Tuberculosis and the Tubercle Bacillus
http://www.100md.com
《新英格兰医药杂志》
At the start of the 20th century, tuberculosis was the second leading cause of death in the United States. One hundred years later, it does not figure among the top 20 causes. Improvements in housing and sanitation, decreased crowding, and the introduction of a number of antituberculous drugs are responsible for that change. Worldwide, however, the story is different. Mycobacterium tuberculosis kills about 3 million people per year, vying with HIV as the single most deadly infectious agent. Add to this the worsening problem of multidrug-resistant mycobacteria, and the need for new therapeutic modalities is urgent.
Fortunately, the advent of genomics, in which high-throughput, automated forms of technology determine the entire DNA sequence of an organism, provides an important new tool against tuberculosis. Knowing the entire genetic complement of an organism potentially allows us to scrutinize its complete metabolic blueprint and pathogenic mechanisms for vulnerabilities that could be exploited by new therapeutics. Molecules of the mycobacterium could also be identified for testing in subunit vaccines or other types of vaccines.
That, at least, is the theory. In fact, the 4,411,529 base pairs of the tubercle bacillus require a formidable effort at decipherment before the bacillus will yield its secrets, and this large amount of new data must be unified with more traditional studies. To serve this need, the editors of Tuberculosis and the Tubercle Bacillus have produced a book of 37 chapters, broadly organized into three sections. The first covers the disease of tuberculosis and examines the epidemiology, clinical presentation, diagnosis, and multidrug-resistance mechanisms of the disease. The coverage is somewhat patchy; for example, the discussion of diagnosis focuses more on the methods suitable for epidemiologic and laboratory investigation of immune mechanisms than on routine hospital practice. Clinicians seeking detailed information on the presentation of the disease or its management should look elsewhere, because the focus of this book is the laboratory scientist.
It is in the other two sections, which consist of descriptions of the molecular makeup of the bacterium and of host–pathogen interactions, that the book excels. Here readers will find comprehensive coverage of the information arising from genome, microarray, and proteomic studies. The description of the components of the cell wall, a fiendishly complex melding of diverse glycolipids, is very good. Various aspects of cellular metabolism, including those of iron handling, cell signaling, transport, and so on, all receive their due. Similarly, the interaction of the bacillus with the macrophage and the acquired immune system are all examined in detail and to telling effect. It would have been helpful to see less of the confusing conflation of data from animal models and human studies that the tuberculosis field seems to love, but the wealth of information gathered in this one book makes it indispensable.
As in any multiauthored book, there is variation in writing style, depth, and quality among contributions, but overall the standard is extremely high. I could find no references more recent than 2003, but this is the nature of the beast, as every editor who has awaited that last laggard chapter and cursed its recalcitrant authors knows too well. This book should become the first choice for readers of a technical bent who wish to know where the study of tuberculosis stands in these first heady years after the advent of genomics. I strongly recommend it.
Ross Coppel, Ph.D.
Monash University
Clayton, VIC 3800, Australia
ross.coppel@med.monash.edu.au(Stewart T. Cole, Kathleen)
Fortunately, the advent of genomics, in which high-throughput, automated forms of technology determine the entire DNA sequence of an organism, provides an important new tool against tuberculosis. Knowing the entire genetic complement of an organism potentially allows us to scrutinize its complete metabolic blueprint and pathogenic mechanisms for vulnerabilities that could be exploited by new therapeutics. Molecules of the mycobacterium could also be identified for testing in subunit vaccines or other types of vaccines.
That, at least, is the theory. In fact, the 4,411,529 base pairs of the tubercle bacillus require a formidable effort at decipherment before the bacillus will yield its secrets, and this large amount of new data must be unified with more traditional studies. To serve this need, the editors of Tuberculosis and the Tubercle Bacillus have produced a book of 37 chapters, broadly organized into three sections. The first covers the disease of tuberculosis and examines the epidemiology, clinical presentation, diagnosis, and multidrug-resistance mechanisms of the disease. The coverage is somewhat patchy; for example, the discussion of diagnosis focuses more on the methods suitable for epidemiologic and laboratory investigation of immune mechanisms than on routine hospital practice. Clinicians seeking detailed information on the presentation of the disease or its management should look elsewhere, because the focus of this book is the laboratory scientist.
It is in the other two sections, which consist of descriptions of the molecular makeup of the bacterium and of host–pathogen interactions, that the book excels. Here readers will find comprehensive coverage of the information arising from genome, microarray, and proteomic studies. The description of the components of the cell wall, a fiendishly complex melding of diverse glycolipids, is very good. Various aspects of cellular metabolism, including those of iron handling, cell signaling, transport, and so on, all receive their due. Similarly, the interaction of the bacillus with the macrophage and the acquired immune system are all examined in detail and to telling effect. It would have been helpful to see less of the confusing conflation of data from animal models and human studies that the tuberculosis field seems to love, but the wealth of information gathered in this one book makes it indispensable.
As in any multiauthored book, there is variation in writing style, depth, and quality among contributions, but overall the standard is extremely high. I could find no references more recent than 2003, but this is the nature of the beast, as every editor who has awaited that last laggard chapter and cursed its recalcitrant authors knows too well. This book should become the first choice for readers of a technical bent who wish to know where the study of tuberculosis stands in these first heady years after the advent of genomics. I strongly recommend it.
Ross Coppel, Ph.D.
Monash University
Clayton, VIC 3800, Australia
ross.coppel@med.monash.edu.au(Stewart T. Cole, Kathleen)