Proteomic Characterization of Host Response to Yersinia Pestis

Proteomic Characterization of Host Response to Yersinia Pestis PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 20

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Book Description
Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.

Proteomic Characterization of Host Response to Yersinia Pestis

Proteomic Characterization of Host Response to Yersinia Pestis PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 20

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Book Description
Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.

Subcellular Proteomic Analysis of Host-pathogen Interactions Using Human Monocytes Exposed to Yersinia Pestis and Yersinia Pseudotuberculosis

Subcellular Proteomic Analysis of Host-pathogen Interactions Using Human Monocytes Exposed to Yersinia Pestis and Yersinia Pseudotuberculosis PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 48

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Book Description
Yersinia pestis, the etiological agent of plague, is of concern to human health both from an infectious disease and a civilian biodefense perspective. While Y. pestis and Y. pseudotuberculosis share more than 90% DNA homology, they have significantly different clinical manifestations. Plague is often fatal if untreated, yet Y. pseudotuberculosis causes severe intestinal distress and is rarely fatal. A better understanding of host response to these closely related pathogens may help explain the different mechanisms of virulence and pathogenesis that result in such different clinical outcomes. The aim of this study was to characterize host protein expression changes in human monocyte-like U937 cells after exposure to Y. pestis and Y. pseudotuberculosis. In order to gain global proteomic coverage of host response, proteins from cytoplasmic, nuclear and membrane fractions of host cells were studied by 2-dimensional differential gel electrophoresis (2-D DIGE) and relative protein expression differences were quantitated. Differentially expressed proteins, with at least 1.5 fold expression changes and p values of 0.01 or less, were identified by MALDI-MS or LC/MS/MS. With these criteria, differential expression was detected in 16 human proteins after Y. pestis exposure and 13 human proteins after Y. pseudotuberculosis exposure, of which only two of the differentially expressed proteins identified were shared between the two exposures. Proteins identified in this study are reported to be involved in a wide spectrum of cellular functions and host defense mechanisms including apoptosis, cytoskeletal rearrangement, protein synthesis and degradation, DNA replication and transcription, metabolism, protein folding, and cell signaling. Notably, the differential expression patterns observed can distinguish the two pathogen exposures from each other and from unexposed host cells. The functions of the differentially expressed proteins identified provide insight on the different virulence and pathogenic mechanisms of Y. pestis and Y. pseudotuberculosis.

Proteomic Characterization of Yersinia Pestis Virulence

Proteomic Characterization of Yersinia Pestis Virulence PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 35

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Book Description
Yersinia pestis, the etiological agent of plague, functions via the Type III secretion mechanism whereby virulence factors are induced upon interactions with a mammalian host. Here, the Y. pestis proteome was studied by two-dimensional differential gel electrophoresis (2-D DIGE) under physiologically relevant growth conditions mimicking the calcium concentrations and temperatures that the pathogen would encounter in the flea vector and upon interaction with the mammalian host. Over 4100 individual protein spots were detected of which hundreds were differentially expressed in the entire comparative experiment. A total of 43 proteins that were differentially expressed between the vector and host growth conditions were identified by mass spectrometry. Expected differences in expression were observed for several known virulence factors including catalase-peroxidase (KatY), murine toxin (Ymt), plasminogen activator (Pla), and F1 capsule antigen (Caf1), as well as putative virulence factors. Chaperone proteins and signaling molecules hypothesized to be involved in virulence due to their role in Type III secretion were also identified. Other differentially expressed proteins not previously reported to contribute to virulence are candidates for more detailed mechanistic studies, representing potential new virulence determinants. For example, several sugar metabolism proteins were differentially regulated in response to lower calcium and higher temperature, suggesting these proteins, while not directly connected to virulence, either represent a metabolic switch for survival in the host environment or may facilitate production of virulence factors. Results presented here contribute to a more thorough understanding of the virulence mechanism of Y. pestis through proteomic characterization of the pathogen under induced virulence.

Profiling the Host-pathogen Interaction of Yersinia Pestis, the Causative Agent of Plague and the Immune Response of the Coyote, a Disease Refractory Host

Profiling the Host-pathogen Interaction of Yersinia Pestis, the Causative Agent of Plague and the Immune Response of the Coyote, a Disease Refractory Host PDF Author: Giulia Vernati
Publisher:
ISBN: 9781124296951
Category : Coyote
Languages : en
Pages : 55

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Book Description
Yersinia pestis, the bacterium responsible for causing plague, is identified by the Centers of Disease Control (CDC) as a category A bioterrorism agent. Although classified as a "high virulence" pathogen, some host species while susceptible to infection, are resistant to disease. As such, coyotes (Canis latrans) generally exhibit mild, if any symptoms during infection, but with stimulation of adaptive immunity as evidenced by development of a humoral immune response. In an effort to further define the nature of the coyote antibody response to plague and its potential role in contributing to the disease-refractory nature of this host, a qualitative serologic analysis was conducted to assess differences and similarities in the anti-plague antibody repertoire when compared with disease-susceptible hosts. Western blots of Yersinia pestis plasmid-encoded recombinant proteins were examined with pooled rabbit, coyote and prairie dog serum from animals with serologically-confirmed Y. pestis infections. The rabbit serum originated from animals which were experimentally infected via aerosol route or subcutaneously with wt Yersinia pestis CO92. The coyote serum was collected from free-range coyotes and the presence of antibodies to Y. pestis F1 antigen serologically confirmed. The prairie dog serum was collected from colony survivors of epizootic outbreak's occurring in two distinct geographic locations i.e. Colorado and Texas. When comparisons among the different species were made, results revealed a similar antibody profile exists between the coyote, Colorado colony prairie dog and rabbits infected subcutaneously. Similarly, the Texas colony prairie dogs shared a similar profile to the rabbits experimentally infected via aerosol route. These results suggest that among other factors, host response may be dependent on the organism's route of entry. Additionally, assessment of the immunogenicity of several Y. pestis virulence proteins, which have been previously characterized in a rodent model, was performed using individual coyote sera samples, which were previously confirmed as either sero-positive or sero-negative. The results revealed that coyotes mount an immune response to many of the same plasmid encoded antigens as do mice. However, the frequency of antibody response to some of the antigens differed between these two host species. Again, this may be attributable to route of infection. In vivo-induced antigen technology (IVIAT) was also employed to identify novel virulence genes of Y. pestis which are up-regulated in vivo during infection in the coyote, and compared to both the rabbit and prairie dog host. Pooled immune coyote serum was adsorbed multiple times with broth cultures of Y. pestis grown at 37°C to remove antibodies reactive to constitutively expressed antigens. Plasmid expression libraries of genomic and pFra/pPst plasmid DNA from a pLcr - strain of Y. pestis was then screened by colony immunoblot using the adsorbed sera. The IVI gene set between hosts were compared, and selected loci, PCR-amplified, cloned, and expressed in their entirety to obtain recombinant products for further study. IVIAT screens against the chromosomal expression library revealed coyote serum to be reactive to five IVI genes. To include: fliP, an inner membrane, flagellar assembly protein; SltY, a soluble lytic transglycosylase protein involved in cell-wall remodeling, and LepA, a highly conserved protein, which facilitates tRNA/ribosomal back-translocation. Upon cross-screening the reactive IVI clones with immune serum from rabbit and prairie dog, it was observed that FliP was uniquely reactive to the coyote serum. Variability of IVI antigen immune signatures suggests differential up-regulation/expression of Y. pestis virulence factors in different animal hosts, and/or differential immune responses to antigens relevant to Y. pestis survival during infection. Although screening of the plasmid expression library did not yield identification of novel genes, reactivity to plasminogen activator and pesticin supports the findings generated in the Western Blot analysis. The data collected through this study provided insight into the dissimilarities and similarities in the immune response of Canis latrans during Y. pestis infection when compared with infected immune sera from plague-sensitive hosts, which may relate to the pattern of immune resistance observed in canines to this otherwise highly lethal bacterial agent.

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 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

Index Medicus

Index Medicus PDF Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 2036

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Book Description
Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

Crossroads between Innate and Adaptive Immunity

Crossroads between Innate and Adaptive Immunity PDF Author: Peter D. Katsikis
Publisher: Springer Science & Business Media
ISBN: 038734814X
Category : Medical
Languages : en
Pages : 241

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Book Description
This compilation presents mini-reviews derived from work presented at the Aegean Conference: "First Crossroads between Innate and Adaptive Immunity," which occurred in October, 2005 at the Hilton Conference Center on the island of Rhodes, Greece. The conference included sessions dedicated to host recognition of and response to pathogens, innate immune networks, antigen presentation, and adaptive immune responses, each headlined by a leading scientist.

Host - Pathogen Interaction

Host - Pathogen Interaction PDF Author: Gottfried Unden
Publisher: John Wiley & Sons
ISBN: 3527682414
Category : Science
Languages : en
Pages : 240

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Book Description
In light of the rapidity increasing incidence rate of bacterial and fungal infections with multi-resistant pathogens, the metabolic changes associated with host-pathogen interactions offer one of the most promising starting points for developing novel antibiotics. . Part one of this comprehensive guide describes the metabolic adaptation of pathogenic microbes in humans, while part two points to routes for the development of novel antibiotics. This is volume six of the book series on drug discovery in infectious diseases by Paul Selzer.

Tracing Pathogens in the Food Chain

Tracing Pathogens in the Food Chain PDF Author: Stanley Brul
Publisher: Elsevier
ISBN: 085709050X
Category : Technology & Engineering
Languages : en
Pages : 639

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Book Description
Successful methods for the detection and investigation of outbreaks of foodborne disease are essential for ensuring consumer safety. Increased understanding of the transmission of pathogens in food chains will also assist efforts to safeguard public health. Tracing pathogens in the food chain reviews key aspects of the surveillance, analysis and spread of foodborne pathogens at different stages of industrial food production and processing. Part one provides an introduction to foodborne pathogen surveillance, outbreak investigation and control. Part two concentrates on subtyping of foodborne pathogens, with chapters on phenoytypic subtyping and pulsed-field gel electrophoresis, as well as emerging methods. The vital topics of method validation and quality assurance are also covered. The focus in Part three is on particular techniques for the surveillance and study of pathogens, such as protein-based analysis, ribotyping and comparative genomics. Finally, Part four focuses on tracing pathogens in specific food chains, such as red meat and game, dairy, fish and shellfish. With its distinguished editors and international team of contributors, Tracing pathogens in the food chain is a standard reference for researchers, public health experts and food industry professionals concerned with the study and control of foodborne disease. - Reviews key aspects of the surveillance, analysis and spread of foodborne pathogens - Provides an overview of method validation and quality assurance - Examines the tracing of pathogens in specific food chains, such as red meat, game and dairy