Global Expression Studies of Yersinia Pestis Pathogenicity

Global Expression Studies of Yersinia Pestis Pathogenicity PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
The aim of these studies continues to be the investigation into the molecular mechanisms that underlie the virulence process in Yersinia pestis. In particular, the focus of this work centers on the identification of novel genes and pathways responsible for the pathogenic properties of this organism. In spite of more than four decades of intense investigation in this field, the dilemma as to what makes Y. pestis such a virulent and lethal pathogen remains unanswered. The method being employed makes use microarray technology (DNA chip) that enables the examination of the global activities of the whole complement of genes in this pathogen. Two primary resources available to the investigators (one directly obtained from a separate CBNP-funded project) make these studies possible: (1) Whole genome comparisons of the genes in Y. pestis and its near neighbors with attenuated or non pathogenic characteristics, and (2) the ability to duplicate in vitro, conditions that mimic the infection process of this pathogen. This year we have extended our studies from the original work of characterizing the global transcriptional regulation in Y. pestis triggered during temperature transition from 26 C to 37 C (roughly conditions found in the flea vector and the mammalian host, respectively) to studies of regulation encountered during shift between growth from conditions of neutral pH to acidic pH (the latter conditions, those mimic the environment found inside macrophages, a likely environment found by these cells during infection.). For this work, DNA arrays containing some 5,000 genes (the entire genome of Y. pestis plus those genes found uniquely in the enteropathogen, and near neighbor, Y. pseudotuberculosis) are used to monitor the simultaneous expression levels of each gene of known and unknown function in Y. pestis. Those genes that are up-regulate under the experimental conditions represent genes potentially involved in the pathogenic process. The ultimate role in pathogenicity of those candidate genes uncovered from these studies will be further ascertained by direct knock outs (gene inactivation) and by in vivo studies using an animal model. Discovery of new virulence factors in Y. pestis will directly impact the development of new signatures for detection and geo-location since it will help us to understand and identify those genes that are essential in making the organism pathogenic. These are genes that cannot be altered or removed from the pathogen and as such constitute the best type of signature that we can utilize in their detection and identification. Applications such as this will also enable the utilization of similar technologies to study other pathogens such as Francisella and Brucella, for which we know substantially less in terms of their modality of virulence.

Global Expression Studies of Yersinia Pestis Pathogenicity

Global Expression Studies of Yersinia Pestis Pathogenicity PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :

Get Book Here

Book Description
The aim of these studies continues to be the investigation into the molecular mechanisms that underlie the virulence process in Yersinia pestis. In particular, the focus of this work centers on the identification of novel genes and pathways responsible for the pathogenic properties of this organism. In spite of more than four decades of intense investigation in this field, the dilemma as to what makes Y. pestis such a virulent and lethal pathogen remains unanswered. The method being employed makes use microarray technology (DNA chip) that enables the examination of the global activities of the whole complement of genes in this pathogen. Two primary resources available to the investigators (one directly obtained from a separate CBNP-funded project) make these studies possible: (1) Whole genome comparisons of the genes in Y. pestis and its near neighbors with attenuated or non pathogenic characteristics, and (2) the ability to duplicate in vitro, conditions that mimic the infection process of this pathogen. This year we have extended our studies from the original work of characterizing the global transcriptional regulation in Y. pestis triggered during temperature transition from 26 C to 37 C (roughly conditions found in the flea vector and the mammalian host, respectively) to studies of regulation encountered during shift between growth from conditions of neutral pH to acidic pH (the latter conditions, those mimic the environment found inside macrophages, a likely environment found by these cells during infection.). For this work, DNA arrays containing some 5,000 genes (the entire genome of Y. pestis plus those genes found uniquely in the enteropathogen, and near neighbor, Y. pseudotuberculosis) are used to monitor the simultaneous expression levels of each gene of known and unknown function in Y. pestis. Those genes that are up-regulate under the experimental conditions represent genes potentially involved in the pathogenic process. The ultimate role in pathogenicity of those candidate genes uncovered from these studies will be further ascertained by direct knock outs (gene inactivation) and by in vivo studies using an animal model. Discovery of new virulence factors in Y. pestis will directly impact the development of new signatures for detection and geo-location since it will help us to understand and identify those genes that are essential in making the organism pathogenic. These are genes that cannot be altered or removed from the pathogen and as such constitute the best type of signature that we can utilize in their detection and identification. Applications such as this will also enable the utilization of similar technologies to study other pathogens such as Francisella and Brucella, for which we know substantially less in terms of their modality of virulence.

Advances in Yersinia Research

Advances in Yersinia Research PDF Author: Alzira Maria Paiva de Almeida
Publisher: Springer Science & Business Media
ISBN: 1461435617
Category : Medical
Languages : en
Pages : 363

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Book Description
This book is a collection of articles written by prominent scientists who gathered in the city of Recife, Brazil, 23-27 October 2010, celebrating the 10th International Symposium on Yersinia. The event is held every four years in a different country and for the Yersinia 2010, an interesting and updated program covering advances in research in Yersiniae was organized. The major advances achieved over the past four years since the last symposium held in Lexington, USA in 2006 were divided into eight chapters: Epidemiology, Clinical, Diagnostic and Therapeutic aspects; Ecology and Modeling; Genomic/Transcriptomics and Large Scale Population; Immune Response and Vaccine; Pathogenesis and Pathogenicity Factors; Cellular Yersiniology; Bacterial Structure and Metabolism: Roles in Pathogenesis and Bacterial Life Style. The purpose of the book is to extend cutting edge knowledge on Yersinia discussed during the 10th International Symposium.

The pathogenic Yersiniae – advances in the understanding of physiology and virulence

The pathogenic Yersiniae – advances in the understanding of physiology and virulence PDF Author: Matthew S. Francis
Publisher: Frontiers E-books
ISBN: 288919258X
Category : Infectious and parasitic diseases
Languages : en
Pages : 200

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Book Description
From early studies of the plague causing agent through to comparatively more recent research defining aspects of the type III secretion mechanism, pathogenic Yersinia have served as an inventive model organism for researchers seeking to understand the complexities of bacteria-host cell interactions. In fact, seminal studies on Yersinia virulence mechanisms contributed to the emergence and recognition of the research field – cellular microbiology. Researching Yersinia infection biology continues to bring to light novel discoveries. Assortments of Yersinia whole genome sequencing projects are providing unparalleled insight into bacterial pathogen evolution and environmental adaptation. This is enabling researchers to identify and define more fascinating virulence and/or survival mechanisms that advance and expand existing perceptions of bacterial-host encounters. Current research is also beginning to bring to light how the pathogenic Yersiniae respond to physicochemical environmental cues to spatially and temporally control their armoury of customized virulence/survival factors. This Research Topic is therefore focused on presenting and summarizing new developments in Yersinia pathogenicity through highlighting cutting-edge studies on the Yersinia-host cell interaction and the network of regulatory control mechanisms that define this outcome. It will also endeavour to address how such findings might influence selection of potential targets for the design and development of anti-Yersinia therapeutic drugs and vaccines, as well as identify translational studies that involve unique and rewarding cooperation between diverse disciplines

Yersinia pestis: Retrospective and Perspective

Yersinia pestis: Retrospective and Perspective PDF Author: Ruifu Yang
Publisher: Springer
ISBN: 9402408908
Category : Medical
Languages : en
Pages : 397

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Book Description
This book addresses nearly every aspect of Y. pestis, approaching it from a new perspective. Topics covered include the history, epidemiology, physiology, ecology, genome, evolution, pathogenesis, host-pathogen interaction, big-data-driven research, vaccines, clinical aspects and future research trends. For centuries, scientists have sought to determine where Y. pestis, the most well-known bacterium and one that has caused a number of high-mortality epidemics throughout human history, comes from, what it is and how it causes the disease. This book works to answer these questions with the help of cutting-edge research results. It not only describes the history of plagues, but also stresses plagues’ effects on human civilization and explores the interaction of Y. pestis with hosts, vectors and the environment to reveal the evolution and pathogenesis. The book offers a valuable guide for researchers and graduate students studying Y. pestis, and will also benefit researchers from other fields, such as infectious diseases, other pathogens and system biology, sharing key insights into bacterial pathogen studies.

The Genus Yersinia:

The Genus Yersinia: PDF Author: Robert D. Perry
Publisher: Springer Science & Business Media
ISBN: 0387721231
Category : Medical
Languages : en
Pages : 454

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Book Description
The 9th International Symposium on Yersinia was held in Lexington, Kentucky, USA on October 10-14, 2006. Over 250 Yersinia researchers from 18 countries gathered to present and discuss their research. In addition to 37 oral presentations, there were 150 poster presentations. This Symposium volume is based on selected presentations from the meeting and contains both reviews and research articles. It is divided into six topic areas: 1) genomics; 2) structure and metabolism; 3) regulatory mechanisms; 4) pathogenesis and host interactions; 5) molecular epidemiology and detection; and 6) vaccine and antimicrobial therapy development. Consequently, this volume covers a wide range of current research areas in the Yersinia field.

The Genus Yersinia

The Genus Yersinia PDF Author: Mikael Skurnik
Publisher: Springer Science & Business Media
ISBN: 0306477599
Category : Science
Languages : en
Pages : 484

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Book Description
For the eighth time the yersiniologists all over the world gathered together when the International Symposium on Yersinia was organized by University of Turku and Turku Microbiology Society in Turku, Finland. Over 250 delegates from 28 countries attended the Symposium. The Symposium logo (Picture 4, next page) presents a bacteriophage attached to the surface of the bacterium. One can easily imagine that most of the aspects covered in this Symposium are included in the logo: the bacteriophage genome encodes for structural proteins, adhesins and effector proteins that interact with the host cell in most intricate ways to carry out their mission. Life of the bacteriophage depends on the tightly regulated interplay between the phage and the host proteins. This all is also true between Yersinia and the different hosts and environments it encounters during its life cycle. This Symposium Proceedings volume is based on the oral and poster presentations given during the Symposium. The volume has been divided into six parts covering topics such as genomics, surface structures, bacteriophages, molecular and cellular pathogenesis, molecular epidemiology and diagnostics, gene regulation, clinical aspects and vaccines. These topics reflect righteously the present trends in the bacteriology research.

Yersinia Pestis OmpX Virulence Factor and Role in Host Cell Attachment, Internalization, and Immune Modulation

Yersinia Pestis OmpX Virulence Factor and Role in Host Cell Attachment, Internalization, and Immune Modulation PDF Author: Anna Maria Kolodziejek
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 354

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Book Description
Yersinia pestis is the causative agent of plague. Multiple virulence determinants contribute to its highly efficient transmission and pathogenicity. These include factors inherited from its enteric predecessors; Y. entrocolitica and Y. pseudotuberculosis, as well as phenotypes that were acquired or lost during Y. pestis evolution. Representatives of a large Enterobacteriaceae Ail/Lom family of outer membrane proteins (Omp) are found in the genomes of all pathogenic Yersiniae . They promote adherence and internalization to epithelial cells, resistance to complement, and survival in macrophages. Even though well studied in enteric Yersiniae, their role in Y. pestis pathogenesis is unknown. To investigate the role of Y. pestis OmpX protein, an Ail homologue, in adherence and internalization to epithelial cells, resistance to complement, and virulence, we generated site-directed mutations in ompX and tested them for loss of any of these phenotypes. Our results demonstrated that OmpX was required for adherence and internalization to epithelial cells, and serum resistance. Infection studies revealed that loss of OmpX delayed the time-to-death in the mouse infection model of pneumonic plague. Because murine serum was not bactericidal for the ompX mutant, the mechanism underlying the delay in time-to-death in mice may be attributed to loss of adhesion/internalization properties, but not serum resistance. When OmpX virulence was assessed in the rat model complete attenuation of virulence was observed. This highlighted the critical role of serum resistance in primary pneumonic plague and showed its relevance for human disease. To resolve conflicting evidence for Y. pestis LPS and OmpX contributions to serum resistance, we expressed the protein in E. coli and its isogenic derivatives with progressively truncated LPS core saccharides. Our results showed that OmpX-mediated serum resistance, adhesiveness, and invasiveness were dependent on LPS core length, but recombinant OmpX displayed these functions in E. coli, independently of other Yersinia proteins and/or LPS. Also, our results showed that OmpX-mediated autoaggregation was required for efficient adhesiveness and internalization but not for serum resistance. Overall, our data present an important contribution to understanding mechanisms of Y. pestis pathogenesis and their significance to human species.

The Prokaryotes

The Prokaryotes PDF Author: Martin Dworkin
Publisher: Springer
ISBN: 9780387334882
Category : Science
Languages : en
Pages : 959

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Book Description
With the launch of its first electronic edition, The Prokaryotes, the definitive reference on the biology of bacteria, enters an exciting new era of information delivery. Subscription-based access is available. The electronic version begins with an online implementation of the content found in the printed reference work, The Prokaryotes, Second Edition. The content is being fully updated over a five-year period until the work is completely revised. Thereafter, material will be continuously added to reflect developments in bacteriology. This online version features information retrieval functions and multimedia components.

Disasters and Public Health

Disasters and Public Health PDF Author: Bruce W. Clements
Publisher: Butterworth-Heinemann
ISBN: 0128019891
Category : Political Science
Languages : en
Pages : 526

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Book Description
Disasters and Public Health: Planning and Response, Second Edition, examines the critical intersection between emergency management and public health. It provides a succinct overview of the actions that may be taken before, during, and after a major public health emergency or disaster to reduce morbidity and mortality. Five all-new chapters at the beginning of the book describe how policy and law drive program structures and strategies leading to the establishment and maintenance of preparedness capabilities. New topics covered in this edition include disaster behavioral health, which is often the most expensive and longest-term recovery challenge in a public health emergency, and community resilience, a valuable resource upon which most emergency programs and responses depend. The balance of the book provides an in-depth review of preparedness, response, and recovery challenges for 15 public health threats. These chapters also provide lessons learned from responses to each threat, giving users a well-rounded introduction to public health preparedness and response that is rooted in experience and practice. - Contains seven new chapters that cover law, vulnerable populations, behavioral health, community resilience, preparedness capabilities, emerging and re-emerging infectious diseases, and foodborne threats - Provides clinical updates by new MD co-author - Includes innovative preparedness approaches and lessons learned from current and historic public health and medical responses that enhance clarity and provide valuable examples to readers - Presents increased international content and case studies for a global perspective on public health

Structural Studies on Toxins and Virulence Factors of Yersinia Pestis

Structural Studies on Toxins and Virulence Factors of Yersinia Pestis PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 11

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Book Description
In this annual report we present our continuing efforts on two or three fronts. We are working on the expression purification and crystallization of complexes of YopB and YopD with other proteins like their chaperones. We have made progress in purifying YopB:YopD:SycD complex. If successful this will help in understanding the translocation mechanism of effector proteins. Our crystallization efforts on YopH and SycD are continuing.