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characterization of an f1 deletion mutant of yersinia pestis co92, pathogenic role of f1 antigen in bubonic and pneumonic plague, and evaluation of sensitivity and specificity of f1 antigen capture-based dipsticks.we evaluated two commercial f1 antigen capture-based immunochromatographic dipsticks, yersinia pestis (f1) smart ii and plague biothreat alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with yersinia pestis co92. to assess the specificities of these dipsticks, an in-frame f1-deficient mutant of co92 (?caf) was generated by homologous recombination and used as a negative control. based on genetic, antigenic/immunologic, and electron mic ...201121367990
landscape and residential variables associated with plague-endemic villages in the west nile region of uganda.plague, caused by the bacteria yersinia pestis, is a severe, often fatal disease. this study focuses on the plague-endemic west nile region of uganda, where limited information is available regarding environmental and behavioral risk factors associated with plague infection. we conducted observational surveys of 10 randomly selected huts within historically classified case and control villages (four each) two times during the dry season of 2006 (n = 78 case huts and n = 80 control huts), which i ...201121363983
a c-terminal region of yersinia pestis yscd binds the outer membrane secretin yscc.yscd is an essential component of the plasmid pcd1-encoded type iii secretion system (t3ss) of yersinia pestis. yscd has a single transmembrane (tm) domain that connects a small n-terminal cytoplasmic region (residues 1 to 121) to a larger periplasmic region (residues 143 to 419). deletion analyses established that both the n-terminal cytoplasmic region and the c-terminal periplasmic region are required for yscd function. smaller targeted deletions demonstrated that a predicted cytoplasmic forkh ...201121357482
chemokine receptor cxcr2 mediates bacterial clearance rather than neutrophil recruitment in a murine model of pneumonic plague.pulmonary infection by yersinia pestis causes pneumonic plague, a necrotic bronchopneumonia that is rapidly lethal and highly contagious. acute pneumonic plague accompanies the up-regulation of pro-inflammatory cytokines and chemokines, suggesting that the host innate immune response may contribute to the development of disease. to address this possibility, we sought to understand the consequences of neutrophil recruitment during pneumonic plague, and we studied the susceptibility of c3h-hen mic ...201121356370
function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size.changes in effective population size impinge on patterns of molecular evolution. notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. this prediction has been validated empirically for several endosymbiont and island taxa. here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidate ...201121349981
levofloxacin cures experimental pneumonic plague in african green monkeys.yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease.201121347450
notes from the field: two cases of human plague--oregon, 2010.plague, caused by yersinia pestis, is enzootic among rodents in the western united states. humans can be infected through 1) the bite of an infected flea carried by a rodent or, rarely, other animals, 2) direct contact with contaminated tissues, or 3) in rare cases, inhalation of respiratory secretions from infected persons or animals. in september 2010, the oregon health authority reported the first two cases of human plague in oregon since 1995 and the only two u.s. cases in 2010.201121346709
fatal laboratory-acquired infection with an attenuated yersinia pestis strain--chicago, illinois, 2009.on september 18, 2009, the chicago department of public health (cdph) was notified by a local hospital of a suspected case of fatal laboratory-acquired infection with yersinia pestis, the causative agent of plague. the patient, a researcher in a university laboratory, had been working along with other members of the laboratory group with a pigmentation-negative (pgm-) attenuated y. pestis strain (kim d27). the strain had not been known to have caused laboratory-acquired infections or human fatal ...201121346706
regulatory effects of camp receptor protein (crp) on porin genes and its own gene in yersinia pestis.the camp receptor protein (crp) is a global bacterial regulator that controls many target genes. the crp-camp complex regulates the ompr-envz operon in e. coli directly, involving both positive and negative regulations of multiple target promoters; further, it controls the production of porins indirectly through its direct action on ompr-envz. auto-regulation of crp has also been established in e. coli. however, the regulation of porin genes and its own gene by crp remains unclear in y. pestis.201121345179
phenotypic and transcriptional analysis of the osmotic regulator ompr in yersinia pestis.the osmotic regulator ompr in escherichia coli regulates differentially the expression of major porin proteins ompf and ompc. in yersinia enterocolitica and y. pseudotuberculosis, ompr is required for both virulence and survival within macrophages. however, the phenotypic and regulatory roles of ompr in y. pestis are not yet fully understood.201121345178
arthropod vectors and vector-borne bacterial pathogens in yosemite national park.ticks, fleas, and vector-borne pathogens were surveyed in diverse small mammals in yosemite national park, california, from 2005 to 2007. a total of 450 unique captures of small mammals was collected during a 3-yr period and yielded 16 species of fleas and 10 species of ticks, including known vectors of anaplasma phagocytophilum and borrelia burgdorferi and plague. serology was performed for a. phagocytophilum, spotted fever group rickettsia spp., b. burgdorferi, and yersinia pestis. a. phagocyt ...201121337955
receptor mimicry as novel therapeutic treatment for biothreat agents.the specter of intentional release of pathogenic microbes and their toxins is a real threat. this article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. the minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the galβ1-4glcnac structure. the botulinum toxin serotypes a ...201021327124
the role of the phopq operon in the pathogenesis of the fully virulent co92 strain of yersinia pestis and the ip32953 strain of yersinia pseudotuberculosis.at the genomic level, yersinia pestis and yersinia pseudotuberculosis are nearly identical but cause very different diseases. y. pestis is the etiologic agent of plague; whereas y. pseudotuberculosis causes a gastrointestinal infection primarily after the consumption of contaminated food. in many gram-negative pathogenic bacteria, phop is part of a two-component global regulatory system in which phoq serves as the sensor kinase, and phop is the response regulator. phop is known to activate a num ...201121320584
a live attenuated strain of yersinia pestis kim as a vaccine against plague.yersinia pestis, the causative agent of plague, is a potential weapon of bioterrorism. y. pestis evades the innate immune system by synthesizing tetra-acylated lipid a with poor toll-like receptor 4 (tlr4)-stimulating activity at 37°c, whereas hexa-acylated lipid a, a potent tlr4 agonist, is made at lower temperatures. synthesis of escherichia coli lpxl, which transfers the secondary laurate chain to the 2'-position of lipid a, in y. pestis results in production of hexa-acylated lipid a at 37°c, ...201121320544
prediction of protein-protein interactions between human host and a pathogen and its application to three pathogenic bacteria.molecular understanding of disease processes can be accelerated if all interactions between the host and pathogen are known. the unavailability of experimental methods for large-scale detection of interactions across host and pathogen organisms hinders this process. here we apply a simple method to predict protein-protein interactions across a host and pathogen organisms. we use homology detection approaches against the protein-protein interaction databases, dip and ipfam in order to predict int ...201121310175
molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor pla.omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in gram-negative bacteria that infect vertebrates or plants. despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. to simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make epo of the plant pathogenic erwinia pyrifoliae exhibit virulence-associated functions of its close homolog, the p ...201121310089
intracellular yersinia pestis expresses general stress response and tellurite resistance proteins in mouse macrophages.yersinia pestis inoculated subcutaneously via fleabite or experimental injection in natural rodent hosts multiply initially in macrophage phagolysosomes. survival and multiplication of y. pestis in this acidic low [ca(2+)] and [mg(2+)] environment likely necessitates compensatory mechanisms involving expression of specific proteins compared to those expressed during extracellular growth. a proteomics approach was used to identify these proteins using mouse macrophage raw264.7 cells infected with ...201121295415
a dog-associated primary pneumonic plague in qinghai province, china.primary pneumonic plague (ppp) caused by yersinia pestis is the most threatening clinical form of plague. an outbreak was reported in july 2009 in qinghai province, china.201121288842
antigenic profiling of yersinia pestis infection in the wyoming coyote (canis latrans).although yersinia pestis is classified as a "high-virulence" pathogen, some host species are variably susceptible to disease. coyotes (canis latrans) exhibit mild, if any, symptoms during infection, but antibody production occurs postinfection. this immune response has been reported to be against the f1 capsule, although little subsequent characterization has been conducted. to further define the nature of coyote humoral immunity to plague, qualitative serology was conducted to assess the antipl ...201121269993
characterization of the rcsc sensor kinase from erwinia amylovora and other enterobacteria.rcsc is a hybrid sensor kinase which contains a sensor domain, a histidine kinase domain, and a receiver domain. we have previously demonstrated that, although the erwinia amylovora rcsc mutant produces more amylovoran than the wild-type (wt) strain in vitro, the mutant remains nonpathogenic on both immature pear fruit and apple plants. in this study, we have comparatively characterized the erwinia rcsc and its homologs from various enterobacteria. results demonstrate that expression of the erwi ...201121261468
tapping the potential of intact cell mass spectrometry with a combined data analytical approach applied to yersinia spp.: detection, differentiation and identification of y. pestis.in the everyday routine of an analytic lab, one is often confronted with the challenge to identify an unknown microbial sample lacking prior information to set the search limits. in the present work, we propose a workflow, which uses the spectral diversity of a commercial database (saramis) to narrow down the search field at a certain taxonomic level, followed by a refined classification by supervised modelling. as supervised learning algorithm, we have chosen a shrinkage discriminant analysis a ...201121239132
systematic analysis of cyclic di-gmp signalling enzymes and their role in biofilm formation and virulence in yersinia pestis.cyclic di-gmp (c-di-gmp) is a signalling molecule that governs the transition between planktonic and biofilm states. previously, we showed that the diguanylate cyclase hmst and the putative c-di-gmp phosphodiesterase hmsp inversely regulate biofilm formation through control of hmshfrs-dependent poly-β-1,6-n-acetylglucosamine synthesis. here, we systematically examine the functionality of the genes encoding putative c-di-gmp metabolic enzymes in yersinia pestis. we determine that, in addition to ...201021219468
yopk regulates the yersinia pestis type iii secretion system from within host cells.the pathogenic yersinia species share a conserved type iii secretion system, which delivers cytotoxic effectors known as yops into target mammalian cells. in all three species, yopk (also called yopq) plays an important role in regulating this process. in cell culture infections, yopk mutants inject higher levels of yops, leading to increase cytotoxicity; however, in vivo the same mutants are highly attenuated. in this work, we investigate the mechanism behind this paradox. using a β-lactamase r ...201121205017
involvement of cd8+ t cell-mediated immune responses in lcrv dna vaccine induced protection against lethal yersinia pestis challenge.yersinia pestis (y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against y. pestis. studies in recent years have suggested the importance of t cell immune responses against y. pestis infection but information ...201121199697
characterization of ppcp1 plasmids in yersinia pestis strains isolated from the former soviet union.complete sequences of 9.5-kb ppcp1 plasmids in three yersinia pestis strains from the former soviet union (fsu) were determined and compared with those of ppcp1 plasmids in three well-characterized, non-fsu y. pestis strains (kim, co92, and 91001). two of the fsu plasmids were from strains c2614 and c2944, isolated from plague foci in russia, and one plasmid was from strain c790 from kyrgyzstan. sequence analyses identified four sequence types among the six plasmids. the ppcp1 plasmids in the fs ...201021197443
hijacking of the pleiotropic cytokine interferon-γ by the type iii secretion system of yersinia pestis.yersinia pestis, the causative agent of bubonic plague, employs its type iii secretion system to inject toxins into target cells, a crucial step in infection establishment. lcrv is an essential component of the t3ss of yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. upon cell contact, lcrv is also released into the surrounding medium where it has been shown to block the ...201021179438
role of the yersinia pestis yersiniabactin iron acquisition system in the incidence of flea-borne plague.plague is a flea-borne zoonosis caused by the bacterium yersinia pestis. y. pestis mutants lacking the yersiniabactin (ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. presumably, ybt is required to provide sufficient iron at the peripheral injection site, suggesting that ybt would be an essential virulence factor for flea-borne plague. here, using a flea-to-mouse transmission model, we show that a ...201021179420
dioxygenases in burkholderia ambifaria and yersinia pestis that hydroxylate the outer kdo unit of lipopolysaccharide.several gram-negative pathogens, including yersinia pestis, burkholderia cepacia, and acinetobacter haemolyticus, synthesize an isosteric analog of 3-deoxy-d-manno-oct-2-ulosonic acid (kdo), known as d-glycero-d-talo-oct-2-ulosonic acid (ko), in which the axial hydrogen atom at the kdo 3-position is replaced with oh. here we report a unique kdo 3-hydroxylase (kdoo) from burkholderia ambifaria and yersinia pestis, encoded by the bamb_0774 (bakdoo) and the y1812 (ypkdoo) genes, respectively. when ...201021178073
polymerase chain reaction (pcr) identification of rodent blood meals confirms host sharing by flea vectors of plague.elucidating feeding relationships between hosts and parasites remains a significant challenge in studies of the ecology of infectious diseases, especially those involving small or cryptic vectors. black-tailed prairie dogs (cynomys ludovicianus) are a species of conservation importance in the north american great plains whose populations are extirpated by plague, a flea-vectored, bacterial disease. using polymerase chain reaction (pcr) assays, we determined that fleas (oropsylla hirsuta) associa ...201021175944
il-17 contributes to cell-mediated defense against pulmonary yersinia pestis infection.pneumonic plague is one of the world's most deadly infectious diseases. the causative bacterium, yersinia pestis, has the potential to be exploited as a biological weapon, and no vaccine is available. vaccinating b cell-deficient mice with d27-plpxl, a live attenuated y. pestis strain, induces cell-mediated protection against lethal pulmonary y. pestis challenge. in this article, we demonstrate that prime/boost vaccination with d27-plpxl confers better protection than prime-only vaccination. the ...201021172869
structure of the metal-dependent deacetylase lpxc from yersinia enterocolitica complexed with the potent inhibitor chir-090 .the first committed step of lipid a biosynthesis is catalyzed by udp-(3-o-((r)-3-hydroxymyristoyl))-n-acetylglucosamine deacetylase, a metal-dependent deacetylase also known as lpxc. because lipid a is essential for bacterial viability, the inhibition of lpxc is an appealing therapeutic strategy for the treatment of gram-negative bacterial infections. here we report the 1.79 å resolution x-ray crystal structure of lpxc from yersinia enterocolitica (yelpxc) complexed with the potent hydroxamate i ...201021171638
oligomeric coiled-coil adhesin yada is a double-edged sword.yersinia adhesin a (yada) is an essential virulence factor for the food-borne pathogens yersinia enterocolitica and yersinia pseudotuberculosis. surprisingly, it is a pseudogene in yersinia pestis. even more intriguing, the introduction of a functional yada gene in y. pestis ev76 was shown to correlate with a decrease in virulence in a mouse model. here, we report that wild type (wt) y. enterocolitica e40, as well as yada-deprived e40 induced the synthesis of neutrophil extracellular traps (nets ...201021170337
[primary pneumonic plague with nosocomial transmission in la libertad, peru 2010].pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of yersinia pestis coming from an animal or from person to person.201021152724
distinct ccr2(+) gr1(+) cells control growth of the yersinia pestis δyopm mutant in liver and spleen during systemic plague.we are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein yopm of the plague bacterium yersinia pestis. in this study, we pursued previous findings that gr1(+) cells are required to selectively limit growth of δyopm y. pestis and that cd11b(+) cells other than polymorphonuclear leukocytes (pmns) are selectively lost in spleens infected with parent y. pestis. when pmns were ablated from mice, δyopm y. pestis grew as well as the parent str ...201021149593
reliable detection of bacillus anthracis, francisella tularensis and yersinia pestis by using multiplex qpcr including internal controls for nucleic acid extraction and amplification.several pathogens could seriously affect public health if not recognized timely. to reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples.201021143837
protection afforded by fluoroquinolones in animal models of respiratory infections with bacillus anthracis, yersinia pestis, and francisella tularensis.successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. bacillus anthracis ames, yersinia pestis co92, and francisella tularensis schu s4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited informat ...201021127743
the effects of low-shear mechanical stress on yersinia pestis virulence.manned space exploration has created a need to evaluate the effects of spacelike stress on pathogenic and opportunistic microbes astronauts could carry with them to the international space station and beyond. yersinia pestis (yp) causes bubonic, septicemic, and pneumonic plague and is capable of killing infected patients within 3-7 days. in this study, low-shear modeled microgravity (lsmmg), a spacelike stress, was used to physically stress yp; and its effects on proliferation, cold growth, and ...201021118021
use of an in vitro pharmacodynamic model to derive a moxifloxacin regimen that optimizes kill of yersinia pestis and prevents emergence of resistance.yersinia pestis, the causative agent of bubonic, septicemic, and pneumonic plague, is classified as a cdc category a bioterrorism pathogen. streptomycin and doxycycline are the "gold standards" for the treatment of plague. however, streptomycin is not available in many countries, and y. pestis isolates resistant to streptomycin and doxycycline occur naturally and have been generated in laboratories. moxifloxacin is a fluoroquinolone antibiotic that demonstrates potent activity against y. pestis ...201021115791
the dependence of the yersinia pestis capsule on pathogenesis is influenced by the mouse background.yersinia pestis is a highly pathogenic gram-negative organism and the causative agent of bubonic and pneumonic plague. y. pestis is capable of causing major epidemics; thus, there is a need for vaccine targets and a greater understanding of the role of these targets in pathogenesis. two prime y. pestis vaccine candidates are the usher-chaperone fimbriae psa and caf. herein we report that y. pestis requires, in a nonredundant manner, both psaa and caf1 to achieve its full pathogenic ability in bo ...201021115720
assessment of comparative genomic hybridization experiment by an in situ synthesized combimatrix microarray with yersinia pestis vaccine strain ev76 dna.the quality of microarray data influences the accuracy of comparative genomic analyses to a large extent. to ensure that the results obtained by using an in situ synthesized microarray are accurate, data quality is to be assessed by evaluating the melting temperature (tm) of probes, probability of false synthesis rates, and fragmentation of labeled targets.201021112487
different strategies for preparation of non-tagged rv270 protein and its efficacy against yersinia pestis challenge.lcrv is an important component for the development of a subunit vaccine against plague. to reduce immunosuppressive activity of lcrv, a recombinant lcrv variant lacking amino acids 271 to 326 (rv270) was prepared by different methods in this study.201021112480
active-site structure of class iv adenylyl cyclase and transphyletic mechanism.adenylyl cyclases (acs) belonging to three nonhomologous classes (ii, iii, and iv) have been structurally characterized, enabling a comparison of the mechanisms of cyclic adenosine 3',5'-monophosphate biosynthesis. we report the crystal structures of three active-site complexes for yersinia pestis class iv ac (ac-iv)-two with substrate analogs and one with product. mn(2+) binds to all three phosphates, and to glu12 and glu136. electropositive residues lys14, arg63, lys76, lys111, and arg113 also ...201021094652
mathematical relationship between cytokine concentrations and pathogen levels during infection.the relationship between concentrations of cytokines and microbial pathogen levels during infection is not clear. in a sub-lethal murine infection model using gram-negative bacterial pathogen yersinia pseudotuberculosis, the serum concentrations (c) of pro-inflammatory cytokines tumor necrosis factor α (tnfα), interferon γ (ifnγ), interleukine-1β (il-1β) and interleukine-18 (il-18) formed a mathematical relationship with the splenic pathogen levels (p) as measured by colony forming unit. naming ...201021093285
accurate, rapid and high-throughput detection of strain-specific polymorphisms in bacillus anthracis and yersinia pestis by next-generation sequencing.abstract:201021092340
contributions of chaperone/usher systems to cell binding, biofilm formation and yersinia pestis virulence.yersinia pestis genome sequencing projects have revealed six intact uncharacterized chaperone/usher systems with the potential to play roles in plague pathogenesis. we cloned each locus and expressed them in the δfim escherichia coli strain aaec185 to test the assembled y. pestis surface structures for various activities. expression of each chaperone/usher locus gave rise to specific novel fibrillar structures on the surface of e. coli. one locus, y0561-0563, was able to mediate attachment to hu ...201021088108
rapid identification and typing of yersinia pestis and other yersinia species by matrix-assisted laser desorption/ionization time-of-flight (maldi-tof) mass spectrometry.accurate identification is necessary to discriminate harmless environmental yersinia species from the food-borne pathogens yersinia enterocolitica and yersinia pseudotuberculosis and from the group a bioterrorism plague agent yersinia pestis. in order to circumvent the limitations of current phenotypic and pcr-based identification methods, we aimed to assess the usefulness of matrix-assisted laser desorption/ionization time-of-flight (maldi-tof) protein profiling for accurate and rapid identific ...201021073689
purification and characterization of a recombinant yersinia pestis v-f1 "reversed" fusion protein for use as a new subunit vaccine against plague.we previously developed a unique recombinant protein vaccine against plague composed of a fusion between the fraction 1 capsular antigen (f1) and the v antigen. to determine if overall expression, solubility, and recovery of the f1-v fusion protein could be enhanced, we modified the original fusion. standard recombinant dna techniques were used to reverse the gene order such that the v antigen coding sequence was fused at its c-terminus to the n-terminus of f1. the f1 secretion signal sequence ( ...201021055471
cynomolgus macaque model for pneumonic plague.a recombinant vaccine (rf1v) is currently being developed for protection against pneumonic plague. an essential component in evaluating efficacy of the rf1v vaccine is the development of a well-understood animal model that shows similarity to human disease. the objective of this study was to determine the inhaled median lethal dose (ld₅₀), evaluate the pathophysiology of disease and identify appropriate study endpoints in a cynomolgus macaque (cm) model of pneumonic plague. eighteen cms were cha ...201021040776
comparison of immunological responses of plague vaccines f1+rv270 and ev76 in chinese-origin rhesus macaque, macaca mulatta.the subunit vaccine sv1 (20 μg f1+10 μg rv270) has been identified as the optimal formulation in mice, which provided a good protection against plague in mice, guinea pigs and rabbits. to compare sv1 and sv2 (200 μg f1+100 μg rv270) with live attenuated vaccine ev76, antibody responses, protective efficacy, cytokines (ifn-γ, tnf-α, il-2, il-4, il-10 and il-12) production, cd4/cd8 ratio and cd69(+) t-cell activation marker were determined in sera of the immunized chinese-origin rhesus macaques, m ...201021039737
yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity.plague is a pandemic human invasive disease caused by the bacterial agent yersinia pestis. we here report a comparison of 17 whole genomes of y. pestis isolates from global sources. we also screened a global collection of 286 y. pestis isolates for 933 snps using sequenom massarray snp typing. we conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission ...201021037571
a procedure for monitoring the presence of the virulence plasmid (pyv) in yersinia pestis under culture conditions.the pathogenicity of yersinia pestis depends on the presence of a virulence plasmid (pyv). the unstable nature of pyv in y. pestis leads to the eventual outgrowth of pyv-less cells due to its higher growth rate. thus, it was necessary to develop procedures to monitor the presence of the plasmid during cultivation, storage, and laboratory manipulations. a procedure was developed to monitor the presence of pyv in y. pestis by using low calcium response and congo red binding techniques. the selecti ...201021034234
yersinia pestis dna sequences in late medieval skeletal finds, bavaria. 201021029555
an experimental study on cellular immunity in pasteurella pestis infection. 194620983007
evaluation of psn, hmur and a modified lcrv protein delivered to mice by live attenuated salmonella as a vaccine against bubonic and pneumonic yersinia pestis challenge.we evaluated the ability of yersinia pestis antigens hmur, psn and modified forms of lcrv delivered by live attenuated salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with y. pestis co92. lcrv196 is a previously described truncated protein that includes aa 131-326 of lcrv and lcrv5214 has been modified to replace five key amino acids required for interaction with the tlr2 receptor. psn is the outer membrane receptor for the siderophore, y ...201020979987
human anti-plague monoclonal antibodies protect mice from yersinia pestis in a bubonic plague model.yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. two virulent factors of y. pestis are the capsid f1 protein and the low-calcium response (lcr) v-protein or v-antigen that have been proven to be the targets for both active and passive immunization. ther ...201020976274
an auto-biotinylated bifunctional protein nanowire for ultra-sensitive molecular biosensing.in order to obtain an ultra-sensitive molecular biosensor, we designed an auto-biotinylated bifunctional protein nanowire (bfpnw) based on the self-assembly of a yeast amyloid protein, sup35, to which protein g and a biotin acceptor peptide (bap) were genetically fused. these auto-biotinylated bfpnws can transfer hundreds of commercially available diagnostic enzymes to an antigen-antibody complex via the biotin-avidin system, greatly enhancing the sensitivity of immune-biosensing. compared to ou ...201020970983
[a protein with missing information about its tertiary structure folds into the compact globular structure].it has been shown by the methods of hydrodynamics (equilibrium ultracentrifugation, velocity sedimentation, intrinsic viscosity) that a fragment of the structural protein cafl (cafl 13.149) from the pili-like fibril yersinia pestis is in the monomeric state and is capable of forming the compact ternary structure spontaneously, without the involvement of chaperone or other subunits. this happens despite the fact that some information about the ternary structure of this protein is provided in fibr ...201020968067
the plague of the philistines and other pestilences in the ancient world: exploring relations between the religious-literary tradition, artistic evidence and scientific proof.in ancient times the term pestilence referred not only to infectious disease caused by yersinia pestis, but also to several different epidemics. we explore the relations between references in the bible and recent scientific evidence concerning some infectious diseases, especially the so-called plague of the philistines and leprosy. in addition, some considerations regarding possible connections among likely infectious epidemic diseases and the ten plagues of egypt are reported. evidence suggesti ...201020956880
contributions of edema factor and protective antigen to the induction of protective immunity by bacillus anthracis edema toxin as an intranasal adjuvant.we have shown that intranasal coapplication of bacillus anthracis protective ag (pa) together with a b. anthracis edema factor (ef) mutant having reduced adenylate cyclase activity (i.e., ef-s414n) enhances anti-pa ab responses, but also acts as a mucosal adjuvant for coadministered unrelated ags. to elucidate the role of edema toxin (edtx) components in its adjuvanticity, we examined how a pa mutant lacking the ability to bind ef (pa-u7) or another mutant that allows the cellular uptake of ef, ...201020952678
in silico comparison of yersinia pestis and yersinia pseudotuberculosis transcriptomes reveals a higher expression level of crucial virulence determinants in the plague bacillus.although yersinia pestis and yersinia pseudotuberculosis are genetically very similar (97% nucleotide sequence identity for most of the chromosomal genes), they exhibit very different patterns of infection. y. pestis causes plague which is usually fatal in the absence of treatment, whereas y. pseudotuberculosis generally triggers non-life-threatening intestinal symptoms. this drastic difference in pathogenicity may result from the acquisition of a few species-specific genes, but also from differ ...201020951640
distinct clones of yersinia pestis caused the black death.from ad 1347 to ad 1353, the black death killed tens of millions of people in europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18(th) century. the etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by yersinia pestis to conclusions that it must have been caused by other pathogens. it has also been disputed whether plague had t ...201020949072
the complete genome sequence and proteomics of yersinia pestis phage yep-phi.yep-phi, a lytic phage of yersinia pestis, was isolated in china and is routinely used as a diagnostic phage for the identification of the plague pathogen. yep-phi has an isometric hexagonal head containing dsdna and a short non-contractile conical tail. in this study, we sequenced the yep-phi genome (genbank accession no. hq333270) and performed proteomics analysis. the genome consists of 38 ,616 bp of dna, including direct terminal repeats of 222 bp, and is predicted to contain 45 orfs. most s ...201020943893
evaluation of rodent bait containing imidacloprid for the control of fleas on commensal rodents in a plague-endemic region of northwest uganda.in recent decades, the majority of human plague cases (caused by yersinia pestis) have been reported from africa. in an effort to reduce the risk of the disease in this area, we evaluated the efficacy of a host-targeted rodent bait containing the insecticide imidacloprid for controlling fleas on house-dwelling commensal rodents in a plague-endemic region of northwestern uganda. results demonstrated that the use of a palatable, rodent-targeted, wax-based bait cube was effective at reducing the pr ...201020939379
detection of yersinia pestis using real-time pcr in patients with suspected bubonic plague.yersinia (y.) pestis, the causative agent of plague, is endemic in natural foci of asia, africa, and america. real-time pcr assays have been described as rapid diagnostic tools, but so far none has been validated for its clinical use. in a retrospective clinical study we evaluated three real-time pcr assays in two different assay formats, 5'-nuclease and hybridization probes assays. lymph node aspirates from 149 patients from madagascar with the clinical diagnosis of bubonic plague were investig ...201020933595
distribution of the putative type vi secretion system core genes in klebsiella spp.the type vi secretion system (t6ss) is a recently characterized secretion system which appears to be involved in bacterial pathogenesis as a potential nano-syringe for the translocation of effector proteins into the eukaryotic host cell cytoplasm. until now no evidence was provided for the presence of t6ss in the genomes of the sequenced representatives of klebsiella spp., including the human opportunistic pathogen klebsiella pneumoniae. however, in a previous study by lawlor et al. (2005), were ...201020932940
the plague and macular degeneration. 201020932580
microbial communication and virulence: lessons from evolutionary theory.at the heart of tackling the huge challenge posed by infectious micro-organisms is the overwhelming need to understand their nature. a major question is, why do some species of bacteria rapidly kill their host whilst others are relatively benign? for example, yersinia pestis, the causative organism of plague, is a highly virulent human pathogen whilst the closely related yersinia pseudotuberculosis causes a much less severe disease. using molecular techniques such as mutating certain genes, micr ...201020929954
a natively unfolded βγ-crystallin domain from hahella chejuensis.to date, very few βγ-crystallins have been identified and structurally characterized. several of them have been shown to bind ca(2+) and thereby enhance their stability without any significant change in structure. although ca(2+)-induced conformational changes have been reported in two putative βγ-crystallins from caulobacter crescentus and yersinia pestis, they are shown to be partially unstructured, and whether they acquire a βγ-crystallin fold is not known. we describe here a βγ-crystallin do ...201020929244
proteobactin and a yersiniabactin-related siderophore mediate iron acquisition in proteus mirabilis.proteus mirabilis causes complicated urinary tract infections (utis). while the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. microarray analysis of p. mirabilis hi4320 cultured under iron limitation identified 45 significantly upregulated genes (p ≤ 0.05) that represent 21 putative iron-regulated systems. two gene clusters, pmi0229-0239 and pmi2596-2605, encode putative siderophore systems. pmi0229-0239 encodes a non-ribosomal ...201020923418
a review of sentinel laboratory performance: identification and notification of bioterrorism agents.the anthrax incident of 2001 in the united states prompted the college of american pathologists (cap), the association of public health laboratories, and the centers for disease control and prevention to develop exercises for laboratory response network (lrn) sentinel laboratories.201020923306
protection in mice passively immunized with serum from cynomolgus macaques and humans vaccinated with recombinant plague vaccine (rf1v).passive transfer models were developed to evaluate the ability of antibodies generated in cynomolgus macaques and humans vaccinated with a recombinant plague vaccine (rf1v) to protect naïve swiss webster mice against pneumonic plague. development of the passive transfer model is intended to support clinical and nonclinical development of the rf1v vaccine. to evaluate protection, unfractionated serum collected from rf1v vaccinated cynomolgus macaques and human volunteers with known antibody titer ...201020920572
range-wide determinants of plague distribution in north america.plague, caused by the bacterium yersinia pestis, is established across western north america, and yet little is known of what determines the broad-scale dimensions of its overall range. we tested whether its north american distribution represents a composite of individual host-plague associations (the "host niche hypothesis"), or whether mammal hosts become infected only at sites overlapping ecological conditions appropriate for plague transmission and maintenance (the "plague niche hypothesis") ...201020889857
two stacked heme molecules in the binding pocket of the periplasmic heme-binding protein hmut from yersinia pestis.the periplasmic binding protein hmut from yersinia pestis (yphmut) is a component of the heme uptake locus hmu and delivers bound hemin to the inner-membrane-localized, atp-binding cassette (abc) transporter hmuuv for translocation into the cytoplasm. the mechanism of this process, heme transport across the inner membrane of pathogenic bacteria, is currently insufficiently understood at the molecular level. here we describe the crystal structures of the substrate-free and heme-bound states of yp ...201020888343
expression, refolding, and initial structural characterization of the y. pestis ail outer membrane protein in lipids.ail is an outer membrane protein and virulence factor of yersinia pestis, an extremely pathogenic, category a biothreat agent, responsible for precipitating massive human plague pandemics throughout history. due to its key role in bacterial adhesion to host cells and bacterial resistance to host defense, ail is a key target for anti-plague therapy. however, little information is available about the molecular aspects of its function and interactions with the human host, and the structure of ail i ...201020883662
a multi-pronged search for a common structural motif in the secretion signal of salmonella enterica serovar typhimurium type iii effector proteins.many pathogenic gram-negative bacteria use a type iii secretion system (t3ss) to deliver effector proteins into the host cell where they reprogram host defenses and facilitate pathogenesis. the first 20-30 n-terminal residues usually contain the 'secretion signal' that targets effector proteins for translocation, however, a consensus sequence motif has never been discerned. recent machine-learning approaches, such as support vector machine (svm)-based identification and evaluation of virulence e ...201020877914
transcriptomic and innate immune responses to yersinia pestis in the lymph node during bubonic plague.a delayed inflammatory response is a prominent feature of infection with yersinia pestis, the agent of bubonic and pneumonic plague. using a rat model of bubonic plague, we examined lymph node histopathology, transcriptome, and extracellular cytokine levels to broadly characterize the kinetics and extent of the host response to y. pestis and how it is influenced by the yersinia virulence plasmid (pyv). remarkably, dissemination and multiplication of wild-type y. pestis during the bubonic stage o ...201020876291
development of a vaccinia virus based reservoir-targeted vaccine against yersinia pestis.yersinia pestis, the causative organism of plague, is a zoonotic organism with a worldwide distribution. although the last plague epidemic occurred in early 1900s, human cases continue to occur due to contact with infected wild animals. in this study, we have developed a reservoir-targeted vaccine against y. pestis, to interrupt transmission of disease in wild animals as a potential strategy for decreasing human disease. a vaccinia virus delivery system was used to express the f1 capsular protei ...201020875494
body lice, yersinia pestis orientalis, and black death. 201020875308
new rural focus of plague, algeria. 201020875302
[preparation of magnetic latexes and their use for the immunodetection of microbial antigens].the possibility of detecting antigens of plague, tularemia, and brucellosis microbes with magnetic latex (ml)-based test systems has been demonstrated. mls were prepared from latexes (polyacroleine microspheres, 1.2-1.8 +/- 0.1 microm) by exposing the particles to a 25-35%-solution of ferrous sulfate for 0.5 h and then to a 15-25%-aqueous solution of ammonia for 0.5 h in a 100 degrees c water bath and dehydrating after each operation. the possibility of preparing magnetic latex immunosorbents (m ...201020873177
characterization of yersinia using maldi-tof mass spectrometry and chemometrics.yersinia are gram-negative, rod-shaped facultative anaerobes, and some of them, yersinia enterocolitica, yersinia pseudotuberculosis, and yersinia pestis, are pathogenic in humans. rapid and accurate identification of yersinia strains is essential for appropriate therapeutic management and timely intervention for infection control. in the past decade matrix-assisted laser desorption ionization time-of-flight (maldi-tof) mass spectrometry (ms) in combination with computer-aided pattern recognitio ...201020866090
simultaneous pathogen detection and antibiotic resistance characterization using snp-based multiplexed oligonucleotide ligation-pcr (mol-pcr).extensive use of antibiotics in both public health and animal husbandry has resulted in rapid emergence of antibiotic resistance in almost all human pathogens, including biothreat pathogens. antibiotic resistance has thus become a major concern for both public health and national security. we developed multiplexed assays for rapid, simultaneous pathogen detection and characterization of ciprofloxacin and doxycycline resistance in bacillus anthracis, yersinia pestis, and francisella tularensis. t ...201020865530
cell membrane is impaired, accompanied by enhanced type iii secretion system expression in yersinia pestis deficient in rova regulator.in the enteropathogenic yersinia species, rova regulates the expression of invasin, which is important for enteropathogenic pathogenesis but is inactivated in yersinia pestis. investigation of the rova regulon in y. pestis at 26 °c has revealed that rova is a global regulator that contributes to virulence in part by the direct regulation of psaefabc. however, the regulatory roles of rova in y. pestis at 37 °c, which allows most virulence factors in mammalian hosts to be expressed, are still poor ...201020862262
mus spretus seg/pas mice resist virulent yersinia pestis, under multigenic control.laboratory mice are well known to be highly susceptible to virulent strains of yersinia pestis in experimental models of bubonic plague. we have found that mus spretus-derived seg/pas (seg) mice are exceptionally resistant to virulent co92 and 6/69 wild type strains. upon subcutaneous injection of 10(2) colony-forming units (cfu), 90% of females and 68% of males survived, compared with only an 8% survival rate for both male and female c57bl/6 mice. furthermore, half of the seg mice survived a ch ...201120861861
znu is the predominant zinc importer in yersinia pestis during in vitro growth but is not essential for virulence.little is known about zn homeostasis in yersinia pestis, the plague bacillus. the znu abc transporter is essential for zinc (zn) uptake and virulence in a number of bacterial pathogens. bioinformatics analysis identified znuabc as the only apparent high-affinity zn uptake system in y. pestis. mutation of znuacb caused a growth defect in chelex-100-treated pmh2 growth medium, which was alleviated by supplementation with submicromolar concentrations of zn. use of transcriptional reporters confirme ...201020855510
sampling port for real-time analysis of bioaerosol in whole body exposure system for animal aerosol model development.multiple factors influence the viability of aerosolized bacteria. the delivery of aerosols is affected by chamber conditions (humidity, temperature, and pressure) and bioaerosol characteristics (particle number, particle size distribution, and viable aerosol concentration). measurement of viable aerosol concentration and particle size is essential to optimize viability and lung delivery. the madison chamber is widely used to expose small animals to infectious aerosols.201120849964
tnfα and ifnγ contribute to f1/lcrv-targeted immune defense in mouse models of fully virulent pneumonic plague.immunization with the yersinia pestis f1 and lcrv proteins improves survival in mouse and non-human primate models of pneumonic plague. f1- and lcrv-specific antibodies contribute to protection, however, the mechanisms of antibody-mediated defense are incompletely understood and serum antibody titers do not suffice as quantitative correlates of protection. previously we demonstrated roles for tumor necrosis factor-alpha (tnfα) and gamma-interferon (ifnγ) during defense against conditionally atte ...201020840834
outer membrane protein x (ail) contributes to yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length.yersinia pestis, the causative agent of plague, is one of the most virulent microorganisms known. the outer membrane protein x (ompx) in y. pestis kim is required for efficient bacterial adherence to and internalization by cultured hep-2 cells and confers resistance to human serum. here, we tested the contribution of ompx to disease progression in the fully virulent y. pestis co92 strain by engineering a deletion mutant and comparing its ability in mediating pneumonic plague to that of the wild ...201020837715
colorado animal-based plague surveillance systems: relationships between targeted animal species and prediction efficacy of areas at risk for humans.human plague risks (yersinia pestis infection) are greatest when epizootics cause high mortality among this bacterium's natural rodent hosts. therefore, health departments in plague-endemic areas commonly establish animal-based surveillance programs to monitor y. pestis infection among plague hosts and vectors. the primary objectives of our study were to determine whether passive animal-based plague surveillance samples collected in colorado from 1991 to 2005 were sampled from high human plague ...200920836802
targeting of lcrv virulence protein from yersinia pestis to dendritic cells protects mice against pneumonic plague.to help design needed new vaccines for pneumonic plague, we targeted the yersinia pestis lcrv protein directly to cd8α(+) dec-205(+) or cd8α(-) dcir2(+) dc along with a clinically feasible adjuvant, poly ic. by studying y. pestis in mice, we could evaluate the capacity of this targeting approach to protect against a human pathogen. the dec-targeted lcrv induced polarized th1 immunity, whereas dcir2-targeted lcrv induced fewer cd4(+) t cells secreting ifn-γ, but higher il-4, il-5, il-10, and il-1 ...201020812236
interannual variability of human plague occurrence in the western united states explained by tropical and north pacific ocean climate variability.plague is a vector-borne, highly virulent zoonotic disease caused by the bacterium yersinia pestis. it persists in nature through transmission between its hosts (wild rodents) and vectors (fleas). during epizootics, the disease expands and spills over to other host species such as humans living in or close to affected areas. here, we investigate the effect of large-scale climate variability on the dynamics of human plague in the western united states using a 56-year time series of plague reports ...201020810830
development of an up-converting phosphor technology-based 10-channel lateral flow assay for profiling antibodies against yersinia pestis.in this study, a 10-channel up-converting phosphor technology-based lateral flow (tc-upt-lf) assay was developed to profile antibodies against yersinia pestis. ten expressed y. pestis proteins were covalently conjugated with an up-converting phosphor particle to develop double-antigen sandwich immunochromatographic strips to detect corresponding antibodies. after optimization one by one, each strip was integrated into a tc-upt-lf disc for simultaneously detection of different antibodies. a scann ...201020801166
modeling the epidemiological history of plague in central asia: palaeoclimatic forcing on a disease system over the past millennium.human cases of plague (yersinia pestis) infection originate, ultimately, in the bacterium's wildlife host populations. the epidemiological dynamics of the wildlife reservoir therefore determine the abundance, distribution and evolution of the pathogen, which in turn shape the frequency, distribution and virulence of human cases. earlier studies have shown clear evidence of climatic forcing on contemporary plague abundance in rodents and humans.201020799946
[effect of yersinia pestis ev 76 lypopolysaccharides with different levels of toxicity on dynamics of tnf-alpha and inf-gamma synthesis by human monocytes].aim. to study dynamics of synthesis of tnf-alpha and inf-gamma by cell line u-937 human monocytes under the effect of yersinia pestis ev 76 lypopolysaccharides (lps) with different levels of toxicity: original lps28 and lps37 as well as their conformationally--changed variants with enhanced toxicity--complex of lps with murine toxin (mt) of y. pestis, and lps modified by biologicall active compound (bac) obtained from human erythrocytes.201020799400
conserved hydrophobic clusters on the surface of the caf1a usher c-terminal domain are important for f1 antigen assembly.the outer membrane usher protein caf1a of the plague pathogen yersinia pestis is responsible for the assembly of a major surface antigen, the f1 capsule. the f1 capsule is mainly formed by thin linear polymers of caf1 (capsular antigen fraction 1) protein subunits. the caf1a usher promotes polymerization of subunits and secretion of growing polymers to the cell surface. the usher monomer (811 aa, 90.5 kda) consists of a large transmembrane β-barrel that forms a secretion channel and three solubl ...201020797400
[comparison of efficacy of tests for differentiation of typical and atypical strains of yersinia pestis and yersinia pseudotuberculosis].to characterize species specificity of officially recommended tests for differentiation of yersiniapestis and yersinia pseudotuberculosis and propose additional tests allowing for more accurate identification.201020795389
further observations on the reaction of bacillus pestis in plague. 190320760881
serum reaction of "bacillus pestis" in plague: a preliminary communication. 190220760591
[the biofilm formation in yersinia pestis strains isolated in astrakhan region].to study biofilm formation in strains of yersinia pestis isolated in 2009 in astrakhan region.201020737679
[sequence analysis of the yada, inv, and ail genes and their expression in the main and nonmain yersinia pestis subspecies and yersinia pseudotuberculosis].the nucleotide sequences of the inv, yada, and ail adhesin-invasin genes were analyzed in 24 strains of the main and nonmain yersinia pestis subspecies, which were isolated from natural plague foci in russia and neighbor countries, and ten y. pseudotuberculosis strains. all of the five plague agent subspecies (main, caucasica, altaica, ulegeica, and hissarica) had the inv and yada genes altered by insertion of the is element and a single nucleotide deletion, respectively, as was earlier observed ...201020734763
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