Tuberculosis Host Pathogen Interactions

This book summarizes the progress in studies of tuberculosis host-pathogen interactions from several perspectives: molecular microbiology, immunology, animal models, clinical studies, epidemiology, and drug discovery. Tuberculosis (TB) remains a severe global public health problem. Complex interactions between environmental, microbial and host factors lead to clinically relevant infections. Studies on bacterial virulence, host-genetic, and immunological factors contributing to the susceptibility to TB provide an ever-growing foundation of knowledge that is critical to finding new interventions. Studies of immune mechanisms against M. tuberculosis infection have identified immunological markers associated with specific phenotypes in the host, providing insight into how they may be used to augment current treatment strategies. Recent advances in diagnosis, therapeutics and vaccines, as well as basic-research oriented studies have shed light on the development of new directions for prevention, treatment and control of TB. Improved understanding of the interplay between the bacterium and host is a key component of reducing incidence worldwide.

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.

M. tuberculosis remains one of the most successful human pathogens known. The causative agent of tuberculosis, it also has a unique ability to persist for years in the infected, apparently healthy host. This dormant organism can be reactivated years, even decades later to cause tuberculosis. This book reviews the most important state-of-the-art approaches currently used to study microbe-host interactions and highlights emerging methodologies.

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.

This volume is a collection of chapters from the leading experts in the relatively new and burgeoning field of persister cell studies. Persisters play a leading role in the recalcitrance of chronic infections, and enable the development of classical antibiotic resistance. The focus of the book is on studies that provide an understanding of the mechanisms of persister formation, antibiotic tolerance and role in disease, at the molecular level.

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.

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.

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.