Systems Biology Of Tuberculosis

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.

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.

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.

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.

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.

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.

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.

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.