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Paul M Arnaboldi, Mariya Sambir, Christina D'Arco, Lauren A Peters, Jos F M L Seegers, Lloyd Mayer, Alison A McCormick, Raymond J Dattwyler
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 subunit vaccine comprised of the Y...
October 13, 2016: Vaccine
Martin Aepfelbacher, Manuel Wolters
Pathogenic bacteria of the genus Yersinia include Y. pestis-the agent of plaque-and two enteropathogens, Y. enterocolitica, and Y. pseudotuberculosis. These pathogens have developed an array of virulence factors aimed at manipulating Rho GTP-binding proteins and the actin cytoskeleton in host cells to cross the intestinal barrier and suppress the immune system. Yersinia virulence factors include outer membrane proteins triggering cell invasion by binding to integrins, effector proteins injected into host cells to manipulate Rho protein functions and a Rho protein-activating exotoxin...
October 16, 2016: Current Topics in Microbiology and Immunology
Didier Raoult
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 plague of the Middle Ages)...
August 2016: Microbiology Spectrum
Ruifu Yang, Yujun Cui, Yujing Bi
Yersinia pestis is a typical zoonotic bacterial pathogen. The following reasons make this pathogen a model for studying zoonotic pathogens: (1) Its unique lifestyle makes Y. pestis an ideal model for studying host-vector-environment-pathogen interactions; (2) population diversity characters in Y. pestis render it a model species for studying monomorphic bacterial evolution; (3) the pathogenic features of bacteria provide us with good opportunities to study human immune responses; (4) typical animal and vector models of Y...
2016: Advances in Experimental Medicine and Biology
Xiangna Zhao, Mikael Skurnik
Bacteriophage play many varied roles in microbial ecology and evolution. This chapter collates a vast body of knowledge and expertise on Yersinia pestis phages, including the history of their isolation and classical methods for their isolation and identification. The genomic diversity of Y. pestis phage and bacteriophage islands in the Y. pestis genome are also discussed because all phage research represents a branch of genetics. In addition, our knowledge of the receptors that are recognized by Y. pestis phage, advances in phage therapy for Y...
2016: Advances in Experimental Medicine and Biology
Wei Sun
Three major plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people in human history. Due to its extreme virulence and the ease of its transmission, Y. pestis has been used purposefully for biowarfare in the past. Currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the United States. Approximately 2000 cases of plague are reported each year to the World Health Organization. However, the potential use of the bacteria in modern times as an agent of bioterrorism and the emergence of a Y...
2016: Advances in Experimental Medicine and Biology
Yujing Bi
As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase...
2016: Advances in Experimental Medicine and Biology
Ruifu Yang, Vladimir L Motin
As omics-driven technologies developed rapidly, genomics, transcriptomics, proteomics, metabolomics and other omics-based data have been accumulated in unprecedented speed. Omics-driven big data in biology have changed our way of research. "Big science" has promoted our understanding of biology in a holistic overview that is impossibly achieved by traditional hypothesis-driven research. In this chapter, we gave an overview of omics-driven research on Y. pestis, provided a way of thinking on Yersinia pestis research in the age of big data, and made some suggestions to integrate omics-based data for systems understanding of Y...
2016: Advances in Experimental Medicine and Biology
Yanping Han, Haihong Fang, Lei Liu, Dongsheng Zhou
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 expression is critical for environmental adaptation or survival, primarily reflected by genetic regulation mediated by transcriptional factors and small regulatory RNAs at the transcriptional and posttranscriptional level, respectively...
2016: Advances in Experimental Medicine and Biology
Zongmin Du, Xiaoyi Wang
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 deadly plague, whereas the other two closely related enteropathogenic Yersinia species merely cause limited gastrointestinal manifestations...
2016: Advances in Experimental Medicine and Biology
Yujun Cui, Yajun Song
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" node that is associated with the Black Death...
2016: Advances in Experimental Medicine and Biology
Vladimir M Dubyanskiy, Aidyn B Yeszhanov
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 plague and predictive models are briefly described...
2016: Advances in Experimental Medicine and Biology
Robert R Brubaker
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 derepression of the pigmentation locus facilitating colonization of the flea vector...
2016: Advances in Experimental Medicine and Biology
Zhizhen Qi, Yujun Cui, Qingwen Zhang, Ruifu Yang
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 composition, and bacterial mass fingerprinting were also used to identify the populations within Y...
2016: Advances in Experimental Medicine and Biology
Barbara Bramanti, Nils Chr Stenseth, Lars Walløe, Xu Lei
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 there were reservoirs for Y...
2016: Advances in Experimental Medicine and Biology
Ricci P H Yue, Harry F Lee, Connor Y H Wu
Infectious diseases have become a rising challenge to mankind in a globalizing world. Yet, little is known about the inland transmission of infectious diseases in history. In this study, we based on the spatio-temporal information of 5559 plague (Yersinia pestis) outbreaks in Europe and its neighboring regions in AD1347-1760 to statistically examine the connection between navigable rivers and plague outbreak. Our results showed that 95.5% of plague happened within 10 km proximity of navigable rivers. Besides, the count of plague outbreak was positively correlated with the width of river and negatively correlated with the distance between city and river...
October 10, 2016: Scientific Reports
R A Alhotan, D V Vedenov, G M Pesti
The use of non-linear regression models in the analysis of biological data has led to advances in poultry nutrition. Spline or broken-line nonlinear regression models are commonly used to estimate nutritional requirements. One particular application of broken-line models is estimating the maximum safe level (MSL) of feed ingredients beyond which the ingredients become toxic, resulting in reduced performance. The objectives of this study were to evaluate the effectiveness of broken-line models (broken-line linear or BLL; and broken-line quadratic or BLQ) in estimating the MSL; to identify the most efficient design of feeding trials by finding the optimal number of ingredient levels and replications; and to re-estimate the MSL of various test ingredients reported in the nutrition literature for comparison purposes...
October 4, 2016: Poultry Science
Tony D Davis, Poornima Mohandas, Maria I Chiriac, Glennon V Bythrow, Luis E N Quadri, Derek S Tan
Biosynthesis of bacterial natural-product virulence factors is emerging as a promising antibiotic target. Many such natural products are produced by nonribosomal peptide synthetases (NRPS) from amino acid precursors. To develop selective inhibitors of these pathways, we have previously described aminoacyl-AMS (sulfamoyladenosine) macrocycles that inhibit NRPS amino acid adenylation domains but not mechanistically-related aminoacyl-tRNA synthetases. To improve the cell permeability of these inhibitors, we explore herein replacement of the α-amino group with an α-hydroxy group...
September 16, 2016: Bioorganic & Medicinal Chemistry Letters
Géraldine San Jose, Emily R Jackson, Amanda Haymond, Chinchu Johny, Rachel L Edwards, Xu Wang, R Carl Brothers, Emma K Edelstein, Audrey R Odom, Helena I Boshoff, Robin D Couch, Cynthia S Dowd
Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production...
October 12, 2016: ACS Infectious Diseases
Amy J Vogler, Roxanne Nottingham, Joseph D Busch, Jason W Sahl, Megan M Shuey, Jeffrey T Foster, James M Schupp, Susan R Smith, Tonie E Rocke, Paul Keim, David M Wagner
Underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. Although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. Here, we investigated tissue samples and Yersinia pestis isolates from a rodent laboratory challenge with strain CO92 using whole genome sequencing and multi-locus variable-number tandem repeat (VNTR) analysis (MLVA). We identified six VNTR mutations that were found to have occurred in vitro during laboratory cultivation rather than in vivo during the rodent challenge...
September 21, 2016: Infection, Genetics and Evolution
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