label-free fab and fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.a unified approach to affinity screening for fab and fc interactions of an antibody for its antigen and fcγr receptor has been developed. an antigen array is used for the fab affinity and cross-reactivity screening and protein a/g proxy is the fcγr receptor. the affinities are derived using a simple 1:1 binding model with a consistent error analysis. the association and dissociation kinetics are measured over optimised times for accurate determination. the fab/fc affinities are derived for ten a ...201526187320
resistance to innate immunity contributes to colonization of the insect gut by yersinia pestis.yersinia pestis, the causative agent of bubonic and pneumonic plague, is typically a zoonotic vector-borne disease of wild rodents. bacterial biofilm formation in the proventriculus of the flea contributes to chronic infection of fleas and facilitates efficient disease transmission. however prior to biofilm formation, ingested bacteria must survive within the flea midgut, and yet little is known about vector-pathogen interactions that are required for flea gut colonization. here we establish a d ...201526177454
backbone structure of yersinia pestis ail determined in micelles by nmr-restrained simulated annealing with implicit membrane solvation.the outer membrane protein ail (attachment invasion locus) is a virulence factor of yersinia pestis that mediates cell invasion, cell attachment and complement resistance. here we describe its three-dimensional backbone structure determined in decyl-phosphocholine (depc) micelles by nmr spectroscopy. the nmr structure was calculated using the membrane function of the implicit solvation potential, eefxpot, which we have developed to facilitate nmr structure calculations in a physically realistic ...201526143069
a new cellular target for yersinia pestis. 201526124192
early emergence of yersinia pestis as a severe respiratory pathogen.yersinia pestis causes the fatal respiratory disease pneumonic plague. y. pestis recently evolved from the gastrointestinal pathogen y. pseudotuberculosis; however, it is not known at what point y. pestis gained the ability to induce a fulminant pneumonia. here we show that the acquisition of a single gene encoding the protease pla was sufficient for the most ancestral, deeply rooted strains of y. pestis to cause pneumonic plague, indicating that y. pestis was primed to infect the lungs at a ver ...201526123398
surface plasmon resonance imaging of pathogens: the yersinia pestis paradigm.yersinia pestis, causing deadly plague, is classified as a group a bioterrorism bacterium. some recent dna-based methods were used for detection of bioterrorism agents.201526105071
cd8α(-) dendritic cells induce antigen-specific t follicular helper cells generating efficient humoral immune responses.recent studies on t follicular helper (tfh) cells have significantly advanced our understanding of t cell-dependent b cell responses. however, little is known about the early stage of tfh cell commitment by dendritic cells (dcs), particularly by the conventional cd8α(+) and cd8α(-) dc subsets. we show that cd8α(-) dcs localized at the interfollicular zone play a pivotal role in the induction of antigen-specific tfh cells by upregulating the expression of icosl and ox40l through the non-canonical ...201526095362
[establishment and evaluation of identification method for yersinia pestis and yersinia pseudotuberculosis].to establish a gene identification method of yersinia pestis and yersinia pseudotuberculosis for plague surveillance.201526080641
diverse genotypes of yersinia pestis caused plague in madagascar in 2007.yersinia pestis is the causative agent of human plague and is endemic in various african, asian and american countries. in madagascar, the disease represents a significant public health problem with hundreds of human cases a year. unfortunately, poor infrastructure makes outbreak investigations challenging.201526069964
[genotyping of yersinia pestis by multiple-locus variable number tandem repeat analysis and its epidemiological characteristics in gansu province]. 201526065103
[analysis of diversity and identification of the genovariants of plague agent strains from mongolian foci].the genetic diversity of yersinia pestis strains from the mongolian natural plague foci has been investigated. a total of 32 strains isolated from western, eastern, and central aimaks, as well as from the territory of the gobi region, have been studied. twenty-four strains belong to the main y. pestis subspecies, while eight belong to other subspecies. there is only one strain of biovar medievalis (genovariant 2.med1) among the strains of the main subspecies, while the rest of the subspecies bel ...201526027368
inactivation of avirulent yersinia pestis on food and food contact surfaces by ultraviolet light and freezing.yersinia pestis, the causative agent of plague, can occasionally be contracted as a naso-pharyngeal or gastrointestinal illness through consumption of contaminated meat. in this study, the use of 254 nm ultraviolet light (uv-c) to inactivate a multi-isolate cocktail of avirulent y. pestis on food and food contact surfaces was investigated. when a commercial uv-c conveyor was used (5 mw/cm(2)/s) 0.5 j/cm(2) inactivated >7 log of the y. pestis cocktail on agar plates. at 0.5 j/cm(2), uv-c inactiva ...201525998808
rapid detection of yersinia pestis recombinant fraction 1 capsular antigen.yersinia pestis, an infectious bacterium that is a causative agent of plague, a disease which has been shown to be one of the most feared in history and which has caused millions of deaths. the capsule-like fraction 1 (f1) antigen expressed by y. pestis is a known specific marker for the identification of the bacteria; therefore, the detection of f1 is important for y. pestis recognition. in this study, a rapid, sensitive, and specific technique, the lateral flow assay (lfa), was successfully de ...201525994256
single-nucleotide polymorphisms reveal spatial diversity among clones of yersinia pestis during plague outbreaks in colorado and the western united western north america, plague epizootics caused by yersinia pestis appear to sweep across landscapes, primarily infecting and killing rodents, especially ground squirrels and prairie dogs. during these epizootics, the risk of y. pestis transmission to humans is highest. while empirical models that include climatic conditions and densities of rodent hosts and fleas can predict when epizootics are triggered, bacterial transmission patterns across landscapes, and the scale at which y. pestis is ...201525988438
[the epidemiology and etiology research of tibetan sheep plague in qinghai plateau].to identify the epidemiology and etiology characteristics of tibetan sheep plague in qinghai plateau.201525975407
correction: yersinia pestis activates both il-1β and il-1 receptor antagonist to modulate lung inflammation during pneumonic plague. 201525970482
[human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. in the last 1500 years and during three dreaded pandemics, millions of people became victims of justinian's plague, the black death, or modern plague. today, y. pestis is endemic in natural foci of asian, african and american countries. due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. in fact, plague is currently c ...201525963643
comparison of models for bubonic plague reveals unique pathogen adaptations to the dermis.vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including yersinia pestis pathogenesis. we expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c.201525939507
thirty-two complete genome assemblies of nine yersinia species, including y. pestis, y. pseudotuberculosis, and y. enterocolitica.the genus yersinia includes three human pathogens, of which yersinia pestis is responsible for >2,000 illnesses each year. to aid in the development of detection assays and aid further phylogenetic elucidation, we sequenced and assembled the complete genomes of 32 strains (across 9 yersinia species).201525931590
transmission efficiency of the plague pathogen (y. pestis) by the flea, xenopsylla skrjabini, to mice and great gerbils.plague, a zoonotic disease caused by yersinia pestis, is characterized by its ability to persist in the plague natural foci. junggar basin plague focus was recently identified in china, with rhombomys opimus (great gerbils) and xenopsylla skrjabini as the main reservoir and vector for plague. no transmission efficiency data of x. skrjabini for y. pestis is available till now.201525928441
selective protective potency of yersinia pestis δnlpd has recently been shown that the nlpd lipoprotein is essential to yersinia pestis virulence and that subcutaneous administration of the nlpd mutant could protect mice against bubonic and pneumonic plague better than the ev vaccine strain [plos one 2009. v. 4. № 9. e7023]. in this study, similar δnlpd mutants were generated on the basis of other y. pestis parent strains, including strains from the subspecies microtus, which is avirulent to guinea pigs and humans. comparative testing confirmed ...201725927007
origins of yersinia pestis sensitivity to the arylomycin antibiotics and the inhibition of type i signal peptidase.yersinia pestis is the etiologic agent of the plague. reports of y. pestis strains that are resistant to each of the currently approved first-line and prophylactic treatments point to the urgent need to develop novel antibiotics with activity against the pathogen. we previously reported that y. pestis strain kim6+, unlike most enterobacteriaceae, is susceptible to the arylomycins, a novel class of natural-product lipopeptide antibiotics that inhibit signal peptidase i (spase). in this study, we ...201525896690
[pcr-derived technology in gene identification and typing of yersinia pestis].application of the pcr-derived technology in gene identification and genotypes of different ecotype yersinia pestis to make the high-throughput experimental results can reflect the epidemic history and compare the diversity in genome, pathogenicity, so that results from these experiments provide an important basis for clinical diagnosis, treatment and origin. but the experiment should be considered typing ability, practicality, budget and other experimental factors or conditions, because each pc ...201525876503
[study of the plasmid profiles and geographical distribution of yersinia pestis in china].to analyze the plasmid features and geographical distribution characteristics of yersinia pestis of different plague foci in china.201525876488
[genotyping techniques in yersinia pestis]. 201525876486
cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit we report the development of a new cationic liposome-hyaluronic acid (ha) hybrid nanoparticle (np) system and present our characterization of these nps as an intranasal vaccine platform using a model antigen and f1-v, a candidate recombinant antigen for yersinia pestis, the causative agent of plague. incubation of cationic liposomes composed of dotap and dope with anionic ha biopolymer led to efficient ionic complexation and formation of homogenous liposome-polymer hybrid nps, as evidenced ...201525869965
pulsed-field gel electrophoresis of yersinia pestis.yersinia pestis is a human pathogen and can cause serious disease. biosafety level 3 (bsl3) is required when handling this microorganism and all work requires a biological safety cabinet. for pulsed-field gel electrophoresis (pfge), dedicated bsl3 pfge equipment or a documented procedure that ensures that all viable bacteria are inactivated is required. all plasticware and glassware that comes into contact with the cultures should be disinfected/sterilized or disposed of in a safe manner, accord ...201525862053
enzootic plague foci, algeria, pcr sequencing of pla, glpd and rpob genes found yersinia pestis in 18/237 (8%) rodents of five species, including apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. multiple spacer typing confirmed a new orientalis variant. rodent survey should be reinforced in this country hosting reemerging plague.201525834736
rcsab is a major repressor of yersinia biofilm development through directly acting on hmscde, hmst, and hmshfrs.biofilm formation in flea gut is important for flea-borne transmission of yersinia pestis. there are enhancing factors (hmshfrs, hmscde, and hmst) and inhibiting one (hmsp) for yersinia pestis biofilm formation. the rcsab regulatory complex acts as a repressor of yesinia biofilm formation, and adaptive pseudogenization of rcsa promotes y. pestis to evolve the ability of biofilm formation in fleas. in this study, we constructed a set of isogenic strains of y. pestis biovar microtus, namely wt (rs ...201525828910
plague bacterium as a transformer species in prairie dogs and the grasslands of western north america.invasive transformer species change the character, condition, form, or nature of ecosystems and deserve considerable attention from conservation scientists. we applied the transformer species concept to the plague bacterium yersinia pestis in western north america, where the pathogen was introduced around 1900. y. pestis transforms grassland ecosystems by severely depleting the abundance of prairie dogs (cynomys spp.) and thereby causing declines in native species abundance and diversity, includ ...201525817984
[change in the habitat of yersinia pestis in the gorno-altaisk natural focus of plague].the paper analyzes the change that occurred in the habitat of the causative agent of plague in its gorno-altaisk natural focus in 1961 to 2012. since 1961 when the plague microbe was found to come from the southern slopes of the saylyugem mountain range, which are located in mongolia, to the northern slopes situated in russia, a gradual expansion of the habitat of yersenia pestis subsp. altaica had commenced in south-eastern altai. during the considered period, the area where epizootic manifesta ...201525812401
role of the phop-phoq gene regulatory system in adaptation of yersinia pestis to environmental stress in the flea digestive tract.the yersinia pestis phopq gene regulatory system is induced during infection of the flea digestive tract and is required to produce adherent biofilm in the foregut, which greatly enhances bacterial transmission during a flea bite. to understand the in vivo context of phopq induction and to determine phop-regulated targets in the flea, we undertook whole-genome comparative transcriptional profiling of y. pestis wt and δphop strains isolated from infected fleas and from temperature-matched in vitr ...201525804213
dermal neutrophil, macrophage and dendritic cell responses to yersinia pestis transmitted by fleas.yersinia pestis, the causative agent of plague, is typically transmitted by the bite of an infected flea. many aspects of mammalian innate immune response early after y. pestis infection remain poorly understood. a previous study by our lab showed that neutrophils are the most prominent cell type recruited to the injection site after intradermal needle inoculation of y. pestis, suggesting that neutrophil interactions with y. pestis may be important in bubonic plague pathogenesis. in the present ...201525781984
yersinia pestis activates both il-1β and il-1 receptor antagonist to modulate lung inflammation during pneumonic plague.pneumonic plague is the most rapid and lethal form of yersinia pestis infection. increasing evidence suggests that y. pestis employs multiple levels of innate immune evasion and/or suppression to produce an early "pre-inflammatory" phase of pulmonary infection, after which the disease is highly inflammatory in the lung and 100% fatal. in this study, we show that il-1β/il-18 cytokine activation occurs early after bacteria enter the lung, and this activation eventually contributes to pulmonary inf ...201525781467
host response during yersinia pestis infection of human bronchial epithelial cells involves negative regulation of autophagy and suggests a modulation of survival-related and cellular growth pathways.yersinia pestis (yp) causes the re-emerging disease plague, and is classified by the cdc and niaid as a highest priority (category a) pathogen. currently, there is no approved human vaccine available and advances in early diagnostics and effective therapeutics are urgently needed. a deep understanding of the mechanisms of host response to yp infection can significantly advance these three areas. we employed the reverse phase protein microarray (rpma) technology to reveal the dynamic states of ei ...201525762983
[genetic basis of the variability of nitrate reduction trait in yersinia pestis strains].the genetic basis of the varying ability to reduce nitrate in strains belonging to different biovars and subspecies of plague-causing microbe has been investigated and the inability to reduce nitrate observed in different intraspecies groups of yersinia pestis has been shown to stem from mutations in different genes involved in the expression of this trait. the absence of denitrifying activity in strains of altaica and hissarica subspecies was not due to a mutation at position 613 of the peripla ...201425715468
climate-driven introduction of the black death and successive plague reintroductions into europe.the black death, originating in asia, arrived in the mediterranean harbors of europe in 1347 ce, via the land and sea trade routes of the ancient silk road system. this epidemic marked the start of the second plague pandemic, which lasted in europe until the early 19th century. this pandemic is generally understood as the consequence of a singular introduction of yersinia pestis, after which the disease established itself in european rodents over four centuries. to locate these putative plague r ...201525713390
generation of a crispr database for yersinia pseudotuberculosis complex and role of crispr-based immunity in conjugation.the clustered regularly interspaced short palindromic repeat - crispr-associated genes (crispr-cas) system is used by bacteria and archaea against invading conjugative plasmids or bacteriophages. central to this immunity system are genomic crispr loci that contain fragments of invading dna. these are maintained as spacers in the crispr loci between direct repeats and the spacer composition in any bacterium reflects its evolutionary history. we analysed the crispr locus sequences of 335 yersinia ...201525712141
further characterization of a highly attenuated yersinia pestis co92 mutant deleted for the genes encoding braun lipoprotein and plasminogen activator protease in murine alveolar and primary human macrophages.we recently characterized the δlpp δpla double in-frame deletion mutant of yersinia pestis co92 molecularly, biologically, and immunologically. while braun lipoprotein (lpp) activates toll-like receptor-2 to initiate an inflammatory cascade, plasminogen activator (pla) protease facilitates bacterial dissemination in the host. the δlpp δpla double mutant was highly attenuated in evoking bubonic and pneumonic plague, was rapidly cleared from mouse organs, and generated humoral and cell-mediated im ...201525697665
differential regulation of the hmscde operon in yersinia pestis and yersinia pseudotuberculosis by the rcs phosphorelay system.yersinia pestis, the agent of plague, forms a biofilm in its flea vector to enhance transmission. y. pestis biofilm development is positively regulated by hmst and hmsd, encoding diguanylate cyclases (dgcs) involved in synthesis of the bacterial second messenger c-di-gmp. rcsa, encoding an auxiliary protein in rcs phosphorelay, is nonfunctional in y. pestis, while in yersinia pseudotuberculosis, rcsa is functional and represses biofilms. previously we showed that rcs phosphorelay negatively regu ...201525672461
[yersinia pestis and plague - an update].the plague of man is a severe, systemic bacterial infectious disease. without antibacterial therapy, the disease is associated with a high case fatality rate, ranging from 40% (bubonic plague) to nearly 100% (septicemic and pneumonic plague). the disease is caused by yersinia pestis, a non-motile, gram-negative, facultative anaerobic bacterium belonging to the family of enterobacteriaceae. in nature, y. pestis has been found in several rodent species and some other small animals such as shrews. ...201425643450
hexa-acylated lps-lipid a deploys the appropriate level of fibrin to confer protection through myd88.fibrin has been demonstrated to function protectively against pathogens in our previous studies, but we observed that a very high level of fibrin played a negative role during infection. we performed this research to address the complication.201525625178
dissemination of a highly virulent pathogen: tracking the early events that define infection.the series of events that occurs immediately after pathogen entrance into the body is largely speculative. key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. we sought to define major events that occur early during infection of a highly virulent pathogen. to this end, we tracked early dissemination of yersinia pestis, a highly pathogenic bacterium that causes bubonic plague in mammals. specifically, ...201525611317
combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.previously, we showed that deletion of genes encoding braun lipoprotein (lpp) and msbb attenuated yersinia pestis co92 in mouse and rat models of bubonic and pneumonic plague. while lpp activates toll-like receptor 2, the msbb acyltransferase modifies lipopolysaccharide. here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (wt) strain co92 or its lpp single and δlpp δmsbb double mutants. while the δail single mutant was minimally attenuated compared to the wt bac ...201525605764
[plasmid types, functions of yersinia pestis and their epidemiological significance]. 201425598268
age at vaccination may influence response to sylvatic plague vaccine (spv) in gunnison's prairie dogs (cynomys gunnisoni).gunnison's prairie dogs (cynomys gunnisoni) have been considered at greater risk from yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. to test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (spv) improved survival, we captured prairie dogs from a c. g. gunnisoni or "mo ...201525589000
prevalence of the generalist flea pulex simulans on black-tailed prairie dogs (cynomys ludovicianus) in new mexico, usa: the importance of considering imperfect detection.if a parasite is not detected during a survey, one of two explanations is possible: the parasite was truly absent or it was present but not detected. we fit occupancy models to account for imperfect detection when combing fleas (siphonaptera) from black-tailed prairie dogs (cynomys ludovicianus) during june-august 2012 in the vermejo park ranch, new mexico, usa. with the use of detection histories from combing events during monthly trapping sessions, we fit occupancy models for two flea species: ...201525588009
the yersinia pestis hmscde regulatory system is essential for blockage of the oriental rat flea (xenopsylla cheopis), a classic plague vector.the second messenger molecule cyclic diguanylate is essential for yersinia pestis biofilm formation that is important for blockage-dependent plague transmission from fleas to mammals. two diguanylate cyclases (dgcs) hmst and y3730 (hmsd) are responsible for biofilm formation in vitro and biofilm-dependent blockage in the oriental rat flea xenopsylla cheopis respectively. here, we have identified a tripartite signalling system encoded by the y3729-y3731 operon that is responsible for regulation o ...201525586342
in vitro antibiotic susceptibilities of yersinia pestis determined by broth microdilution following clsi vitro susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of yersinia pestis by the broth microdilution method at two temperatures, 28°c and 35°c, following clinical and laboratory standards institute (clsi) methods. the y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, β-lactams, cephalosporins, and carbapenems. only a 1-well shift was observed for the majority of antibiotics between the two tempe ...201525583720
solid-state nmr of the yersinia pestis outer membrane protein ail in lipid bilayer nanodiscs sedimented by ultracentrifugation.solid-state nmr studies of sedimented soluble proteins has been developed recently as an attractive approach for overcoming the size limitations of solution nmr spectroscopy while bypassing the need for sample crystallization or precipitation (bertini et al. proc natl acad sci usa 108(26):10396-10399, 2011). inspired by the potential benefits of this method, we have investigated the ability to sediment lipid bilayer nanodiscs reconstituted with a membrane protein. in this study, we show that nan ...201525578899
seasonal fluctuations of small mammal and flea communities in a ugandan plague focus: evidence to implicate arvicanthis niloticus and crocidura spp. as key hosts in yersinia pestis transmission.the distribution of human plague risk is strongly associated with rainfall in the tropical plague foci of east africa, but little is known about how the plague bacterium is maintained during periods between outbreaks or whether environmental drivers trigger these outbreaks. we collected small mammals and fleas over a two year period in the west nile region of uganda to examine how the ecological community varies seasonally in a region with areas of both high and low risk of human plague cases.201525573253
hmsb enhances biofilm formation in yersinia pestis.the hmshfrs operon is responsible for biosynthesis and translocation of biofilm matrix exopolysaccharide. yersinia pestis expresses the two sole diguanylate cyclases hmst and hmsd and the sole phosphodiesterase hmsp, which are specific for biosynthesis and degradation, respectively, of 3',5'-cyclic diguanosine monophosphate (c-di-gmp), a second messenger promoting exopolysaccharide production. in this work, the phenotypic assays indicates that y. pestis srna hmsb enhances the production of c-di- ...201425566205
primary case of human pneumonic plague occurring in a himalayan marmot natural focus area gansu province, china.a case of primary pneumonic plague (ppp) caused by yersinia pestis is reported. this case occurred in the largest plague area in china. the patient died after contact with a dog that had captured an infected marmot. three of 151 contacts were shown to be positive for antibody against f1 antigen by indirect hemagglutination assay, but none had clinical symptoms. there was no secondary case.201525555623
using surface-enhanced raman spectroscopy and electrochemically driven melting to discriminate yersinia pestis from y. pseudotuberculosis based on single nucleotide polymorphisms within unpurified polymerase chain reaction amplicons.the development of sensors for the detection of pathogen-specific dna, including relevant species/strain level discrimination, is critical in molecular diagnostics with major impacts in areas such as bioterrorism and food safety. herein, we use electrochemically driven denaturation assays monitored by surface-enhanced raman spectroscopy (sers) to target single nucleotide polymorphisms (snps) that distinguish dna amplicons generated from yersinia pestis, the causative agent of plague, from the cl ...201525551670
the trophic responses of two different rodent-vector-plague systems to climate change.plague, the causative agent of three devastating pandemics in history, is currently a re-emerging disease, probably due to climate change and other anthropogenic changes. without understanding the response of plague systems to anthropogenic or climate changes in their trophic web, it is unfeasible to effectively predict years with high risks of plague outbreak, hampering our ability for effective prevention and control of the disease. here, by using surveillance data, we apply structural equatio ...201525540277
lps modification promotes maintenance of yersinia pestis in fleas.yersinia pestis, the causative agent of plague, can be transmitted by fleas by two different mechanisms: by early-phase transmission (ept), which occurs shortly after flea infection, or by blocked fleas following long-term infection. efficient flea-borne transmission is predicated upon the ability of y. pestis to be maintained within the flea. signature-tagged mutagenesis (stm) was used to identify genes required for y. pestis maintenance in a genuine plague vector, xenopsylla cheopis. the stm s ...201525533446
pneumonic plague outbreak, northern madagascar, 2011.yersinia pestis, the causative agent of plague, is endemic to madagascar, particularly to the central highlands. although plague has not been previously reported in northern madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. molecular typing of y. pestis isolated from 2 survivors and 5 rattus rattus rat samples identified the madaga ...201525530466
comparison of virulence between the yersinia pestis microtus 201, an avirulent strain to humans, and the vaccine strain ev in rhesus macaques, macaca mulatta.our previous study has demonstrated that yersinia pestis microtus 201 is a low virulent strain to the chinese-origin rhesus macaques, macaca mulatta, and can protect it against high dose of virulent y. pestis challenge by subcutaneous route. to investigate whether the y. pestis microtus 201 can be used as a live attenuated vaccine candidate, in this study its intravenous virulence was determined and compared with the live attenuated vaccine strain ev in the chinese-origin rhesus macaque model. t ...201425483697
a new class of salicylic acid derivatives for inhibiting yoph of yersinia pestis.previously, we identified a class of salicylic acid derivatives that display inhibitory activity against the protein tyrosine phosphatase yoph from yersinia pestis. because docking study suggested that the large phenyl ring attaching to the salicylic acid core might be exposed to the solvent and might not contribute significantly to binding, we have developed a new class of compounds that no longer contain this phenyl ring. we first devised a synthetic scheme for the compounds and then developed ...201425468042
kinetic epitope mapping of monoclonal antibodies raised against the yersinia pestis virulence factor lcrv.five monoclonal antibodies, mab7.3, mab29.3, mab46.3, mab12.3 and mab36.3, raised to the lcrv virulence factor from yersinia pestis were characterised for their fab affinity against the purified protein and their fc affinity to protein a/g as a proxy for the fcγr receptor. kinetic measurements were performed label-free in a localised particle plasmon array reader. the fc-proteina/g complex first-order half-life was determined for each antibody and fell in the range of 0.8-3.8h. the fab first-ord ...201525461137
silencing urease: a key evolutionary step that facilitated the adaptation of yersinia pestis to the flea-borne transmission route.the arthropod-borne transmission route of yersinia pestis, the bacterial agent of plague, is a recent evolutionary adaptation. yersinia pseudotuberculosis, the closely related food-and water-borne enteric species from which y. pestis diverged less than 6,400 y ago, exhibits significant oral toxicity to the flea vectors of plague, whereas y. pestis does not. in this study, we identify the yersinia urease enzyme as the responsible oral toxin. all y. pestis strains, including those phylogenetically ...201425453069
influence of the lipid membrane environment on structure and activity of the outer membrane protein ail from yersinia pestis.the surrounding environment has significant consequences for the structural and functional properties of membrane proteins. while native structure and function can be reconstituted in lipid bilayer membranes, the detergents used for protein solubilization are not always compatible with biological activity and, hence, not always appropriate for direct detection of ligand binding by nmr spectroscopy. here we describe how the sample environment affects the activity of the outer membrane protein ail ...201525433311
purification and biochemical characterisation of glmu from yersinia pestis.antibiotic resistance has emerged as a real threat to mankind, rendering many compounds ineffective in the fight against bacterial infection, including for significant diseases such as plague caused by yersinia pestis. essential genes have been identified as promising targets for inhibiting with new classes of compounds. previously, the gene encoding the bifunctional udp-n-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate n-acetyltransferase enzyme glmu was confirmed as an essential ge ...201525417006
crp acts as a transcriptional repressor of the ypo1635-phopq-ypo1632 operon in yersinia pestis.yersinia pestis is the causative agent of plague. both cyclic amp receptor protein (crp) and phop are involved in regulating virulence-related genes in y. pestis. the phopq loci are transcribed as two distinct operons, ypo1635-phopq-ypo1632 and phopq-ypo1632. in the present work, the regulation of the first operon by crp was investigated using primer extension, lacz fusion, electrophoretic mobility shift assay, and dnase i footprinting assays. the results showed that crp bound to a dna region ov ...201525413606
[genotyping on yersinia pestis isolated from yunnan province by clustered-regularly-interspaced-short palindromic-repeats]. 201425394344
[regional genotyping and the geographical distribution regarding yersinia pestis isolates in china].to type yersinia (y.) pestis isolates under different regions (dfr) and to observe their geographical distributions in china.201425376688
caspase-3 mediates the pathogenic effect of yersinia pestis yopm in liver of c57bl/6 mice and contributes to yopm's function in spleen.the virulence protein yopm of the plague bacterium yersinia pestis has different dominant effects in liver and spleen. previous studies focused on spleen, where yopm inhibits accumulation of inflammatory dendritic cells. in the present study we focused on liver, where pmn function may be directly undermined by yopm without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. mice were infected with parent and δyopm-1 y. pestis kim ...201425372388
transcriptional regulation of the waaae-coad operon by phop and rcsab in yersinia pestis biovar microtus. 201425359466
yersinia pestis targets neutrophils via complement receptor 3.yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type iii secretion system. yet, the mechanism for target cell selection remains a mystery. here we investigate the interaction of yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. we find that interactions with primary immune cells rely on multiple factors. first, the bacterial adhesin ...201525359083
draft genome sequences of yersinia pestis strains from the 1994 plague epidemic of surat and 2002 shimla outbreak in india.we report the first draft genome sequences of the strains of plague-causing bacteria, yersinia pestis, from india. these include two strains from the surat epidemic (1994), one strain from the shimla outbreak (2002) and one strain from the plague surveillance activity in the deccan plateau region (1998). genome size for all four strains is ~4.49 million bp with 139-147 contigs. average sequencing depth for all four genomes was 21x.201425320451
a non-stationary relationship between global climate phenomena and human plague incidence in madagascar.plague, a zoonosis caused by yersinia pestis, is found in asia and the americas, but predominantly in africa, with the island of madagascar reporting almost one third of human cases worldwide. plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the el niño southern oscillation (enso). the effects of enso on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the indian ocean dipole ( ...201425299064
caenorhabditis elegans bacterial pathogen resistant bus-4 mutants produce altered mucins.caenorabditis elegans bus-4 glycosyltransferase mutants are resistant to infection by microbacterium nematophilum, yersinia pestis and yersinia pseudotuberculosis and have altered susceptibility to two leucobacter species verde1 and verde2. our objective in this study was to define the glycosylation changes leading to this phenotype to better understand how these changes lead to pathogen resistance. we performed maldi-tof ms, tandem ms and gc/ms experiments to reveal fine structural detail for t ...201425296196
effect of nanovaccine chemistry on humoral immune response kinetics and maturation.acute respiratory infections represent a significant portion of global morbidity and mortality annually. there is a critical need for efficacious vaccines against respiratory pathogens. to vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. we have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective ...201425285425
[development and testing of an enzyme immunoassay-based monoclonal test system for the detection of the yersinia pestis v antigen].an enzyme immunoassay-based test system for y. pestis v antigen detection was developed. the specificity and sensitivity of this system met the requirements for medical immunobiological preparations for the identification of causative agents of highly fatal diseases. the sensitivity of the test system was assessed, and its high specificity was also demonstrated: the test system did not detect bacterial cells of closely related (four y. pseudotuberculosis strains) and heterologous microorganism s ...201425272741
differential contribution of tryptophans to the folding and stability of the attachment invasion locus transmembrane β-barrel from yersinia pestis.attachment invasion locus (ail) protein of yersinia pestis is a crucial outer membrane protein for host invasion and determines bacterial survival within the host. despite its importance in pathogenicity, surprisingly little is known on ail biophysical properties. we investigate the contribution of micelle concentrations and interface tryptophans on the ail β-barrel refolding and unfolding processes. our results reveal that barrel folding is surprisingly independent of micelle amounts, but proce ...201425266561
dynamics of crispr loci in microevolutionary process of yersinia pestis strains.the potential use of crispr loci genotyping to elucidate population dynamics and microevolution of 146 yersinia pestis strains from different biovars and locations was investigated in this work. the majority of strains from the orientalis biovar presented specific spacer arrays, allowing for the establishment of a crispr signature for their respective isolates. twenty-one new spacers were found in the y. pestis strains from plague foci in brazil. ninety-three (64%) strains were grouped in the g1 ...201425265542
yersinia pestis and the three plague pandemics--authors' reply. 201425253401
yersinia pestis and the three plague pandemics. 201425253400
yersinia pestis and the three plague pandemics. 201425253399
the multifaceted nature of nlrp12.nlrs are a class of cytoplasmic prrs with various functions, ranging from pathogen/damage sensing to the modulation of inflammatory signaling and transcriptional control of mhc and related genes. in addition, some nlrs have been implicated in preimplantation and prenatal development. nlrp12 (also known as rno, pypaf7, and monarch-1), a member of the family containing an n-terminal pyd, a nbd, and a c-terminal lrr region, is one of the first described nlr proteins whose role remains controversial ...201425249449
s1p-dependent trafficking of intracellular yersinia pestis through lymph nodes establishes buboes and systemic infection.pathologically swollen lymph nodes (lns), or buboes, characterize yersinia pestis infection, yet how they form and function is unknown. we report that colonization of the draining ln (dln) occurred due to trafficking of infected dendritic cells and monocytes in temporally distinct waves in response to redundant chemotactic signals, including through ccr7, ccr2, and sphingosine-1-phospate (s1p) receptors. retention of multiple subsets of phagocytes within peripheral lns using the s1p receptor ago ...201425238098
plague's partners in crime.the hallmark of bubonic plague is the presence of grotesquely swollen lymph nodes, called buboes. this frenzied inflammatory response to yersinia pestis is poorly understood. in this issue of immunity, st. john et al. (2014) explore the mechanism by which y. pestis spreads and thus leads to this striking lymphadenopathy.201425238090
the importance of the magnesium transporter mgtb for virulence of yersinia pseudotuberculosis and yersinia has been shown to be an important signal controlling gene regulation via the phopq two-component regulatory system for a range of gram-negative bacteria, including yersinia pestis and yersinia pseudotuberculosis. the magnesium ion transporter mgtb is part of the complex phopq regulon, being upregulated in response to low mg(2+). despite the presence of other mg(2+) transport systems in yersinia, inactivation of mgtb had a significant effect on the ability of the bacteria to scavenge this ...201425234474
functional characterization of yersinia pestis aerobic glycerol metabolism.yersinia pestis biovar orientalis isolates have lost the capacity to ferment glycerol. herein we provide experimental validation that a 93 bp in-frame deletion within the glpd gene encoding the glycerol-3-phosphate dehydrogenase present in all biovar orientalis strains is sufficient to disrupt aerobic glycerol fermentation. furthermore, the inability to ferment glycerol is often insured by a variety of additional mutations within the glpfkx operon which prevents glycerol internalization and conv ...201425220241
yersinia murine toxin is not required for early-phase transmission of yersinia pestis by oropsylla montana (siphonaptera: ceratophyllidae) or xenopsylla cheopis (siphonaptera: pulicidae).plague, caused by yersinia pestis, is characterized by quiescent periods punctuated by rapidly spreading epizootics. the classical 'blocked flea' paradigm, by which a blockage forms in the flea's proventriculus on average 1-2 weeks post-infection (p.i.), forces starving fleas to take multiple blood meals, thus increasing opportunities for transmission. recently, the importance of early-phase transmission (ept), which occurs prior to blockage formation, has been emphasized during epizootics. whil ...201425187626
genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of yersinia pestis in deep tissue.rapid growth in deep tissue is essential to the high virulence of yersinia pestis, causative agent of plague. to better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (tn-seq) to systematically probe the y. pestis genome for elements contributing to fitness during infection. more than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent y. pestis. each mutant ...201425139902
chromosomal rearrangement features of yersinia pestis strains from natural plague foci in china.the yersinia pestis chromosome contains a large variety and number of insert sequences that have resulted in frequent chromosome rearrangement events. to identify the chromosomal rearrangement features of y. pestis strains from five typical plague foci in china and study spontaneous dna rearrangements potentially stabilized in certain lineages of y. pestis genomes, we examined the linking mode of locally collinear blocks (lcbs) in 30 y. pestis strains by a polymerase chain reaction-based method. ...201425114008
functional and structural analysis of hica3-hicb3, a novel toxin-antitoxin system of yersinia pestis.the mechanisms involved in the virulence of yersinia pestis, the plague pathogen, are not fully understood. in previous research, we found that a y. pestis mutant lacking the hicb3 (ypo3369) putative orphan antitoxin was attenuated for virulence in a murine model of bubonic plague. toxin-antitoxin systems (tass) are widespread in prokaryotes. most bacterial species possess many tass of several types. in type ii tass, the toxin protein is bound and neutralized by its cognate antitoxin protein in ...201425112480
a yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.bacterial proteins destined for the tat pathway are folded before crossing the inner membrane and are typically identified by an n-terminal signal peptide containing a twin arginine motif. translocation by the tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. in the fully virulent co92 strain of yersinia pestis, the tata gene was deleted. the mutant was assayed for loss of virule ...201425101850
inactivation of avirulent pgm(+) and δpgm yersinia pestis by ultraviolet light (uv-c).yersinia pestis is the causative agent of bubonic plague. though not considered a foodborne pathogen, y. pestis can survive, and even grow, in some foods, and the foodborne route of transmission is not without precedent. as such, concerns exist over the possible intentional contamination of foods with this deadly pathogen. here we report the inactivation of avirulent (pyv-minus) strains of y. pestis by ultraviolet light (uv-c, 254 nm). two strains of y. pestis containing an intact pgm virulence ...201425084659
transcriptomic response to yersinia pestis: rig-i like receptor signaling response is detrimental to the host against plague.bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. in this study, rna-sequencing technology was used to analyze the responses of human monocytes thp1 to yersinia pestis infection. over 6000 genes were differentially expressed over the 12 h infection. kinetic responses of pathogen recognition receptor signaling pathways, apoptosis, antigen processing, and presentation pathway and coagulation system were analyzed in detail. among them, r ...201425064677
yersinia pestis in pulex irritans fleas during plague outbreak, madagascar. 201425061697
improving the th1 cellular efficacy of the lead yersinia pestis rf1-v subunit vaccine using sa-4-1bbl as a novel adjuvant.the lead candidate plague subunit vaccine is the recombinant fusion protein rf1-v adjuvanted with alum. while alum generates th2 regulated robust humoral responses, immune protection against yersinia pestis has been shown to also involve th1 driven cellular responses. therefore, the rf1-v-based subunit vaccine may benefit from an adjuvant system that generates a mixed th1 and humoral immune response. we herein assessed the efficacy of a novel sa-4-1bbl costimulatory molecule as a th1 adjuvant to ...201425045812
adenosine a1 receptor antagonist, l-97-1, improves survival and protects the kidney in a rat model of cecal ligation and puncture induced sepsis.previously it was reported that combining antibiotics with l-97-1, an adenosine a1 receptor antagonist, significantly improves survival and blocks acute lung injury induced by yersinia pestis co 99 in a rat model of pneumonic plague. in the current studies using a conscious rat model of cecal ligation and puncture (clp) sepsis, l-97-1 was administered in daily intravenous infusions in combination with antibiotics to simulate the use of l-97-1 as an anti-sepsis therapeutic in the clinical setting ...201425041842
multiple roles of myd88 in the immune response to the plague f1-v vaccine and in protection against an aerosol challenge of yersinia pestis co92 in mice.the current candidate vaccine against yersinia pestis infection consists of two subunit proteins: the capsule protein or f1 protein and the low calcium response v protein or v-antigen. little is known of the recognition of the vaccine by the host's innate immune system and how it affects the acquired immune response to the vaccine. thus, we vaccinated toll-like receptor (tlr) 2, 4, and 2/4-double deficient, as well as signal adaptor protein myd88-deficient mice. we found that tlr4 and myd88 appe ...201424995344
iqgap1 is important for activation of caspase-1 in macrophages and is targeted by yersinia pestis type iii effector yopm.yopm is a leucine-rich repeat (lrr)-containing effector in several yersinia species, including yersinia pestis and y. pseudotuberculosis. different yersinia strains encode distinct yopm isoforms with variable numbers of lrrs but conserved c-terminal tails. a 15-lrr isoform in y. pseudotuberculosis ypiii was recently shown to bind and inhibit caspase-1 via a yltd motif in lrr 10, and attenuation of yopm(-) ypiii was reversed in mice lacking caspase-1, indicating that caspase-1 inhibition is a maj ...201424987096
plague epizootic cycles in central asia.infection thresholds, widely used in disease epidemiology, may operate on host abundance and, if present, on vector abundance. for wildlife populations, host and vector abundances often vary greatly across years and consequently the threshold may be crossed regularly, both up- and downward. moreover, vector and host abundances may be interdependent, which may affect the infection dynamics. theory predicts that if the relevant abundance, or combination of abundances, is above the threshold, then ...201424966205
yersinia pseudotuberculosis st42 (o:1) strain misidentified as yersinia pestis by mass spectrometry analysis.we report here the draft sequence of strain ceb14_0017, alias hiad_dup, recovered from a human patient and initially identified as yersinia pestis by mass spectrometry analysis. genotyping based on tandem repeat polymorphism assigned the strain to yersinia pseudotuberculosis sequence type 42 (st42). the total assembly length is 4,894,739 bp.201424926044
genetic variations of live attenuated plague vaccine strains (yersinia pestis ev76 lineage) during laboratory passages in different countries.plague, one of the most devastating infectious diseases in human history, is caused by the bacterial species yersinia pestis. a live attenuated y. pestis strain (ev76) has been widely used as a plague vaccine in various countries around the world. here we compared the whole genome sequence of an ev76 strain used in china (ev76-cn) with the genomes of y. pestis wild isolates to identify genetic variations specific to the ev76 lineage. we identified 6 snps and 6 indels (insertions and deletions) d ...201424905600
bartonella spp. and yersinia pestis reservoirs, cusco, peru. 201424857245
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