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functional recruitment of the human complement inhibitor c4bp to yersinia pseudotuberculosis outer membrane protein ail.ail is a 17-kda chromosomally encoded outer membrane protein that mediates serum resistance (complement resistance) in the pathogenic yersiniae (yersinia pestis, y. enterocolitica, and y. pseudotuberculosis). in this article, we demonstrate that y. pseudotuberculosis ail from strains pb1, 2812/79, and ypiii/pib1 (serotypes o:1a, o:1b, and o:3, respectively) can bind the inhibitor of the classical and lectin pathways of complement, c4b-binding protein (c4bp). binding was observed irrespective of ...201222467648
a curve of thresholds governs plague epizootics in central asia.a core concept of infectious disease epidemiology is the abundance threshold, below which an infection is unable to invade or persist. there have been contrasting theoretical predictions regarding the nature of this threshold for vector-borne diseases, but for infections with an invertebrate vector, it is common to assume a threshold defined by the ratio of vector and host abundances. here, we show in contrast, both from field data and model simulations, that for plague (yersinia pestis) in kaza ...201222449078
ail protein binds ninth type iii fibronectin repeat (9fniii) within central 120-kda region of fibronectin to facilitate cell binding by yersinia pestis.the yersinia pestis adhesin molecule ail interacts with the extracellular matrix protein fibronectin (fn) on host cells to facilitate efficient delivery of cytotoxic yop proteins, a process essential for plague virulence. a number of bacterial pathogens are known to bind to the n-terminal region of fn, comprising type i fn (fni) repeats. using proteolytically generated fn fragments and purified recombinant fn fragments, we demonstrated that ail binds the centrally located 120-kda fragment contai ...201222447929
the natural history and incidence of yersinia pestis and prospects for vaccination.plague is an ancient, serious, infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. this paper discusses the natural history of the bacterium and its evolution into a flea-vectored bacterium able to transmit bubonic plague. it reviews the incidence of plague in the modern world and charts the history of vaccines which have been used to protect against the flea-vectored disease, which erupts as bubonic plague. current approaches to vaccine d ...201222442294
identification by cdna cloning of abundant srnas in a human-avirulent yersinia pestis strain grown under five different growth conditions.srna regulation is supposedly involved in the stress response of a pathogen during infection. yersinia pestis, the etiologic agent of plague, must encounter temperature and microenvironment changes, given its lifestyle. here, we used the cdna cloning approach to discover full-length srna candidates that are highly expressed in y. pestis under five different growth conditions.201222439729
use of a public telephone hotline to detect urban plague cases.current methods for vector-borne disease surveillance are limited by time and cost. to avoid human infections from emerging zoonotic diseases, it is important that the united states develop cost-effective surveillance systems for these diseases. this study examines the methodology used in the surveillance of a plague epizootic involving tree squirrels (sciurus niger) in denver colorado, during the summer of 2007. a call-in centre for the public to report dead squirrels was used to direct animal ...201222429398
prioritizing risks and uncertainties from intentional release of selected category a pathogens.this paper synthesizes available information on five category a pathogens (bacillus anthracis, yersinia pestis, francisella tularensis, variola major and lassa) to develop quantitative guidelines for how environmental pathogen concentrations may be related to human health risk in an indoor environment. an integrated model of environmental transport and human health exposure to biological pathogens is constructed which 1) includes the effects of environmental attenuation, 2) considers fomite cont ...201222412915
yersinia--flea interactions and the evolution of the arthropod-borne transmission route of plague.yersinia pestis, the causative agent of plague, is unique among the enteric group of gram-negative bacteria in relying on a blood-feeding insect for transmission. the yersinia-flea interactions that enable plague transmission cycles have had profound historical consequences as manifested by human plague pandemics. the arthropod-borne transmission route was a radical ecologic change from the food-borne and water-borne transmission route of yersinia pseudotuberculosis, from which y. pestis diverge ...201222406208
yersinia pestis: examining wildlife plague surveillance in china and the usa.plague is a zoonotic disease caused by the bacterium yersinia pestis lehmann and neumann, 1896. although it is essentially a disease of rodents, plague can also be transmitted to people. historically, plague has caused massive morbidity and mortality events in human populations, and has recently been classified as a reemerging disease in many parts of the world. this public health threat has led many countries to set up wild and domestic animal surveillance programs in an attempt to monitor plag ...201222405453
contrasted patterns of selection on mhc-linked microsatellites in natural populations of the malagasy plague reservoir.plague (yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. the black rat (rattus rattus) is the main host involved in the plague focus of the central highlands of madagascar. black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of madagascar) are susceptible. various lines of evidence suggest a role for the major histocompatibility complex (mhc) in pla ...201222403713
climate predictors of the spatial distribution of human plague cases in the west nile region of uganda.east africa has been identified as a region where vector-borne and zoonotic diseases are most likely to emerge or re-emerge and where morbidity and mortality from these diseases is significant. understanding when and where humans are most likely to be exposed to vector-borne and zoonotic disease agents in this region can aid in targeting limited prevention and control resources. often, spatial and temporal distributions of vectors and vector-borne disease agents are predictable based on climatic ...201222403328
a toll/interleukin (il)-1 receptor domain protein from yersinia pestis interacts with mammalian il-1/toll-like receptor pathways but does not play a central role in the virulence of y. pestis in a mouse model of bubonic plague.the toll/interleukin (il)-1 receptor (tir) domain is an essential component of eukaryotic innate immune signalling pathways. interaction between tir domains present in toll-like receptors and associated adaptors initiates and propagates an immune signalling cascade. proteins containing tir domains have also been discovered in bacteria. studies have subsequently shown that these proteins are able to modulate mammalian immune signalling pathways dependent on tir interactions and that this may repr ...201222403187
synthesis, characterization, and antimicrobial activity of silver carbene complexes derived from 4,5,6,7-tetrachlorobenzimidazole against antibiotic resistant bacteria.silver n-heterocyclic carbene complexes have been shown to have great potential as antimicrobial agents, affecting a wide spectrum of both gram-positive and gram-negative bacteria. a new series of three silver carbene complexes (sccs) based on 4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested against a panel of clinical strains of bacteria. the imidazolium salts and their precursors were characterized by elemental analysis, mass spectrometry, (1)h and (13)c nmr spe ...201222402409
using comparative genomics for inquiry-based learning to dissect virulence of escherichia coli o157:h7 and yersinia pestis.genomics and bioinformatics are topics of increasing interest in undergraduate biological science curricula. many existing exercises focus on gene annotation and analysis of a single genome. in this paper, we present two educational modules designed to enable students to learn and apply fundamental concepts in comparative genomics using examples related to bacterial pathogenesis. students first examine alignments of genomes of escherichia coli o157:h7 strains isolated from three food-poisoning o ...201222383620
plague in the genomic area.with plague being not only a subject of interest for historians, but still a disease of public health concern in several countries, mainly in africa, there were hopes that analyses of the yersinia pestis genomes would put an end to this deadly epidemic pathogen. genomics revealed that y. pestis isolates evolved from yersinia pseudotuberculosis in central asia some millennia ago, after the acquisition of two y. pestis-specific plasmids balanced genomic reduction parallel with the expansion of ins ...201222369155
yersinia pestis lineages in mongolia.whole genome sequencing allowed the development of a number of high resolution sequence based typing tools for yersinia (y.) pestis. the application of these methods on isolates from most known foci worldwide and in particular from china and the former soviet union has dramatically improved our understanding of the population structure of this species. in the current view, y. pestis including the non or moderate human pathogen y. pestis subspecies microtus emerged from yersinia pseudotuberculosi ...201222363455
human louse-transmitted infectious diseases.several of the infectious diseases associated with human lice are life-threatening, including epidemic typhus, relapsing fever, and trench fever, which are caused by rickettsia prowazekii, borrelia recurrentis, and bartonella quintana, respectively. although these diseases have been known for several centuries, they remain a major public health concern in populations living in poor-hygiene conditions because of war, social disruption, severe poverty, or gaps in public health management. poor-hyg ...201222360386
comparative genomics of 2009 seasonal plague (yersinia pestis) in new mexico.plague disease caused by the gram-negative bacterium yersinia pestis routinely affects animals and occasionally humans, in the western united states. the strains native to the north american continent are thought to be derived from a single introduction in the late 19(th) century. the degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of north american plague are highly desired. to assay genetic diversity ...201222359605
rational design of pathogen-mimicking amphiphilic materials as nanoadjuvants.an opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. this study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. biodegradable amphiphilic polyanhydrides possess the unique ...201122355713
development and comparison of two assay formats for parallel detection of four biothreat pathogens by using suspension microarrays.microarrays provide a powerful analytical tool for the simultaneous detection of multiple pathogens. we developed diagnostic suspension microarrays for sensitive and specific detection of the biothreat pathogens bacillus anthracis, yersinia pestis, francisella tularensis and coxiella burnetii. two assay chemistries for amplification and labeling were developed, one method using direct hybridization and the other using target-specific primer extension, combined with hybridization to universal arr ...201222355407
structure of the cytoplasmic domain of yersinia pestis yscd, an essential component of the type iii secretion system.the yersinia pestis yscd protein is an essential component of the type iii secretion system. yscd consists of an n-terminal cytoplasmic domain (residues 1-121), a transmembrane linker (122-142) and a large periplasmic domain (143-419). both the cytoplasmic and the periplasmic domains are required for the assembly of the type iii secretion system. here, the structure of the yscd cytoplasmic domain solved by sad phasing is presented. although the three-dimensional structure is similar to those of ...201222349221
an encapsulated yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. we previously reported that oral inoculation of a live attenuated yersinia pseudotuberculosis, the recent ancestor of yersinia pestis, provided protection against bubonic plague. however, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined.201222348169
immuno-pcr--a new tool for paleomicrobiology: the plague paradigm.the cause of past plague pandemics was controversial but several research teams used pcr techniques and dental pulp as the primary material to reveal that they were caused by yersinia pestis. however, the degradation of dna limits the ability to detect ancient infections.201222347507
establishment of a swiss webster mouse model of pneumonic plague to meet essential data elements under the animal rule.a recombinant vaccine (rf1v) is being developed for protection against pneumonic plague. this study was performed to address essential data elements to establish a well-characterized swiss webster mouse model for licensing the rf1v vaccine using the fda's animal rule. these elements include the documentation of challenge material characteristics, aerosol exposure parameters, details of the onset and severity of clinical signs, pathophysiological response to disease, and relevance to human diseas ...201222336286
enumeration of bacteriophage particles: comparative analysis of the traditional plaque assay and real-time qpcr- and nanosight-based assays.bacteriophages are increasingly being utilized and considered for various practical applications, ranging from decontaminating foods and inanimate surfaces to human therapy; therefore, it is important to determine their concentrations quickly and reliably. traditional plaque assay (pa) is the current "gold standard" for quantitating phage titers. however, it requires at least 18 h before results are obtained, and they may be significantly influenced by various factors. therefore, two alternative ...201122334864
the yersinia pestis rcs phosphorelay inhibits biofilm formation by repressing transcription of the diguanylate cyclase gene hmst.yersinia pestis, which causes bubonic plague, forms biofilms in fleas, its insect vectors, as a means to enhance transmission. biofilm development is positively regulated by hmst, encoding a diguanylate cyclase that synthesizes the bacterial second messenger cyclic-di-gmp. biofilm development is negatively regulated by the rcs phosphorelay signal transduction system. in this study, we show that rcs-negative regulation is accomplished by repressing transcription of hmst.201222328676
hfq regulates biofilm gut blockage that facilitates flea-borne transmission of yersinia pestis.the plague bacillus yersinia pestis can achieve transmission by biofilm blockage of the foregut proventriculus of its flea vector. hfq is revealed to be essential for biofilm blockage formation and acquisition and fitness of y. pestis during flea gut infection, consistent with posttranscriptional regulatory mechanisms in plague transmission.201222328669
staphylococcus epidermidis biofilms: functional molecules, relation to virulence, and vaccine potential.medical device-associated infections, most frequently caused by staphylococcus epidermidis and staphylococcus aureus, are of increasing importance in modern medicine. the formation of adherent, multilayered bacterial biofilms is crucial in the pathogenesis of these infections. polysaccharide intercellular adhesin (pia), a homoglycan of β-1,6-linked 2-acetamido-2-deoxy-d: -glucopyranosyl residues, of which about 15% are non-n-acetylated, is central to biofilm accumulation in staphylococci. it tra ...200922328030
construction and screening of attenuated δphop/q salmonella typhimurium vectored plague vaccine candidates.preclinical studies evaluating plague vaccine candidates have demonstrated that the f1 and v protein antigens of yersinia pestis confer protection against challenge from virulent strains. live-attenuated δphop/q salmonella typhimurium recombinants were constructed expressing either f1, v antigens, f1 and v antigens, or a f1-v fusion from asd (+) balanced-lethal plasmids. to improve antigen delivery, genes encoding plague antigens were modified in order to localize antigens to specific bacterial ...201222327496
large is fast, small is tight: determinants of speed and affinity in subunit capture by a periplasmic chaperone.the chaperone/usher pathway assembles surface virulence organelles of gram-negative bacteria, consisting of fibers of linearly polymerized protein subunits. fiber subunits are connected through 'donor strand complementation': each subunit completes the immunoglobulin (ig)-like fold of the neighboring subunit by donating the seventh β-strand in trans. whereas the folding of ig domains is a fast first-order process, folding of ig modules into the fiber conformation is a slow second-order process. ...201222321795
multiplexed electrochemical detection of yersinia pestis and staphylococcal enterotoxin b using an antibody microarray.the combimatrix antibody microarray is a versatile, sensitive detection platform based on the generation and transduction of electrochemical signals following antigen binding to surface antibodies. the sensor chip described herein is comprised of microelectrodes coupled to an adjacent bio-friendly matrix coated with antibodies to the biological pathogens yersinia pestis and bacillus anthracis, and the bacterial toxin staphylococcal enterotoxin b (seb). using this system, we were able to detect s ...201022319302
insights from genomic comparisons of genetically monomorphic bacterial pathogens.some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called 'genetically monomorphic bacteria'. it has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. the genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. some ...201222312053
evaluation and modification of off-host flea collection techniques used in northwest uganda: laboratory and field studies.quantifying the abundance of host-seeking fleas is critical for assessing risk of human exposure to flea-borne disease agents, including yersinia pestis, the etiological agent of plague. yet, reliable measures of the efficacy of existing host-seeking flea collection methods are lacking. in this study, we compare the efficacy of passive and active methods for the collection of host-seeking fleas in both the laboratory and human habitations in a plague-endemic region of northwest uganda. in the la ...201222308790
[toxicity and cytokine-inducing activity of lipopolysaccharide of virulent yersinia pestis 231 strain].determine correlation between toxicity and cytokine inducing activity of parent and conformation modified forms of lipopolysaccharides (lps) of virulent yersinia pestis strain.201122308722
pulmonary infection by yersinia pestis rapidly establishes a permissive environment for microbial proliferation.disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. during the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. in a coinfection model of pneumonic plague, it appears that yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. yersinia pseudotube ...201222308352
the genome, evolution and diversity of mycobacterium ulcerans.mycobacterium ulcerans (m. ulcerans) causes a devastating infection of the skin and underlying tissue commonly known as buruli ulcer (bu). genetic analyses indicate that m. ulcerans has a common ancestor with mycobacterium marinum (m. marinum) and has diverged from this fish and human pathogen perhaps around a million years ago. m. ulcerans is characterized by minimal genetic diversity and since it has a highly clonal population structure, genetic differences between individual isolates reflect ...201222306192
evidence of yersinia pestis dna from fleas in an endemic plague area of zambia.yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. the disease is usually transmitted among wild rodents through a flea vector. the sources and routes of transmission of plague are poorly researched in africa, yet remains a concern in several sub-saharan countries. in zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenan ...201222280795
genome analyses highlight the different biological roles of cellulases.cellulolytic enzymes have been the subject of renewed interest owing to their potential role in the conversion of plant lignocellulose to sustainable biofuels. an analysis of ∼1,500 complete bacterial genomes, presented here, reveals that ∼40% of the genomes of sequenced bacteria encode at least one cellulase gene. most of the bacteria that encode cellulases are soil and marine saprophytes, many of which encode a range of enzymes for cellulose hydrolysis and also for the breakdown of the other c ...201222266780
probing the substrate and acceptor specificity of the γ-glutamyltranspeptidase.abstract. γ-glutamyl transpeptidase (ggt) is a two-substrate enzyme that plays a central role in glutathione metabolism and is a potential target for drug design. ggt catalyze the cleavage of γ-glutamyl donor substrates, and the transfer of the γ-glutamyl moiety to an amine of an acceptor substrate or water. although structures of bacterial ggt have revealed details of the protein-ligand interactions at the donor site, the acceptor substrate site is relatively undefined. the recent identificatio ...201222257032
polymorphisms in the lcrv gene of yersinia enterocolitica and their effect on plague protective immunity.current efforts to develop plague vaccines focus on lcrv, a polypeptide that resides at the tip of type iii secretion needles. lcrv-specific antibodies block yersinia pestis type iii injection of yop effectors into host immune cells, thereby enabling phagocytes to kill the invading pathogen. earlier work reported that antibodies against y. pestis lcrv cannot block type iii injection by yersinia enterocolitica strains and suggested that lcrv polymorphisms may provide for escape from lcrv-mediated ...201222252870
structure of the yersinia pestis fabv enoyl-acp reductase and its interaction with two 2-pyridone inhibitors.the recently discovered fabv enoyl-acp reductase, which catalyzes the last step of the bacterial fatty acid biosynthesis (fas-ii) pathway, is a promising but unexploited drug target against the reemerging pathogen yersinia pestis. the structure of y. pestis fabv in complex with its cofactor reveals that the enzyme features the common architecture of the short-chain dehydrogenase reductase superfamily, but contains additional structural elements that are mostly folded around the usually flexible ...201222244758
[structural analysis of genes participating in melibiose fermentation and isocitrate lyase production in yersinia pestis strains of main and non main subspecies].comparative analysis of nucleotide sequences of genes participating in melibiose fermentation and isocitrate lyase production was conducted in 90 natural yersinia pestis strains of main and non main subspecies. it was ascertained that the lack of the ability to utilize disaccharide melibiose in strains of the main subspecies is caused by integration of the insertion sequence is285 at 73 bp from the beginning of the structural gene melb that encodes the transport protein galactoside permease. in ...201122232920
structural insights into ripc, a putative citrate lyase β subunit from a yersinia pestis virulence operon.yersinia pestis remains a threat, with outbreaks of plague occurring in rural areas and its emergence as a weapon of bioterrorism; thus, an improved understanding of its various pathogenicity pathways is warranted. the rip (required for intracellular proliferation) virulence operon is required for y. pestis survival in interferon-γ-treated macrophages and has been implicated in lowering macrophage-produced nitric oxide levels. ripc, one of three gene products from the rip operon, is annotated as ...201222232161
manganese transporters yfe and mnth are fur-regulated and important for the virulence of yersinia pestis.yersinia pestis has a flea-mammal-flea transmission cycle, and is a zoonotic pathogen that causes the systemic diseases bubonic and septicaemic plague in rodents and humans, as well as pneumonic plague in humans and non-human primates. bubonic and pneumonic plague are quite different diseases that result from different routes of infection. manganese (mn) acquisition is critical for the growth and pathogenesis of a number of bacteria. the yfe/sit and/or mnth systems are the two prominent mn trans ...201222222497
Humoral and cellular immune responses to Yersinia pestis infection in long-term recovered plague patients.Plague is one of the most dangerous diseases and is caused by Yersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n=65) recovered from Y. pestis infection during the past 16 years were investigated using protein microarray and enzyme-linked immunospot assay (Elispot). The seroprevealence to F1 antigen in all recovered patients is 7 ...201122190397
[Detection and identification of highly pathogenic bacteria within the framework of the EQADeBa project--Part I: Samples containing living pathogens].Bacillus anthracis, Yersinia pestis, Francisella tularensis, Brucella sp., Bulkholderia mallei are B. pseudomallei are highly pathogenic bacteria of potential bioterrorism risk. To support the early warning and rapid response capacity to ensure an effective reaction to bioterrorist attacks the international project "Establishment of Quality Assurances for Detection of Highly Pathogenic Bacteria of Potential Bioterrorism Risk" (EQADeBa) has been established. The aim of the project was establishme ...201122184939
VALIDATION OF QUANTITATIVE ELISAs FOR MEASURING ANTI-YERSINIA PESTIS F1 AND V ANTIBODY CONCENTRATIONS IN NONHUMAN PRIMATE SERA.This study systematically validated two quantitative enzyme-linked immunosorbent assays (ELISAs) for determining Yersinia pestis anti-F1 or anti-V IgG concentration in cynomolgus macaque sera. The results demonstrated that these ELISAs are reliable, reproducible, and suitable for their intended use to measure both anti-F1 and anti-V IgG in monkey sera following vaccination with a heterologous recombinant fusion F1-V protein (rF1-V). Statistical analysis demonstrated assay precision, accuracy, sp ...201222181824
Development of Phage-Based Single Chain Fv Antibody Reagents for Detection of Yersinia pestis.Most Yersinia pestis strains are known to express a capsule-like antigen, fraction 1 (F1)(.) F1 is encoded by the caf1 gene located on the large 100-kb pFra plasmid, which is found in Y. pestis but not in closely related species such as Yersinia enterocolytica and Yersinia pseudotuberculosis. In order to find antibodies specifically binding to Y. pestis we screened a large single chain Fv antibody fragment (scFv) phage display library using purified F1 antigen as a selection target. Different fo ...201122174746
[reasons of low epizootic activity of natural foci of plague in russia at the beginning of the 21st century].establish the main reasons of low epizootic activity of natural foci of plague in russian federation in 2000-2009.201122145344
microchip capillary electrophoresis of multi-locus vntr analysis for genotyping of bacillus anthracis and yersinia pestis in microbial forensic cases.bacillus anthracis and yersinia pestis are etiological agents of anthrax and plague respectively, and are also considered among the most feared potential bioterrorism agents. these microorganisms show intraspecies genome homogeneity, making strains differentiation difficult, while strains identification and comparison with known genotypes may be crucial for naturally occurring outbreaks vs. bioterrorist events discrimination.here an mlva application for b. anthracis and y. pestis strains differe ...201222139674
a transposon site hybridization screen identifies galu and wecbc as important for survival of yersinia pestis in murine macrophages.yersinia pestis is able to survive and replicate within murine macrophages. however, the mechanism by which y. pestis promotes its intracellular survival is not well understood. to identify genes that are important for y. pestis survival in macrophages, a library comprised of ∼31,500 y. pestis kim6+ transposon insertion mutants (input pool) was subjected to negative selection in primary murine macrophages. genes underrepresented in the output pool of surviving bacteria were identified by transpo ...201122139502
the structure of lsrb from yersinia pestis complexed with autoinducer-2.the crystal structure of lsrb from yersinia pestis complexed with autoinducer-2 (ai-2; space group p2(1)2(1)2(1), unit-cell parameters a = 40.61, b = 61.03, c = 125.23 å) has been solved by molecular replacement using the structure of lsrb from salmonella typhimurium (pdb entry 1tjy) and refined to r = 0.180 (r(free) = 0.213) at 1.75 å resolution. the electron density for bound ai-2 and the stereochemistry of the ai-2-binding site are consistent with bound ai-2 adopting the (2r,4s)-2-methyl-2,3, ...201122139152
reflectron maldi tof and maldi tof/tof mass spectrometry reveal novel structural details of native lipooligosaccharides.lipooligosaccharides (los) are powerful gram-negative glycolipids that evade the immune system and invade host animal and vegetal cells. the structural elucidation of los is pivotal to understanding the mechanisms of infection at the molecular level. the amphiphilic nature of los has been the main obstacle for structural analysis by matrix-assisted laser desorption/ionization (maldi) mass spectrometry (ms). our approach has resolved this important issue and has permitted us to obtain reflectron ...201122124985
antibodies for biodefense.potential bioweapons are biological agents (bacteria, viruses, and toxins) at risk of intentional dissemination. biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the us following the 2001 anthrax attack. this review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. these antibodies aim to protect against primary potential bioweapons, or category a agents a ...201122123065
suitability of commercial transport media for biological pathogens under nonideal conditions.there is extensive data to support the use of commercial transport media as a stabilizer for known clinical samples; however, there is little information to support their use outside of controlled conditions specified by the manufacturer. furthermore, there is no data to determine the suitability of said media for biological pathogens, specifically those of interest to the us military. this study evaluates commercial off-the-shelf (cots) transport media based on sample recovery, viability, and q ...201122121364
genotyping yersinia pestis in historical plague. 201122115066
Characterization of the Na?/H? antiporter from Yersinia pestis.Yersinia pestis, the bacterium that historically accounts for the Black Death epidemics, has nowadays gained new attention as a possible biological warfare agent. In this study, its Na?/H? antiporter is investigated for the first time, by a combination of experimental and computational methodologies. We determined the protein's substrate specificity and pH dependence by fluorescence measurements in everted membrane vesicles. Subsequently, we constructed a model of the protein's structure and val ...201122102858
population differences in host immune factors may influence survival of gunnison's prairie dogs (cynomys gunnisoni) during plague outbreaks.over the past 40 yr, epizootics of plague (yersinia pestis) in northern arizona have reduced populations of the gunnison's prairie dog (cynomys gunnisoni), with the exception of a large population found in the aubrey valley (av). to examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005-2006 from av and a neighboring population near seligman (se), arizona. we quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-li ...201122102668
assessment of a recombinant f1-v fusion protein vaccine intended to protect canada lynx (lynx canadensis) from plague.as part of an ongoing restoration program in colorado, usa, we evaluated adverse reactions and seroconversion in captive canada lynx (lynx canadensis) after vaccination with a recombinant f1-v fusion protein vaccine against yersinia pestis, the bacterium that causes plague. ten adult female lynx received the f1-v vaccine; 10 source- and age-matched lynx remained unvaccinated as controls. all of the vaccinated and control lynx remained apparently healthy throughout the confinement period. we obse ...201122102659
Application of nanoparticles for the detection and sorting of pathogenic bacteria by flow-cytometry.In this paper we will describe a new developed contribution of fluorescence nano-crystal (q-dots) as a fluorescence label for detecting pathogenic bacteria by flow cytometry (FCM) and the use of nano-magnetic particles to improve bacterial sorting by Flow cytometry cell sorting (FACS).FCM or FACS systems are based upon single cell detection by light scatter and Immunofluorescence labeling signals. The common FACS systems are based upon single or dual excitation as excitation source both for ligh ...201222101709
[Immunobiological properties of Yersinia pestis antigens].The present review contains information concerning immunobiological properties of plague microbe antigens. All of the identified antigens are evaluated in relation to pathogenicity of Yersinia pestis namely a resistance to phagocytosis, toxicity, adhesiveness etc. as well as persistence ability and adaptation to variable environment. In addition, the role of antigens in immunogenicity of living plague microbe for experimental animals is considered. The data concerning mechanisms of antigenic con ...201122096987
Evaluation of CD4+/CD8+ T-cell expression and IFN-?, perforin secretion for B-T constructs of F1 and V antigens of Yersinia pestis.Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Understanding the immune response generated by epitopes recognized by CD4+ and CD8+ T cells is important for the development of safe and effective vaccines designed to promote protective cellular immunity. Apart from humoral response, CD4+ T cells have shown to have a major role in combating the pneumonic form of the disease. In the present stud ...201122094541
early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of seg mice.background. although laboratory mice are usually highly susceptible to yersinia pestis, we recently identified a mouse strain (seg) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. methods. the kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in seg and susceptible c57bl/6j mice after subcutan ...201222090450
yersinia pestis acrab-tolc in antibiotic resistance and virulence.the efflux pump acrab is important in the antibiotic resistance and virulence of several pathogenic bacteria. we report that deletion of the yersinia pestis acrab-tolc homolog leads to increased susceptibility to diverse substrates, including, though unlike in escherichia coli, the aminoglycosides. neither is the y. pestis pump affected by the efflux pump inhibitor phenylalanine-arginine beta-naphthylamide. in mouse plague models, pump deletion does not have a significant effect on tissue coloni ...201122083483
Structural insights into Ail-mediated adhesion in Yersinia pestis.Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ...201122078566
Conserved Structural Mechanisms for Autoinhibition in IpaH Ubiquitin Ligases.The IpaH family of novel E3 ligase (NEL) enzymes occur in a variety of pathogenic and commensal bacteria that interact with eukaryotic hosts. We demonstrate that the leucine-rich repeat (LRR) substrate recognition domains of different IpaH enzymes autoinhibit the enzymatic activity of the adjacent catalytic novel E3 ligase domain by two distinct but conserved structural mechanisms. Autoinhibition is required for the in vivo biological activity of two IpaH enzymes in a eukaryotic model system. Au ...201222065585
a protective epitope in type iii effector yope is a major cd8 t cell antigen during primary infection with yersinia pseudotuberculosis.virulence in human-pathogenic yersinia species is associated with a plasmid-encoded type iii secretion system that translocates a set of yop effector proteins into host cells. one effector, yope, functions as a rho gtpase-activating protein (gap). in addition to acting as a virulence factor, yope can function as a protective antigen. c57bl/6 mice infected with attenuated yersinia pestis generate a dominant h2-k(b)-restricted cd8 t cell response to an epitope in the n-terminal domain of yope (yop ...201222064714
Identification of three oligo-/polysaccharide-specific ligases in Yersinia enterocolitica.In lipopolysaccharide (LPS) biosynthesis of Gram-negative bacteria the lipid A-core oligosaccharide (LA-core) and O-polysaccharide (O-PS) biosynthesis pathways proceed separately and converge in periplasmic space where the waaL-encoded ligase joins O-PS onto LA-core. Enterobacterial common antigen (ECA) biosynthesis follows that of O-PS except that ECA is usually ligated to phosphatidylglycerol (PG) and only rarely to LA-core. In Yersinia enterocolitica serotype O:3 LPS is composed of LA-inner c ...201222053911
extraction, purification, and identification of yersiniabactin, the siderophore of yersinia pestis.this unit describes in detail the extraction, purification, and identification of yersiniabactin the siderophore of yersinia pestis. iron is essential for bacterial growth. although relatively abundant, access to iron is limited in nature by low solubility. this problem is exacerbated for pathogenic bacteria, which must also defeat the host organism's innate defenses, including mechanisms to sequester iron. one solution to these problems is production of water soluble, small molecules with high ...201122045585
A proteome reference map and virulence factors analysis of Yersinia pestis 91001.In this report, we carried out the in-depth proteomic analysis of Yersinia pestis strain 91001 under in vitro flea-simulated condition using three technique routes, SDS-PAGE combined with LTQ-FT, two-dimensional liquid chromatography peptide (2D-LC peptide) separation combined with LTQ-FT and intact protein separation followed by 2D-LC peptide separation combined with LTQ-FT. Totally, 1926 proteins (13082 peptides) were identified, covering 46.50% (1926/4142) of the predicted proteome. Transcrip ...201222040741
Genomics: Plague's progress. 201122031436
plague genome: the black death decoded. 201122031418
Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges.The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical devel ...201222028978
lack of antimicrobial resistance in yersinia pestis isolates from 17 countries in the americas, africa, and asia.yersinia pestis is the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. plasmid (inca/c)-mediated multidrug resistance in y. pestis was reported in 1995 in madagascar and has generated considerable public health concern, most recently because of the identification of inca/c multidrug-resistant plasmids in other zoonotic pathogens. here, we demonstrate no resistance in 392 y. pestis isolates from 17 countries to eight antimicrobials used for trea ...201222024826
the outer membrane protein a (ompa) of yersinia pestis promotes intracellular survival and virulence in mice.the plague bacterium yersinia pestis has a number of well-described strategies to protect itself from both host cells and soluble factors. in an effort to identify additional anti-host factors, we employed a transposon site hybridization (trash)-based approach to screen 10(5)y. pestis mutants in an in vitro infection system. in addition to loci encoding various components of the well-characterized type iii secretion system (t3ss), our screen unambiguously identified ompa as a pro-survival gene. ...201222023991
phenotypical characterization of mongolian yersinia pestis strains.abstract although mongolia is regarded as one of the possible places of plague radiation, only few data are available from mongolian yersinia pestis strains. in this study a total of 100 mongolian y. pestis strains isolated from wild mammals and their parasites between the years 1960 and 2007 were analyzed for their phenotype. all strains grew well on selective cefsulodin-irgasan-novobiocin agar and were positive for the f1-antigen, the f1-gene (caf1), and the plasminogen activator gene (pla). ...201122022819
Bartonella quintana in Ethiopian lice.Head and clothing lice from Jimma, Ethiopia were investigated for pathogenic bacteria. Genomic DNA from pools of lice was subjected to PCR analysis for Bartonella spp., Borrelia spp. Coxiella burnetii, Rickettsia spp. and Yersinia pestis. All 102 lice pools were negative for the afore mentioned pathogens, with the exception of Bartonella species found among 6 of 65 (9.2%) head lice pools and1 of 33 clothing lice pools. Identification was achieved by sequencing the ribosomal intragenic transcribe ...201122019400
enhanced humoral and mucosal immune responses after intranasal immunization with chimeric multiple antigen peptide of lcrv antigen epitopes of yersinia pestis coupled to palmitate in mice.yersinia pestis is the causative agent of the most deadly disease plague. f1 and v antigens are the major vaccine candidates. six protective epitopes of v antigen of varying length (15-25aa) were assembled on a lysine backbone as multiple antigen peptide (map) using standard fmoc chemistry. palmitate was coupled at amino terminus end. amino acid analysis, sds-page, immunoblot and immunoreactivity proved the authenticity of map. map was immunized intranasally encapsulated in plga (polylactide-co- ...201122001881
functional characterization and biological significance of yersinia pestis lipopolysaccharide biosynthesis genes.in silico analysis of available bacterial genomes revealed the phylogenetic proximity levels of enzymes responsible for biosynthesis of lipopolysaccharide (lps) of yersinia pestis, the cause of plague, to homologous proteins of closely related yersinia spp. and some other bacteria (serratia proteamaculans, erwinia carotovora, burkholderia dolosa, photorhabdus luminescens and others). isogenic y. pestis mutants with single or double mutations in 14 genes of lps biosynthetic pathways were construc ...201121999543
An experimentally-supported genome-scale metabolic network reconstruction for Yersinia pestis CO92.Yersinia pestis is a gram-negative bacterium that causes plague, a disease linked historically to the Black Death in Europe during the Middle Ages and to several outbreaks during the modern era. Metabolism in Y. pestis displays remarkable flexibility and robustness, allowing the bacterium to proliferate in both warm-blooded mammalian hosts and cold-blooded insect vectors such as fleas.201121995956
A draft genome of Yersinia pestis from victims of the Black Death.Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome ...201121993626
Bacteriophage-resistant mutants in Yersinia pestis: identification of phage receptors and attenuation for mice.Bacteriophages specific for Yersinia pestis are routinely used for plague diagnostics and could be an alternative to antibiotics in case of drug-resistant plague. A major concern of bacteriophage therapy is the emergence of phage-resistant mutants. The use of phage cocktails can overcome this problem but only if the phages exploit different receptors. Some phage-resistant mutants lose virulence and therefore should not complicate bacteriophage therapy.201121980477
in vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria.silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. here, the bactericidal activity of four silver carbene complexes (sccs) with different formulations, including nanoparticles (nps) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections.201221972270
role of the yersinia pestis ail protein in preventing a protective polymorphonuclear leukocyte response during bubonic plague.the ability of yersinia pestis to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. in this study, we examined the effect of ail, a 17-kda outer membrane protein that protects y. pestis against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. the y. pestis ail mutant was attenuated for virulence in both rodent models. the attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but ...201121969002
Molecular characterization of transcriptional regulation of rovA by PhoP and RovA in Yersinia pestis.Yersinia pestis is the causative agent of plague. The two transcriptional regulators, PhoP and RovA, are required for the virulence of Y. pestis through the regulation of various virulence-associated loci. They are the global regulators controlling two distinct large complexes of cellular pathways.201121966533
biochemical, structural and molecular dynamics analyses of the potential virulence factor ripa from yersinia pestis.human diseases are attributed in part to the ability of pathogens to evade the eukaryotic immune systems. a subset of these pathogens has developed mechanisms to survive in human macrophages. yersinia pestis, the causative agent of the bubonic plague, is a predominately extracellular pathogen with the ability to survive and replicate intracellularly. a previous study has shown that a novel rip (required for intracellular proliferation) operon (ripa, ripb and ripc) is essential for replication an ...201121966419
PhoP and OxyR transcriptional regulators contribute to Yersinia pestis virulence and survival within Galleria mellonella.The virulence of Yersinia pestis KIM6+ was compared with multiple isolates of Yersinia pseudotuberculosis and Yersinia enterocolitica toward larvae of the greater wax moth Galleria mellonella. Although Y. pestis and Y. pseudotuberculosis were able to cause lethal infection in G. mellonella, these species appeared less virulent than the majority of Y. enterocolitica strains tested. Y. pestis survived primarily within hemocytes of G. mellonella, and induced a strong antibacterial peptide response ...201121964409
determination of post-culture processing with carbohydrates by maldi-ms and tms derivatization gc-ms.biological materials generally require stabilization to retain activity or viability in a dry form. a number of industrial products, such as vaccines, probiotics and biopesticides have been produced as dry preparations. the same methods and materials used for stabilizing commercial microbial products may be applicable to preserving biothreat pathogens in a dry form. this is a likely step that may be encountered when looking at samples from terrorism attempts since only spores, such as those from ...201121962653
effects of temperature on the transmission of yersinia pestis by the flea, xenopsylla cheopis, in the late phase period.traditionally, efficient flea-borne transmission of yersinia pestis, the causative agent of plague, was thought to be dependent on a process referred to as blockage in which biofilm-mediated growth of the bacteria physically blocks the flea gut, leading to the regurgitation of contaminated blood into the host. this process was previously shown to be temperature-regulated, with blockage failing at temperatures approaching 30°c; however, the abilities of fleas to transmit infections at different t ...201121958555
Population structure of the Yersinia pseudotuberculosis complex according to multilocus sequence typing.Multilocus sequence analysis of 417 strains of Yersinia pseudotuberculosis revealed that it is a complex of four populations, three of which have been previously assigned species status [Y. pseudotuberculosis sensu stricto (s.s.), Yersinia pestis and Yersinia similis] and a fourth population, which we refer to as the Korean group, which may be in the process of speciation. We detected clear signs of recombination within Y. pseudotuberculosis s.s. as well as imports from Y. similis and the Korean ...201121951486
[stabilization energy of the compact caf1(13-149) subunit from yersinia pestis].it has been shown by a variety of methods (circular dichroism, viscosimetry, intrinsic fluorescence, and fluorescence of labels) that, as in the case of small globular proteins the folding-unfolding transition in the caf1(13-149) subunit under the action of two denaturants (urea and 1,3-dimethylurea) occurs between two major states (unfolded and compact). however, the free energy of the compact structure is only 8/9-9/2 kj/mol (similar values for single-domain small proteins are in the range of ...201121950061
plague and climate: scales matter.plague is enzootic in wildlife populations of small mammals in central and eastern asia, africa, south and north america, and has been recognized recently as a reemerging threat to humans. its causative agent yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scale ...201121949648
Gene flow in a Yersinia pestis vector, Oropsylla hirsuta, during a plague epizootic.Appreciating how Yersinia pestis, the etiological agent of plague, spreads among black - tailed prairie dog (Cynomys ludovicianus) colonies (BTPD), is vital to wildlife conservation programs in North American grasslands. A little - studied aspect of the system is the role of Y. pestis vectors, i.e. fleas, play in the spreading of plague in natural settings. We investigated the genetic structure and variability of a common prairie dog flea (Oropsylla hirsuta) in BTPD colonies in order to examine ...201121946710
chemical scaffolds with structural similarities to siderophores of nonribosomal peptide-polyketide origin as novel antimicrobials against mycobacterium tuberculosis and yersinia pestis.mycobacterium tuberculosis (mtb) and yersinia pestis (yp) produce siderophores with scaffolds of nonribosomal peptide-polyketide origin. compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against mtb and yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. several new antimicrobials were identified, including some with increased potency in the iron-li ...201121940166
[Fleas notified on Microtus fuscus foci in Sichuan province].To analyzed the variant information on the indices regarding fleas from natural foci of Microtus plague in Sichuan epidemic area during 2000 to 2008.201121933540
phylogeography and molecular epidemiology of yersinia pestis in madagascar.plague was introduced to madagascar in 1898 and continues to be a significant human health problem. it exists mainly in the central highlands, but in the 1990s was reintroduced to the port city of mahajanga, where it caused extensive human outbreaks. despite its prevalence, the phylogeography and molecular epidemiology of y. pestis in madagascar has been difficult to study due to the great genetic similarity among isolates. we examine island-wide geographic-genetic patterns based upon whole-geno ...201121931876
resistance to plague among black-tailed prairie dog populations.abstract in some rodent species frequently exposed to plague outbreaks caused by yersinia pestis, resistance to the disease has evolved as a population trait. as a first step in determining if plague resistance has developed in black-tailed prairie dogs (cynomys ludovicianus), animals captured from colonies in a plague-free region (south dakota) and two plague-endemic regions (colorado and texas) were challenged with y. pestis at one of three doses (2.5, 250, or 2500 mouse ld50s). south dakota p ...201121923261
aoac smpr 2010.002. standard method performance requirements for polymerase chain reaction (pcr) methods for detection of yersinia pestis in aerosol collection filters and/or liquids. 201121919366
role of immune response in yersinia pestis infection.yersinia pestis (y. pestis) is an infamous pathogen causing plague pandemics throughout history and is a selected agent of bioterrorism threatening public health. y. pestis was first isolated by alexandre yersin in 1894 in hong kong and in the following years from all continents. plague is enzootic in different rodents and their fleas in africa, north and south america, and asia, including the middle/far east and ex-ussr countries. comprehending the multifaceted interaction between y. pestis and ...201121918303
developing live vaccines against plague.three great plague pandemics caused by the gram-negative bacterium yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. plague is endemic in many parts of the world. in addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. injectable subunit vaccines are being developed in the united states and united kingdom.  however, the live attenuated y. pestis-ev niieg strain has been u ...201121918302
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