genetic regulation of yersinia pestis.y. pestis exhibits dramatically different traits of pathogenicity and transmission, albeit their close genetic relationship with its ancestor-y. pseudotuberculosis, a self-limiting gastroenteric pathogen. y. pestis is evolved into a deadly pathogen and transmitted to mammals and/or human beings by infected flea biting or directly contacting with the infected animals. various kinds of environmental changes are implicated into its complex life cycle and pathogenesis. dynamic regulation of gene exp ...201627722865
pathology and pathogenesis of yersinia pestis.various types of animal models of plague have been developed, including mice, rats, guinea pigs, and nonhuman primates. studies have indicated that rodent and nonhuman primate models of pneumonic plague closely resemble the human disease and that the pathologic changes that occur during bubonic plague are very similar in rodents, nonhuman primates, and humans. in this section, the pathological changes caused by y. pestis in different animal models are described. the bacterium y. pestis causes de ...201627722864
genome and evolution of yersinia pestis.this chapter summarizes researches on genome and evolution features of yersinia pestis, the young pathogen that evolved from y. pseudotuberculosis at least 5000 years ago. y. pestis is a highly clonal bacterial species with closed pan-genome. comparative genomic analysis revealed that genome of y. pestis experienced highly frequent rearrangement and genome decay events during the evolution. the genealogy of y. pestis includes five major branches, and four of them seemed raised from a "big bang" ...201627722863
ecology of yersinia pestis and the epidemiology of plague.this chapter summarizes information about the natural foci of plague in the world. we describe the location, main hosts, and vectors of yersinia pestis. the ecological features of the hosts and vectors of plague are listed, including predators - birds and mammals and their role in the epizootic. the epizootic process in plague and the factors affecting the dynamics of epizootic activity of natural foci of y. pestis are described in detail. the mathematical models of the epizootic process in plag ...201627722862
physiology of yersinia pestis.this chapter outlines the physiology of yersinia pestis with emphasis on identifying unique functions required for tissue invasion and acute disease. these activities are opposed to often incompatible processes expressed by very closely related yersinia pseudotuberculosis, which causes localized gastrointestinal infection. gain of new information in y. pestis entailed lateral transfer of plasminogen activator and anti-phagocytic capsular antigen via the plasmids ppcp and pmt, respectively, and d ...201627722861
taxonomy of yersinia pestis.this chapter summarized the taxonomy and typing works of yersinia pestis since it's firstly identified in hong kong in 1894. phenotyping methods that based on phenotypic characteristics, including biotyping, serotyping, antibiogram analysis, bacteriocin typing, phage typing, and plasmid typing, were firstly applied in classification of y. pestis in subspecies level. and then, with the advancement of molecular biological technology, the methods based on outer membrane protein profiles, fatty acid ...201627722860
discovery of the plague pathogen: lessons learned.plague resulted in three pandemics in history; however, its causative pathogen was isolated until the third pandemic in hong kong in 1894. at that time, two famous researchers, dr. alexandre yersin and dr. shibasaburo kitasato, went to hk, in order to identify the pathogen. the two great researchers had done a lot of work to isolate and identify the causative pathogen. however, dr. alexandre yersin reported the real pathogen for plague, and we now acknowledge his work by nominating the pathogen' ...201627722859
plague: a disease which changed the path of human civilization.plague caused by yersinia pestis is a zoonotic infection, i.e., it is maintained in wildlife by animal reservoirs and on occasion spills over into human populations, causing outbreaks of different entities. large epidemics of plague, which have had significant demographic, social, and economic consequences, have been recorded in western european historical documents since the sixth century. plague has remained in europe for over 1400 years, intermittently disappearing, yet it is not clear if the ...201627722858
[ancient yersinia pestis genomes for tracing the origins and spreading of plague past epidemics]. 201627615168
plazomicin is effective in a non-human primate pneumonic plague model.the efficacy of plazomicin for pneumonic plague was evaluated in a non-human primate model. african green monkeys challenged with a lethal aerosol of yersinia pestis [median (range) of 98 (15-331) ld50s] received placebo (n=12) or 'humanized' dose regimens (6.25, 12.5 or 25mg/kg every 24h) of plazomicin (n=52) after the onset of fever for a duration of 5 or 10days. all animals treated with placebo died, while 36 plazomicin-treated animals survived through study end. the majority (33/36) were eit ...201627614915
yersinia pestis caf1 protein: effect of sequence polymorphism on intrinsic disorder propensity, serological cross-reactivity and cross-protectivity of isoforms.yersinia pestis caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. it is generally conserved between globally distributed y. pestis strains, but y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in georgia and armenia were reported to carry a single substitution of alanine to serine. we investigated polymorphism of the caf1 sequences among other y. pestis subsp. microtus strains, which have a ...201627606595
effect of natural polymorphism on structure and function of the yersinia pestis outer membrane porin f (ompf protein): a computational study.the yersinia pestis outer membrane porin f (ompf) is a transmembrane protein located in the outer membrane of this gram-negative bacterium which is the causative agent of plague, where it plays a significant role in controlling the selective permeability of the membrane. the amino acid sequences of ompf proteins from 48 y. pestis strains representing all currently available phylogenetic groups of this gram-negative bacterium were recently deduced. comparison of these amino acid sequences reveale ...201627593697
molecular, serological and epidemiological observations after a suspected outbreak of plague in nyimba, eastern zambia.plague is a re-emerging zoonotic disease caused by the bacterium yersinia pestis. the disease has caused periodic global devastation since the first outbreak in the 6th century. two months after a suspected plague outbreak in nyimba district, samples were collected from 94 livestock (goats and pigs), 25 rodents, 6 shrews and 33 fleas. enzyme-linked immunosorbent assay (elisa) and polymerase chain reaction (pcr) techniques were used to investigate the presence of y. pestis, which showed that 16.0 ...201727578859
a high-coverage yersinia pestis genome from a sixth-century justinianic plague victim.the justinianic plague, which started in the sixth century and lasted to the mid eighth century, is thought to be the first of three historically documented plague pandemics causing massive casualties. historical accounts and molecular data suggest the bacterium yersinia pestis as its etiological agent. here we present a new high-coverage (17.9-fold) y. pestis genome obtained from a sixth-century skeleton recovered from a southern german burial site close to munich. the reconstructed genome enab ...201627578768
biological warfare in the 17th century. 201627533653
evaluation of whole cell fixation methods for the analysis of nanoscale surface features of yersinia pestis kim.manipulation of viable yersinia pestis (etiologic agent of plague) in the laboratory usually necessitates elevated biosafety and biocontainment procedures, even with avirulent or vaccine strains. to facilitate downstream biochemical or physical analyses in a biosafety level 1 laboratory environment, effective inactivation without affecting its intrinsic properties is critical. here, we report on the morphological and biochemical changes to y. pestis surfaces following four different fixation met ...201627527609
xenopsylla brasiliensis fleas in plague focus areas, madagascar. 201627513742
outbreak of plague in a high malaria endemic region - nyimba district, zambia, march-may 2015.outbreaks of plague have been recognized in zambia since 1917 (1). on april 10, 2015, zambia's ministry of health was notified by the eastern provincial medical office of possible bubonic plague cases in nyimba district. eleven patients with acute fever and cervical lymphadenopathy had been evaluated at two rural health centers during march 28-april 9, 2015; three patients died. to confirm the outbreak and develop control measures, the zambia ministry of health's field epidemiology training prog ...201627513350
plasmid ppcp1-derived srna hmsa promotes biofilm formation of yersinia pestis.the ability of yersinia pestis to form a biofilm is an important characteristic in flea transmission of this pathogen. y. pestis laterally acquired two plasmids (ppcp1and pmt1) and the ability to form biofilms when it evolved from yersinia pseudotuberculosis. small regulatory rnas (srnas) are thought to play a crucial role in the processes of biofilm formation and pathogenesis.201627492011
cell-free determination of binary complexes that comprise extended protein-protein interaction networks of yersinia pestis.binary protein interactions form the basic building blocks of molecular networks and dynamic assemblies that control all cellular functions of bacteria. although these protein interactions are a potential source of targets for the development of new antibiotics, few high-confidence data sets are available for the large proteomes of most pathogenic bacteria. we used a library of recombinant proteins from the plague bacterium yersinia pestis to probe planar microarrays of immobilized proteins that ...201627489291
resistance of mice of the 129 background to yersinia pestis maps to multiple loci on chromosome 1.yersinia pestis is a gram-negative bacterium that is the causative agent of bubonic and pneumonic plague. it is commonly acquired by mammals such as rodents and humans via the bite of an infected flea. we previously reported that multiple substrains of the 129 mouse background are resistant to pigmentation locus-negative (pgm(-)) yersinia pestis and that this phenotype maps to a 30-centimorgan (cm) region located on chromosome 1. in this study, we have further delineated this plague resistance l ...201627481241
manipulation of interleukin-1β and interleukin-18 production by yersinia pestis effectors yopj and yopm and redundant impact on virulence. 201627474778
plague in iran: its history and current status.plague remains a public health concern worldwide, particularly in old foci. multiple epidemics of this disease have been recorded throughout the history of iran. despite the long-standing history of human plague in iran, it remains difficult to obtain an accurate overview of the history and current status of plague in iran.201627457063
classic spotlight: studies on the low-calcium response of yersinia pestis reveal the secrets of plague pathogenesis. 201627413177
adjunctive corticosteroid treatment against yersinia pestis improves bacterial clearance, immunopathology, and survival in the mouse model of bubonic plague.plague is initiated by yersinia pestis, a highly virulent bacterial pathogen. in late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. the ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. in the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administr ...201627402776
[sympatric speciation of the plague microbe yersinia pestis: monohostal specialization in the host-parasite marmot-flea (marmota sibirica-oropsylla silantiewi) system].an ecological scenario of the origin of the plague microbe that is interpreted in the light of modern darwinism (synthetic theory of evolution) is presented. it is shown that the plague microbe emerged from a clone of the psychrophilic saprozoonotic pseudotuberculosis microbe yersinia pseudotuberculosis o:1b in the mountain steppe landscapes of central asia in the sartan time, 22000-15000 years ago, in the monohostal mongolian marmot (marmota sibirica)-flea (oropsylla silantiewi) host-parasite s ...201627396172
reannotation of yersinia pestis strain 91001 based on omics data.yersinia pestis is among the most dangerous human pathogens, and systematic research of this pathogen is important in bacterial pathogenomics research. to fully interpret the biological functions, physiological characteristics, and pathogenesis of y. pestis, a comprehensive annotation of its entire genome is necessary. the emergence of omics-based research has brought new opportunities to better annotate the genome of this pathogen. here, the complete genome of y. pestis strain 91001 was reannot ...201627382076
proteolysis of plasminogen activator inhibitor-1 by yersinia pestis remodulates the host environment to promote virulence.essentials effect of plasminogen activator inhibitor (pai)-1 on plague and its y. pestis cleavage is unknown. an intranasal mouse model of infection was used to determine the role of pai-1 in pneumonic plague. pai-1 is cleaved and inactivated by the pla protease of y. pestis in the lung airspace. pai-1 impacts both bacterial outgrowth and the immune response to respiratory y. pestis infection. click to hear dr bock discuss pathogen activators of plasminogen.201627377187
plague in arab maghreb, 1940-2015: a review.we reviewed the epidemiology of 49 plague outbreaks that resulted in about 7,612 cases in 30 localities in the arabic maghreb (mauritania, morocco, algeria, tunisia, libya, and egypt) over 75 years. between 1940 and 1950, most cases recorded in morocco (75%) and egypt (20%), resulted from plague imported to mediterranean harbors and transmitted by rat ectoparasites. by contrast, the re-emergence of plague in the southern part of western sahara in 1953 and in northeast libya in 1976 was traced to ...201627376053
differential regulation of c-di-gmp metabolic enzymes by environmental signals modulates biofilm formation in yersinia pestis.cyclic diguanylate (c-di-gmp) is essential for yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. two diguanylate cyclases (dgcs), hmst and hmsd and one phosphodiesterase (pde), hmsp are responsible for the synthesis and degradation of c-di-gmp in y. pestis. here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-gmp levels, and expression of hmst, hmsd, and hmsp in y. ...201627375563
[isolation and biological characteristics on yersinia pestis phage yp060].to isolate and identify the characteristics of yersinia pestis phage yp060 from mice nests in yunnan plague focus.201627346118
immunosuppressive yersinia effector yopm binds dead box helicase ddx3 to control ribosomal s6 kinase in the nucleus of host cells.yersinia outer protein m (yopm) is a crucial immunosuppressive effector of the plaque agent yersinia pestis and other pathogenic yersinia species. yopm enters the nucleus of host cells but neither the mechanisms governing its nucleocytoplasmic shuttling nor its intranuclear activities are known. here we identify the dead-box helicase 3 (ddx3) as a novel interaction partner of y. enterocolitica yopm and present the three-dimensional structure of a yopm:ddx3 complex. knockdown of ddx3 or inhibitio ...201627300509
historical y. pestis genomes reveal the european black death as the source of ancient and modern plague pandemics.ancient dna analysis has revealed an involvement of the bacterial pathogen yersinia pestis in several historical pandemics, including the second plague pandemic (europe, mid-14(th) century black death until the mid-18(th) century ad). here we present reconstructed y. pestis genomes from plague victims of the black death and two subsequent historical outbreaks spanning europe and its vicinity, namely barcelona, spain (1300-1420 cal ad), bolgar city, russia (1362-1400 ad), and ellwangen, germany ( ...201627281573
the effect of growth temperature on the nanoscale biochemical surface properties of yersinia pestis.yersinia pestis, the causative agent of plague, has been responsible for several recurrent, lethal pandemics in history. currently, it is an important pathogen to study owing to its virulence, adaptation to different environments during transmission, and potential use in bioterrorism. here, we report on the changes to y. pestis surfaces in different external microenvironments, specifically culture temperatures (6, 25, and 37 °c). using nanoscale imaging coupled with functional mapping, we illust ...201627259520
mortality risk factors show similar trends in modern and historic populations exposed to plague.plague has been responsible for two major historic pandemics (6th-8th century ce; 14th-19th century ce) and a modern one. the recent malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria yersinia pestis. between september 2014 and april 2015, outbreaks of bubonic and pneumonic plague hit the malagasy population. two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. the ...201627249524
a rapid molecular test for determining yersinia pestis susceptibility to ciprofloxacin by the quantification of differentially expressed marker genes.standard antimicrobial susceptibility tests used to determine bacterial susceptibility to antibiotics are growth dependent and time consuming. the long incubation time required for standard tests may render susceptibility results irrelevant, particularly for patients infected with lethal bacteria that are slow growing on agar but progress rapidly in vivo, such as yersinia pestis. here, we present an alternative approach for the rapid determination of antimicrobial susceptibility, based on the qu ...201627242774
evaluation of yersinia pestis transmission pathways for sylvatic plague in prairie dog populations in the western u.s.sylvatic plague, caused by the bacterium yersinia pestis, is periodically responsible for large die-offs in rodent populations that can spillover and cause human mortalities. in the western us, prairie dog populations experience nearly 100% mortality during plague outbreaks, suggesting that multiple transmission pathways combine to amplify plague dynamics. several alternate pathways in addition to flea vectors have been proposed, such as transmission via direct contact with bodily fluids or inha ...201627234457
season of deltamethrin application affects flea and plague control in white-tailed prairie dog (cynomys leucurus) colonies, colorado, 2008 and 2009, we evaluated the duration of prophylactic deltamethrin treatments in white-tailed prairie dog ( cynomys leucurus ) colonies and compared effects of autumn or spring dust application in suppressing flea numbers and plague. plague occurred before and during our experiment. overall, flea abundance tended to increase from may or june to september, but it was affected by deltamethrin treatment and plague dynamics. success in trapping prairie dogs (animals caught/trap days) declined ...201627195680
effect of storage time and storage conditions on antibody detection in blood samples collected on filter paper.using filter paper to collect blood from wildlife for antibody analysis can be a powerful technique to simplify the collection, transport, and storage of blood samples. despite these advantages, there are limited data that detail how long these samples can be stored and how storage conditions affect antibody longevity. we used blood samples collected on filter paper from coyotes experimentally infected with yersinia pestis to determine optimum sample storage conditions over time. blood samples c ...201627187032
[comparative analysis of the mlva25- and mlva7-typing according to their ability to ascertain focal affiliation of yersinia pestis strains by the example of isolates from the central-caucasian highland natural plague focus].comparative analysis of the mlva25- and mlva7-typing ability to evaluate focal belonging of y. pestis strains by the example of bv. medievalis isolates from the central-caucasian highland natural plague focus was carried out. the mlva25-types of-82 isolates from this area were determined and included into the database containing information on 949 y. pestis strains from other natural foci of russia and other countries. categorical-upgma dendrograms were created on the bases of the data concernin ...201627183721
epidemiological analysis of the eyam plague outbreak of 1665-1666.plague, caused by the bacterium yersinia pestis, is one of the deadliest infectious diseases in human history, and still causes worrying outbreaks in africa and south america. despite the historical and current importance of plague, several questions remain unanswered concerning its transmission routes and infection risk factors. the plague outbreak that started in september 1665 in the derbyshire village of eyam claimed 257 lives over 14 months, wiping out entire families. since previous attemp ...201627170724
ecological opportunity, evolution, and the emergence of flea-borne plague.the plague bacillus yersinia pestis is unique among the pathogenic enterobacteriaceae in utilizing an arthropod-borne transmission route. transmission by fleabite is a recent evolutionary adaptation that followed the divergence of y. pestis from the closely related food- and waterborne enteric pathogen yersinia pseudotuberculosis a combination of population genetics, comparative genomics, and investigations of yersinia-flea interactions have disclosed the important steps in the evolution and eme ...201627160296
[advance to the research of the climate factor effect on the distribution of plague].plague is an anthropozoonotic disease caused by the yersinia pestis ,which developed by many factors including local climate factors. in recent years, more and more studies on the effects of climate on plague were conducted. according to the researches, climate factors (mainly the rainfall and temperature) affected the development and distribution of plague by influencing the abundance of plague host animals and fleas index. the climate also affected the epidemic dynamics and the scope of plague ...201627141906
assessment of live plague vaccine candidates.since its creation in the early twentieth century, live plague vaccine ev has been successfully applied to millions of people without severe complications. this vaccine has been proven to elicit protection against both bubonic and pneumonic plague, and it is still in use in populations at risk mainly in the countries of the former soviet union. despite extensive efforts in developing subunit vaccines, there is a reviving interest in creation of a precisely attenuated strain of yersinia pestis su ...201627076149
multiple antigens of yersinia pestis delivered by live recombinant attenuated salmonella vaccine strains elicit protective immunity against plague.based on our improved novel salmonella vaccine delivery platform, we optimized the recombinant attenuated salmonella typhimurium vaccine (rasv) χ12094 to deliver multiple yersinia pestis antigens. these included lcrv196 (amino acids, 131-326), psn encoded on pya5383 and f1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. oral immunization with χ12094(pya5383) simultaneously stimulated high antibody titers to lcrv, psn and f1 in mice and presented comp ...201627060051
oral vaccination against plague using yersinia pseudotuberculosis.yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. because antibiotic resistant strains of yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. the vaccine strategy described here is based on an oral vaccination wi ...201727046452
[on the origin of hypervirulence of the causative agent of plague].the attempt to combine yersinia pseudotuberculosis and yersinia pestis into one species has been unsupported by microbiologists due to the specific features of the epidemiology and clinical presentations of their induced diseases and to basic differences in their virulence. pseudotuberculosis is predominantly a relatively mild human intestinal infection transmitted through contaminated food and plague is an acute generalized disease with high mortality, which is most frequently transmitted by th ...201627029142
expression and association of the yersinia pestis translocon proteins, yopb and yopd, are facilitated by nanolipoprotein particles.yersinia pestis enters host cells and evades host defenses, in part, through interactions between yersinia pestis proteins and host membranes. one such interaction is through the type iii secretion system, which uses a highly conserved and ordered complex for yersinia pestis outer membrane effector protein translocation called the injectisome. the portion of the injectisome that interacts directly with host cell membranes is referred to as the translocon. the translocon is believed to form a por ...201627015536
temporal progression of pneumonic plague in blood of nonhuman primate: a transcriptomic analysis.early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. the latter could be critical, especially as antibiotic resistance is becoming widespread. in order to examine pre-symptomatic illness, african green monkeys were challenged intranasally with aerosolized yersinia pestis strain co92 and ...201627003632
extraction of aerosol-deposited yersinia pestis from indoor surfaces to determine bacterial environmental decay.public health and decontamination decisions following an event that causes indoor contamination with a biological agent require knowledge of the environmental persistence of the agent. the goals of this study were to develop methods for experimentally depositing bacteria onto indoor surfaces via aerosol, evaluate methods for sampling and enumerating the agent on surfaces, and use these methods to determine bacterial surface decay. a specialized aerosol deposition chamber was constructed, and met ...201626944839
plague in china 2014-all sporadic case report of pneumonic plague.yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. pneumonic plague is rarer than bubonic and septicemic plague. we report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in china in 2014.201626895880
structure of d-alanine-d-alanine ligase from yersinia pestis: nucleotide phosphate recognition by the serine loop.d-alanyl-d-alanine is an essential precursor of bacterial peptidoglycan and is synthesized by d-alanine-d-alanine ligase (ddl) with hydrolysis of atp; this reaction makes ddl an important drug target for the development of antibacterial agents. five crystal structures of ddl from yersinia pestis (ypddl) were determined at 1.7-2.5 å resolution: apo, amp-bound, adp-bound, adenosine 5'-(β,γ-imido)triphosphate-bound, and d-alanyl-d-alanine- and adp-bound structures. ypddl consists of three domains, ...201626894530
manipulation of interleukin-1β and interleukin-18 production by yersinia pestis effectors yopj and yopm and redundant impact on virulence.innate immunity plays a central role in resolving infections by pathogens. host survival during plague, caused by the gram-negative bacterium yersinia pestis, is favored by a robust early innate immune response initiated by il-1β and il-18. these cytokines are produced by a two-step mechanism involving nf-κb-mediated pro-cytokine production and inflammasome-driven maturation into bioactive inflammatory mediators. because of the anti-microbial effects induced by il-1β/il-18, it may be desirable f ...201626884330
spatial distribution patterns of plague hosts: point pattern analysis of the burrows of great gerbils in kazakhstan.the spatial structure of a population can strongly influence the dynamics of infectious diseases, yet rarely is the underlying structure quantified. a case in point is plague, an infectious zoonotic disease caused by the bacterium yersinia pestis. plague dynamics within the central asian desert plague focus have been extensively modelled in recent years, but always with strong uniformity assumptions about the distribution of its primary reservoir host, the great gerbil (rhombomys opimus). yet, w ...201526877580
a deadly path: bacterial spread during bubonic plague.yersinia pestis causes bubonic plague, a fulminant disease where host immune responses are abrogated. recently developed in vivo models of plague have resulted in new ideas regarding bacterial spread in the body. deciphering bacterial spread is key to understanding y. pestis and the immune responses it encounters during infection.201626875618
two distinct yersinia pestis populations causing plague among humans in the west nile region of uganda.plague is a life-threatening disease caused by the bacterium, yersinia pestis. since the 1990s, africa has accounted for the majority of reported human cases. in uganda, plague cases occur in the west nile region, near the border with democratic republic of congo. despite the ongoing risk of contracting plague in this region, little is known about y. pestis genotypes causing human disease.201626866815
effect of temperature and relative humidity on the development times and survival of synopsyllus fonquerniei and xenopsylla cheopis, the flea vectors of plague in madagascar.plague, a zoonosis caused by yersinia pestis, is found in asia, the americas but mainly in africa, with the island of madagascar reporting almost one third of human cases worldwide. in the highlands of madagascar, plague is transmitted predominantly by two flea species which coexist on the island, but differ in their distribution. the endemic flea, synopsyllus fonquerniei, dominates flea communities on rats caught outdoors, while the cosmopolitan flea, xenopsylla cheopis, is found mostly on rats ...201626864070
polymorphism of the cysteine protease yopt from yersinia pestis.antibiotic therapy of plague is hampered by the recent isolation of yersinia pestis strain resistant to all of antibiotics recommended for cure. this has constrained a quest for new antimicrobials taking aim at alternative targets. recently y. pestis cysteine protease yopt has been explored as a potential drug target. targets conserved in the pathogen populations should be more efficacious; therefore, we evaluated intraspecies variability in yopt genes and their products. 114 y. pestis isolates ...201626845766
infection prevalence, bacterial loads, and transmission efficiency in oropsylla montana (siphonaptera: ceratophyllidae) one day after exposure to varying concentrations of yersinia pestis in blood.unblocked fleas can transmit yersinia pestis, the bacterium that causes plague, shortly (≤4 d) after taking an infectious bloodmeal. investigators have measured so-called early-phase transmission (ept) efficiency in various fleas following infection with highly bacteremic blood (≥10(8 )cfu/ml). to date, no one has determined the lower limit of bacteremia required for fleas to acquire and transmit infection by ept, though knowing this threshold is central to determining the length of time a host ...201626843450
feeding behavior modulates biofilm-mediated transmission of yersinia pestis by the cat flea, ctenocephalides felis.the cat flea, ctenocephalides felis, is prevalent worldwide, will parasitize animal reservoirs of plague, and is associated with human habitations in known plague foci. despite its pervasiveness, limited information is available about the cat flea's competence as a vector for yersinia pestis. it is generally considered to be a poor vector, based on studies examining early-phase transmission during the first week after infection, but transmission potential by the biofilm-dependent proventricular- ...201626829486
[risk assessments and control strategies of plague in five key surveillance counties, zhejiang province].to analyze the epidemiology data on plague in five counties in zhejiang province and to evaluate the risk of plague in theses areas.201526813723
eighteenth century yersinia pestis genomes reveal the long-term persistence of an historical plague focus.the 14th-18th century pandemic of yersinia pestis caused devastating disease outbreaks in europe for almost 400 years. the reasons for plague's persistence and abrupt disappearance in europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in europe itself, or successive disease introductions from other locations. here we present five y. pestis genomes from one of the last european outbreaks of plague, from 1722 in marseille, france. the lineage id ...201626795402
whole genome multilocus sequence typing as an epidemiologic tool for yersinia pestis.human plague is a severe and often fatal zoonotic disease caused by yersinia pestis. for public health investigations of human cases, nonintensive whole genome molecular typing tools, capable of defining epidemiologic relationships, are advantageous. whole genome multilocus sequence typing (wgmlst) is a recently developed methodology that simplifies genomic analyses by transforming millions of base pairs of sequence into character data for each gene. we sequenced 13 us y. pestis isolates with kn ...201626778487
detections of yersinia pestis east of the known distribution of active plague in the united states.we examined fleas collected from black-tailed prairie dog (cynomys ludovicianus) burrows from 2009 through 2011 in five national park units east of the known distribution of active plague across the northern great plains for the presence of yersinia pestis. across all national park units, oropsylla tuberculata and oropsylla hirsuta were the most common fleas collected from prairie dog burrows, 42.4% and 56.9%, respectively, of the 3964 fleas collected from burrow swabbing. using a nested pcr ass ...201626771845
genotyping yersinia pestis in historical plague: evidence for long-term persistence of y. pestis in europe from the 14th to the 17th century.ancient dna (adna) recovered from plague victims of the second plague pandemic (14th to 17th century), excavated from two different burial sites in germany, and spanning a time period of more than 300 years, was characterized using single nucleotide polymorphism (snp) analysis. of 30 tested skeletons 8 were positive for yersinia pestis-specific nucleic acid, as determined by qpcr targeting the pla gene. in one individual (mp-19-ii), the pla copy number in dna extracted from tooth pulp was as hig ...201626760973
survival protein a is essential for virulence in yersinia pestis.plague is a highly pathogenic disease caused by the bacterium yersinia pestis. there is currently no vaccine available for prophylaxis and antibiotic resistant strains have been isolated, thus there is a need for the development of new countermeasures to treat this disease. survival protein a (sura) is a chaperone that has been linked to virulence in several species of bacteria, including the close relative yersinia pseudotuberculosis. in this study, we aimed to evaluate the role of sura in viru ...201626724738
modeling the ecologic niche of plague in sylvan and domestic animal hosts to delineate sources of human exposure in the western united states.plague has been established in the western united states (us) since 1900 following the west coast introduction of commensal rodents infected with yersinia pestis via early industrial shipping. over the last century, plague ecology has transitioned through cycles of widespread human transmission, urban domestic transmission among commensal rodents, and ultimately settled into the predominantly sylvan foci that remain today where it is maintained alternatively by enzootic and epizootic transmissio ...201526713244
the hmst 3' untranslated region mediates c-di-gmp metabolism and biofilm formation in yersinia pestis.yersinia pestis, the cause of plague, forms a biofilm in the proventriculus of its flea vector to enhance transmission. biofilm formation in y. pestis is regulated by the intracellular levels of cyclic diguanylate (c-di-gmp). in this study, we investigated the role of the 3' untranslated region (3'utr) in hmst mrna, a transcript that encodes a diguanylate cyclase that stimulates biofilm formation in y. pestis by synthesizing the second messenger c-di-gmp. deletion of the 3'utr increased the half ...201626711808
pneumonic plague: the darker side of yersinia pestis.inhalation of the bacterium yersinia pestis results in primary pneumonic plague. pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of y. pestis as a biological weapon. importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of y. p ...201626698952
nineteen whole-genome assemblies of yersinia pestis subsp. microtus, including representatives of biovars caucasica, talassica, hissarica, altaica, xilingolensis, and ulegeica.the etiologic agent of plague, yersinia pestis, includes two subspecies, of which y. pestis subsp. microtus contains the strains that cause only occasional diseases in humans that are not accompanied by human-to-human transmission. here, we report the draft genome sequences of 19 y. pestis strains (across 6 biovars of y. pestis subsp. microtus).201526634751
plague in a pediatric patient: case report and use of polymerase chain reaction as a diagnostic aid.we report a case of bubonic plaque in a 7-year-old patient who presented with a core temperature of 107°f, seizures, vomiting, altered mental status, and septic shock. this case highlights the utility of polymerase chain reaction (pcr) as a diagnostic aid for rapid presumptive identification of yersinia pestis as well as the importance of correlating pcr results with clinical data. we discuss the various manifestations of plague as they relate to infection control, postexposure prophylaxis, anti ...201426625461
high-throughput screening (hts) by nmr guided identification of novel agents targeting the protein docking domain of yoph.recently we described a novel approach, named high-throughput screening (hts) by nmr that allows the identification, from large combinatorial peptide libraries, of potent and selective peptide mimetics against a given target. here, we deployed the "hts by nmr" approach for the design of novel peptoid sequences targeting the n-terminal domain of yersinia outer protein h (yoph-nt), a bacterial toxin essential for the virulence of yersinia pestis. we aimed at disrupting the protein-protein interact ...201626592695
the origin of a killer revealed by bronze age yersinia genomes.bubonic plaque is caused by yersinia pestis, a deadly pathogen that left deep scars in human history. rasmussen et al. (2015) have now retrieved y. pestis genomes from 2,800- to 5,000-year-old human teeth, shedding new light on origins of the strain that brought black death to europe 670 years ago.201526567502
isothermal solid-phase amplification system for detection of yersinia pestis.dna amplification is required for most molecular diagnostic applications, but conventional polymerase chain reaction (pcr) has disadvantages for field testing. isothermal amplification techniques are being developed to respond to this problem. one of them is the recombinase polymerase amplification (rpa) that operates at isothermal conditions without sacrificing specificity and sensitivity in easy-to-use formats. in this work, rpa was used for the optical detection of solid-phase amplification o ...201626563112
comparative proteomic studies of yersinia pestis strains isolated from natural foci in the republic of georgia.yersinia pestis, the causative agent of plague, is a highly virulent bacterium responsible for millions of human deaths throughout history. in the last decade, two natural plague foci have been described in the republic of georgia from which dozens of y. pestis strains have been isolated. analyses indicate that there are genetic differences between these strains, but it is not known if these differences are also reflected in protein expression. we chose four strains of y. pestis (1390, 1853, 294 ...201526528469
viability of yersinia pestis subcultures in agar stabs.since its identification as the causative agent of plague in 1894, thousands of yersinia pestis strains have been isolated and stored. here, we report the ability of y. pestis to survive up to 47 years in agar stabs, in rubber-stoppered tubes, under refrigeration (+4 to +10°c), although overall subculture recovery rates were poor and inversely related to the length of time stored. genetic characterization of virulence gene presence among these subcultures was suggestive of significant variation ...201626524218
a review of methods for subtyping yersinia pestis: from phenotypes to whole genome sequencing.numerous subtyping methods have been applied to yersinia pestis with varying success. here, we review the various subtyping methods that have been applied to y. pestis and their capacity for answering questions regarding the population genetics, phylogeography, and molecular epidemiology of this important human pathogen. methods are evaluated in terms of expense, difficulty, transferability among laboratories, discriminatory power, usefulness for different study questions, and current applicabil ...201626518910
virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from yersinia the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (dhfr) as a means of a novel drug therapy against plague. potential inhibitors of dhfr from yersinia pestis (ypdhfr) were selected by virtual screening and subjected to docking, molecular dynamics (md) simulations, and poisson-boltzmann surface area method, in order to evaluate their interactions in the active sites of ypdhfr and human dhfr (hssdhfr). the results suggested selectivity for three compound ...201626494420
dissociation of tissue destruction and bacterial expansion during bubonic plague.activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease pla, which activates plasmin and inactivates fibrinolysis inhibitors. pla is encoded by the ppla plasmid. following intradermal inoculation, y. pestis has the capacity to multiply in and cause destruction of the lymph node (ln) drainin ...201526484539
complete protection against pneumonic and bubonic plague after a single oral efficient vaccine against plague is currently available. we previously showed that a genetically attenuated yersinia pseudotuberculosis producing the yersinia pestis f1 antigen was an efficient live oral vaccine against pneumonic plague. this candidate vaccine however failed to confer full protection against bubonic plague and did not produce f1 stably.201526473734
spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague.during pneumonic plague, the bacterium yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. this lesion development and persistence are poorly understood. here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (rna-seq) analysis to identify transcriptional differences between lesion microenvironments. we show that cellular pathways involved in leukocyte migration an ...201526463167
reconstruction of an ancestral yersinia pestis genome and comparison with an ancient sequence.we propose the computational reconstruction of a whole bacterial ancestral genome at the nucleotide scale, and its validation by a sequence of ancient dna. this rare possibility is offered by an ancient sequence of the late middle ages plague agent. it has been hypothesized to be ancestral to extant yersinia pestis strains based on the pattern of nucleotide substitutions. but the dynamics of indels, duplications, insertion sequences and rearrangements has impacted all genomes much more than the ...201526450112
intramuscular immunization of mice with a live-attenuated triple mutant of yersinia pestis co92 induces robust humoral and cell-mediated immunity to completely protect animals against pneumonic plague.earlier, we showed that the δlpp δmsbb δail triple mutant of yersinia pestis co92 with deleted genes encoding braun lipoprotein (lpp), an acyltransferase (msbb), and the attachment invasion locus (ail), respectively, was avirulent in a mouse model of pneumonic plague. in this study, we further evaluated the immunogenic potential of the δlpp δmsbb δail triple mutant and its derivative by different routes of vaccination. mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) r ...201526446423
yersinia pestis and yersinia pseudotuberculosis infection: a regulatory rna perspective.yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. an ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. one idea is that c ...201526441890
molecualr cloning of the capsular antigen f1 of yersinia pestis in pbad/giii plasmid.yersinia pestis which is the causative agent of pneumonic plague and distributed in all continents has led to many deaths during the history. because of its high mortality rate, it must be diagnosed and treated at the earliest time post infection and therefore, rapid diagnostic tests are required. in the present study, we cloned the coding sequence of f1 capsular antigen of the bacteria in the pbad/giii plasmid for later expression and purification of the protein to produce poly and monoclonal a ...201726430461
[analysis of the nucleotide sequence of a cryptic plasmid from yersinia pestis strains in the central caucasian high-mountain plague focus].an analysis of a 5.4-kbp cryptic plasmid detected in the course of whole-genome sequencing of the yersinia pestis medieval biovar isolated in the russian central caucasian high-mountain plague focus was performed. the identification of the nucleotide sequence of this cryptic plasmid and its structural and functional analysis revealed that it contained eight open reading frames, among which the following genes were identified: the rep gene of a replication protein, the virb6 gene of a type-iv sec ...201526410928
genome assemblies for 11 yersinia pestis strains isolated in the caucasus region.yersinia pestis, the causative agent of plague, is endemic to the caucasus region but few reference strain genome sequences from that region are available. here, we present the improved draft or finished assembled genomes from 11 strains isolated in the nation of georgia and surrounding countries.201526383663
finished genome assembly of yersinia pestis ev76d and kim, we sequenced the completed genome of yersinia pestis ev76d and kim 10v, two genomes used as references in assay development, to improved high-quality draft status.201526383662
burrowing owls, pulex irritans, and plague.western burrowing owls (athene cunicularia hypugaea) are small, ground-dwelling owls of western north america that frequent prairie dog (cynomys spp.) towns and other grasslands. because they rely on rodent prey and occupy burrows once or concurrently inhabited by fossorial mammals, the owls often harbor fleas. we examined the potential role of fleas found on burrowing owls in plague dynamics by evaluating prevalence of yersinia pestis in fleas collected from burrowing owls and in owl blood. dur ...201526367482
role of the yersinia yopj protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes.polymorphonuclear leukocytes, in addition to their direct bactericidal activities, produce cytokines involved in the activation and regulation of the innate and adaptive immune response to infection. in this study we evaluated the cytokine response of human pmns following incubation with the pathogenic yersinia species. yersinia pestis strains with the pcd1 virulence plasmid, which encodes cytotoxic yop proteins that are translocated into host cells, stimulated little or no cytokine production c ...201626361732
[on the origin of yersinia pestis, a causative agent of the plague: a concept of population-genetic macroevolution in transitive environment].an ecological scenario is proposed for the origin of causative agent of the plague (the bacterium yersenia pestis) from the clone of pseudotuberculous microbe of the first serotype y. pseudotuberculosis o:1b. disclosed are the conditions of gradual intrusion of psychrophile saprozoonosis ancestor into the blood of the primary host, mongolian tarbagan marmot marmota sibirica. as an inductor of speciation acted the sartan cooling that occurred in the end of late pleistocene under conditions of ari ...201526353398
the role of early-phase transmission in the spread of yersinia pestis.early-phase transmission (ept) of yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. we review evidence demonstrating ept and current knowledge on its biological and biomechanical processes. we discuss the importance of ept in the epizootic spread of y. pestis and its role in the maintenance of plague bacteria in nature. we further address the role of ept in the epidemiology of plague.201526336267
the perfect burrow, but for what? identifying local habitat conditions promoting the presence of the host and vector species in the kazakh plague system.the wildlife plague system in the pre-balkhash desert of kazakhstan has been a subject of study for many years. much progress has been made in generating a method of predicting outbreaks of the disease (infection by the gram negative bacterium yersinia pestis) but existing methods are not yet accurate enough to inform public health planning. the present study aimed to identify characteristics of individual mammalian host (rhombomys opimus) burrows related to and potentially predictive of the pre ...201526325073
use of insecticide delivery tubes for controlling rodent-associated fleas in a plague endemic region of west nile, uganda.plague is a primarily flea-borne rodent-associated zoonosis that is often fatal in humans. our study focused on the plague-endemic west nile region of uganda where affordable means for the prevention of human plague are currently lacking. traditional hut construction and food storage practices hinder rodent exclusion efforts, and emphasize the need for an inexpensive but effective host-targeted approach for controlling fleas within the domestic environment. here we demonstrate the ability of an ...201426309315
redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of yoph: virulence factor of yersinia pestis.yoph is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing yersinia sp. bacteria. inactivation of yoph activity would lead to the loss of bacterial pathogenicity. we have studied the inhibitory properties of aurintricarboxylic acid (ata) against yoph phosphatase and found that at nanomolar concentrations ata reversibly decreases the activity of yoph. computational docking studies indicated that in all binding poses ata bi ...201526286963
the lcrg tip chaperone protein of the yersinia pestis type iii secretion system is partially folded.the type iii secretion system (t3ss) is essential in the pathogenesis of yersinia pestis, the causative agent of plague. a small protein, lcrg, functions as a chaperone to the tip protein lcrv, and the lcrg-lcrv interaction is important in regulating protein secretion through the t3ss. the atomic structure of the lcrg family is currently unknown. however, because of its predicted helical propensity, many have suggested that the lcrg family forms a coiled-coil structure. here, we show by nmr and ...201526259880
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
characterization of a cynomolgus macaque model of pneumonic plague for evaluation of vaccine efficacy.the efficacy of a recombinant plague vaccine (rf1v) was evaluated in cynomolgus macaques (cms) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of yersinia pestis strain colorado 92. cms were vaccinated with a range of rf1v doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. the humoral immune response following vaccination was evaluated with anti-rf1, anti-rv, and anti-rf1 ...201526224691
plague in egypt: disease biology, history and contemporary analysis: a minireview.plague is a zoonotic disease with a high mortality rate in humans. unfortunately, it is still endemic in some parts of the world. also, natural foci of the disease are still found in some countries. thus, there may be a risk of global plague re-emergence. this work reviews plague biology, history of major outbreaks, and threats of disease re-emergence in egypt. based on the suspected presence of potential natural foci in the country, the global climate change, and the threat posed by some neighb ...201526199744
map of f1 and v antigens from yersinia pestis astride innate and adaptive immune response.yersinia pestis, a causative agent of plague, has a plethora of armors to fight against major components of innate immunity and survive within host cells. dendritic cells and macrophages are important antigen presenting cells for effective immune response. this report is focused on the changes in dc activation and tlr2 and tlr4 expression on macrophages induced by map of f1 and v antigens of y. pestis. f1 and v maps bear potential synthetic t and b cell epitopes from f1 and v protein respectivel ...201526188288
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