A comprehensive collection of perspectives by experts in mycobacterial molecular biology

Mycobacterium tuberculosis causes one in four avoidable deaths in the developing world and kills more adults than malaria, AIDS, and all tropical diseases combined. Tuberculosis was named a global health emergency by the World Health Organization, a distinction no other disease has received. Although the study of mycobacterial genetics has expanded dramatically, with new investigations into mycobacterial growth, replication, metabolism, physiology, drug susceptibility, and virulence, most of the problems in tuberculosis control that existed in 2000 remain today.

Advances in our understanding of mycobacterial genetics have been reflected in exciting recent developments. New diagnostic approaches can identify drug resistance within a few hours, promising new drugs are progressing through the pipeline and into the clinic, and a range of newly developed vaccines are being evaluated. It is an exciting time as the fruits of 30 years of intensive genetic investigation are finally beginning to emerge.

Written by leading experts in the field,Molecular Genetics of Mycobacteria, Second Edition,

This book is an invaluable resource for anyone interested in the molecular genetics and molecular biology of mycobacteria.

Contributors ix

Preface xvii

I. Genomes, Genomics, and Genetic Exchange

1. Gene Transfer inMycobacterium tuberculosis: Shuttle Phasmids to Enlightenment 3
William R. Jacobs, Jr.

2. Mycobacterial Pathogenomics and Evolution 27
Daria Bottai, Timothy P. Stinear, Philip Supply, and Roland Brosch

3. BCG Vaccines 49
Vanessa Tran, Jun Liu, and Marcel A. Behr

4. Distributive Conjugal Transfer: New Insights into Horizontal Gene Transfer and Genetic Exchange in Mycobacteria 61
Keith M. Derbyshire and Todd A. Gray

5. Molecular Genetics of Mycobacteriophages 81
Graham F. Hatfull

6. Genetics of Phage Lysis 121
Madalena Pimentel

Ii. Gene Expression and Regulation

7. Sigma Factors: Key Molecules inMycobacterium tuberculosisPhysiology and Virulence 137
Riccardo Manganelli

8. Transcription Factor Binding Site Mapping Using ChIP-Seq 161
Suma Jaini, Anna Lyubetskaya, Antonio Gomes, Matthew Peterson, Sang Tae Park, Sahadevan Raman, Gary Schoolnik, and James Galagan

9. Noncoding RNA in Mycobacteria 183
Kristine B. Arnvig, Teresa Cortes, and Douglas B. Young

10. Two-Component Regulatory Systems of Mycobacteria 209
Tanya Parish

11. Regulated Expression Systems for Mycobacteria and Their Applications 225
Dirk Schnappinger and Sabine Ehrt

Iii. The Mycobacterial Proteome

12.Mycobacterium tuberculosisin the Proteomics Era 241
Martin Gengenbacher, Jeppe Mouritsen, Olga T. Schubert, Ruedi Aebersold, and Stefan H. E. Kaufmann

13. Structural Annotation of theMycobacterium tuberculosisProteome 261
Nagasuma Chandra, Sankaran Sandhya, and Praveen Anand

14. Cyclic AMP Signaling in Mycobacteria 281
Gwendowlyn S. Knapp and Kathleen A. McDonough

IV. Metabolism

15. The Physiology and Genetics of Oxidative Stress in Mycobacteria 299
Bridgette M. Cumming, Dirk Lamprecht, Ryan M. Wells, Vikram Saini, James H. Mazorodze, and Adrie J. C. Steyn

16. Metabolomics of Central Carbon Metabolism inMycobacterium tuberculosis323
Anthony D. Baughn and Kyu Y. Rhee

17. Mycobacterial Lipidomics 341
Emilie Layre, Reem Al-Mubarak, John T. Belisle, and D. Branch Moody

18. Genetics of Mycobacterial Trehalose Metabolism 361
Rainer Kalscheuer and Hendrik Koliwer-Brandl

19. Metallobiology of Tuberculosis 377
G. Marcela Rodriguez and Olivier Neyrolles

20. Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria 389
Gregory M. Cook, Kiel Hards, Catherine Vilcheze, Travis Hartman, and Michael Berney

V. Genetics of Drug Resistance

21. Molecular Basis of Drug Resistance inMycobacterium tuberculosis413
Keira A. Cohen, William R. Bishai, and Alexander S. Pym

22. Resistance to Isoniazid and Ethionamide inMycobacterium tuberculosis: Genes, Mutations, and Causalities 431
Catherine Vilcheze and William R. Jacobs, Jr.

23. The Molecular Genetics of Fluoroquinolone Resistance inMycobacterium tuberculosis455
Claudine Mayer and Howard Takiff

24. Mechanisms of Pyrazinamide Action and Resistance 479
Ying Zhang, Wanliang Shi, Wenhong Zhang, and Denis Mitchison

25. Genetic Strategies for Identifying New Drug Targets 493
Andrej Trauner, Christopher M. Sassetti, and Eric J. Rubin

VI. Genetics of Membrane and Cell Wall Biosynthesis

26. Genetics of Peptidoglycan Biosynthesis 513
Martin S. Pavelka, Jr., Sebabrata Mahapatra, and Dean C. Crick

27. Genetics of Mycobacterial Arabinogalactan and Lipoarabinomannan Assembly 535
Monika Jankute, Shipra Grover, Helen L. Birch, and Gurdyal S. Besra

28. Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids 559
Mamadou Daffe, Dean C. Crick, and Mary Jackson

29. The Molecular Genetics of Mycolic Acid Biosynthesis 611
Jakub Paweczyk and Laurent Kremer

VII. Genetics of Macromolecular Biosynthesis

30. Nucleotide Metabolism and DNA Replication 635
Digby F. Warner, Joanna C. Evans, and Valerie Mizrahi

31. Double-Strand DNA Break Repair in Mycobacteria 657
Michael S. Glickman

32. The Pup-Proteasome System of Mycobacteria 667
Nadine J. Bode and K. Heran Darwin

33.Mycobacterium tuberculosisSerine/Threonine Protein Kinases 681
Sladjana Prisic and Robert N. Husson

VIII. The Mycobacterial Lifestyle, Persistence, and Macrophage Survival

34. The Spectrum of Drug Susceptibility in Mycobacteria 711
Bree B. Aldridge, Iris Keren, and Sarah M. Fortune

35. The Sculpting of theMycobacterium tuberculosisGenome by Host CellDerived Pressures 727
David G. Russell, Wonsik Lee, Shumin Tan, Neelima Sukumar, Maria Podinovskaia, Ruth J. Fahey, and Brian C. VanderVen

36. Evasion of Innate and Adaptive Immunity byMycobacterium tuberculosis747
Michael F. Goldberg, Neeraj K. Saini, and Steven A. Porcelli

37. Mycobacterial Biofilms 773
Jacobs P. Richards and Anil K. Ojha

Index 785