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a personal view of how paleomicrobiology aids our understanding of the role of lice in plague pandemics.we have been involved in the field of paleomicrobiology since 1998, when we used dental pulp to identify yersinia pestis as the causative agent of the great plague of marseille (1720). we recently designed a specific technique, "suicide pcr," that can prevent contamination. a controversy arose between two teams, with one claiming that dna must be altered to amplify it and the other group claiming that demographic data did not support the role of y. pestis in the black death (i.e., the great plag ...201627726806
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
complete genome sequence of pigmentation-negative yersinia pestis strain cadman.here, 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
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
avoiding pandemic fears in the subway and conquering the platypus.metagenomics is increasingly used not just to show patterns of microbial diversity but also as a culture-independent method to detect individual organisms of intense clinical, epidemiological, conservation, forensic, or regulatory interest. a widely reported metagenomic study of the new york subway suggested that the pathogens yersinia pestis and bacillus anthracis were part of the "normal subway microbiome." in their article in msystems, hsu and collaborators (msystems 1(3):e00018-16, 2016, htt ...201727832215
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
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
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
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
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
investigation of and response to 2 plague cases, yosemite national park, california, usa, 2015.in 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
a self-quenching-resistant carbon nanodot powder with multicolored solid-state fluorescence for ultra-fast staining of various representative bacterial species within one minute.in this study, we prepared self-quenching-resistant solid-state fluorescent carbon nanodots (sfcds) without any other solid matrices. the sfcds were prepared using a one-step microwave synthesis method through precise control of the heating power and time. the resulting sfcd powder showed excitation-dependent emission behavior with a maximum fluorescence quantum yield of 40%. the multicolored sfcds were successfully used as fluorescent agents for rapid staining of 14 representative bacterial spe ...201627874136
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
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
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
two isoforms of yersinia pestis plasminogen activator pla: intraspecies distribution, intrinsic disorder propensity, and contribution to virulence.it 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
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
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
characterization of yersinia species by protein profiling using automated microfluidic capillary electrophoresis.yersinia pestis is a biological agent of high risk to national security due to its ability to be easily disseminated and transmitted among humans. if y. pestis was to be utilized in a deliberate disease outbreak it would be essential to rapidly and accurately identify the agent. current identification methods for yersinia species are limited by their reliance on cultivation, the time taken to achieve results and/or the use of protocols that are not amenable for field use. faster identification m ...201728019002
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
evolution and structural dynamics of bacterial glycan binding adhesins.infectious disease processes like bacterial adherence or the activity of secreted toxins frequently gain host and tissue specificity by glycan binding interactions with the host glycome. recent functional and structural studies highlight the high niche specialization of bacterial lectins, but also reveal a remarkable plasticity in their glycan binding sites and mechanisms, to adapt to host glycome dynamics or changing environmental conditions at the site of infection. in this review we put empha ...201628043017
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
upconversion nanocrystals mediated lateral-flow nanoplatform for in vitro detection.upconversion phosphors (ucps) that are free from interference from biological sample autofluorescence have attracted attention for in vivo and in vitro bioapplications. however, ucps need to be water-dispersible, nanosized, and highly luminous to realize broad applications. therefore, the aim of this research is to develop ucps that meet these comprehensive criteria for in vitro diagnosis. to combine nano size with high luminous intensity, β-nayf4:yb(3+),er(3+) upconversion nanocrystals (ucnps) ...201728067495
the fleas (siphonaptera) in iran: diversity, host range, and medical importance.flea-borne diseases have a wide distribution in the world. studies on the identity, abundance, distribution and seasonality of the potential vectors of pathogenic agents (e.g. yersinia pestis, francisella tularensis, and rickettsia felis) are necessary tools for controlling and preventing such diseases outbreaks. the improvements of diagnostic tools are partly responsible for an easier detection of otherwise unnoticed agents in the ectoparasitic fauna and as such a good taxonomical knowledge of ...201728068343
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
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
mplex: a method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling.the continued emergence and spread of infectious agents is of great concern, and systems biology approaches to infectious disease research can advance our understanding of host-pathogen relationships and facilitate the development of new therapies and vaccines. molecular characterization of infectious samples outside of appropriate biosafety containment can take place only subsequent to pathogen inactivation. herein, we describe a modified folch extraction using chloroform/methanol that facilita ...201728091625
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
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
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
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
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
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
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
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
crispr elements in yersinia pestis acquire new repeats by preferential uptake of bacteriophage dna, and provide additional tools for evolutionary studies.the remarkable repetitive elements called crisprs (clustered regularly interspaced short palindromic repeats) consist of repeats interspaced with non-repetitive elements or 'spacers'. crisprs are present in both archaea and bacteria, in association with genes involved in dna recombination and repair. in the yersinia pestis genome, three such elements are found at three distinct loci, one of them being highly polymorphic. the authors have sequenced a total of 109 alleles of the three y. pestis cr ...200528202106
[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
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
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
in vitro and in vivo activity of omadacycline against two biothreat pathogens: bacillus anthracis and yersinia pestis.introduction: the in vitro activity and in vivo efficacy of omadacycline (omc) were evaluated against the causative pathogens of anthrax and plague, bacillus anthracis and yersinia pestis, respectively.methods: minimum inhibitory concentrations (mics) of omc were determined by microbroth dilution according to clsi guidelines for 30 isolates each of y. pestis and b. anthracis the in vivo efficacy of omadacycline was studied at a range of dosages in both a post exposure prophylaxis (pep) murine mo ...201728223382
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
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
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
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
[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
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
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
redefining the differences in gene content between yersinia pestis and yersinia pseudotuberculosis using large-scale comparative genomics.yersinia pestis, the causative agent of plague, is best known for historical pandemics, but still actively causes disease in many parts of the world. y. pestis is a recently derived clone of the pathogenic species yersinia pseudotuberculosis, but is more associated with human infection. numerous studies have documented genomic changes since the two species differentiated, although all of these studies used a relatively small sample set for defining these differences. in this study, we compared t ...201528348813
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
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
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
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
[dynamics of f1 antibody responses to yersinia pestis infection in rhombomys opimus].objective: to observe the dynamics of antibody response in great gerbils infected with yersinia pestis in experiment. method: a total of 211 great gerbils were captured in the southern margin of plague natural focus of junggar basin of the xinjiang uygur autonomous region in 2011. among them, there were 167 great gerbils without infection of y. pestis and 44 great gerbils infected by y.pestis. y.pestis no. 2504 was employed for this experimental strain, which was strong toxic strain with negativ ...201728395471
preparing for biological threats: addressing the needs of pregnant women.intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. we review what is known about the maternal and fetal effects of seven biological threats: bacillus anthracis (anthrax); variola virus (smallpox); clostridium botulinum toxin (botulism); burkholderia mallei (glanders) and burkholderia pseudomallei (melioidosis); yersinia pestis (plague); francisella tularensis (tularemia); and rickettsia ...201728398677
potential roles of pigs, small ruminants, rodents, and their flea vectors in plague epidemiology in sinda district, eastern zambia.a cross-sectional study was conducted in the eastern part of zambia that previously reported a plague outbreak. the aim of the study was to evaluate the potential role of pigs, goats, and sheep as sero-surveillance hosts for monitoring plague, and to investigate the flea vectors and potential reservoir hosts to establish the current status of plague endemicity in the district. serum samples were collected from 96 rodents, 10 shrews, 245 domestic pigs, 232 goats, and 31 sheep, whereas 106 organs ...201728399281
disease surveillance of california ground squirrels ( spermophilus beecheyi ) in a drive-through zoo in oregon, usa.rodents and other small wild mammals are often considered to be pests and vectors for disease in zoos that house small populations of valuable threatened and endangered animals. in 2005, three nonhuman primates at a drive-through zoo in oregon, us, acquired tularemia from an unknown source. due to an abundance of california ground squirrels ( spermophilus beecheyi ) on zoo grounds, we instituted serosurveillance of this species from july through september 2008 to determine the prevalence of anti ...201728418764
yersinia pestis resists predation by acanthamoeba castellanii and exhibits prolonged intracellular survival.plague is a flea-borne rodent-associated zoonotic disease caused by yersinia pestis the disease is characterized by epizootics with high rodent mortalities, punctuated by interepizootic periods when the bacterium persists in an unknown reservoir. this study investigates the interaction between y. pestis and the ubiquitous soil free-living amoeba (fla) acanthamoeba castellanii to assess if the bacterium can survive within soil amoebae and whether intracellular mechanisms are conserved between inf ...201728455335
responses of juvenile black-tailed prairie dogs ( cynomys ludovicianus ) to a commercially produced oral plague vaccine delivered at two doses.we confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (rcn-f1/v307) expressing yersinia pestis v and f1 antigens. forty-five juvenile black-tailed prairie dogs ( cynomys ludovicianus ) were randomly divided into three treatment groups (n=15 animals/group). animals in the first group received one standard-dose vaccine bait (5×10(7) plaque-forming units [pfu]; std). the second group received a lower-dose bait (1×10(7) pfu; ...201728463626
[advance on genome research of yersinia pestis bacteriophage].completion of the genome sequences on yersinia pestis bacteriophage offered unprecedented opportunity for researchers to carry out related genomic studies. this review was based on the genomic sequences and provided a genomic perspective in describing the essential features of genome on yersinia pestis bacteriophage. based on the comparative genomics, genetic evolutionary relationship was discussed. description of functions from the gene prediction and protein annotation provided evidence for fu ...201728468083
detection of yersinia pestis in complex matrices by intact cell immunocapture and targeted mass spectrometry.we describe an immunoaffinity-liquid chromatography-tandem mass spectrometry (immuno-lc-ms/ms) protocol for the direct (i.e., without prior culture), sensitive and specific detection of yersinia pestis in complex matrices. immunoaffinity enables isolation and concentration of intact bacterial cells from food and environmental samples. after protein extraction and digestion, suitable proteotypic peptides corresponding to three y. pestis-specific protein markers (murine toxine, plasminogen activat ...201728478558
identification and characterization of a neutralizing monoclonal antibody that provides complete protection against yersinia pestis.yersinia pestis (y. pestis) has caused an alarming number of deaths throughout recorded human history, and novel prophylactics and therapeutics are necessary given its potential as a bioweapon. only one monoclonal antibody has been identified to date that provides complete protection against y. pestis. here, we describe a second novel murine monoclonal antibody (f2h5) that provided complete protection against y. pestis 141 infection when administered prophylactically to balb/c mice (100 μg intra ...201728486528
swabbing prairie dog burrows for fleas that transmit yersinia pestis: influences on efficiency.scientists and health-care professionals sometimes use a swabbing technique to collect fleas from rodent burrows, and later test the fleas for yersinia pestis, the causative agent of plague. detection of y. pestis is enhanced when large pools of fleas are available. the following study investigated factors that might affect the rate at which fleas are collected from burrows in colonies of black-tailed prairie dogs (cynomys ludovicianus). data were collected from 13 colonies in new mexico during ...201728486652
rationally designed tlr4 ligands for vaccine adjuvant discovery.adjuvant properties of bacterial cell wall components like mpla (monophosphoryl lipid a) are well described and have gained fda approval for use in vaccines such as cervarix. mpla is the product of chemically modified lipooligosaccharide (los), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are fe ...201728487429
efficacy of a fipronil bait in reducing the number of fleas (oropsylla spp.) infesting wild black-tailed prairie dogs.bubonic plague (yersinia pestis) is a deadly zoonosis with black-tailed prairie dogs (cynomys ludovicianus) as a reservoir host in the united states. systemic insecticides are a promising means of controlling the vectors, oropsylla spp. fleas, infesting these prairie dogs, subsequently disrupting the y. pestis cycle. the objective of this study was to conduct a field trial evaluating the efficacy of a grain rodent bait containing fipronil (0.005%) against fleas infesting prairie dogs. the study ...201728504448
glutathionylation of yersinia pestis lcrv and its effects on plague pathogenesis.glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. here we show that yersinia pestis lcrv, a secreted protein capping the type iii secretion machine, is glutathionylated at cys(273) and that this modification promotes association with host ribosomal protein s3 (rps3), moderates y. pestis type iii effector transport and killing of macropha ...201728512097
flea and small mammal species composition in mixed-grass prairies: implications for the maintenance of yersinia pestis.maintenance of sylvatic plague in prairie dogs (cynomis spp.) was once thought unlikely due to high mortality rates; yet more recent findings indicate that low-level enzootic plague may be maintained in susceptible prairie dog populations. another hypothesis for the maintenance of sylvatic plague involves small mammals, other than prairie dogs, as an alternative reservoir in the sylvatic plague system. these hypotheses, however, are not mutually exclusive, as both prairie dogs and small mammals ...201728520514
draft genome sequence of the luminescent strain vibrio campbellii lb102, isolated from a black tiger shrimp (penaeus monodon) broodstock rearing system.we report here the genome sequence of vibrio campbellii lb102, isolated from the broodstock rearing system of a shrimp hatchery in india. sequence analysis revealed the presence of effector toxins of the type iii (yopt, sharing 39% identity with yersinia pestis) and type vi (vgrg-3 and hemolysin coregulated protein of v. cholerae) secretion systems.201728522707
evidence of infection with leptospira interrogans and spotted fever group rickettsiae among rodents in an urban area of osaka city, japan.we examined 33 rodents captured in an urban area of osaka city, japan for igg antibodies against seoul virus, severe fever with thrombocytopenia syndrome virus, hepatitis e virus, leptospira interrogans, yersinia pestis, spotted fever, typhus and scrub typhus group rickettsiae. we found that 3 (9.1%) and 1 (3.0%) of the 33 rodents had antibodies against l. interrogans and spotted fever group rickettsiae, respectively. dnas of leptospires were detected from 2 of the 3 seropositive rodents, but dn ...201728529271
yersinia pestis yopk inhibits bacterial adhesion to host cells by binding to the extracellular matrix adaptor protein matrilin-2.pathogenic yersiniae harbor a type iii secretion system (t3ss) that injects yersinia outer protein (yop) into host cells. yopk has been shown to control yop translocation and prevent inflammasome recognition of the t3ss by the innate immune system. here, we demonstrate that yopk inhibits bacterial adherence to host cells by binding to the extracellular matrix adaptor protein matrilin-2 (matn2). yopk binds to matn2, and deleting amino acids 91 to 124 disrupts binding of yopk to matn2. a yopk null ...201728533472
zinc transporters ybtx and znuabc are required for the virulence of yersinia pestis in bubonic and pneumonic plague in mice.a number of bacterial pathogens require the znuabc zinc (zn(2+)) transporter and/or a second zn(2+) transport system to overcome zn(2+) sequestration by mammalian hosts. previously we have shown that in addition to znuabc, yersinia pestis possesses a second zn(2+) transporter that involves components of the yersiniabactin (ybt), siderophore-dependent iron transport system. synthesis of the ybt siderophore and ybtx, a member of the major facilitator superfamily, are both critical components of th ...201728540946
pcr incorporation of polyoxometalate modified deoxynucleotide triphosphates and their application in molecular electrochemical sensing of yersinia pestis.redox-labeled nucleotides are of increasing interest for the fabrication of next generation molecular tools and should meet requirements of being thermally stable, sensitive, and compatible with polymerase-mediated incorporation while also being electrochemically discriminable. the synthesis and characterization of keggin and dawson polyoxometalate-deoxynucleotide (pom-dntp) bioconjugates linked through 7-deaza-modified purines is described. the modified pom-dntps were used for polymerase-based ...201728544266
functionalization promotes pathogen-mimicking characteristics of polyanhydride nanoparticle adjuvants.rational design of adjuvants and delivery systems will promote development of next-generation vaccines to control emerging and re-emerging diseases. to accomplish this, understanding the immune-enhancing properties of new adjuvants relative to those induced by natural infections can help with the development of pathogen-mimicking materials that will effectively initiate innate immune signaling cascades. in this work, the surfaces of polyanhydride nanoparticles composed of sebacic acid (sa) and 1 ...201728556563
novel ctl epitopes identified through a y. pestis proteome-wide analysis in the search for vaccine candidates against plague.the causative agent of plague, yersinia pestis, is a highly virulent pathogen and a potential bioweapon. depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. the latter has a high fatality rate. in the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the f1 and lcrv antigens are currently under clinical trials. it is well known tha ...201728606812
thermal stability and rheological properties of the "non-stick" caf1 biomaterial.the ability to culture cells in three dimensions has many applications, from drug discovery to wound healing. 3d cell culture methods often require appropriate scaffolds that mimic the cellular environments of different tissue types. the choice of material from which these scaffolds are made is of paramount importance, as its properties will define the manner in which cells interact with the scaffold. caf1 is a protein polymer that is secreted from its host organism, yersinia pestis, to enable e ...201728632140
sylvatic plague vaccine partially protects prairie dogs (cynomys spp.) in field trials.sylvatic plague, caused by yersinia pestis, frequently afflicts prairie dogs (cynomys spp.), causing population declines and local extirpations. we tested the effectiveness of bait-delivered sylvatic plague vaccine (spv) in prairie dog colonies on 29 paired placebo and treatment plots (1-59 ha in size; average 16.9 ha) in 7 western states from 2013 to 2015. we compared relative abundance (using catch per unit effort (cpue) as an index) and apparent survival of prairie dogs on 26 of the 29 paired ...201728643091
crispr-cas12a-assisted recombineering in bacteria.clustered regularly interspaced short palindromic repeat (crispr)-cas12a (cpf1) has emerged as an effective genome editing tool in many organisms. here, we developed and optimized a crispr-cas12a-assisted recombineering system to facilitate genetic manipulation in bacteria. using this system, point mutations, deletions, insertions, and gene replacements can be easily generated on the chromosome or native plasmids in escherichia coli, yersinia pestis, and mycobacterium smegmatis because crispr-ca ...201728646112
host iron nutritional immunity induced by a live yersinia pestis vaccine strain is associated with immediate protection against plague.prompt and effective elicitation of protective immunity is highly relevant for cases of rapidly deteriorating fatal diseases, such as plague, which is caused by yersinia pestis. here, we assessed the potential of a live vaccine to induce rapid protection against this infection. we demonstrated that the y. pestis ev76 live vaccine protected mice against an immediate lethal challenge, limiting the multiplication of the virulent pathogen and its dissemination into circulation. ex vivo analysis of y ...201728680860
a bivalent anthrax-plague vaccine that can protect against two tier-1 bioterror pathogens, bacillus anthracis and yersinia pestis.bioterrorism remains as one of the biggest challenges to global security and public health. since the deadly anthrax attacks of 2001 in the united states, bacillus anthracis and yersinia pestis, the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the cdc as tier-1 biothreat agents. currently, there is no food and drug administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vacci ...201728694806
crystal structure of yersinia pestis virulence factor yfea reveals two polyspecific metal-binding sites.gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (sbps) to transport transition metals through the periplasm. the sbps share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. in yersinia pestis, the causative agent of plague, yfea (ypo2439, y1897), an sbp, is important for full virulence during mammalian infectio ...201728695856
atp binding and hydrolysis disrupts the high-affinity interaction between the heme abc transporter hmuuv and its cognate substrate binding protein.using the energy of atp hydrolysis abc transporters catalyze the trans-membrane transport of molecules. in bacteria they partner with a high affinity substrate binding protein (sbp) to import essential micronutrients. atp binding by type-i abc transporters (importers of amino acids, sugars, peptides, small ions) stabilizes the interaction between the transporter and the sbp, thus allowing transfer of the substrate from the latter to the former. in type-ii abc transporters (importers of trace ele ...201728710276
identification of risk factors associated with transmission of plague disease in eastern zambia.plague is a fatal, primarily rodent-flea-borne zoonotic disease caused by yersinia pestis. the identification of risk factors of plague was investigated through questionnaire interview and conducting focus group discussion (fgd) in sinda and nyimba of eastern zambia. a total of 104 questionnaires were administered to individual respondents and 20 groups consisting of 181 discussants, which comprised fgd team in this study. the study revealed that trapping, transportation, and preparation of rode ...201728722614
structural insights into the yersinia pestis outer membrane protein ail in lipid bilayers.yersinia pestis the causative agent of plague, is highly pathogenic and poses very high risk to public health. the outer membrane protein ail (adhesion invasion locus) is one of the most highly expressed proteins on the cell surface of y. pestis, and a major target for the development of medical countermeasures. ail is essential for microbial virulence and is critical for promoting the survival of y. pestis in serum. structures of ail have been determined by x-ray diffraction and solution nmr sp ...201728726410
an integrated computational-experimental approach reveals yersinia pestis genes essential across a narrow or a broad range of environmental conditions.the world health organization has categorized plague as a re-emerging disease and the potential for yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. environmental temperature is a key signal which regulates virulence of the bacterium. the bacterium normally grows outside the human host at 28 °c. therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °c is central to the develo ...201728732479
integrated sers-based microdroplet platform for the automated immunoassay of f1 antigens in yersinia pestis.the development of surface-enhanced raman scattering (sers)-based microfluidic platforms has attracted significant recent attention in the biological sciences. sers is a highly sensitive detection modality, with microfluidic platforms providing many advantages over microscale methods, including high analytical throughput, facile automation, and reduced sample requirements. accordingly, the integration of sers with microfluidic platforms offers significant utility in chemical and biological exper ...201728737374
curative treatment of severe gram-negative bacterial infections by a new class of antibiotics targeting lpxc.the infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. it has been suggested that an antibiotic targeting lpxc of the lipid a biosynthetic pathway in gram-negative bacteria is a promising strategy for curing gram-negative bacterial infections. however, experimental proof of this concept is lacking. here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of lpxc, an essential enzyme in the biosynthesis of the lipid a c ...201728743813
paleoproteomics of the dental pulp: the plague paradigm.chemical decomposition and fragmentation may limit the detection of ancient host and microbial dna while some proteins can be detected for extended periods of time. we applied paleoproteomics on 300-year-old dental pulp specimens recovered from 16 individuals in two archeological funeral sites in france, comprising one documented plague site and one documented plague-negative site. the dental pulp paleoproteome of the 16 teeth comprised 439 peptides representative of 30 proteins of human origin ...201728746380
competition is the basis of the transport mechanism of the nhab na+/h+ exchanger from klebsiella pneumoniae.na+/h+ exchange is essential for survival of all organisms, having a role in the regulation of the intracellular na+ concentration, ph and cell volume. furthermore, na+/h+ exchangers were shown to be involved in the virulence of the bacterium yersinia pestis, indicating they might be potential targets for novel antibiotic treatments. the model system for na+/h+ exchangers is the nhaa transporter from escherichia coli, ecnhaa. therefore, the general transport mechanism of nhaa exchangers is curre ...201728750048
serological and pcr investigation of yersinia pestis in potential reservoir hosts from a plague outbreak focus in zambia.plague is a bacterial zoonotic disease, caused by yersinia pestis. rodents are the natural hosts with fleas as the vehicle of disease transmission. domestic and wild dogs and cats have also been identified as possible disease hosts. in zambia, plague outbreaks have been reported in the southern and eastern regions in the last 20 years. based on these observations, y. pestis could possibly be endemically present in the area.201728754138
the feoabc locus of yersinia pestis likely has two promoters causing unique iron regulation.the feoabc ferrous transporter is a wide-spread bacterial system. while the feoabc locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoabc in yersinia pestis appears to be unique. none of the non-iron responsive transcriptional regulators that control expression of feoabc in other bacteria do so in y. pestis. another unique factor is the iron and fur regulation of the y. pestis feoabc locus occurs during microaerobic but not aerobic g ...201728785546
small-scale die-offs in woodrats support long-term maintenance of plague in the u.s. southwest.our longitudinal study of plague dynamics was conducted in north-central new mexico to identify which species in the community were infected with plague, to determine the spatial and temporal patterns of the dynamics of plague epizootics, and to describe the dynamics of yersinia pestis infection within individual hosts. a total of 3156 fleas collected from 535 small mammals of 8 species were tested for y. pestis dna. nine fleas collected from six southern plains woodrats (neotoma micropus) and f ...201728792853
aggregation-induced-emission materials with different electric charges as an artificial tongue: design, construction, and assembly with various pathogenic bacteria for effective bacterial imaging and discrimination.imaging-based total bacterial count and type identification of bacteria play crucial roles in clinical diagnostics, public health, biological and medical science, and environmental protection. herein, we designed and synthesized a series of tetraphenylethenes (tpes) functionalized with one or two aldehyde, carboxylic acid, and quaternary ammonium groups, which were successfully used as fluorescent materials for rapid and efficient staining of eight kinds of representative bacterial species, incl ...201728809473
patterns of human plague in uganda, 2008-2016.plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-saharan africa. during 2008-2016, a combination of active surveillance and laboratory testing in the plague-endemic west nile region of uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. although the mortality rate was 7% among suspected cases, it ...201728820134
eight whole-genome assemblies of yersinia pestis subsp. microtus bv. caucasica isolated from the common vole (microtus arvalis) plague focus in dagestan, russia.we here report the draft genome sequences of 8 yersinia pestis subsp. microtus bv. caucasica strains isolated from the east caucasian (previous name, dagestan) mountain focus (no. 39), representing the most ancient branch of the 0.pe2 phylogroup circulating in populations of common voles (microtus arvalis).201728839028
induction of type i interferon through a non-canonical toll-like receptor 7 pathway during yersinia pestis infection.yersinia pestis causes bubonic, pneumonic and septicemic plague, diseases that are rapidly lethal to most mammals, including humans. plague develops as a consequence of bacterial neutralization of the host's innate immune response, which permits uncontrolled growth and causes the systemic hyperactivation of the inflammatory response. we previously found that host type i interferon (ifn) signaling is induced during y. pestis infection and contributes to neutrophil depletion and disease. in this w ...201728847850
hmsc controls yersinia pestis biofilm formation in response to redox environment.yersinia pestis biofilm formation, controlled by intracellular levels of the second messenger molecule cyclic diguanylate (c-di-gmp), is important for blockage-dependent plague transmission from fleas to mammals. hmscde is a tripartite signaling system that modulates intracellular c-di-gmp levels to regulate biofilm formation in y. pestis. previously, we found that y. pestis biofilm formation is stimulated in reducing environments in an hmscde-dependent manner. however, the mechanism by which hm ...201728848715
characterization of yersinia pestis interactions with human neutrophils in vitro.yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. the bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and y. pestis have been demonstrated in vivo. in contrast to macrophages, neutrophils have been considered non-permissive to y. pestis intracellular survival. several s ...201728848716
protein abundances can distinguish between naturally-occurring and laboratory strains of yersinia pestis, the causative agent of plague.the rapid pace of bacterial evolution enables organisms to adapt to the laboratory environment with repeated passage and thus diverge from naturally-occurring environmental ("wild") strains. distinguishing wild and laboratory strains is clearly important for biodefense and bioforensics; however, dna sequence data alone has thus far not provided a clear signature, perhaps due to lack of understanding of how diverse genome changes lead to convergent phenotypes, difficulty in detecting certain type ...201728854255
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