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the use of colorimetric sensor arrays to discriminate between pathogenic bacteria.a colorimetric sensor array is a high-dimensional chemical sensor that is cheap, compact, disposable, robust, and easy to operate, making it a good candidate technology to detect pathogenic bacteria, especially potential bioterrorism agents like yersinia pestis and bacillus anthracis which feature on the center for disease control and prevention's list of potential biothreats. here, a colorimetric sensor array was used to continuously monitor the volatile metabolites released by bacteria in soli ...201323671629
yersinia pestis dna from skeletal remains from the 6(th) century ad reveals insights into justinianic plague.yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. these include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the black death. previous studies have confirmed that y. pestis caused these two more recent pandemics. however, a highly spirited debate still continues as to whether y ...201323658525
proteolytic processing of the yersinia pestis yapg autotransporter by the omptin protease pla and the contribution of yapg to murine plague pathogenesis.autotransporter protein secretion represents one of the simplest forms of secretion across gram-negative bacterial membranes. once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. to better understand the role of autotransporters in disease, our research focused on the autotransp ...201323657527
[ecological-geographic landscapes of natural plague foci in china viii. typing of natural plague foci].since plague is an important natural focus zoonosis, the typing of natural plague foci becomes one of the elements in understanding the nature and developing related prevention program of the disease. natural foci of plague are composed by four fundamental parts which include eco-geographical landscape (natural plague foci), hosts, vectors and pathogens (yersinia pestis) that comprehensively interact through the large temporal scale of evolution. human activities have had great impact on the foc ...201323648259
cyclic amp receptor protein is a repressor of adenylyl cyclase gene cyaa in yersinia pestis.yersinia pestis is one of the most dangerous pathogens. the cyclic amp receptor protein (crp) is required for the full virulence of y. pestis, and it acts as a transcriptional regulator to control a large regulon, which includes several virulence-associated genes. the regulatory action of crp is triggered only by binding to the small molecule cofactor cyclic amp (camp). camp is synthesized from adenosine triphosphate by the adenylyl cyclase encoded by cyaa. in the present work, the regulation of ...201323647342
early apoptosis of macrophages modulated by injection of yersinia pestis yopk promotes progression of primary pneumonic plague.yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. the bacterial type iii secretion system (t3ss) injects 7 effector proteins into host cells and their combined activities are necessary to establish infection. y. pestis infection of the lungs proceeds as a biphasic inflammatory response believed to be regulated through the control of apoptosis and pyroptosis by a single, w ...201323633954
growth of a pyv-bearing yersinia pestis kim5 in retail raw ground pork.yersinia pestis can cause oropharyngeal plague as a result of consumption or handling of meat from infected animals. thus, food naturally or intentionally contaminated can have a role in the dissemination of oropharyngeal plague. the growth of a conditionally virulent pyv-bearing rifampicin-resistant y. pestis kim5 (rif-y. pestis kim5) in retail raw ground pork (rgp) was studied at temperatures ranging from 4 to 30°c. at 4°c, rif-y. pestis kim5 did not grow but survived. in rgp, rif-y. pestis ki ...201323627929
transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in yersinia pestis [corrected].the etiologic agent of bubonic plague, yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. though the closely related enteric pathogen y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in y. pestis has been unclear. in this study we performed transcriptional profiling experiments to identify y. pestis quorum sensing regulated functions. our analysis revealed that acyl-homoserine lactone-based quorum s ...201323620823
structural basis for hypermodification of the wobble uridine in trna by bifunctional enzyme mnmc.methylaminomethyl modification of uridine or 2-thiouridine (mnm5u34 or mnm5s2u34) at the wobble position of trnas specific for glutamate, lysine and arginine are observed in escherichia coli and allow for specific recognition of codons ending in a or g. in the biosynthetic pathway responsible for this post-transcriptional modification, the bifunctional enzyme mnmc catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5u34) to mnm5u34. mnmc catalyzes the fl ...201323617613
optimized methods for biofilm analysis in yersinia pestis. 201323611136
identification of anziaic acid, a lichen depside from hypotrachyna sp., as a new topoisomerase poison inhibitor.topoisomerase inhibitors are effective for antibacterial and anticancer therapy because they can lead to the accumulation of the intermediate dna cleavage complex formed by the topoisomerase enzymes, which trigger cell death. here we report the application of a novel enzyme-based high-throughput screening assay to identify natural product extracts that can lead to increased accumulation of the dna cleavage complex formed by recombinant yersinia pestis topoisomerase i as part of a larger effort t ...201323593306
effects of low-temperature flea maintenance on the transmission of yersinia pestis by oropsylla montana.yersinia pestis, the causative agent of plague, is primarily a rodent-associated, flea-borne zoonosis maintained in sylvatic foci throughout western north america. transmission to humans is mediated most commonly by the flea vector oropsylla montana and occurs predominantly in the southwestern united states. with few exceptions, previous studies showed o. montana to be an inefficient vector at transmitting y. pestis at ambient temperatures, particularly when such fleas were fed on susceptible ho ...201323590319
a live attenuated strain of yersinia pestis δyscb provides protection against bubonic and pneumonic plagues in mouse model.to develop a safe and effective live plague vaccine, the δyscb mutant was constructed based on yersinia pestis biovar microtus strain 201 that is avirulent to humans, but virulent to mice. the virulence, immunogenicity and protective efficacy of the δyscb mutant were evaluated in this study. the results showed that the δyscb mutant was severely attenuated, elicited a higher f1-specific antibody titer and provided protective efficacy against bubonic and pneumonic plague in mouse model. the δyscb ...201323588087
the hemophore hasa from yersinia pestis (hasayp) coordinates hemin with a single residue, tyr75, and with minimal conformational change.hemophores from serratia marcescens (hasa(sm)) and pseudomonas aeruginosa (hasa(p)) bind hemin between two loops, which harbor the axial ligands h32 and y75. hemin binding to the y75 loop triggers closing of the h32 loop and enables binding of h32. because yersinia pestis hasa (hasa(yp)) presents a gln at position 32, we determined the structures of apo- and holo-hasa(yp). surprisingly, the q32 loop in apo-hasa(yp) is already in the closed conformation, but no residue from the q32 loop binds hem ...201323578210
counting small rna in pathogenic bacteria.here, we present a modification to single-molecule fluorescence in situ hybridization that enables quantitative detection and analysis of small rna (srna) expressed in bacteria. we show that short (~200 nucleotide) nucleic acid targets can be detected when the background of unbound singly dye-labeled dna oligomers is reduced through hybridization with a set of complementary dna oligomers labeled with a fluorescence quencher. by neutralizing the fluorescence from unbound probes, we were able to s ...201323577771
infrared spectroscopic evidence of a redox-dependent conformational change involving ion binding residue nqrb-d397 in the na(+)-pumping nadh:quinone oxidoreductase from vibrio cholerae.the na(+)-pumping nadh:quinone oxidoreductase (na(+)-nqr) is a unique respiratory enzyme that conserves energy by translocating na(+) through the plasma membrane. found only in prokaryotes, the enzyme serves as the point of entry of electrons into the respiratory chain in many pathogens, including vibrio cholerae and yersinia pestis. in this study, a combined electrochemical and fourier transform infrared (ftir) spectroscopic approach revealed that na(+)-nqr undergoes significant conformational ...201323566241
alexandre yersin's explorations (1892-1894) in french indochina before the discovery of the plague bacillus.alexandre yersin, the great french discoverer of yersinia pestis, was a keen explorer of unknown lands. at the age of 30, a member of the french colonial health service, he set off to fulfil his intimate dream and explore other continents. for almost two years and three long expeditions, he journeyed through widely unknown regions in the province of the french indochina, in southeast asia, territories of vietnam, cambodia and laos. this article presents vignettes from his explorations. during hi ...201223560756
the kdpd/kdpe two-component system: integrating k⁺ homeostasis and virulence.the two-component system (tcs) kdpd/kdpe, extensively studied for its regulatory role in potassium (k(+)) transport, has more recently been identified as an adaptive regulator involved in the virulence and intracellular survival of pathogenic bacteria, including staphylococcus aureus, entero-haemorrhagic escherichia coli, salmonella typhimurium, yersinia pestis, francisella species, photorhabdus asymbiotica, and mycobacteria. key homeostasis requirements monitored by kdpd/kdpe and other tcss suc ...201323555240
characterization of residual medium peptides from yersinia pestis cultures.here we demonstrate that when yersinia pesitis is grown in laboratory media, peptides from the medium remain associated with cellular biomass even after washing and inactivation of the bacteria by different methods. these peptides are characteristic of the type of growth medium and of the manufacturer of the medium, reflecting the specific composition of the medium. we analyzed biomass-associated peptides from cultures of two attenuated strains of yersinia pestis [kim d27 (pgm-) and kim d1 (lcr- ...201323550890
intranasal prophylaxis with cpg oligodeoxynucleotide can protect against yersinia pestis infection.immunomodulatory agents potentially represent a new class of broad-spectrum antimicrobials. here, we demonstrate that prophylaxis with immunomodulatory cytosine-phosphate-guanidine (cpg) oligodeoxynucleotide (odn), a toll-like receptor 9 (tlr9) agonist, confers protection against yersinia pestis, the etiologic agent of plague. the data establish that intranasal administration of cpg odn 1 day prior to lethal pulmonary exposure to y. pestis strain kim d27 significantly improves survival of c57bl/ ...201323545300
a strain of yersinia pestis with a mutator phenotype from the republic of georgia.we describe here a strain of yersinia pestis, g1670a, which exhibits a baseline mutation rate elevated 250-fold over wild-type y. pestis. the responsible mutation, a c to t substitution in the muts gene, results in the transition of a highly conserved leucine at position 689 to arginine (muts(l689r)). when the mutsl 689r protein of g1670a was expressed in a δmuts derivative of y. pestis strain ev76, mutation rates observed were equivalent to those observed in g1670a, consistent with a causal ass ...201323521061
context-dependent protein folding of a virulence peptide in the bacterial and host environments: structure of an sych-yoph chaperone-effector complex.yersinia pestis injects numerous bacterial proteins into host cells through an organic nanomachine called the type 3 secretion system. one such substrate is the tyrosine phosphatase yoph, which requires an interaction with a cognate chaperone in order to be effectively injected. here, the first crystal structure of a sych-yoph complex is reported, determined to 1.9 å resolution. the structure reveals the presence of (i) a nonglobular polypeptide in yoph, (ii) a so-called β-motif in yoph and (iii ...201323519663
fibrin facilitates both innate and t cell-mediated defense against yersinia pestis.the gram-negative bacterium yersinia pestis causes plague, a rapidly progressing and often fatal disease. the formation of fibrin at sites of y. pestis infection supports innate host defense against plague, perhaps by providing a nondiffusible spatial cue that promotes the accumulation of inflammatory cells expressing fibrin-binding integrins. this report demonstrates that fibrin is an essential component of t cell-mediated defense against plague but can be dispensable for ab-mediated defense. g ...201323487423
multiple antigen peptide containing b and t cell epitopes of f1 antigen of yersinia pestis showed enhanced th1 immune response in murine model.yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. apart from humoral response, cell-mediated protection plays a major role in combating the disease. fraction 1 capsular antigen (f1-ag) of y. pestis has long been exploited as a vaccine candidate. in this study, f1-multiple antigenic peptide (f1-map or map)-specific cell-mediated and cytokine responses were studied in murine model. map consisting ...201323480362
protecting against plague: towards a next-generation vaccine.the causative organism of plague is the bacterium yersinia pestis. advances in understanding the complex pathogenesis of plague infection have led to the identification of the f1- and v-antigens as key components of a next-generation vaccine for plague, which have the potential to be effective against all forms of the disease. here we review the roles of f1- and v-antigens in the context of the range of virulence mechanisms deployed by y. pestis, in order to develop a greater understanding of th ...201323480179
whole-genome sequencing and comparative analysis of yersinia pestis, the causative agent of a plague outbreak in northern peru.the plague is a zoonotic disease caused by the bacterium yersinia pestis. here, we report the complete genome sequence of the y. pestis strain ins, which was isolated from swollen lymph gland aspirate (bubo aspirate) of an infected patient from a pneumonic outbreak in 2010 in northern peru.201323469360
b and t cell epitope mapping and study the humoral and cell mediated immune response to b-t constructs of yscf antigen of yersinia pestis.yscf antigen, a type iii secretion protein has recently been shown partial protection in murine model. five peptides of yscf antigen were predicted using dnastar and t-cell prediction software. peptides were synthesised and authenticated using competitive, direct binding immunoassay with anti yscf/peptide sera raised in mice. peptide p1 and p2 were found to be b cell epitope while p3 was minor b cell epitope. p4 peptide was a pure t cell epitope based on lymphoproliferative response, cytokines p ...201323465748
probabilistic models for crispr spacer content evolution.the crispr/cas system is known to act as an adaptive and heritable immune system in eubacteria and archaea. immunity is encoded in an array of spacer sequences. each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. even in closely related strains, spacer content is very dynamic and evolves quickly. standard models of nucleotide evolution cannot be applied to quantify its rate of change since processes other than single nucleotide changes determ ...201323442002
application of chromosomal dna and protein targeting for the identification of yersinia pestis.a comprehensive strategy was developed and validated for the identification of pathogens from closely related near neighbors using both chromosomal and protein biomarkers, with emphasis on distinguishing yersinia pestis from the ancestral bacterium yersinia pseudotuberculosis.201323436733
induction of the yersinia pestis phop-phoq regulatory system in the flea and its role in producing a transmissible infection.transmission of yersinia pestis is greatly enhanced after it forms a bacterial biofilm in the foregut of the flea vector that interferes with normal blood feeding. here we report that the ability to produce a normal foregut-blocking infection depends on induction of the y. pestis phop-phoq two-component regulatory system in the flea. y. pestis phop-negative mutants achieved normal infection rates and bacterial loads in the flea midgut but produced a less cohesive biofilm both in vitro and in the ...201323435973
rapid focused sequencing: a multiplexed assay for simultaneous detection and strain typing of bacillus anthracis, francisella tularensis, and yersinia pestis.the intentional release of bacillus anthracis in the united states in 2001 has heightened concern about the use of pathogenic microorganisms in bioterrorism attacks. many of the deadliest bacteria, including the class a select agents bacillus anthracis, francisella tularensis, and yersinia pestis, are highly infectious via the pulmonary route when released in aerosolized form. hence, rapid, sensitive, and reliable methods for detection of these biothreats and characterization of their potential ...201323418519
natural history of yersinia pestis pneumonia in aerosol-challenged balb/c mice.after a relatively short untreated interval, pneumonic plague has a mortality approaching 100%. we employed a murine model of aerosol challenge with yersinia pestis to investigate the early course of pneumonic plague in the lung, blood, and spleen. we fit a mathematical model to all data simultaneously. the model fit to the data was acceptable. the number of organisms in the lung at baseline was estimated to be 135 (median) or 1,184 (mean) cfu/g. the doubling time was estimated as 1.5 to 1.7 h. ...201323403418
inheritance of the lysozyme inhibitor ivy was an important evolutionary step by yersinia pestis to avoid the host innate immune response.yersinia pestis (the plague bacillus) and its ancestor, yersinia pseudotuberculosis (which causes self-limited bowel disease), encode putative homologues of the periplasmic lysozyme inhibitor ivy and the membrane-bound lysozyme inhibitor mlic. the involvement of both inhibitors in virulence remains subject to debate.201323402825
[highly contagious diseases with human-to-human transmission].highly contagious diseases are caused by various biological agents that pose a risk to individuals and may have a potential for public health impact. they result in high mortality and morbidity rates, might cause public panic and therefore require special measures. the pathogens that can be easily disseminated or transmitted from person to person are the riskiest for clinicians (ebola virus, marburg virus, lassa virus, crimean-congo hemorrhagic fever virus, variola major, sars virus and yersinia ...201223386507
crystallization of the acyl-coa thioesterase tesb from yersinia pestis.yersinia pestis is a highly virulent human pathogen and is the causative agent of bubonic plague. spread through the bite of infected fleas, plague epidemics have marked important events in history, including the justinian plague (6th century), the black death (14th century) which decimated nearly one quarter of the european population, and more recently the orientalis plague (1894). to date, deaths are still being reported and, without treatment, the disease kills most people within 4 days. one ...201323385765
integrating high-content imaging and chemical genetics to probe host cellular pathways critical for yersinia pestis infection.the molecular machinery that regulates the entry and survival of yersinia pestis in host macrophages is poorly understood. here, we report the development of automated high-content imaging assays to quantitate the internalization of virulent y. pestis co92 by macrophages and the subsequent activation of host nf-κb. implementation of these assays in a focused chemical screen identified kinase inhibitors that inhibited both of these processes. rac-2-ethoxy-3 octadecanamido-1-propylphosphocholine ( ...201323383093
fast and simple detection of yersinia pestis applicable to field investigation of plague foci.yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. there is now a convenient and effective test (f1-dipstick) for the rapid identification of y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the f1 capsule is mostly produced at 37°c. the plasminogen activator (pla), a key virulence factor encoded by a y. pestis-specific plasmid, is ...201323383008
reciprocal regulation of ph 6 antigen gene loci by phop and rova in yersinia pestis biovar microtus.to explore the transcriptional regulation of the psaef and psaabc loci by the rova and phop regulators in yersinia pestis.201323374131
recombinant salmonella vaccination technology and its application to human bacterial pathogens.salmonella enterica is a gram-negative intracellular bacterial pathogen which causes salmonellosis in humans and animals. during the past several decades, extensive studies have shown that the attenuated salmonella vaccine vector is an optimal vehicle for delivering passenger antigens to mucosal sites to induce humoral, cellular, and mucosal immunity. this immunity leads to protection against challenges with the wild-type pathogens from which the passenger antigens were derived. a myriad of stud ...201323360265
rfal is required for yersinia pestis type iii secretion and virulence.yersinia pestis, the causative agent of plague, uses a type iii secretion system (t3ss) to inject cytotoxic yop proteins directly into the cytosol of mammalian host cells. the t3ss can also be activated in vitro at 37°c in the absence of calcium. the chromosomal gene rfal (waal) was recently identified as a virulence factor required for proper function of the t3ss. rfal functions as a ligase that adds the terminal n-acetylglucosamine to the lipooligosaccharide core of y. pestis. we previously sh ...201323357388
pathogenicity of yersinia pestis synthesis of 1-dephosphorylated lipid a.synthesis of escherichia coli lpxl, which transfers a secondary laurate chain to the 2' position of lipid a, in yersinia pestis produced bisphosphoryl hexa-acylated lipid a at 37°c, leading to significant attenuation of virulence. our previous observations also indicated that strain χ10015(pcd1ap) (δlpxp32::p(lpxl) lpxl) stimulated a strong inflammatory reaction but sickened mice before recovery and retained virulence via intranasal (i.n.) infection. the development of live, attenuated y. pestis ...201323357387
the sycn/yscb chaperone-binding domain of yopn is required for the calcium-dependent regulation of yop secretion by yersinia pestis.numerous gram-negative bacterial pathogens employ type iii secretion systems (t3sss) to inject effector proteins into eukaryotic cells. the activation of the type iii secretion (t3s) process is tightly controlled in all t3sss. in yersinia pestis, the secretion of effector proteins, termed yersinia outer proteins (yops), is regulated by the activity of the yopn/sycn/yscb/tyea complex. yopn is a secreted protein that interacts with the sycn/yscb chaperone via an n-terminal chaperone-binding domain ...201323355975
local persistence and extinction of plague in a metapopulation of great gerbil burrows, kazakhstan.speculation on how the bacterium yersinia pestis re-emerges after years of absence in the prebalkhash region in kazakhstan has been ongoing for half a century, but the mechanism is still unclear. one of the theories is that plague persists in its reservoir host (the great gerbil) in so-called hotspots, i.e. small regions in which the conditions remain favourable for plague to persist during times where the conditions in the prebalkhash region as a whole have become unfavourable for plague persis ...201223351373
identification of novel protein-protein interactions of yersinia pestis type iii secretion system by yeast two hybrid system.type iii secretion system (t3ss) of the plague bacterium y. pestis encodes a syringe-like structure consisting of more than 20 proteins, which can inject virulence effectors into host cells to modulate the cellular functions. here in this report, interactions among the possible components in t3ss of yersinia pestis were identified using yeast mating technique. a total of 57 genes, including all the pcd1-encoded genes except those involved in plasmid replication and partition, pseudogenes, and th ...201323349800
plague outbreak in libya, 2009, unrelated to plague in algeria.after 25 years of no cases of plague, this disease recurred near tobruk, libya, in 2009. an epidemiologic investigation identified 5 confirmed cases. we determined ribotypes, not1 restriction profiles, and is100 and is1541 hybridization patterns of strains isolated during this outbreak. we also analyzed strains isolated during the 2003 plague epidemic in algeria to determine whether there were epidemiologic links between the 2 events. our results demonstrate unambiguously that neighboring but in ...201323347743
yersinia pestis plasminogen activator gene homolog in rat tissues. 201323347636
development of a panel of recombinase polymerase amplification assays for detection of biothreat agents.syndromic panels for infectious disease have been suggested to be of value in point-of-care diagnostics for developing countries and for biodefense. to test the performance of isothermal recombinase polymerase amplification (rpa) assays, we developed a panel of 10 rpas for biothreat agents. the panel included rpas for francisella tularensis, yersinia pestis, bacillus anthracis, variola virus, and reverse transcriptase rpa (rt-rpa) assays for rift valley fever virus, ebola virus, sudan virus, and ...201323345286
partial retraction: yadbc of yersinia pestis, a new virulence determinant for bubonic plague. 201323335642
colocalized delivery of adjuvant and antigen using nanolipoprotein particles enhances the immune response to recombinant antigens.subunit antigen-based vaccines can provide a number of important benefits over traditional vaccine candidates, such as overall safety. however, because of the inherently low immunogenicity of these antigens, methods for colocalized delivery of antigen and immunostimulatory molecules (i.e., adjuvants) are needed. here we report a robust nanolipoprotein particle (nlp)-based vaccine delivery platform that facilitates the codelivery of both subunit antigens and adjuvants. ni-chelating nlps (ninlps) ...201323331082
identification and characterization of small rnas in yersinia pestis.yersinia pestis, the etiologic agent of plague, is closely related to yersinia pseudotuberculosis evolutionarily but has a very different mode of infection. the rna-binding regulatory protein, hfq, mediates regulation by small rnas (srnas) and is required for virulence of both y. pestis and y. pseudotuberculosis. moreover, hfq is required for growth of y. pestis, but not y. pseudotuberculosis, at 37°c. together, these observations suggest that srnas play important roles in the virulence and surv ...201323324607
yersinia infection tools-characterization of structure and function of adhesins.among the seventeen species of the gram-negative genus yersinia, three have been shown to be virulent and pathogenic to humans and animals-y. enterocolitica, y. pseudotuberculosis, and y. pestis. in order to be so, they are armoured with various factors that help them adhere to tissues and organelles, cross the cellular barrier and escape the immune system during host invasion. the group of proteins that mediate pathogen-host interactions constitute adhesins. invasin, ail, yada, yadb, yadc, pla, ...201223316485
subtyping brazilian yersinia pestis strains by pulsed-field gel electrophoresis.we subtyped brazilian yersinia pestis strains by pulsed-field gel electrophoresis (pfge). this was done with 22 brazilian y. pestis strains: 17 from an outbreak and 5 from endemic routine surveillance. the strains were divided into 2 groups (i and ii), 8 subgroups (a-h) and 19 pfge profiles or pulsotypes. pfge did not separate outbreak from non-outbreak strains, as identical pulsotype patterns were found among outbreak strains and strains obtained from surveillance. however, it was able to detec ...201323315882
inhibitors of the yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.the bacterial protein tyrosine phosphatase yoph is an essential virulence determinant in yersinia pestis and a potential antibacterial drug target. here we report our studies of screening for small molecule inhibitors of yoph using both high throughput and in silico approaches. the identified inhibitors represent a diversity of chemotypes and novel ptyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. we demonstrate that the ...201323294700
[ecological-geographic landscapes of natural plague foci in china vii. typing of natural plague foci].to group and characterize natural plague foci in china.201223290901
efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. we compared the efficacy of a ciprofloxacin (cin) and gentamicin (gen) combination therapy with that of each antibiotic administered alone (i) against yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). in vitro, the cin+gen combinat ...201223285069
fur is a repressor of biofilm formation in yersinia pestis.yersinia pestis synthesizes the attached biofilms in the flea proventriculus, which is important for the transmission of this pathogen by fleas. the hmshfrs operons is responsible for the synthesis of exopolysaccharide (the major component of biofilm matrix), which is activated by the signaling molecule 3', 5'-cyclic diguanylic acid (c-di-gmp) synthesized by the only two diguanylate cyclases hmst, and ypo0449 (located in a putative operonypo0450-0448).201223285021
evaluation of the filmarray® system for detection of bacillus anthracis, francisella tularensis and yersinia pestis.to evaluate the sensitivity and specificity of the biofire diagnostics filmarray(®) system in combination with their biothreat panel for the detection of bacillus anthracis (ba), francisella tularensis (ft) and yersinia pestis (yp) dna, and demonstrate the detection of ba spores.201323279070
structural basis for the specific recognition of dual receptors by the homopolymeric ph 6 antigen (psa) fimbriae of yersinia pestis.the ph 6 antigen (psa) of yersinia pestis consists of fimbriae that bind to two receptors: β1-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. despite the ubiquitous presence of either moiety on the surface of many mammalian cells, y. pestis appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. the molecular mechanism of this apparent selectivity is not clear. site-directed mu ...201223277582
a yersinia pestis-specific, lytic phage preparation significantly reduces viable y. pestis on various hard surfaces experimentally contaminated with the bacterium.five y. pestis bacteriophages obtained from various sources were characterized to determine their biological properties, including their taxonomic classification, host range and genomic diversity. four of the phages (ypp-g, y, r and ypsp-g) belong to the podoviridae family, and the fifth phage (ypsp-pst) belongs to the myoviridae family, of the order caudovirales comprising of double-stranded dna phages. the genomes of the four podoviridae phages were fully sequenced and found to be almost ident ...201223275868
the structure of the deacetylase domain of escherichia coli pgab, an enzyme required for biofilm formation: a circularly permuted member of the carbohydrate esterase 4 family.bacterial biofilm formation is an extremely widespread phenomenon involving the secretion of a protective exopolysaccharide matrix which helps the bacteria to attach to surfaces and to overcome a variety of stresses in different environments. this matrix may also include proteins, lipids, dna and metal ions. its composition depends on the bacterial species and growth conditions, but one of the most widely found components is polymeric β-1,6-n-acetyl-d-glucosamine (pga). several studies have sugg ...201223275162
deletion of the braun lipoprotein-encoding gene and altering the function of lipopolysaccharide attenuate the plague bacterium.braun (murein) lipoprotein (lpp) and lipopolysaccharide (lps) are major components of the outer membranes of enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating toll-like receptors 2 and 4, respectively. expanding on earlier studies that demonstrated a role played by lpp in yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbb in-frame deletion mutant incapable of producing an acyltransferase t ...201223275092
structure and function of cytidine monophosphate kinase from yersinia pseudotuberculosis, essential for virulence but not for survival.the need for new antibiotics has become pressing in light of the emergence of antibiotic-resistant strains of human pathogens. yersinia pestis, the causative agent of plague, is a public health threat and also an agent of concern in biodefence. it is a recently emerged clonal derivative of the enteric pathogen yersinia pseudotuberculosis. previously, we developed a bioinformatic approach to identify proteins that may be suitable targets for antimicrobial therapy and in particular for the treatme ...201223271832
historical variations in mutation rate in an epidemic pathogen, yersinia pestis.the genetic diversity of yersinia pestis, the etiologic agent of plague, is extremely limited because of its recent origin coupled with a slow clock rate. here we identified 2,326 snps from 133 genomes of y. pestis strains that were isolated in china and elsewhere. these snps define the genealogy of y. pestis since its most recent common ancestor. all but 28 of these snps represented mutations that happened only once within the genealogy, and they were distributed essentially at random among ind ...201223271803
combining real-time polymerase chain reaction using sybr green i detection and sequencing to identify vertebrate bloodmeals in fleas.programs that aim to control vector-borne zoonotic diseases require information on zoonotic hosts and on the feeding behavior of bridging vectors that are capable of transmitting pathogens from those hosts to humans. here we describe an assay developed to identify bloodmeals in field-collected cat fleas (ctenocephalides felis bouché) to assess this species' potential role as a yersinia pestis bridging vector in a plague-endemic region of uganda. our assay uses a single primer set and sybr green ...023270174
autoregulation of phop/phoq and positive regulation of the cyclic amp receptor protein-cyclic amp complex by phop in yersinia pestis.yersinia pestis is one of the most dangerous bacterial pathogens. phop and cyclic amp receptor protein (crp) are global regulators of y. pestis, and they control two distinct regulons that contain multiple virulence-related genes. the phop regulator and its cognate sensor phoq constitute a two-component regulatory system. the regulatory activity of crp is triggered only by binding to its cofactor camp, which is synthesized from atp by adenylyl cyclase (encoded by cyaa). however, the association ...201323264579
yersinia pestis insecticidal-like toxin complex (tc) family proteins: characterization of expression, subcellular localization, and potential role in infection of the flea vector.toxin complex (tc) family proteins were first identified as insecticidal toxins in photorhabdus luminescens and have since been found in a wide range of bacteria. the genome of yersinia pestis, the causative agent of bubonic plague, contains a locus that encodes the tc protein homologues yita, yitb, yitc, and yipa and yipb. previous microarray data indicate that the tc genes are highly upregulated by y. pestis while in the flea vector; however, their role in the infection of fleas and pathogenes ...201223249165
omics strategies for revealing yersinia pestis virulence.omics has remarkably changed the way we investigate and understand life. omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. in this review, we summarize omics-driven studies to reveal the virulence features of yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. these studies serve as ...201223248778
toward a molecular pathogenic pathway for yersinia pestis yopm.yopm is one of the six "effector yops" of the human-pathogenic yersinia, but its mechanism has not been defined. after delivery to j774a.1 monocyte-like cells, yopm can rapidly bind and activate the serine/threonine kinases rsk1 and prk2. however, in infected mice, effects of y. pestis yopm have been seen only after 24-48 h post-infection (p.i.). to identify potential direct effects of yopm in-vivo we tested for effects of yopm at 1 h and 16-18 h p.i. in mice infected systemically with 10(6) bac ...201223248776
small oversights that led to the great plague of marseille (1720-1723): lessons from the past.in recent decades, the issue of emerging and re-emerging infectious diseases has become an increasingly important area of concern in public health. today, like centuries ago, infectious diseases confront us with the fear of death and have heavily influenced social behaviors and policy decisions at local, national and international levels. remarkably, an infectious disease such as plague, which is disseminated from one country to another mainly by commercial transportation, remains today, as it w ...201323246639
the yersinia virulence effector yopm binds caspase-1 to arrest inflammasome assembly and processing.inflammasome assembly activates caspase-1 and initiates the inflammatory cell death program pyroptosis, which is protective against numerous pathogens. consequently, several pathogens, including the plague causing bacterium yersinia pestis, avoid activating this pathway to enhance their virulence. however, bacterial molecules that directly modulate the inflammasome have yet to be identified. examining the contribution of yersinia type iii secretion effectors to caspase-1 activation, we identifie ...201223245324
biomolecular interactions of small-molecule inhibitors affecting the yoph protein tyrosine phosphatase.we have developed competitive and direct binding methods to examine small-molecule inhibitors of protein tyrosine phosphatase activity. focusing on the yersinia pestis outer protein h, a potent bacterial protein tyrosine phosphatase, we describe how an understanding of the kinetic interactions involving yersinia pestis outer protein h, peptide substrates, and small-molecule inhibitors of protein tyrosine phosphatase activity can be beneficial for inhibitor screening, and we further translate the ...201323241354
evaluation of protective potential of yersinia pestis outer membrane protein antigens as possible candidates for a new-generation recombinant plague vaccine.plague caused by yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. although the u.s. food and drug administration recently approved levofloxacin, there is no approved human vaccine against plague. the capsular antigen f1 and the low-calcium-response v antigen (lcrv) of y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to f1 and lcrv to provide protection against y. pestis f1(-) strains or those which harbor variants of lc ...201323239803
beyond an aflp genome scan towards the identification of immune genes involved in plague resistance in rattus rattus from madagascar.genome scans using amplified fragment length polymorphism (aflp) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. this study follows on from an aflp genome scan in the black rat (rattus rattus), the reservoir of plague (yersinia pestis infection) in madagascar. we successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with ...201323237097
lcrh, a class ii chaperone from the type three secretion system, has a highly flexible native structure.the type three secretion system is a large and complex protein nano-machine that many gram-negative pathogens employ to infect host cells. a key structure of this machine is a proteinaceous pore that inserts into the target membrane and forms a channel for bacterial toxins to flow from bacteria into the host cell. the pore is mainly formed from two large membrane proteins called "translocators." importantly, effective secretion and thus pore formation of the translocators depend on their binding ...201323233673
[detection and identification of highly pathogenic bacteria within the framework of the eqadeba project--part ii: samples containing inactivated pathogens].the aim of the studies was analysis of methods applied and results of detection and identification of bacillus anthracis, yersinia pestis, francisella tularensis, brucella sp., bulkholderia mallei and b. pseudomallei in inactivated samples obtained within the framework of the third external quality assessment exercise (eqae) in the project ,,establishment of quality assurances for detection of highly pathogenic bacteria of potential bioterrorism risk (eqadeba)".201223230707
use of rich bhi medium instead of synthetic tmh medium for gene regulation study in yersinia pestis.this study is to verify the use of rich bhi medium to substitute synthetic media for gene regulation studies in yersinia pestis.201223228833
hunger for iron: the alternative siderophore iron scavenging systems in highly virulent yersinia.low molecular weight siderophores are used by many living organisms to scavenge scarcely available ferric iron. presence of at least a single siderophore-based iron acquisition system is usually acknowledged as a virulence-associated trait and a pre-requisite to become an efficient and successful pathogen. currently, it is assumed that yersiniabactin (ybt) is the solely functional endogenous siderophore iron uptake system in highly virulent yersinia (yersinia pestis, y. pseudotuberculosis, and y ...201223226687
host stress and immune responses during aerosol challenge of brown norway rats with yersinia pestis.inhalation exposure models are becoming the preferred method for the comparative study of respiratory infectious diseases due to their resemblance to the natural route of infection. to enable precise delivery of pathogen to the lower respiratory tract in a manner that imposes minimal biosafety risk, nose-only exposure systems have been developed. early inhalation exposure technology for infectious disease research grew out of technology used in asthma research where predominantly the collison ne ...201223226684
lcrv mutants that abolish yersinia type iii injectisome function.lcrv, the type iii needle cap protein of pathogenic yersinia, has been proposed to function as a tether between yscf, the needle protein, and yopb-yopd to constitute the injectisome, a conduit for the translocation of effector proteins into host cells. further, insertion of lcrv-capped needles from a calcium-rich environment into host cells may trigger the low-calcium signal for effector translocation. here, we used a genetic approach to test the hypothesis that the needle cap responds to the lo ...201323222719
genome-level transcription data of yersinia pestis analyzed with a new metabolic constraint-based approach.constraint-based computational approaches, such as flux balance analysis (fba), have proven successful in modeling genome-level metabolic behavior for conditions where a set of simple cellular objectives can be clearly articulated. recently, the necessity to expand the current range of constraint-based methods to incorporate high-throughput experimental data has been acknowledged by the proposal of several methods. however, these methods have rarely been used to address cellular metabolic respon ...201223216785
yersinia pestis: new evidence for an old infection.the successful reconstruction of an ancient bacterial genome from archaeological material presents an important methodological advancement for infectious disease research. the reliability of evolutionary histories inferred by the incorporation of ancient data, however, are highly contingent upon the level of genetic diversity represented in modern genomic sequences that are publicly accessible, and the paucity of available complete genomes restricts the level of phylogenetic resolution that can ...201223209603
blood meal identification in off-host cat fleas (ctenocephalides felis) from a plague-endemic region of uganda.the cat flea, ctenocephalides felis, is an inefficient vector of the plague bacterium (yersinia pestis) and is the predominant off-host flea species in human habitations in the west nile region, an established plague focus in northwest uganda. to determine if c. felis might serve as a y. pestis bridging vector in the west nile region, we collected on- and off-host fleas from human habitations and used a real-time polymerase chain reaction-based assay to estimate the proportion of off-host c. fel ...201223208882
inactivation of vegetative bacterial threat agents on environmental surfaces.following a wide-area biological terror attack, numerous decontamination technologies, techniques, and strategies will be required for rapid remediation. establishing an understanding of how disinfectants will perform under field conditions is of critical importance. the purpose of this study was to determine the efficacy of several liquid decontaminants, when used to inactivate vegetative biological agents on environmental surfaces. aluminum, carpet, concrete, glass, and wood coupons were inocu ...201323208274
yopk controls both rate and fidelity of yop translocation.yersinia pestis, the causative agent of plague, utilizes a type iii secretion system (t3ss) to intoxicate host cells. the injection of t3ss substrates must be carefully controlled, and dysregulation leads to altered infection kinetics and early clearance of y. pestis. while the sequence of events leading up to cell contact and initiation of translocation has received much attention, the regulatory events that take place after effector translocation is less understood. here we show that the regul ...201323205707
characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.yersinia pestis causes bubonic and pneumonic plague in humans. the pneumonic infection is the most severe and invariably fatal if untreated. because of its high virulence, ease of delivery and precedent of use in warfare, y. pestis is considered as a potential bioterror agent. no licensed plague vaccine is currently available in the us. laboratory research with virulent strains requires appropriate biocontainment (i.e., biosafety level 3 (bsl-3) for procedures that generate aerosol/droplets) and ...201323195858
early sensing of yersinia pestis airway infection by bone marrow cells.bacterial infection of the lungs triggers a swift innate immune response that involves the production of cytokines and chemokines that promote recruitment of immune cells from the bone marrow (bm) into the infected tissue and limit the ability of the pathogen to replicate. recent in vivo studies of pneumonic plague in animal models indicate that the pulmonary pro-inflammatory response to airway infection with yersinia pestis is substantially delayed in comparison to other pathogens. consequently ...201223189271
structure and uptake mechanism of bacteriocins targeting peptidoglycan renewal.bacteriocins are narrow-spectrum protein antibiotics released to kill related bacteria of the same niche. uptake of bacteriocins depends critically on the presence of an uptake receptor in the outer membrane, a translocation pore and an energy-dependent activating system of the inner membrane. most bacteriocins act on the inner membrane as pore-forming toxins or they target cytoplasmic dna/rna and ribosomal synthesis respectively. only two bacteriocins are known to become activated in the peripl ...201223176517
using a bacteriocin structure to engineer a phage lysin that targets yersinia pestis.purified phage lysins present an alternative to traditional antibiotics and work by hydrolysing peptidoglycan. phage lysins have been developed against gram-positive pathogens such as bacillus anthracis and streptococcus pneumoniae, where the peptidoglycan layer is exposed on the cell surface. addition of the lysin to a bacterial culture results in rapid death of the organism. gram-negative bacteria are resistant to phage lysins because they contain an outer membrane that protects the peptidogly ...201223176506
multiple antigen peptide consisting of b- and t-cell epitopes of f1 antigen of y. pestis showed enhanced humoral and mucosal immune response in different strains of mice.yersinia pestis is a causative agent of plague. f1 and v antigen based vaccines have shown remarkable protection in experimental animals. in order to develop epitope based immunogen, three b and one t-cell epitopes of f1 antigen with palmitate residue at amino terminal were assembled on a lysine backbone as multiple antigen peptide (map or f1-map). map was characterized by sds-page, immunoblot and immunoreactivity with anti f1 sera. map was entrapped in plga (polylactide-co-glycolide) microparti ...201323174507
[reservation forms of plague infectious agent in tuva natural focus].data characterizing the reservation forms of plague infectious agent in tuva natural focus are presented in the review. yersinia pestis was shown to persist most of the year in citellophilus tesquorum altaicus imago --the main carrier, getting into the animal organism only for a short time. an increased ability to aggregate in autumn and accumulate in clumps of c. tesquorum altaicus females that are more adapted to survive the cold season compared with males promote the persistence of the microo ...201223163049
resistance to plague of mus spretus seg/pas mice requires the combined action of at least four genetic factors.we have previously described seg/pas as the first mouse inbred strain able to survive subcutaneous injection of virulent yersinia pestis, the agent of plague, and we identified yprl1, yprl2 and yprl3 as three quantitative trait loci (qtls) controlling this exceptional phenotype in females from a backcross between seg/pas and c57bl/6 strains. we have now developed congenic strains to further characterize the extent and effect of these genomic regions. in this study, we confirm the importance of t ...201323151488
lipopolysaccharide of yersinia pestis, the cause of plague: structure, genetics, biological properties.the present review summarizes data pertaining to the composition and structure of the carbohydrate moiety (core oligosaccharide) and lipid component (lipid a) of the various forms of lipopolysaccharide (lps), one of the major pathogenicity factors ofyersinia pestis, the cause of plague. the review addresses the functions and the biological significance of genes for the biosynthesis of lps, as well as the biological properties of lps in strains from various intraspecies groups ofy. pestis and the ...201223150803
modeling bacteriophage amplification as a predictive tool for optimized maldi-tof ms-based bacterial detection.matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) is a valuable tool for rapid bacterial detection and identification but is limited by the need for relatively high cell count samples, which have been grown under strictly controlled conditions. these requirements can be eliminated by the natural infection of a viable bacterial species of interest with a host-specific phage. this produces a rapid increase in phage protein concentrations in comparison to b ...201223147819
a multi-omic systems approach to elucidating yersinia virulence mechanisms.the underlying mechanisms that lead to dramatic differences between closely related pathogens are not always readily apparent. for example, the genomes of yersinia pestis (yp) the causative agent of plague with a high mortality rate and yersinia pseudotuberculosis (ypt) an enteric pathogen with a modest mortality rate are highly similar with some species specific differences; however the molecular causes of their distinct clinical outcomes remain poorly understood. in this study, a temporal mult ...201323147219
x-ray structure of the yersinia pestis heme transporter hmuuv.hmuuv is a bacterial atp-binding cassette (abc) transporter that catalyzes heme uptake into the cytoplasm of the gram-negative pathogen yersinia pestis. we report the crystal structure of hmuuv at 3.0 å resolution in a nucleotide-free state, which features a heme translocation pathway in an outward-facing conformation, poised to accept a heme from the cognate periplasmic binding protein hmut. a new assay allowed us to determine in vitro rates of hmuuv-catalyzed heme transport into proteoliposome ...201223142986
genomic comparison of escherichia coli o104:h4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage stx2.in may of 2011, an enteroaggregative escherichia coli o104:h4 strain that had acquired a shiga toxin 2-converting phage caused a large outbreak of bloody diarrhea in europe which was notable for its high prevalence of hemolytic uremic syndrome cases. several studies have described the genomic inventory and phylogenies of strains associated with the outbreak and a collection of historical e. coli o104:h4 isolates using draft genome assemblies. we present the complete, closed genome sequences of a ...201223133618
a new generation microarray for the simultaneous detection and identification of yersinia pestis and bacillus anthracis in food.the use of microarrays as a multiple analytic system has generated increased interest and provided a powerful analytical tool for the simultaneous detection of pathogens in a single experiment. a wide array of applications for this technology has been reported. a low density oligonucleotide microarray was generated from the genetic sequences of y. pestis and b. anthracis and used to fabricate a microarray chip. the new generation chip, consisting of 2,240 spots in 4 quadrants with the capability ...201223125935
cell-mediated immune response to epitopic map (multiple antigen peptide) construct of lcrv antigen of yersinia pestis in murine model.yersinia pestis is the causative agent of plague. cellular immunity seems to play an important role in defense against this disease. the subunit vaccine based on v (lcr v) antigen has been proved to be immunogenic in animals and in humans. the multiple antigen peptide (map), incorporating all the relevant b and t cell epitopes is highly immunogenic in mice through intranasal route of immunization in plga particles containing cpg-odn as an immunoadjuvant inducing humoral and mucosal immune respon ...201223121976
a survey of rodent-borne pathogens carried by wild rattus spp. in northern vietnam.to examine the prevalence of human pathogens carried by rats in urban areas in hanoi and hai phong, vietnam, we live-trapped 100 rats in january 2011 and screened them for a panel of bacteria and viruses. antibodies against leptospira interrogans (22·0%), seoul virus (14·0%) and rat hepatitis e virus (23·0%) were detected in rats, but antibodies against yersinia pestis were not detected. antibodies against l. interrogans and seoul virus were found only in adult rats. in contrast, antibodies to r ...201323114204
rapid detection and identification of yersinia pestis from food using immunomagnetic separation and pyrosequencing.interest has recently been renewed in the possible use of y. pestis, the causative agent of plague, as a biological weapon by terrorists. the vulnerability of food to intentional contamination coupled with reports of humans having acquired plague through eating infected animals that were not adequately cooked or handling of meat from infected animals makes the possible use of y. pestis in a foodborne bioterrorism attack a reality. rapid, efficient food sample preparation and detection systems th ...201223091729
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