isolation of francisella tularensis and yersinia pestis from blood cultures by plasma purification and immunomagnetic separation accelerates antibiotic susceptibility determination.the early symptoms of tularemia and plague, which are caused by francisella tularensis and yersinia pestis infection, respectively, are common to other illnesses, resulting in a low index of suspicion among clinicians. moreover, because these diseases can be treated only with antibiotics, rapid isolation of the bacteria and antibiotic susceptibility testing (ast) are preferable. blood cultures of patients may serve as a source for bacteria isolation. however, due to the slow growth rates of f. t ...201728293231
a field study of plague and tularemia in rodents, western iran.kurdistan province in iran is a historical focus for plague and tularemia. this study aimed at assessing the current status of these two foci by studying their rodent reservoirs.201728165869
β-hydroxyacyl-acyl carrier protein dehydratase (fabz) from francisella tularensis and yersinia pestis: structure determination, enzymatic characterization, and cross-inhibition studies.the bacterial system for fatty acid biosynthesis (fas) contains several enzymes whose sequence and structure are highly conserved across a vast array of pathogens. this, coupled with their low homology and difference in organization compared to the equivalent system in humans, makes the fas pathway an excellent target for antimicrobial drug development. to this end, we have cloned, expressed, and purified the β-hydroxyacyl-acyl carrier protein dehydratase (fabz) from both francisella tularensis ...201626818694
[maldi-tof ms analysis for yersinia pestis, vibrio cholera, and francisella tularensis identification].numerous studies showed that a new technology for the clinical microbiology laboratories, matrix-assisted laser desorption ionization--time of flight mass spectrometry (maldi-tof ms), allows fast, accurate, and effective identification of most clinically relevant microorganisms to be implemented. in the present review, we discuss applications of this approach for identification and typing of extremely dangerous pathogens--yersinia pestis, vibrio cholera, and francisella tularensis, including the ...201526182660
[effect of serotonin on immune competent cells of biomodels under the conditions of vaccination against plague and tularemia].comparative evaluation of the effect of exogenic serotonin on the development of apoptosis and proliferative activity of immune system cells of biomodels in vivo and in vitro in the dynamic of immunity forming against plague and tularemia.201525842950
helicobacter himalayensis sp. nov. isolated from gastric mucosa of marmota himalayana.a gram-stain-negative, microaerophilic strain, 80(ys1)t, with a spiral-shaped morphology and 1-2 sheathed flagella at each end of the cells was isolated from the gastric mucosa of marmota himalayana, the animal reservoir of yersinia pestis in china, on the qinghai-tibet plateau. the strain grew at 30, 35 and 42 °c, but not at 25 °c. growth was in the form of a thinly spreading film on brain heart infusion agar containing 8 % sheep blood under microaerobic conditions. the strain did not hydrolyse ...201525736414
a survey of rodent-borne pathogens carried by wild rattus spp. in northern 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
a replication-defective human type 5 adenovirus-based trivalent vaccine confers complete protection against plague in mice and nonhuman primates.currently, no plague vaccine exists in the united states for human use. the capsular antigen (caf1 or f1) and two type 3 secretion system (t3ss) components, the low-calcium-response v antigen (lcrv) and the needle protein yscf, represent protective antigens of yersinia pestis we used a replication-defective human type 5 adenovirus (ad5) vector and constructed recombinant monovalent and trivalent vaccines (rad5-lcrv and rad5-yfv) that expressed either the codon-optimized lcrv or the fusion gene d ...201627170642
occurrence and analysis of irp2 virulence gene in isolates of klebsiella pneumoniae and enterobacter spp. from microbiota and hospital and community-acquired infections.eighty-five isolates of klebsiella pneumoniae and enterobacter spp., originating from hospital- and community-acquired infections and from oropharyngeal and faecal microbiota from patients in recife-pe, brazil, were analyzed regarding the presence of irp2 gene. this is a yersinia typical gene involved in the synthesis of siderophore yersiniabactin. dna sequencing confirmed the identity of irp2 gene in five k. pneumoniae, five enterobacter aerogenes and one enterobacter amnigenus isolates. to our ...201627133266
structural and functional characterization of the lps transporter lptde from gram-negative pathogens.incorporation of lipopolysaccharide (lps) into the outer membrane of gram-negative bacteria is essential for viability, and is accomplished by a two-protein complex called lptde. we solved crystal structures of the core lptde complexes from yersinia pestis, klebsiella pneumoniae, pseudomonas aeruginosa, and a full-length structure of the k. pneumoniae lptde complex. our structures adopt the same plug and 26-strand β-barrel architecture found recently for the shigella flexneri and salmonella typh ...201627161977
in vivo transcriptional profiling of yersinia pestis reveals a novel bacterial mediator of pulmonary inflammation.inhalation of yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. the disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses that ultimately prove fatal. very little is known about the bacterial and host factors that contribute to the rapid biphasic progression of pneumonic plague. in this work, we analyzed the in vivo transcription k ...201525691593
intranasal delivery of a protein subunit vaccine using a tobacco mosaic virus platform protects against pneumonic plague.yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. it has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. when aerosolized, y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. currently, there is no fda approved plague vaccine. the current lead vaccine candidate, a parenterally administered protein ...201627745954
enumeration of bacteriophage particles: comparative analysis of the traditional plaque assay and real-time qpcr- and nanosight-based assays.bacteriophages are increasingly being utilized and considered for various practical applications, ranging from decontaminating foods and inanimate surfaces to human therapy; therefore, it is important to determine their concentrations quickly and reliably. traditional plaque assay (pa) is the current "gold standard" for quantitating phage titers. however, it requires at least 18 h before results are obtained, and they may be significantly influenced by various factors. therefore, two alternative ...201122334864
structure-activity relationships of the mepicides: n-acyl and o-linked analogs of fr900098 as inhibitors of dxr from mycobacterium tuberculosis and yersinia pestis.despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. the methylerythritol phosphate (mep) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. we and others have explored inhibitors of the mep pathway as novel antibacterial agents. mycobacterium tuberculosis, the ...201627676224
paleogenetics and past infections: the two faces of the coin of human immune evolution.with the advent of next-generation sequencing, paleogenetics has considerably expanded over the past few years and notably encompassed the characterization of the genomes of archaic humans who lived more than 30,000 years ago. these paleogenetics investigations have revealed that admixture between modern and archaic humans occurred, with neanderthals having contributed to 1.5% to 2.1% of modern eurasian genomes, and denisovans to 3% to 6% of modern melanesian genomes and to approximately 0.2% of ...201627337483
selectivity of pyridone- and diphenyl ether-based inhibitors for the yersinia pestis fabv enoyl-acp reductase.the enoyl-acp reductase (enr) catalyzes the last reaction in the elongation cycle of the bacterial type ii fatty acid biosynthesis (fas-ii) pathway. while the fabi enr is a well-validated drug target in organisms such as mycobacterium tuberculosis and staphylococcus aureus, alternate enr isoforms have been discovered in other pathogens, including the fabv enzyme that is the sole enr in yersinia pestis (ypfabv). previously, we showed that the prototypical enr inhibitor triclosan was a poor inhibi ...201627136302
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
the origin of behçet's disease geoepidemiology: possible role of a dual microbial-driven genetic is recognised that the genetic profiles that give rise to chronic inflammatory diseases, under the influence of environmental agents, might have been implicated in the host defence mechanism against lethal infections in the past. behçet's disease (bd) is an immune-mediated inflammatory disease, expressed as vasculitis, triggered by environmental factors in genetically susceptible individuals. we carried out a review of published data to draw up an evolutionary adaptation model, as author's pe ...201724447390
replacing arginine 33 for alanine in the hemophore hasa from pseudomonas aeruginosa causes closure of the h32 loop in the apo-protein.previous characterization of hemophores from serratia marcescens (hasas), pseudomonas aeruginosa (hasap), and yersinia pestis (hasayp) showed that hemin binds between two loops, where it is axially coordinated by h32 and y75. the y75 loop is structurally conserved in all three hemophores and harbors conserved ligand y75. the other loop contains h32 in hasas and hasap, but a noncoordinating q32 in hasayp. the h32 loop in apo-hasas and apo-hasap is in an open conformation, which places h32 about 3 ...201627074415
nuclear magnetic resonance characterization of the type iii secretion system tip chaperone protein pcrg of pseudomonas aeruginosa.lung infection with pseudomonas aeruginosa is the leading cause of death among cystic fibrosis patients. to initiate infection, p. aeruginosa assembles a protein nanomachine, the type iii secretion system (t3ss), to inject bacterial proteins directly into target host cells. an important regulator of the p. aeruginosa t3ss is the chaperone protein pcrg, which forms a complex with the tip protein, pcrv. in addition to its role as a chaperone to the tip protein, pcrg also regulates protein secretio ...201526451841
mesaconase activity of class i fumarase contributes to mesaconate utilization by burkholderia xenovorans.pseudomonas aeruginosa, yersinia pestis, and many other bacteria are able to utilize the c5-dicarboxylic acid itaconate (methylenesuccinate). itaconate degradation starts with its activation to itaconyl coenzyme a (itaconyl-coa), which is further hydrated to (s)-citramalyl-coa, and citramalyl-coa is finally cleaved into acetyl-coa and pyruvate. the xenobiotic-degrading betaproteobacterium burkholderia xenovorans possesses a p. aeruginosa-like itaconate degradation gene cluster and is able to gro ...201526070669
the n terminus of type iii secretion needle protein yscf from yersinia pestis functions to modulate innate immune responses.the type iii secretion system is employed by many pathogens, including the genera yersinia, shigella, pseudomonas, and salmonella, to deliver effector proteins into eukaryotic cells. the injectisome needle is formed by the polymerization of a single protein, e.g., yscf (yersinia pestis), pscf (pseudomonas aeruginosa), prgi (salmonella enterica spi-1), ssag (salmonella enterica spi-2), or mxih (shigella flexneri). in this study, we demonstrated that the n termini of some needle proteins, particul ...201525644012
bacterial itaconate degradation promotes pathogenicity.itaconate (methylenesuccinate) was recently identified as a mammalian metabolite whose production is substantially induced during macrophage activation. this compound is a potent inhibitor of isocitrate lyase, a key enzyme of the glyoxylate cycle, which is a pathway required for the survival of many pathogens inside the eukaryotic host. here we show that numerous bacteria, notably many pathogens such as yersinia pestis and pseudomonas aeruginosa, have three genes for itaconate degradation. they ...201424657929
replacing the axial ligand tyrosine 75 or its hydrogen bond partner histidine 83 minimally affects hemin acquisition by the hemophore hasap from pseudomonas aeruginosa.hemophores from pseudomonas aeruginosa (hasap), serratia marcescens (hasasm), and yersinia pestis (hasayp) bind hemin between two loops. one of the loops harbors conserved axial ligand tyr75 (y75 loop) in all three structures, whereas the second loop (h32 loop) contains axial ligand his32 in hasap and hasasm, but a noncoordinating gln32 in hasayp. binding of hemin to the y75 loop of hasap or hasasm causes a large rearrangement of the h32 loop that allows his32 coordination. the q32 loop in apo-h ...201424625274
a type iii secretion system inhibitor targets yopd while revealing differential regulation of secretion in calcium-blind mutants of yersinia pestis.numerous gram-negative pathogens rely upon type iii secretion (t3s) systems to cause disease. several small-molecule inhibitors of the type iii secretion systems have been identified; however, few targets of these inhibitors have been elucidated. here we report that 2,2'-thiobis-(4-methylphenol) (compound d), inhibits type iii secretion in yersinia pestis, yersinia pseudotuberculosis, and pseudomonas aeruginosa. yopd, a protein involved in the formation of the translocon and regulatory processes ...201424247143
outbreak of human pneumonic plague with dog-to-human and possible human-to-human transmission--colorado, june-july 2014.on july 8, 2014, the colorado department of public health and environment (cdphe) laboratory identified yersinia pestis, the bacterium that causes plague, in a blood specimen collected from a man (patient a) hospitalized with pneumonia. the organism had been previously misidentified as pseudomonas luteola by an automated system in the hospital laboratory. an investigation led by tri-county health department (tchd) revealed that patient a's dog had died recently with hemoptysis. three other perso ...201525928467
a recombinant raccoon poxvirus vaccine expressing both yersinia pestis f1 and truncated v antigens protects animals against lethal previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rrcn) expressing yersinia pestis antigens (f1 and v307-a truncated version of the v protein) provided superior protection against plague challenge compared to individual single antigen constructs. to reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (spv) control program for prairie dogs, a dual antigen construct is more ...201426344891
detection of rickettsia felis, rickettsia typhi, bartonella species and yersinia pestis in fleas (siphonaptera) from africa.little is known about the presence/absence and prevalence of rickettsia spp, bartonella spp. and yersinia pestis in domestic and urban flea populations in tropical and subtropical african countries.201425299702
three new species of fleas belonging to the genus macrostylophora from the three-striped ground squirrel, lariscus insignis, in java.three new species of fleas belonging to the genus macrostylophora (siphonaptera, ceratophyllidae) are described from the three-striped ground squirrel, lariscus insignis, from tjibodas, west java (jawa barat), indonesia at an elevation of 1500 m. macrostylophora larisci sp. n. is described from three male specimens, macrostylophora debilitata sp. n. is described from one male and macrostylophora wilsoni sp. n. is described from one female. non-genital morphological characters of the female speci ...201424810381
beyond helper phage: using "helper cells" to select peptide affinity ligands.peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. however, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. when selecting peptidic ligands from display libraries, it is important to: 1) ensure efficient display; 2) maximize the ability to select high affinity ligands; and 3) minimize the effect of the display context on binding. the "helper cell" packaging system has been described as a ...201627626637
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
bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells.bacterial pathogens have evolved specific effector proteins that, by interfacing with host kinase signalling pathways, provide a mechanism to evade immune responses during infection. although these effectors contribute to pathogen virulence, we realized that they might also serve as valuable synthetic biology reagents for engineering cellular behaviour. here we exploit two effector proteins, the shigella flexneri ospf protein and yersinia pestis yoph protein, to rewire kinase-mediated responses ...201222820255
fibrinolytic and procoagulant activities of yersinia pestis and salmonella enterica.pla of the plague bacterium yersinia pestis and pgte of the enteropathogen salmonella enterica are surface-exposed, transmembrane β-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, and both proteases are established virulence factors. pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and α2-antiplasmin, inactivation of the thrombin-activable fibrinolysi ...201526149012
a bivalent typhoid live vector vaccine expressing both chromosome- and plasmid-encoded yersinia pestis antigens fully protects against murine lethal pulmonary plague attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. a major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without overattenuating the live vaccine. here we used a live attenuated salmonella enterica serovar typhi strain to create a bivalent mucosal plague vaccine that produces both the protective f1 capsular antigen of yersinia pestis and the lcrv ...201525332120
bacterial pathogens activate plasminogen to breach tissue barriers and escape from innate immunity.both coagulation and fibrinolysis are tightly connected with the innate immune system. infection and inflammation cause profound alterations in the otherwise well-controlled balance between coagulation and fibrinolysis. many pathogenic bacteria directly exploit the host's hemostatic system to increase their virulence. here, we review the capacity of bacteria to activate plasminogen. the resulting proteolytic activity allows them to breach tissue barriers and evade innate immune defense, thus pro ...201626485450
host-parasite associations in small mammal communities in semiarid savanna ecosystems of east africa.despite the established importance of rodents as reservoirs of vector-borne zoonoses in east africa, there is relatively limited information regarding the infestation parameters and host associations of ectoparasites that vector many such pathogens among small mammals in this region. between 2009 and 2013, small mammals were live-trapped in the semiarid savanna of kenya. a subset of these individual hosts, including 20 distinct host taxa, was examined for ectoparasites, which were identified to ...201627113102
bacteria and vampirism in cinema.a vampire is a non-dead and non-alive chimerical creature, which, according to various folklores and popular superstitions, feeds on blood of the living to draw vital force. vampires do not reproduce by copulation, but by bite. vampirism is thus similar to a contagious disease contracted by intravascular inoculation with a suspected microbial origin. in several vampire films, two real bacteria were staged, better integrated than others in popular imagination: yersinia pestis and treponema pallid ...201323916557
stabilization of biothreat diagnostic samples through vitrification matrices.diagnostics for biothreat agents require sample shipment to reference labs for diagnosis of disease; however high/fluctuating temperatures during sample transport negatively affect sample quality and results. vitrification additives preserve sample integrity for molecular-based assay diagnostics in the absence of refrigeration by imparting whole molecule stability to a plethora of environmental insults. therefore, we have evaluated commercially available vitrification matrices' (biomatrica's clo ...201424742968
[application of pulsed field gel electrophoresis for molecular typing of causative agents of especially dangerous infections].the macro-restriction analysis of the microorganism dna with the use of gel electrophoresis in pulsed field (pfge typing, pulse electrophoresis) is applied in molecular biology to study the clonal structure and typing of causative agents of infectious diseases. determining the degree of the relationship and definition of epidemiological interrelations of studied isolates, as well as studying the evolutionary history of pathogens, is performed by comparing dna restriction patterns. this review pr ...201526665739
ancient pathogen dna in archaeological samples detected with a microbial detection array.ancient human remains of paleopathological interest typically contain highly degraded dna in which pathogenic taxa are often minority components, making sequence-based metagenomic characterization costly. microarrays may hold a potential solution to these challenges, offering a rapid, affordable, and highly informative snapshot of microbial diversity in complex samples without the lengthy analysis and/or high cost associated with high-throughput sequencing. their versatility is well established ...201424603850
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
[detection of yersinia enterocolitica bacteriophage phiye-f10 lysis spectrum and analysis of the relationship between lysis ability and virulence gene of yersinia enterocolitica].to determine the lysis spectrum of yersinia enterocolitica bacteriophage phiye-f10 and to analyze the relationship between the lysis ability of phiye-f10 and the virulence gene of yersinia enterocolitica. to observe the lysis ability of the phage phiye-f10 to the different yersinia strains with the double-layer technique. the strains used in this study including 213 of yersinia enterocolitica and 36 of yersinia pseudotuberculosis and 1 of yersinia pestis. the virulence genes of these yersinia en ...201627396162
yersinia virulence factors - a sophisticated arsenal for combating host defences.the human pathogens yersinia pseudotuberculosis and yersinia enterocolitica cause enterocolitis, while yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. all three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to ad ...201627347390
'add, stir and reduce': yersinia spp. as model bacteria for pathogen evolution.pathogenic species in the yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. the advent of large-scale population genomic studies has greatly accelerated the progress in this field, and yersinia pestis, yersinia pseudotuberculosis and yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. in this review, we highlight the ge ...201626876035
homology analysis and cross-immunogenicity of ompa from pathogenic yersinia enterocolitica, yersinia pseudotuberculosis and yersinia pestis.the outer membrane protein a (ompa) is one of the intra-species conserved proteins with immunogenicity widely found in the family of enterobacteriaceae. here we first confirmed ompa is conserved in the three pathogenic yersinia: yersinia pestis, yersinia pseudotuberculosis and pathogenic yersinia enterocolitica, with high homology at the nucleotide level and at the amino acid sequence level. the identity of ompa sequences for 262 y. pestis strains, 134 y. pseudotuberculosis strains and 219 patho ...201526435220
molecular docking based screening of neem-derived compounds with the ns1 protein of influenza virus.different strains of influenza virus are affecting a large number of people worldwide to combat with influenza virus destruction, numerous synthetic antiviral medicines are available for influenza virus in the market. but still there was a need for the development of drug which will target all the strains of influenza virus. for this purpose conserved residues within the influenza virus ns1 protein have been found by aligning all the available sequences of existing strains from the national cent ...201526339153
yersinia adhesin a (yada)--beauty & beast.the trimeric autotransporter adhesin yersinia adhesin a is the prototype of the type vc secretion systems. it is expressed by enteropathogenic yersinia enterocolitica and yersinia pseudotuberculosis strains, but not by yersinia pestis. a characteristic trait of yada is its modular composition and trimeric nature. yada consists of an n-terminal passenger domain which is exposed on the bacterial cell surface. the translocation of this passenger onto the surface is facilitated by a c-terminal β-bar ...201525604505
yersiniabase: a genomic resource and analysis platform for comparative analysis of yersinia.yersinia is a gram-negative bacteria that includes serious pathogens such as the yersinia pestis, which causes plague, yersinia pseudotuberculosis, yersinia enterocolitica. the remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. with the advances in sequencing technologies, many genomes of yersinia have been sequenced. however ...201525591325
coregulation of host-adapted metabolism and virulence by pathogenic yersiniae.deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. the enteric pathogenic yersinia species yersinia pseudotuberculosis and yersinia enterocolitica and the causative agent of plague, yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference ...201425368845
development of real-time pcr assays for specific detection of hmsh, hmsf, hmsr, and irp2 located within the 102-kb pgm locus of yersinia pestis.virulent isolates of three pathogenic yersinia species (yersinia pestis, yersinia pseudotuberculosis, and yersinia enterocolitica) harbor a 102-kb chromosomal region which encodes elements critical for virulence. a 35-kb high pathogenicity island is contained in this region, is a known virulence determinant, contains irp1 and irp2 iron-regulating genes. an additional segment, the 68-kb high pathogenicity island, contains genetic elements responsible for conferring the y. pestis pigmentation phen ...201425261118
canis lupus familiaris involved in the transmission of pathogenic yersinia spp. in investigate canines carrying pathogens associated with human illness, we studied their roles in transmitting and maintaining pathogenic yersinia spp. we examined different ecological landscapes in china for the distribution of pathogenic yersinia spp. in canis lupus familiaris, the domestic dog. the highest number of pathogenic yersinia enterocolitica was shown from the tonsils (6.30%), followed by rectal swabs (3.63%) and feces (1.23%). strains isolated from plague free areas for c. lupus fa ...201424861841
a recombinant bivalent fusion protein rve confers active and passive protection against yersinia enterocolitica infection in the present study, a bivalent chimeric protein rve comprising immunologically active domains of yersinia pestis lcrv and yope was assessed for its prophylactic abilities against yersinia enterocolitica o:8 infection in murine model. mice immunized with rve elicited significantly higher antibody titers with substantial contribution from the rv component (3:1 ratio). robust and significant resistance to y. enterocolitica infection with 100% survival (p<0.001) was seen in rve vaccinated mice whe ...201424486353
homology analysis of pathogenic yersinia species yersinia enterocolitica, yersinia pseudotuberculosis, and yersinia pestis based on multilocus sequence typing.we developed a multilocus sequence typing (mlst) scheme and used it to study the population structure and evolutionary relationships of three pathogenic yersinia species. mlst of these three yersinia species showed a complex of two clusters, one composed of yersinia pseudotuberculosis and yersinia pestis and the other composed of yersinia enterocolitica. within the first cluster, the predominant y. pestis sequence type 90 (st90) was linked to y. pseudotuberculosis st43 by one locus difference, a ...201424131695
acquisition of omptin reveals cryptic virulence function of autotransporter yape in yersinia pestis.autotransporters, the largest family of secreted proteins in gram-negative bacteria, perform a variety of functions, including adherence, cytotoxicity and immune evasion. in yersinia pestis the autotransporter yape has adhesive properties and contributes to disease in the mouse model of bubonic plague. here, we demonstrate that omptin cleavage of y. pestis yape is required to mediate bacterial aggregation and adherence to eukaryotic cells. we demonstrate that omptin cleavage is specific for the ...201323701256
detection and isolation of yersinia pestis without fraction 1 antigen by monoclonal antibody in foods and water.most available immunoassays for yersinia pestis are based on the detection of fraction 1 antigen (f1) when yersiniae are grown at 37°c. a monoclonal antibody (mab) was developed based on the detection of surface antigens that are not f1. f1-deficient y. pestis cells were induced and used to immunize balb/c mice from which mab (immunoglobulin g1), which specifically recognizes y. pestis, with or without f1, was obtained. this mab (6b5) did not cross-react with enteric bacteria, including yersinia ...201222947461
exploring the sequence-structure-function relationship for the intrinsically disordered βγ-crystallin hahellin.βγ-crystallins are a superfamily of proteins containing crystallin-type greek key motifs. some βγ-crystallin domains have been shown to bind ca(2+). hahellin is a newly identified intrinsically disordered βγ-crystallin domain from hahella chejuensis. it folds into a typical βγ-crystallin structure upon ca(2+) binding and acts as a ca(2+)-regulated conformational switch. besides hahellin, another two putative βγ-crystallins from caulobacter crescentus and yersinia pestis are shown to be partially ...201728393629
fleas of black-footed ferrets and their potential role in the movement of plague.sylvatic plague is one of the major impediments to the recovery of the black-footed ferret ( mustela nigripes ) because it decimates their primary prey species, prairie dogs ( cynomys spp.), and directly causes mortality in ferrets. fleas are the primary vector of yersinia pestis , the causative agent of sylvatic plague. the goal of this research was to better understand the flea fauna of ferrets and the factors that might influence flea abundance on ferrets. fleas from ferrets were tested for y ...201728384062
unique case of disseminated plague with multifocal osteomyelitis.plague is a disease caused by yersinia pestis. septicemic and pneumonic plague have a high mortality rate if untreated. here we describe the challenges of accurately diagnosing a nonfatal pediatric case of septicemic plague with involvement of multiple organs; to our knowledge, the first documented case of multifocal plague osteomyelitis.201728379405
a starvation-induced regulator, rovm, acts as a switch for planktonic/biofilm state transition in yersinia pseudotuberculosis.the transition between the planktonic state and the biofilm-associated state is a key developmental decision for pathogenic bacteria. biofilm formation by yersinia pestis is regulated by hmshfrs genes (β-1, 6-n-acetyl-d-glucosamine synthesis operon) in its flea vector and in vitro. however, the mechanism of biofilm formation in yersinia pseudotuberculosis remains elusive. in this study, we demonstrate that the lysr-type regulator rovm inversely regulates biofilm formation and motility in y. pseu ...201728377623
yersinia effector protein yopo mediated phosphorylation of host gelsolin causes calcium-independent activation leading to disruption of actin dynamics.pathogenic yersinia bacteria cause a range of human diseases. to modulate and evade host immune systems, these yersiniae inject effector proteins into host macrophages. one such protein, the serine/threonine kinase yopo (ypka in yersinia pestis), uses monomeric actin as bait to recruit and phosphorylate host actin polymerization - regulating proteins, including the actin-severing protein gelsolin, in order to disrupt actin filaments and thus impair phagocytosis. however, the yopo phosphorylation ...201728280241
[genotyping by crispr and regional distribution of yersinia pestis in qinghai-plateau from 1954 to 2011].objective: to investigate the crispr genotypes (clusters) and regional distribution of yersinia pestis in qinghai-plateau. methods: one hundred and two isolates of y. pestis isolated from human plague patients, host animal and insect vectors from qinghai-plateau were selected. the dnas were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. three crispr loci ypa, ypb and ypc of 102 isolates of y. pesits were amplified and sequenced, and then the cr ...201728260338
mechanism study on a plague outbreak driven by the construction of a large reservoir in southwest china (surveillance from 2000-2015).plague, a yersinia pestis infection, is a fatal disease with tremendous transmission capacity. however, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma.201728257423
immunogenesis in white mice infected with yersinia pestis with different plasmid composition.morphological changes in the immunocompetent organs of white mice with experimental plague infection manifested in activation of the immune response of different degree and pathological process of different severity that depended on the plasmid composition of y. pestis. widening of the t-dependent zones in the immune organs of white mice infected with isogenic strains of y. pestis with different plasmid composition attests to activation of cellular immunity. our findings allow considering y. pes ...201728243913
high resolution solid-state nmr spectroscopy of the yersinia pestis outer membrane protein ail in lipid membranes.the outer membrane protein ail (adhesion invasion locus) is one of the most abundant proteins on the cell surface of yersinia pestis during human infection. its functions are expressed through interactions with a variety of human host proteins, and are essential for microbial virulence. structures of ail have been determined by x-ray diffraction and solution nmr spectroscopy, but those samples contained detergents that interfere with functionality, thus, precluding analysis of the structural bas ...201728239773
environmental microbial forensics and archaeology of past pandemics.the development of paleomicrobiology with new molecular techniques such as metagenomics is revolutionizing our knowledge of microbial evolution in human history. the study of microbial agents that are concomitantly active in the same biological environment makes it possible to obtain a picture of the complex interrelations among the different pathogens and gives us the perspective to understand the microecosystem of ancient times. this research acts as a bridge between disciplines such as archae ...201728233511
pneumonic plague transmission, moramanga, madagascar, 2015.during a pneumonic plague outbreak in moramanga, madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. phylogenetic analysis showed that the yersinia pestis isolates belonged to group q3, different from the previous outbreak.201728221119
inhaled liposomal ciprofloxacin protects against a lethal infection in a murine model of pneumonic plague.inhalation of yersinia pestis can lead to pneumonic plague, which without treatment is inevitably fatal. two novel formulations of liposome-encapsulated ciprofloxacin, 'ciprofloxacin for inhalation' (cfi, lipoquin(®)) and 'dual release ciprofloxacin for inhalation' (drcfi, pulmaquin(®)) containing cfi and ciprofloxacin solution, are in development. these were evaluated as potential therapies for infection with y. pestis. in a murine model of pneumonic plague, human-like doses of aerosolized cfi, ...201728220110
[experimental observation on the histopathological and ultrastructural pathology of great gerbils (rhombomys opimus) in the junggar basin by subcutaneous injecting of yersinia pestis].objective: to understand the histopathological and ultrastructural pathology changes of great gerbils in the junggar basin to yersinia pestis infection. methods: forty captured great gerbils from the junggar basin that tested negative for anti-f1 antibodies were infected. the y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the junggar basin in 2005 with a median lethal dose (ld(50)) of <10 cfu/ml, was used in this study. forty great gerbils were divided int ...201728219158
an interaction between the inner rod protein ysci and the needle protein yscf is required to assemble the needle structure of the yersinia type three secretion system.the type iii secretion system is a highly conserved virulence mechanism that is widely distributed in gram-negative bacteria. it has a syringe-like structure composed of a multi-ring basal body that spans the bacterial envelope and a projecting needle that delivers virulence effectors into host cells. here, we showed that the yersinia inner rod protein ysci directly interacts with the needle protein yscf inside the bacterial cells and that this interaction depends on amino acid residues 83-102 i ...201728196868
defining the ail ligand-binding surface: hydrophobic residues in two extracellular loops mediate cell and extracellular matrix binding to facilitate yop delivery.yersinia pestis, the causative agent of plague, binds host cells to deliver cytotoxic yop proteins into the cytoplasm that prevent phagocytosis and generation of proinflammatory cytokines. ail is an eight-stranded β-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. following the deletion of each of the four extracellular loops that potentially interact with host cells, the ail-δloop 2 and ail-δloop 3 mutant proteins had no cell- ...201728167671
a noise trimming and positional significance of transposon insertion system to identify essential genes in yersinia pestis.massively parallel sequencing technology coupled with saturation mutagenesis has provided new and global insights into gene functions and roles. at a simplistic level, the frequency of mutations within genes can indicate the degree of essentiality. however, this approach neglects to take account of the positional significance of mutations - the function of a gene is less likely to be disrupted by a mutation close to the distal ends. therefore, a systematic bioinformatics approach to improve the ...201728165493
successful treatment of human plague with oral ciprofloxacin.the us food and drug administration recently approved ciprofloxacin for treatment of plague (yersina pestis infection) based on animal studies. published evidence of efficacy in humans is sparse. we report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.201728125398
effectiveness of fipronil as a systemic control agent against xenopsylla cheopis (siphonaptera: pulicidae) in madagascar.fipronil was evaluated as a systemic control agent for the rat flea xenopsylla cheopis (rothschild), the main vector of yersinia pestis (yersin), the causative agent of plague, in madagascar. the effectiveness of fipronil as a systemic control agent against x. cheopis was assessed by determining the toxicity values of the "lethal dose 50" (ld50). two techniques were used to evaluate the systemic action of the insecticide on the vector: 1) an artificial feeding device filled with blood-fipronil m ...201728122816
wildlife plague surveillance near the china-kazakhstan border: 2012-2015.plague is a zoonotic disease caused by the bacterium yersinia pestis. this pathogen can be transmitted by fleas and has an enzootic cycle, circulating among small mammals, and occasionally epizootic cycles, infecting other species. in china, infected wild rodents are primarily reservoirs of y. pestis and are related to human infection (int. j. infect. dis., 33, 2015 and 67; bmc microbiol., 9, 2009 and 205). because shepherd dogs prey on and eat rodents (e.g. marmots and mice), they are valuable ...201728117561
yersinia pestis acetyltransferase-mediated dual acetylation at the serine and lysine residues enhances the auto-ubiquitination of ubiquitin ligase march8 in human cells.lysine acetylation is known as a post translational modification (ptm) by histone acetyltransferases (hat) that modifies histones and non-histone proteins to regulate gene expression. serine acetylation, however, is reported in mammalian hosts by serine acetyltransferase of yersinia pestis (yopj) during infection. the protein target and cellular function of bacterial yopj in mammalian systems are not fully addressed. here we report dual acetylation at the serine and lysine residues by transientl ...201728103160
inferring infection hazard in wildlife populations by linking data across individual and population scales.our ability to infer unobservable disease-dynamic processes such as force of infection (infection hazard for susceptible hosts) has transformed our understanding of disease transmission mechanisms and capacity to predict disease dynamics. conventional methods for inferring foi estimate a time-averaged value and are based on population-level processes. because many pathogens exhibit epidemic cycling and foi is the result of processes acting across the scales of individuals and populations, a flex ...201728090753
comparative ability of oropsylla montana and xenopsylla cheopis fleas to transmit yersinia pestis by two different mechanisms.transmission of yersinia pestis by flea bite can occur by two mechanisms. after taking a blood meal from a bacteremic mammal, fleas have the potential to transmit the very next time they feed. this early-phase transmission resembles mechanical transmission in some respects, but the mechanism is unknown. thereafter, transmission occurs after yersinia pestis forms a biofilm in the proventricular valve in the flea foregut. the biofilm can impede and sometimes completely block the ingestion of blood ...201728081130
yersinia pestis halotolerance illuminates plague reservoirs.the plague agent yersinia pestis persists for years in the soil. two millennia after swiping over europe and north africa, plague established permanent foci in north africa but not in neighboring europe. mapping human plague foci reported in north africa for 70 years indicated a significant location at <3 kilometers from the mediterranean seashore or the edge of salted lakes named chotts. in algeria, culturing 352 environmental specimens naturally containing 0.5 to 70 g/l nacl yielded one y. pes ...201728054667
functional and structural analysis of a highly-expressed yersinia pestis small rna following infection of cultured macrophages.non-coding small rnas (srnas) are found in practically all bacterial genomes and play important roles in regulating gene expression to impact bacterial metabolism, growth, and virulence. we performed transcriptomics analysis to identify srnas that are differentially expressed in yersinia pestis that invaded the human macrophage cell line thp-1, compared to pathogens that remained extracellular in the presence of host. using ultra high-throughput sequencing, we identified 37 novel and 143 previou ...201628030576
plague vaccine development: current research and future trends.plague is one of the world's most lethal human diseases caused by yersinia pestis, a gram-negative bacterium. despite overwhelming studies for many years worldwide, there is no safe and effective vaccine against this fatal disease. inhalation of y. pestis bacilli causes pneumonic plague, a fast growing and deadly dangerous disease. f1/lcrv-based vaccines failed to provide adequate protection in african green monkey model in spite of providing protection in mice and cynomolgus macaques. there is ...201628018363
new insights into autoinducer-2 signaling as a virulence regulator in a mouse model of pneumonic plague.the enterobacteriaceae family members, including the infamous yersinia pestis, the causative agent of plague, have a highly conserved interbacterial signaling system that is mediated by the autoinducer-2 (ai-2) quorum-sensing molecule. the ai-2 system is implicated in regulating various bacterial virulence genes in diverse environmental niches. deletion of the gene encoding the synthetic enzyme for the ai-2 substrate, luxs, leads to either no significant change or, paradoxically, an increase in ...201727981238
two isoforms of yersinia pestis plasminogen activator pla: intraspecies distribution, intrinsic disorder propensity, and contribution to has been shown previously that several endemic y. pestis isolates with limited virulence contained the i259 isoform of the outer membrane protease pla, while the epidemic highly virulent strains possessed only the t259 pla isoform. our sequence analysis of the pla gene from 118 y. pestis subsp. microtus strains revealed that the i259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. analysis of the effects of the i ...201627936190
the yersinia type iii secretion effector yopm is an e3 ubiquitin ligase that induced necrotic cell death by targeting nlrp3.yersinia pestis uses type iii effector proteins to target eukaryotic signaling systems. the yersinia outer protein (yop) m effector from the y. pestis strain is a critical virulence determinant; however, its role in y. pestis pathogenesis is just beginning to emerge. here we first identify yopm as the structural mimic of the bacterial ipah e3 ligase family in vitro, and establish that the conserved cld motif in its n-terminal is responsible for the e3 ligase function. furthermore, we show that n ...201627929533
the yersinia pestis effector yopm inhibits pyrin inflammasome activation.type iii secretion systems (t3ss) are central virulence factors for many pathogenic gram-negative bacteria, and secreted t3ss effectors can block key aspects of host cell signaling. to counter this, innate immune responses can also sense some t3ss components to initiate anti-bacterial mechanisms. the yersinia pestis t3ss is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines il-1β and il-18, which are typically processed into their mature forms b ...201627911947
host transcriptomic responses to pneumonic plague reveal that yersinia pestis inhibits both the initial adaptive and innate immune responses in mice.pneumonic plague is the most deadly form of infection caused by yersinia pestis and can progress extremely fast. however, our understanding on the host transcriptomic response to pneumonic plague is insufficient. here, we used rna-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or ev76, a live attenuated vaccine strain lacking the pigmentation locus. approximately 600 differentially expressed genes (degs) were detected in lungs from both ...201727876297
investigation of and response to 2 plague cases, yosemite national park, california, usa, august 2015, plague was diagnosed for 2 persons who had visited yosemite national park in california, usa. one case was septicemic and the other bubonic. subsequent environmental investigation identified probable locations of exposure for each patient and evidence of epizootic plague in other areas of the park. transmission of yersinia pestis was detected by testing rodent serum, fleas, and rodent carcasses. the environmental investigation and whole-genome multilocus sequence typing of y. pes ...201627870634
modeling of spatio-temporal variation in plague incidence in madagascar from 1980 to 2007.plague is an infectious disease caused by the bacterium yersinia pestis, which, during the fourteenth century, caused the deaths of an estimated 75-200 million people in europe. plague epidemics still occur in africa, asia and south america. madagascar is today one of the most endemic countries, reporting nearly one third of the human cases worldwide from 2004 to 2009. the persistence of plague in madagascar is associated with environmental and climatic conditions. in this paper we present a cas ...201627839576
a method for characterizing the type iii secretion system's contribution to pathogenesis: homologous recombination to generate yersinia pestis type iii secretion system mutants.the type iii (t3s) secretion system of many gram-negative bacteria is a surface-exposed protein secretion apparatus used to directly inject bacterial effector molecules into eukaryotic cells. these effector molecules contribute to bacterial pathogenesis in many ways, and have been shown to be crucial for infectivity. here, we describe a protocol for using homologous recombination to generate t3s system mutants to assess the role of different t3s system proteins in bacterial pathogenesis.201727837489
measurement of effector protein translocation using phosphorylatable epitope tags and phospho-specific antibodies.numerous bacterial pathogens employ specialized protein secretion machineries to directly inject anti-host proteins, termed effector proteins, into eukaryotic cells. effector proteins carrying small phosphorylatable tags can be used to detect and quantify effector protein injection. here, we describe the use of the elk- and gsk-tags to detect the translocation of the y. pestis yope effector protein into raw 264.7 macrophage-like cells using immunoblot analysis with phospho-specific antibodies.201727837486
in vivo photo-cross-linking to study t3s interactions demonstrated using the yersinia pestis t3s system.cross-linking of proteins is effective in determining protein-protein interactions. the use of photo-cross-linkers was developed to study protein interactions in several manners. one method involved the incorporation of photo-activatable cross-linking groups into chemically synthesized peptides. a second approach relies on incorporation of photo-activatable cross-linking groups into proteins using trnas with chemically bound photo-activatable amino acids with suppressor trnas translational syste ...201727837480
blue native protein electrophoresis to study the t3s system using yersinia pestis as a model.since the introduction of blue native, clear native, and high-resolution clear native electrophoresis to study protein complexes of eukaryotic, bacterial, and archaeal cells, the technique has been used primarily to study physiological systems that are found in abundance within the cell. systems involved in oxidative phosphorylation, electron transport, membrane transporters, and secretion systems have been studied using these techniques. these microscale techniques are ideal due to the minimal ...201727837479
climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial india.immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. however, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. plague presents an optimal system for interrogating such couplings: yersinia pestis transmission exerts intense selective pressure driving the local persistence of disease resistance among ...201627791071
complete genome sequence of pigmentation-negative yersinia pestis strain, we report the genome sequence of yersinia pestis strain cadman, an attenuated strain lacking the pgm locus. y. pestis is the causative agent of plague and generally must be worked with under biosafety level 3 (bsl-3) conditions. however, strains lacking the pgm locus are considered safe to work with under bsl-2 conditions.201627789646
molecular history of plague.plague, a deadly zoonose caused by the bacterium yersinia pestis, has been firmly documented in 39 historical burial sites in eurasia that date from the bronze age to two historical pandemics spanning the 6th to 18th centuries. palaeomicrobiologic data, including gene and spacer sequences, whole genome sequences and protein data, confirmed that two historical pandemics swept over europe from probable asian sources and possible two-way-ticket journeys back from europe to asia. these investigation ...201627615720
vntr diversity in yersinia pestis isolates from an animal challenge study reveals the potential for in vitro mutations during laboratory cultivation.underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. here, we investigated tissue samples and yersinia pestis isolates from a rodent laboratory challenge with strain co92 using whole genome sequencing and multi-locus variable-number tandem repeat (vntr) analysis (mlva). we identified six vntr mutations that were found to have occu ...201627664903
perspectives on yersinia pestis: a model for studying zoonotic pathogens.yersinia pestis is a typical zoonotic bacterial pathogen. the following reasons make this pathogen a model for studying zoonotic pathogens: (1) its unique lifestyle makes y. pestis an ideal model for studying host-vector-environment-pathogen interactions; (2) population diversity characters in y. pestis render it a model species for studying monomorphic bacterial evolution; (3) the pathogenic features of bacteria provide us with good opportunities to study human immune responses; (4) typical ani ...201627722871
bacteriophages of yersinia pestis.bacteriophage play many varied roles in microbial ecology and evolution. this chapter collates a vast body of knowledge and expertise on yersinia pestis phages, including the history of their isolation and classical methods for their isolation and identification. the genomic diversity of y. pestis phage and bacteriophage islands in the y. pestis genome are also discussed because all phage research represents a branch of genetics. in addition, our knowledge of the receptors that are recognized by ...201627722870
plague vaccines: status and future.three major plague pandemics caused by the gram-negative bacterium yersinia pestis have killed nearly 200 million people in human history. due to its extreme virulence and the ease of its transmission, y. pestis has been used purposefully for biowarfare in the past. currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the united states. approximately 2000 cases of plague are reported each year to the world health organization. however, the pote ...201627722869
immunology of yersinia pestis a pathogen of plague, yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. to survive in the host and maintain a persistent infection, yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. for example, infections with this organism are biphasic, involving an initial "noninflammatory" phase whe ...201627722867
yersinia pestis in the age of big omics-driven technologies developed rapidly, genomics, transcriptomics, proteomics, metabolomics and other omics-based data have been accumulated in unprecedented speed. omics-driven big data in biology have changed our way of research. "big science" has promoted our understanding of biology in a holistic overview that is impossibly achieved by traditional hypothesis-driven research. in this chapter, we gave an overview of omics-driven research on y. pestis, provided a way of thinking on yers ...201627722866
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