Tuberculosis and the Tubercle Bacillus

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.

Contributors

Preface

Section I: Towards Edward Jenner’s Revenge: Developing an Effective Tuberculosis Vaccine

A. Basic Immunology

1 Innate Immune Responses to Tuberculosis
Jeffrey S. Schorey and Larry S. Schlesinger

2 Cytokines and Chemokines in Mycobacterium tuberculosis Infection
Racquel Domingo-Gonzalez, Oliver Prince, Andrea Cooper, and Shabaana Khader

3 Regulation of Immunity to Tuberculosis
Susanna Brighenti and Diane J. Ordway

4 The Memory Immune Response to Tuberculosis
Joanna R. Kirman, Marcela I. Henao-Tamayo, and Else Marie Agger

5 Pathology of Tuberculosis: How the Pathology of Human Tuberculosis Informs and Directs Animal Models
Randall J. Basaraba and Robert L. Hunter

B. Animal Models

6 Animal Models of Tuberculosis: An Overview
Ann Williams and Ian M. Orme

7 Mouse and Guinea Pig Models of Tuberculosis
Ian M. Orme and Diane J. Ordway

8 Non-Human Primate Models of Tuberculosis
Juliet C. Peña and Wen-Zhe Ho

9 Experimental Infection Models of Tuberculosis in Domestic Livestock
Bryce M. Buddle, H. Martin Vordermeier, and R. Glyn Hewinson

C. Vaccines

10 Clinical Testing of Tuberculosis Vaccine Candidates
Mark Hatherill, Dereck Tait, and Helen McShane

D. Human Immunology

11 Human Immunology of Tuberculosis
Thomas J. Scriba, Anna K. Coussens, and Helen A. Fletcher

12 The Immune Interaction between HIV-1 Infection and Mycobacterium tuberculosis
Elsa du Bruyn and Robert John Wilkinson

Section II: Drug Discovery and Development: State of the Art and Future Directions

13 Preclinical Efficacy Testing of New Drug Candidates
Eric L. Nuermberger

14 Oxidative Phosphorylation as a Target Space for Tuberculosis: Success, Caution, and Future Directions
Gregory M. Cook, Kiel Hards, Elyse Dunn, Adam Heikal, Yoshio Nakatani, Chris Greening, Dean C. Crick, Fabio L. Fontes, Kevin Pethe, Erik Hasenoehrl, and Michael Berney

15 Targeting Phenotypically Tolerant Mycobacterium tuberculosis
Ben Gold and Carl Nathan

Section III: Biomarkers and Diagnostics

16 Tuberculosis Diagnostics: State of the Art and Future Directions
Madhukar Pai, Mark P. Nicol, and Catharina C. Boehme

17 Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays
Madhukar Pai and Marcel Behr

18 Impact of the GeneXpert MTB/RIF Technology on Tuberculosis Control
Wendy Susan Stevens, Lesley Scott, Lara Noble, Natasha Gous, and Keertan Dheda

Section IV: Host and Strain Diversity

19 The Role of Host Genetics (and Genomics) in Tuberculosis
Vivek Naranbhai

20 The Evolutionary History, Demography, and Spread of the Mycobacterium tuberculosis Complex
Maxime Barbier and Thierry Wirth

21 Impact of Genetic Diversity on the Biology of Mycobacerium tuberculosis Complex Strains
Stefan Niemann, Matthias Merker, Thomas Kohl, and Philip Supply

22 Evolution of Mycobacterium tuberculosis: New Insights into Pathogenicity and Drug Resistance
Eva C. Boritsch and Roland Brosch

Section V: The Signature Problem of Tuberculosis Persistence

23 Acid-Fast Positive and Acid-Fast Negative Mycobacterium tuberculosis: The Koch Paradox
Catherine Vilchèze and Laurent Kremer

24 Mycobacterial Biofilms: Revisiting Tuberculosis Bacilli in Extracellular Necrotizing Lesions
Randall J. Basaraba and Anil K. Ojha

25 Killing Mycobacterium tuberculosis In Vitro: What Model Systems Can Teach Us
Tracy L. Keiser and Georgiana E. Purdy

26 Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence
Melissa Richard-Greenblatt and Yossef Av-Gay

27 DNA Replication in Mycobacterium tuberculosis
Zanele Ditse, Meindert H. Lamers, and Digby F. Warner

28 The Sec Pathways and Exportomes of Mycobacterium tuberculosis
Brittany K. Miller, Katelyn E. Zulauf, and Miriam Braunstein

29 The Role of ESX-1 in Mycobacterium tuberculosis Pathogenesis
Ka-Wing Wong

30 The Minimal Unit of Infection: Mycobacterium tuberculosis in the Macrophage
Brian C. VanderVen, Lu Huang, Kyle H. Rohde, and David G. Russell

31 Metabolic Perspectives on Persistence
Travis E. Hartman, Zhe Wang, Robert S. Jansen, Susana Gardete, and Kyu Y. Rhee

32 Phenotypic Heterogeneity in Mycobacterium tuberculosis
Neeraj Dhar, John McKinney, and Giulia Manina

33 Mycobacterium tuberculosis in the Face of Host-Imposed Nutrient Limitation
Michael Berney and Linda Berney-Meyer

Index

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