studies on a broader range of at proteins are needed in order to determine whether a stability diffe ...201324118465
early host cell targets of yersinia pestis during primary pneumonic plague.inhalation of yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. using a fret-based probe to quantitate injection of effector proteins by the y. pestis ...201324098126
strategy for sensitive and specific detection of yersinia pestis in skeletons of the black death pandemic.yersinia pestis has been identified as the causative agent of the black death pandemic in the 14(th) century. however, retrospective diagnostics in human skeletons after more than 600 years are critical. we describe a strategy following a modern diagnostic algorithm and working under strict ancient dna regime for the identification of medieval human plague victims. an initial screening and dna quantification assay detected the y. pestis specific pla gene of the high copy number plasmid ppcp1. re ...201324069445
fpsac: fast phylogenetic scaffolding of ancient contigs.recent progress in ancient dna sequencing technologies and protocols has lead to the sequencing of whole ancient bacterial genomes, as illustrated by the recent sequence of the yersinia pestis strain that caused the black death pandemic. however, sequencing ancient genomes raises specific problems, because of the decay and fragmentation of ancient dna among others, making the scaffolding of ancient contigs challenging.201324068034
duration of plague (yersinia pestis) outbreaks in black-tailed prairie dog (cynomys ludovicianus) colonies of northern colorado.plague, caused by the bacterium yersinia pestis, triggers die-offs in colonies of black-tailed prairie dogs (cynomys ludovicianus), but the time-frame of plague activity is not well understood. we document plague activity in fleas from prairie dogs and their burrows on three prairie dog colonies that suffered die-offs. we demonstrate that y. pestis transmission occurs over periods from several months to over a year in prairie dog populations before observed die-offs.201324057801
a sensitive & specific multiplex pcr assay for simultaneous detection of bacillus anthracis, yersinia pestis, burkholderia pseudomallei & brucella species.bacillus anthracis, yersinia pestis, burkholderia pseudomallei and brucella species are potential biowarfare agents. classical bacteriological methods for their identification are cumbersome, time consuming and of potential risk to the handler.201324056564
plague gives surprises in the first decade of the 21st century in the united states and worldwide.plague is an ancient disease caused by the bacterium yersinia pestis and transmitted by rodent flea bites that continues to surprise us with first-ever events. this review documents plague in human cases in the 1st decade of the 21st century and updates our knowledge of clinical manifestations, transmission during outbreaks, diagnostic testing, antimicrobial treatment, and vaccine development. in the united states, 57 persons were reported to have the disease, of which seven died. worldwide, 21, ...201324043686
determination of srna expressions by rna-seq in yersinia pestis grown in vitro and during infection.small non-coding rnas (srnas) facilitate host-microbe interactions. they have a central function in the post-transcriptional regulation during pathogenic lifestyles. hfq, an rna-binding protein that many srnas act in conjunction with, is required for y. pestis pathogenesis. however, information on how yersinia pestis modulates the expression of srnas during infection is largely unknown.201324040259
thiamine triphosphatase and the cyth superfamily of proteins.the cyth superfamily of proteins was named after its two founding members, the cyab adenylyl cyclase from aeromonas hydrophila, and the human 25-kda thiamine triphosphatase (thtpase). members of this superfamily of proteins exist in all organisms, including bacteria, archaeons, fungi, plants, and animals (except birds), and can be traced back to the last universal common ancestor. their sequences include several charged residues involved in divalent cation and triphosphate binding. indeed, all m ...201324021036
[analysis on genotype distributions and epidemiological characteristics of yersinia pestis plague foci in gansu province].to study the genotype distributions and epidemiological characteristics of yersinia pestis in gansu province.201324016429
outer membrane proteins ail and ompf of yersinia pestis are involved in the adsorption of t7-related bacteriophage yep-phi.yep-phi is a t7-related bacteriophage specific to yersinia pestis, and it is routinely used in the identification of y. pestis in china. yep-phi infects y. pestis grown at both 20°c and 37°c. it is inactive in other yersinia species irrespective of the growth temperature. based on phage adsorption, phage plaque formation, affinity chromatography, and western blot assays, the outer membrane proteins of y. pestis ail and ompf were identified to be involved, in addition to the rough lipopolysacchar ...201324006436
[molecular typing of yersinia pestis].techniques for differentiating single bacterial isolates into intraspecies clusters corresponding to subspecies, biovars, and natural foci are reviewed. the techniques under consideration are reproducible under different laboratory settings. a version of the intraspecies classification of y. pestis that is in harmony with the international code of nomencláture of bacteria is suggested.201324003506
the effects of modeled microgravity on growth kinetics, antibiotic susceptibility, cold growth, and the virulence potential of a yersinia pestis ymoa-deficient mutant and its isogenic parental strain.previously, we reported that there was no enhancement in the virulence potential (as measured by cell culture infections) of the bacterial pathogen yersinia pestis (yp) following modeled microgravity/clinorotation growth. we have now further characterized the effects of clinorotation (cr) on yp growth kinetics, antibiotic sensitivity, cold growth, and yp's virulence potential in a murine model of infection. surprisingly, none of the aforementioned phenotypes were altered. to better understand wh ...201323988036
[the sensitivity of plague agent from siberian natural focuses of disease to antibacterial preparations in vitro].the comparative analysis was applied concerning antimicrobic action of different groups of antibacterial preparations on the plague agent strains isolated from siberian natural focuses of disease. the analysis was applied to results obtained using such different methods as disco-diffusive technique, serial dilution and hicomb mic test. it is established that freshly isolated cultures of yersinia pestis have high sensitivity to antibacterial preparations of different groups. the results obtained ...201323984554
yersinia pestis subverts the dermal neutrophil response in a mouse model of bubonic plague.the majority of human yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. once in the dermis, y. pestis can evade the host's innate immune response and subsequently disseminate to the draining lymph node (dln). there, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. in this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d. ...201323982068
prophylaxis and therapy of plague.plague has been a scourge of mankind for centuries, and outbreaks continue to the present day. the virulence mechanisms employed by the etiological agent yersinia pestis are reviewed in the context of the available prophylactic and therapeutic strategies for plague. although antibiotics are available, resistance is emerging in this dangerous pathogen. therapeutics used in the clinic are discussed and innovative approaches to the design and development of new therapeutic compounds are reviewed. c ...201323977937
decontamination of a hospital room using gaseous chlorine dioxide: bacillus anthracis, francisella tularensis, and yersinia pestis.this study assessed the efficacy of gaseous chlorine dioxide for inactivation of bacillus anthracis, francisella tularensis, and yersinia pestis in a hospital patient care suite. spore and vegetative cells of bacillus anthracis sterne 34f2, spores of bacillus atrophaeus atcc 9372 and vegetative cells of both francisella tularensis atcc 6223 and yersinia pestis a1122 were exposed to gaseous chlorine dioxide in a patient care suite. organism inactivation was then assessed by log reduction in viabl ...201323971883
serologic survey of plague in animals, western iran. 201323968721
quinto tiberio angelerio and new measures for controlling plague in 16th-century alghero, sardinia.plague, a zoonotic disease caused by the bacterium yersinia pestis, has been responsible for at least 3 pandemics. during 1582-1583, a plague outbreak devastated the seaport of alghero in sardinia. by analyzing contemporary medical texts and local documentation, we uncovered the pivotal role played by the protomedicus of alghero, quinto tiberio angelerio (1532-1617), in controlling the epidemic. angelerio imposed rules and antiepidemic measures new to the 16th-century sanitary system of sardinia ...201323968598
analysis of autoinducer-2 quorum sensing in yersinia pestis.the autoinducer-2 (ai-2) quorum-sensing system has been linked to diverse phenotypes and regulatory changes in pathogenic bacteria. in the present study, we performed a molecular and biochemical characterization of the ai-2 system in yersinia pestis, the causative agent of plague. in strain co92, the ai-2 signal is produced in a luxs-dependent manner, reaching maximal levels of 2.5 μm in the late logarithmic growth phase, and both wild-type and pigmentation (pgm) mutant strains made equivalent l ...201323959719
role of yersinia pestis toxin complex family proteins in resistance to phagocytosis by polymorphonuclear leukocytes.yersinia pestis carries homologues of the toxin complex (tc) family proteins, which were first identified in other gram-negative bacteria as having potent insecticidal activity. the y. pestis tc proteins are neither toxic to fleas nor essential for survival of the bacterium in the flea, even though tc gene expression is highly upregulated and much more of the tc proteins yita and yipa are produced in the flea than when y. pestis is grown in vitro. we show that tc(+) and tc(-) y. pestis strains a ...201323959716
persistence of black-tailed prairie-dog populations affected by plague in northern colorado, usa.the spatial distribution of prairie dog (cynomys ludovicianus) colonies in north america has changed from large, contiguous populations to small, isolated colonies in metapopulations. one factor responsible for this drastic change in prairie-dog population structure is plague (caused by the bacterium yersinia pestis). we fit stochastic patch occupancy models to 20 years of prairie-dog colony occupancy data from two discrete metapopulations (west and east) in the pawnee national grassland in colo ...201323951717
short report: exposing laboratory-reared fleas to soil and wild flea feces increases transmission of yersinia pestis.laboratory-reared oropsylla montana were exposed to soil and wild-caught oropsylla montana feces for 1 week. fleas from these two treatments and a control group of laboratory-reared fleas were infected with yersinia pestis, the etiological agent of plague. fleas exposed to soil transmitted y. pestis to mice at a significantly greater rate (50.0% of mice were infected) than control fleas (23.3% of mice were infected). although the concentration of y. pestis in fleas did not differ among treatment ...201323939709
a high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases.many proteobacteria use n-acyl-homoserine lactone (acyl-hsl) quorum sensing to control specific genes. acyl-hsl synthesis requires unique enzymes that use s-adenosyl methionine as an acyl acceptor and amino acid donor. we developed and executed an enzyme-coupled high-throughput cell-free screen to discover acyl-hsl synthase inhibitors. the three strongest inhibitors were equally active against two different acyl-hsl synthases: burkholderia mallei bmai1 and yersinia pestis yspi. two of these inhi ...201323924613
proposed reclassification of pasteurella lymphangitidis sneath & stevens 1990 as yersinia pseudotuberculosis.the 16s rrna gene sequences of pasteurella lymphangitidis, yersinia pseudotuberculosis and yersinia pestis were found to be identical and multilocus sequence analysis could not discriminate between the three species. the susceptibility to a y. pseudotuberculosis phage and the presence of the y. pseudotuberculosis-specific invasin gene in p. lymphangitidis indicate that the latter should be reclassified as y. pseudotuberculosis.201323919959
bacteria and vampirism in cinema.a vampire is a non-dead and non-alive chimerical creature, which, according to various folklores and popular superstitions, feeds on blood of the living to draw vital force. vampires do not reproduce by copulation, but by bite. vampirism is thus similar to a contagious disease contracted by intravascular inoculation with a suspected microbial origin. in several vampire films, two real bacteria were staged, better integrated than others in popular imagination: yersinia pestis and treponema pallid ...201323916557
evaluation of yadc protein delivered by live attenuated salmonella as a vaccine against plague.yersinia pestis yadb and yadc are two new outer membrane proteins related with its pathogenicity. here, codon optimized yadc, yadc810 (aa 32-551) or yadbc antigen genes delivered by live attenuated salmonella strains are evaluated in mice for induction of protective immune responses against y. pestis co92 through subcutaneous (s.c.) or intranasal (i.n.) challenge. our findings indicate that mice immunized with salmonella synthesizing yadc, yadc810 or yadbc develop significant serum igg responses ...201323913628
preclinical safety assessment of a recombinant plague vaccine (rf1v).a recombinant vaccine (rf1v) is being developed to protect adults 18 to 55 years of age from fatal pneumonic plague caused by aerosolized yersinia pestis. a comprehensive series of studies was conducted to evaluate the general toxicity and local reactogenicity of the rf1v vaccine prior to first use in humans. toxicity was evaluated in cd-1 mice vaccinated with control material and three dosage concentrations of rf1v with or without alhydrogel(®) by intramuscular (im) injection on study days 1, 2 ...201323908395
seroprevalence of hantavirus and yersinia pestis antibodies in professionals from the plague control program.professionals who handle rodents in the field and in the laboratory are at risk of infection by the microorganis mharbored by these animals.201323904080
reverse transcription-pcr-electrospray ionization mass spectrometry for rapid detection of biothreat and common respiratory pathogens.electrospray ionization mass spectrometry (esi-ms) analysis of reverse transcription (rt)-pcr amplicons from human respiratory samples allows for broad pathogen identification approximately 8 h after collection. we investigated the performance characteristics of a high-throughput rt-pcr-coupled esi-ms assay for distinguishing biothreat (bt) agents from common bacterial, fungal, and viral respiratory pathogens in bronchoalveolar lavage (bal) fluid specimens from subjects with suspected respirator ...201323903543
fibrinolytic and coagulative activities of yersinia pestis.the outer membrane protease pla belongs to the omptin protease family spread by horizontal gene transfer into gram-negative bacteria that infect animals or plants. pla has adapted to support the life style of the plague bacterium yersinia pestis. pla has a β-barrel fold with 10 membrane-spanning β strands and five surface loops, and the barrel surface contains bound lipopolysaccharide (lps) that is critical for the conformation and the activity of pla. the biological activity of pla is influence ...201323898467
earthquakes and plague during byzantine times: can lessons from the past improve epidemic preparedness.natural disasters have always been followed by a fear of infectious diseases. this raised historical debate about one of the most feared scenarios: the outbreak of bubonic plague caused by yersinia pestis. one such event was recorded in the indian state maharashtra in 1994 after an earthquake. in multidisciplinary historical approach to the evolution of plague, many experts ignore the possibility of natural foci and their activation. this article presents historical records from the byzantine em ...201323883083
mutated and bacteriophage t4 nanoparticle arrayed f1-v immunogens from yersinia pestis as next generation plague vaccines.pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism yersinia pestis poses a serious threat for deliberate use as a bioterror agent. currently, there is no fda approved vaccine against plague. the polymeric bacterial capsular protein f1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response v antigen, has high propensity to aggregate, thus affecting its purification and vaccine ef ...201323853602
plague detection by anti-carbohydrate antibodies. 201323843253
yersinia pestis infection in cats: abcd guidelines on prevention and management.plague, the medieval 'black death', is caused by a gram-negative coccobacillus, yersinia pestis, which also infects cats. as in people, it is transmitted from rodents through flea bites; it occurs in asia, africa and the americas in flea-infested regions, all year round, and where rodent reservoirs are abundant. a poor prognosis is associated with high fever, and the pulmonary and septicaemic forms. antibiotic therapy, flea control and avoidance of rodent contacts have made this infection manage ...201323813820
[the development and implementation of polymerase chain reaction to detect in real-time operation mode yersinia pestis in field material].the article presents the results of development and practical implementation of system of polymerase chain reaction testing in real-time operation mode to detect agent of plague infield material. in laboratory conditions the system demonstrated good results and hence it was applied in conditions of field laboratory of epidemiologic team during planned epizootologic examination of gorno-altaisk hot spot of plague. the sampling consisted of more than 1400 objects. it was demonstrated that high sen ...201323808025
[relationships of the plague pathogen and vector from different parasitic systems].the specific features of interaction of the strains of the plague microbe of the main subspecies, which circulate in the area of natural foci of mongolia and china, with citellophilus tesquorum sungaris fleas, the major vector of the plague pathogen in a transbaikalian natural focus, as well as with xenopsylla cheopis ones, the classical vector, were revealed. experiments used virulent yersinia pestis strains, such as i-3230 isolated from c.tesquorum in mongolia in 1998 and 2155 isolated from hu ...201323805481
features of variable number of tandem repeats in yersinia pestis and the development of a hierarchical genotyping scheme.variable number of tandem repeats (vntrs) that are widely distributed in the genome of yersinia pestis proved to be useful markers for the genotyping and source-tracing of this notorious pathogen. in this study, we probed into the features of vntrs in the y. pestis genome and developed a simple hierarchical genotyping system based on optimized vntr loci.201323805236
group-theoretic models of the inversion process in bacterial genomes.the variation in genome arrangements among bacterial taxa is largely due to the process of inversion. recent studies indicate that not all inversions are equally probable, suggesting, for instance, that shorter inversions are more frequent than longer, and those that move the terminus of replication are less probable than those that do not. current methods for establishing the inversion distance between two bacterial genomes are unable to incorporate such information. in this paper we suggest a ...201423793228
study of effectiveness of bioluminescent reporter phage assay on y. pseudotuberculosis strains.the method describes the phage-mediated transduction of a bioluminescent phenotype to cultivated y. pseudotuberculosis cells which are subsequently measured using a microplate luminometer. reporter phage assay is rapid detection technique and its efficiency is not affected by presence of contaminating bacteria, no sample preparation is needed and it has the ability to test multiple samples simultaneously in a 96-well microtiter plate format. experiments were performed to develop the rapid detect ...201323787513
na+/h+ antiport is essential for yersinia pestis virulence.na(+)/h(+) antiporters are ubiquitous membrane proteins that play a central role in the ion homeostasis of cells. in this study, we examined the possible role of na(+)/h(+) antiport in yersinia pestis virulence and found that y. pestis strains lacking the major na(+)/h(+) antiporters, nhaa and nhab, are completely attenuated in an in vivo model of plague. the y. pestis derivative strain lacking the nhaa and nhab genes showed markedly decreased survival in blood and blood serum ex vivo. complemen ...201323774602
human single-chain urokinase is activated by the omptins pgte of salmonella enterica and pla of yersinia pestis despite mutations of active site residues.fibrinolysis is important in cell migration and tightly regulated by specific inhibitors and activators; of the latter, urokinase (upa) associates with enhancement of cell migration. active upa is formed through cleavage of the single-chain upa (scupa). the salmonella enterica strain 14028r cleaved human scupa at the peptide bond lys158-ile159, the site cleaved also by the physiological activator human plasmin. the cleavage led to activation of scupa, while no cleavage or activation were detecte ...201323763588
plague circulation and population genetics of the reservoir rattus rattus: the influence of topographic relief on the distribution of the disease within the madagascan focus.landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. plague (yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in africa. human seroprevalence data for the major plague focus of madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. plague is primarily a disease of rodents. we therefore investigated ...201323755317
live-attenuated yersinia pestis vaccines.plague caused by yersinia pestis is one of the most dangerous infectious diseases. there is no ideal plague vaccine available for human use, but a number of licensed killed whole-cell and live-attenuated vaccines have been available in the past. currently, there are a number of vaccines under development, including live-attenuated, dna and subunit vaccines, among others. this review deals with the development of live-attenuated plague vaccines. traditionally, live-attenuated plague vaccines have ...201323750796
structural modifications of bacterial lipopolysaccharide that facilitate gram-negative bacteria evasion of host innate immunity.bacterial lipopolysaccharide (lps), a cell wall component characteristic of gram-negative bacteria, is a representative pathogen-associated molecular pattern that allows mammalian cells to recognize bacterial invasion and trigger innate immune responses. the polysaccharide moiety of lps primary plays protective roles for bacteria such as prevention from complement attacks or camouflage with common host carbohydrate residues. the lipid moiety, termed lipid a, is recognized by the toll-like recept ...201323745121
acquisition of omptin reveals cryptic virulence function of autotransporter yape in yersinia pestis.autotransporters, the largest family of secreted proteins in gram-negative bacteria, perform a variety of functions, including adherence, cytotoxicity and immune evasion. in yersinia pestis the autotransporter yape has adhesive properties and contributes to disease in the mouse model of bubonic plague. here, we demonstrate that omptin cleavage of y. pestis yape is required to mediate bacterial aggregation and adherence to eukaryotic cells. we demonstrate that omptin cleavage is specific for the ...201323701256
structure of the yersinia pestis tip protein lcrv refined to 1.65 å resolution.the human pathogen yersinia pestis requires the assembly of the type iii secretion system (t3ss) for virulence. the structural component of the t3ss contains an external needle and a tip complex, which is formed by lcrv in y. pestis. the structure of an lcrv triple mutant (k40a/d41a/k42a) in a c273s background has previously been reported to 2.2 å resolution. here, the crystal structure of lcrv without the triple mutation in a c273s background is reported at a higher resolution of 1.65 å. overal ...201323695558
francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.pulmonary exposure to francisella tularensis is associated with severe lung pathology and a high mortality rate. the lack of induction of classical inflammatory mediators, including il1-β and tnf-α, during early infection has led to the suggestion that f. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. to gain more insight into the host response to francisella infection during the acute stage, transcriptomic analysis was performed on lung t ...201323690939
physiological levels of glucose induce membrane vesicle secretion and affect the lipid and protein composition of yersinia pestis cell surfaces.yersinia pestis grown with physiologic glucose increased cell autoaggregation and deposition of extracellular material, including membrane vesicles. membranes were characterized, and glucose had significant effects on protein, lipid, and carbohydrate profiles. these effects were independent of temperature and the biofilm-related locus pgm and were not observed in yersinia pseudotuberculosis.201323686263
[detection of yersinia pestis srna by digoxigenin-labeled northern blot].with the application of high-throughput sequencing methods, more and more srnas are required to be verified. in this study, we developed the digoxigenin-labeled northern blot method for detection of yersinia pestis srna.201323678576
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