Download or read book Systems Biology of Tuberculosis written by Johnjoe McFadden and published by Springer Science & Business Media. This book was released on 2012-12-09 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book starts with a general introduction into the relevance of systems biology for understanding tuberculosis. This will be followed by several chapters which describe the application of systems biology to various aspects of the study of the pathogen, Mycobacterium tuberculosis, and its interaction with the host. The book provides the reader with an account of how the new science of systems biology is providing novel insights into the ancient scourge of tuberculosis. It will also describe how systems biology can be applied to the control of tuberculosis, including the development of new treatments, vaccines and diagnostics.

Download or read book Mycobacterium Tuberculosis Molecular Infection Biology Pathogenesis Diagnostics and New Interventions written by Seyed Ehtesham Hasnain and published by Springer Nature. This book was released on 2019-11-30 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews recent advances in the molecular and infection biology, pathology, and molecular epidemiology of Mycobacterium tuberculosis, as well as the identification and validation of novel molecular drug targets for the treatment of this mycobacterial disease. Despite being completely curable, tuberculosis is still one of the leading global causes of death. M. tuberculosis, the causative organism – one of the smartest pathogens known – adopts highly intelligent strategies for survival and pathogenesis. Presenting a wealth of information on the molecular infection biology of M. tuberculosis, as well as nontuberculous mycobacteria (NTM), the book provides an overview of the functional role of the PE/PPE group of proteins, which is exclusive to the genus Mycobacteria, of host-pathogen interactions, and virulence. It also explores the pathogenesis of the infection, pathology, epidemiology, and diagnosis of NTM. Finally it discusses current and novel approaches in vaccine development against tuberculosis, including the role of nanotechnology. With state-of-the-art contributions from experts in the respective domains, this book is an informative resource for practitioners as well as medical postgraduate students and researchers.

Download or read book Systems Biological Approaches in Infectious Diseases written by Helena I. Boshoff and published by Springer Science & Business Media. This book was released on 2007-01-15 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book brings together the various fields of functional genomics and systems biology that provide information on metabolic function. There is special emphasis on the identification of drug targets. The book includes practical examples from the various "omic" sciences as well as theoretical examples of how integrated knowledge of these sciences can be applied to drug discovery. It is of interest to researchers in the pharmaceutical drug discovery environment.

Download or read book A Systems Biology Framework for Modeling Metabolic Enzyme Inhibition of Mycobacterium Tuberculosis written by and published by . This book was released on 2009 with total page 23 pages. Available in PDF, EPUB and Kindle. Book excerpt: Background: Because metabolism is fundamental in sustaining microbial life, drugs that target pathogen-specific metabolic enzymes and pathways can be very effective. In particular, the metabolic challenges faced by intracellular pathogens, such as Mycobacterium tuberculosis, residing in the infected host provide novel opportunities for therapeutic intervention. Results: We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in its metabolic pathways are inhibited. Combining detailed models of enzyme kinetics, a complete metabolic network description as modeled by flux balance analysis, and a dynamic cell population growth model, we quantitatively modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the growth of M. tuberculosis in a medium whose carbon source was restricted to fatty acids, and that of the 5'-O-(N-salicylsulfamoyl) adenosine inhibitor in a medium with low-iron concentration. Conclusion: The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions/ constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on in vitro growth of M. tuberculosis cells.

Download or read book Tuberculosis and the Tubercle Bacillus written by William R. Jacobs, Jr. and published by John Wiley & Sons. This book was released on 2020-07-15 with total page 741 pages. Available in PDF, EPUB and Kindle. Book excerpt: Can today's innovative practices and molecular tools tame this ancient disease? One third of the world's population is infected with tuberculosis (TB), with about 10 million new cases annually. To combat TB and its agent, Mycobacterium tuberculosis, the World Health Organization launched The End TB Strategy, which aims to slash the suffering and cost of TB by 2035. This makes the second edition of Tuberculosis and the Tubercle Bacillus, edited by Jacobs, McShane, Mizrahi, and Orme, an extremely valuable resource for scientists and clinicians. The editors have gathered their colleagues from around the world to present the latest on the molecular biology of M. tuberculosis and related species, the host-pathogen interactions that enable invasion, and the host's immune response to M. tuberculosis infection. The basic, clinical, and translational research presented in this book supports the goals of WHO's End TB Strategy by driving toward the development of effective vaccines, rapid molecular diagnostics, and anti-TB drugs. Creating an effective tuberculosis vaccine. Understand the innate and adaptive immune response to M. tuberculosis infection, its study in established animal models, and how this information is being used to develop new vaccines against TB. Formulating new antituberculosis drugs. Learn the challenges and methods for evaluating new drugs in preclinical trials with a focus on drugs that work against "persisters" and those that act on the electron transport complex and ATP synthase of M. tuberculosis. Overcoming the challenges of diagnosing tuberculosis. Review new diagnostic tools that are simple, rapid, affordable, specific, sensitive, and safe, including molecular-based diagnostic methods such as GeneXpert MTB/RIF. Using molecular, genomic, and bioinformatics tools to understand the biology and evolution of Mycobacterium. Explore current research on the molecular mechanisms that M. tuberculosis uses to evade the immune system, enter a state of nonreplicating persistence, and become reactivated. The second edition of Tuberculosis and the Tubercle Bacillus presents the latest research on a microorganism that is exquisitely well adapted to its human host. This pathogen continues to confound scientists, clinicians, and public health specialists, who will all find much valuable information in this comprehensive set of reviews.

Download or read book Prokaryotic Systems Biology written by Nevan J. Krogan, PhD and published by Springer. This book was released on 2015-11-30 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on innovative experimental and computational approaches for charting interaction networks in bacterial species. The first part of the volume consists of nine chapters, focusing on biochemical and genetics and genomics approaches including yeast two hybrid, metagenomics, affinity purification in combination with mass spectrometry, chromatin-immunoprecipitation coupled with sequencing, large-scale synthetic genetic screens, and quantitative-based mass spectrometry strategies for mapping the bacterial physical, functional, substrate, and regulatory interaction networks needed for interpreting biological networks, inferring gene function, enzyme discovery, and identifying new drug targets. The second part comprises five chapters, covering the network of participants for protein folding and complex enzyme maturation. It also covers the structural approaches required to understand bacterial intramembrane proteolysis and the structure and function of bacterial proteins involved in surface polysaccharides, outer membrane, and envelope assembly. This volume concludes with a focus on computational and comparative genomics approaches, especially network-based methods for predicting physical or functional interactions, and integrative analytical approaches for generating more reliable information on bacterial gene function. This book provides foundational knowledge in the understanding of prokaryotic systems biology by illuminating how bacterial genes f unction within the framework of global cellular processes. The book will enable the microbiology community to create substantive resources for addressing many pending unanswered questions, and facilitate the development of new technologies that can be applied to other bacterial species lacking experimental data. ​ ​

Download or read book Disease Control Priorities Third Edition Volume 6 written by King K. Holmes and published by World Bank Publications. This book was released on 2017-11-06 with total page 506 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.

Download or read book Strain Variation in the Mycobacterium tuberculosis Complex Its Role in Biology Epidemiology and Control written by Sebastien Gagneux and published by Springer. This book was released on 2017-11-06 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: Until about 10 years ago, the general view in the field was that Mycobacterium tuberculosis, the causative agent of human tuberculosis was a “clone” with insufficient natural sequence variation between clinical strains to be considered biologically and epidemiologically “relevant”. This view has now changed quite dramatically thanks to the –omics revolution, particularly the advent of next generation DNA sequencing. Large-scale comparative genomic studies over the last few years have revealed that M. tuberculosis clinical strains are more genetically diverse than appreciated previously. Moreover, an increasing number of experimental and epidemiological studies are showing that this genetic diversity also translates into important phenotypic variation. Taken together, these findings have led to a paradigm shift, such that currently phylogenetic diversity among M. tuberculosis clinical strains is being considered in the development of new tools to combat tuberculosis. The purpose of this book is to bring together a series of contributions from some of the most influential groups working on various aspects of M. tuberculosis diversity, and which through their work have contributed to the this paradigm shift. This includes authors focusing on the evolution of M. tuberculosis in relation to other members of the M. tuberculosis complex adapted to animals, the co-evolution between M. tuberculosis and humans, the phenotypic consequences of strains diversity both from an experimental and epidemiological point of view, the ecology and evolution of drug resistant tuberculosis, the diversity and evolution of the BCG vaccine strains, and the use of mathematical modelling to study strain diversity and drug resistance in human tuberculosis. No such book has ever been published, and given the paradigm shift described above, this book will be a valuable resource both for established researchers as well as new scientists, clinicians and public health officials joining the growing field of tuberculosis research.

Download or read book The Population Biology of Tuberculosis written by Christopher Dye and published by Princeton University Press. This book was released on 2015-07-07 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite decades of developments in immunization and drug therapy, tuberculosis remains among the leading causes of human mortality, and no country has successfully eradicated the disease. Reenvisioning tuberculosis from the perspective of population biology, this book examines why the disease is so persistent and what must be done to fight it. Treating tuberculosis and its human hosts as dynamic, interacting populations, Christopher Dye seeks new answers to key questions by drawing on demography, ecology, epidemiology, evolution, and population genetics. Dye uses simple mathematical models to investigate how cases and deaths could be reduced, and how interventions could lead to TB elimination. Dye's analysis reveals a striking gap between the actual and potential impact of current interventions, especially drug treatment, and he suggests placing more emphasis on early case detection and the treatment of active or incipient tuberculosis. He argues that the response to disappointingly slow rates of disease decline is not to abandon long-established principles of chemotherapy, but to implement them with greater vigor. Summarizing epidemiological insights from population biology, Dye stresses the need to take a more inclusive view of the factors that affect disease, including characteristics of the pathogen, individuals and populations, health care systems, and physical and social environments. In broadening the horizons of TB research, The Population Biology of Tuberculosis demonstrates what must be done to prevent, control, and defeat this global threat in the twenty-first century.

Download or read book Understanding the Dynamics of Biological Systems written by Werner Dubitzky and published by Springer Science & Business Media. This book was released on 2011-01-07 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is intended as a communication platform to bridge the cultural, conceptual, and technological gap among the key systems biology disciplines of biology, mathematics, and information technology. To support this goal, contributors were asked to adopts an approach that appeals to audiences from different backgrounds.

Download or read book Evolutionary Systems Biology of the Mycobacterium Tuberculosis Complex written by Alvaro Chiner Oms and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium Tuberculosis written by and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis associated granuloma formation can be viewed as a structural immune response that can contain and halt the spread of the pathogen. In several mammalian hosts, including non-human primates, Mtb granulomas are often hypoxic, although this has not been observed in wild type murine infection models. While a presumed consequence, the structural contribution of the granuloma to oxygen limitation and the concomitant impact on Mtb metabolic viability and persistence remains to be fully explored. We develop a multiscale computational model to test to what extent in vivo Mtb granulomas become hypoxic, and investigate the effects of hypoxia on host immune response efficacy and mycobacterial persistence. Our study integrates a physiological model of oxygen dynamics in the extracellular space of alveolar tissue, an agent-based model of cellular immune response, and a systems biology-based model of Mtb metabolic dynamics. Our theoretical studies suggest that the dynamics of granuloma organization mediates oxygen availability and illustrates the immunological contribution of this structural host response to infection outcome. Furthermore, our integrated model demonstrates the link between structural immune response and mechanistic drivers influencing Mtbs adaptation to its changing microenvironment and the qualitative infection outcome scenarios of clearance, containment, dissemination, and a newly observed theoretical outcome of transient containment. We observed hypoxic regions in the containment granuloma similar in size to granulomas found in mammalian in vivo models of Mtb infection. In the case of the containment outcome, our model uniquely demonstrates that immune response mediated hypoxic conditions help foster the shift down of bacteria through two stages of adaptation similar to thein vitro non-replicating persistence (NRP) observed in the Wayne model of Mtb dormancy. Finally, the adaptation in part contributes to the ability of Mtb to remain dormant for years after initial infection.

Download or read book Systems Microbiology written by Brian Douglas Robertson and published by Caister Academic Press Limited. This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Systems biology is the study of the dynamic interactions of more than one component in a biological system in order to understand and predict the behavior of the system as a whole. Systems biology is a rapidly expanding discipline fuelled by the 'omics' era and new technological advances that have increased the precision of data. A focus on simple single cell organisms, such as bacteria, aids tractability and means that systems microbiology is a rapidly maturing science. Recommended for all microbiology laboratories, this book contains cutting-edge reviews by world-leading experts on the systems biology of microorganisms. As well as covering theoretical approaches and mathematical modeling, the book includes case studies on single microbial species of bacteria and archaea, and it explores the systems analysis of microbial phenomena, such as chemotaxis and phagocytosis. The topics covered include: the mathematical models for systems biology * systems biology of Escherichia coli metabolism * bacterial chemotaxis * systems biology of infection * host-microbe interactions * phagocytosis * system-level study of metabolism in Mycobacterium tuberculosis * systems biology of Sulfolobus.

Download or read book Pathogenesis of Mycobacterium tuberculosis and its Interaction with the Host Organism written by Jean Pieters and published by Springer. This book was released on 2013-12-12 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis is one of the most notorious pathogens on earth, causing the death of approximately 1.5 million people annually. A major problem in the fight against tuberculosis is the emergence of strains that have acquired resistance to all available antibiotics. One key to the success of M. tuberculosis as a pathogen is its ability to circumvent host immune responses at different levels. This is not only a result of the special makeup of M. tuberculosis in terms of genetic diversity and DNA metabolism and its possession of specialized secretion systems, but also of its ability to hijack the host’s innate immune defence mechanisms. In this volume, researchers from different disciplines provide a topical overview of the diverse mechanisms that contribute to the virulence of M. tuberculosis, ranging from their genetic, metabolic and molecular makeup, as well as the complex strategies these bacteria utilize to escape immune destruction within infected hosts.

Download or read book ESX 1 A Novel Alternative Secretion System in Mycobacterium Tuberculosis that Mediates the Host pathogen Interaction written by Sarah A. Stanley and published by . This book was released on 2006 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis is one of the world's most successful pathogens, infecting approximately one-third of humanity. This remarkable bacterium has infected human beings for millennia, and has evolved mechanisms for the manipulation of host biology to create an optimal environment for bacterial survival and growth. Here we describe the identification and characterization of ESX-1, the first alternative secretion system identified in M. tuberculosis, and show its fundamental importance for virulence. We have identified three genes, Rv3870, Rv3871, and Rv3877, that encode components of the ESX-1 secretion system, which functions to secrete ESAT-6 and CFP-10, proteins with dual functions as immunodominant antigens and virulence factors. Components and substrates of ESX-1 are required for full virulence of M. tuberculosis in both mice and macrophages. The ESX-1 secretion system functions to subvert host cell biology, and is required for the suppression of Interleukin-12 (IL-12) and Tumor Necrosis Factor-alpha (TNF-alpha). ESX-1 is also required for the induction, both in vivo and in vitro, of type I Interferons (IFNs), cytokines usually associated with an anti-viral immune response. We show that the induction of type I IFNs may be a pathogenic strategy that enhances virulence of M. tuberculosis. We also examine the role of the ESAT-6 and CFP-10 in the protective immune response in M. tuberculosis. We find that restoration of a functional ESX-1 system to the live attenuated vaccine strain mycobacterium Bacille Calmette-Guerin results in an increase in immunogenicity of this strain, which may lead to the development of more a more effective vaccine. These studies identify ESX-1 mediated secretion of ESAT-6 and CFP-10 to one of the most important pathways identified in M. tuberculosis, both for virulence of the organism and for induction of the protective immune response to infection, and begin to describe the mechanisms by which ESX-1 secretion regulates host biology and the outcome of infection.

Download or read book A Multi scale Approach to Designing Therapeutics for Tuberculosis written by and published by . This book was released on 2015 with total page 19 pages. Available in PDF, EPUB and Kindle. Book excerpt: Approximately one third of the world's population is infected with Mycobacterium tuberculosis. Limited information about how the immune system fights M. tuberculosis and what constitutes protection from the bacteria impact our ability to develop effective therapies for tuberculosis. We present an in vivo systems biology approach that integrates data from multiple model systems and over multiple length and time scales into a comprehensive multi-scale and multi-compartment view of the in vivo immune response to M. tuberculosis. Lastly, we describe computational models that can be used to study (a) immunomodulation with the cytokines tumor necrosis factor and interleukin 10, (b) oral and inhaled antibiotics, and (c) the effect of vaccination.

Download or read book Genomics and Systems Biology of Tuberculosis 2009 JGI User Meeting written by and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: James Galagan from the Broad Institute spoke about the "Genomics and Systems Biology of TB" on March 26, 2009 during the 4th Annual User Meeting.