
Molecular Genetics of Mycobacteria
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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,
- Discusses key areas of current research in mycobacterial genetics
- Explains the genetics of the physiology, metabolism, and drug sensitivities of M. tuberculosis
- Presents genetic approaches for manipulating M. tuberculosis
This book is an invaluable resource for anyone interested in the molecular genetics and molecular biology of mycobacteria.
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Content
Contributors ix
Preface xvii
I. Genomes, Genomics, and Genetic Exchange
1. Gene Transfer in Mycobacterium 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 in Mycobacterium tuberculosis Physiology 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 tuberculosis in the Proteomics Era 241
Martin Gengenbacher, Jeppe Mouritsen, Olga T. Schubert, Ruedi Aebersold, and Stefan H. E. Kaufmann
13. Structural Annotation of the Mycobacterium tuberculosis Proteome 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 in Mycobacterium tuberculosis 323
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 in Mycobacterium tuberculosis 413
Keira A. Cohen, William R. Bishai, and Alexander S. Pym
22. Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities 431
Catherine Vilcheze and William R. Jacobs, Jr.
23. The Molecular Genetics of Fluoroquinolone Resistance in Mycobacterium tuberculosis 455
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 Pawelczyk 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 tuberculosis Serine/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 the Mycobacterium tuberculosis Genome by Host Cell-Derived 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 by Mycobacterium tuberculosis 747
Michael F. Goldberg, Neeraj K. Saini, and Steven A. Porcelli
37. Mycobacterial Biofilms 773
Jacobs P. Richards and Anil K. Ojha
Index 785
Contributors
RUEDI AEBERSOLD
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli Strasse 16, 8093 Zurich, and Faculty of Science, University of Zurich, 8057 Zurich, Switzerland
BREE B. ALDRIDGE
Department of Molecular Biology & Microbiology and Department of Biomedical Engineering, Tufts University, Boston, MA 02111, and Medford, MA 02155
REEM AL-MUBARAK
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523
PRAVEEN ANAND
Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India
KRISTINE B. ARNVIG
Mycobacterial Research Division, National Institute for Medical Research, London NW7 1AA, United Kingdom
ANTHONY D. BAUGHN
Department of Microbiology, University of Minnesota, 420 Delaware St. SE, MMC196, Mayo Building Room 1020, Minneapolis, MN 55455
MARCEL A. BEHR
McGill International TB Centre, Montreal, Quebec, Canada, H3G 1A4
JOHN T. BELISLE
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523
MICHAEL BERNEY
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
GURDYAL S. BESRA
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
HELEN L. BIRCH
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
WILLIAM R. BISHAI
Johns Hopkins School of Medicine, The Center for TB Research, 1550 Orleans St., CRBII, Room 103, Baltimore, MD 21287
NADINE J. BODE
Department of Microbiology, New York University School of Medicine, 550 First Avenue, MSB 236, New York, NY 10016
DARIA BOTTAI
Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia Università di Pisa, Pisa, Italy
ROLAND BROSCH
Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France
NAGASUMA CHANDRA
Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India
KEIRA A. COHEN
KwaZulu-Natal Research Institute for TB and HIV (K-RITH), Nelson R. Mandela School of Medicine, 719 Umbilo Road, Durban, South Africa, and Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115
GREGORY M. COOK
University of Otago, Department of Microbiology and Immunology, Dunedin, New Zealand
TERESA CORTES
Mycobacterial Research Division, National Institute for Medical Research, London NW7 1AA, United Kingdom
DEAN C. CRICK
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682
BRIDGETTE M. CUMMING
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa
MAMADOU DAFFé
CNRS, Institut de Pharmacologie et de Biologie Structurale, Département Mécanismes Moléculaires des Infections Mycobactériennes, and the Université de Toulouse Paul Sabatier, F-31077 Toulouse, France
K. HERAN DARWIN
Department of Microbiology, New York University School of Medicine, 550 First Avenue, MSB 236, New York, NY 10016
KEITH M. DERBYSHIRE
Division of Genetics, Wadsworth Center, New York State Department of Health, and Department of Biomedical Sciences, University at Albany, Albany, NY 12201
SABINE EHRT
Department of Microbiology and Immunology, Weill Medical College, and Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065
JOANNA C. EVANS
Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, P/Bag X3, Rondebosch 7700, South Africa
RUTH J. FAHEY
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
SARAH M. FORTUNE
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
JAMES GALAGAN
Department of Biomedical Engineering, Bioinformatics Program, and National Emerging Infectious Diseases Laboratory, Boston University, Boston, MA 02215, and Broad Institute of MIT and Harvard, Cambridge, MA 02142
MARTIN GENGENBACHER
Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany
MICHAEL S. GLICKMAN
Immunology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10803
MICHAEL F. GOLDBERG
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
ANTONIO GOMES
Bioinformatics Program, Boston University, Boston, MA 02215
TODD A. GRAY
Division of Genetics, Wadsworth Center, New York State Department of Health, and Department of Biomedical Sciences, University at Albany, Albany, NY 12201
SHIPRA GROVER
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
KIEL HARDS
University of Otago, Department of Microbiology and Immunology, Dunedin, New Zealand
TRAVIS HARTMAN
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
GRAHAM F. HATFULL
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260
ROBERT N. HUSSON
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115
MARY JACKSON
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682
WILLIAM R. JACOBS, JR.
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
SUMA JAINI
Department of Biomedical Engineering and National Emerging Infectious Diseases Laboratory, Boston University, Boston, MA 02115
MONIKA JANKUTE
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
RAINER KALSCHEUER
Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
STEFAN H. E. KAUFMANN
Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany
IRIS KEREN
Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, MA 02115
GWENDOWLYN S. KNAPP
Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, Albany, NY 12201-2002
HENDRIK KOLIWER-BRANDL
Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
LAURENT KREMER
Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier 2 et 1, CNRS; UMR 5235, case 107; and INSERM, DIMNP, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
DIRK LAMPRECHT
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa
EMILIE LAYRE
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
WONSIK LEE
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
JUN LIU
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8
ANNA LYUBETSKAYA
Bioinformatics Program, Boston University, Boston, MA 02215
SEBABRATA MAHAPATRA
Mycobacteria Research...
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