Contents

Contributors

Preface

I. GENOMES, GENOMICS, AND GENETIC EXCHANGE

1. Gene Transfer in Mycobacterium tuberculosis: Shuttle Phasmids to Enlightenment

William R. Jacobs, Jr.

2. Mycobacterial Pathogenomics and Evolution

Daria Bottai, Timothy P. Stinear, Philip Supply, and Roland Brosch

3. BCG Vaccines

Vanessa Tran, Jun Liu, and Marcel A. Behr

4. Distributive Conjugal Transfer: New Insights into Horizontal Gene Transfer and Genetic Exchange in Mycobacteria

Keith M. Derbyshire and Todd A. Gray

5. Molecular Genetics of Mycobacteriophages

Graham F. Hatfull

6. Genetics of Phage Lysis

Madalena Pimentel

II. GENE EXPRESSION AND REGULATION

7. Sigma Factors: Key Molecules in Mycobacterium tuberculosis Physiology and Virulence

Riccardo Manganelli

8. Transcription Factor Binding Site Mapping Using ChIP-Seq

Suma Jaini, Anna Lyubetskaya, Antonio Gomes, Matthew Peterson, Sang Tae Park, Sahadevan Raman, Gary Schoolnik, and James Galagan

9. Noncoding RNA in Mycobacteria

Kristine B. Arnvig, Teresa Cortes, and Douglas B. Young

10. Two-Component Regulatory Systems of Mycobacteria

Tanya Parish

11. Regulated Expression Systems for Mycobacteria and Their Applications

Dirk Schnappinger and Sabine Ehrt

III. THE MYCOBACTERIAL PROTEOME

12. Mycobacterium tuberculosis in the Proteomics Era

Martin Gengenbacher, Jeppe Mouritsen, Olga T. Schubert, Ruedi Aebersold, and Stefan H. E. Kaufmann

13. Structural Annotation of the Mycobacterium tuberculosis Proteome

Nagasuma Chandra, Sankaran Sandhya, and Praveen Anand

14. Cyclic AMP Signaling in Mycobacteria

Gwendowlyn S. Knapp and Kathleen A. McDonough

IV. METABOLISM

15. The Physiology and Genetics of Oxidative Stress in Mycobacteria

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

Anthony D. Baughn and Kyu Y. Rhee

17. Mycobacterial Lipidomics

Emilie Layre, Reem Al-Mubarak, John T. Belisle, and D. Branch Moody

18. Genetics of Mycobacterial Trehalose Metabolism

Rainer Kalscheuer and Hendrik Koliwer-Brandl

19. Metallobiology of Tuberculosis

G. Marcela Rodriguez and Olivier Neyrolles

20. Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria

Gregory M. Cook, Kiel Hards, Catherine Vilchèze, Travis Hartman, and Michael Berney

V. GENETICS OF DRUG RESISTANCE

21. Molecular Basis of Drug Resistance in Mycobacterium tuberculosis

Keira A. Cohen, William R. Bishai, and Alexander S. Pym

22. Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities

Catherine Vilchèze and William R. Jacobs, Jr.

23. The Molecular Genetics of Fluoroquinolone Resistance in Mycobacterium tuberculosis

Claudine Mayer and Howard Takiff

24. Mechanisms of Pyrazinamide Action and Resistance

Ying Zhang, Wanliang Shi, Wenhong Zhang, and Denis Mitchison

25. Genetic Strategies for Identifying New Drug Targets

Andrej Trauner, Christopher M. Sassetti, and Eric J. Rubin

VI. GENETICS OF MEMBRANE AND CELL WALL BIOSYNTHESIS

26. Genetics of Peptidoglycan Biosynthesis

Martin S. Pavelka, Jr., Sebabrata Mahapatra, and Dean C. Crick

27. Genetics of Mycobacterial Arabinogalactan and Lipoarabinomannan Assembly

Monika Jankute, Shipra Grover, Helen L. Birch, and Gurdyal S. Besra

28. Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Mamadou Daffé, Dean C. Crick, and Mary Jackson

29. The Molecular Genetics of Mycolic Acid Biosynthesis

Jakub Pawełstrok;czyk and Laurent Kremer

VII. GENETICS OF MACROMOLECULAR BIOSYNTHESIS

30. Nucleotide Metabolism and DNA Replication

Digby F. Warner, Joanna C. Evans, and Valerie Mizrahi

31. Double-Strand DNA Break Repair in Mycobacteria

Michael S. Glickman

32. The Pup-Proteasome System of Mycobacteria

Nadine J. Bode and K. Heran Darwin

33. Mycobacterium tuberculosis Serine/Threonine Protein Kinases

Sladjana Prisic and Robert N. Husson

VIII. THE MYCOBACTERIAL LIFESTYLE, PERSISTENCE, AND MACROPHAGE SURVIVAL

34. The Spectrum of Drug Susceptibility in Mycobacteria

Bree B. Aldridge, Iris Keren, and Sarah M. Fortune

35. The Sculpting of the Mycobacterium tuberculosis Genome by Host Cell–Derived Pressures

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

Michael F. Goldberg, Neeraj K. Saini, and Steven A. Porcelli

37. Mycobacterial Biofilms

Jacobs P. Richards and Anil K. Ojha

Index

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 Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523

RICCARDO MANGANELLI

Department of Molecular Medicine, University of Padova, Italy

CLAUDINE MAYER

Unité de Microbiologie Structurale, Institut Pasteur; UMR 3528 du CNRS; and Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015, Paris, France

JAMES H. MAZORODZE

KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa

KATHLEEN A. MCDONOUGH

Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, and Department of Biomedical Sciences, University at Albany, Albany, NY 12222

DENIS MITCHISON

Centre for Infection, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom

VALERIE MIZRAHI

Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, P/Bag X3, Rondebosch 7700, South Africa

D. BRANCH MOODY

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

JEPPE MOURITSEN

Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli Strasse 16, 8093 Zurich, Switzerland

OLIVIER NEYROLLES

Centre National de la Recherche Scientifique & Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France

ANIL K. OJHA

Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261

TANYA PARISH

Infectious Disease Research Institute, Seattle, WA 98102, and Queen Mary University of London, London, United Kingdom

SANG TAE PARK

Macrogen Clinical Laboratory, Macrogen Corp, Rockville, MD 20850

MARTIN S. PAVELKA, JR.

Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642

JAKUB PAWEŁCZYK

Institute for Medical Biology, Polish Academy of Sciences, Lodz, Poland

MATTHEW PETERSON

Department of Biomedical Engineering, Boston University, Boston, MA 02215

MADALENA PIMENTEL

Centro de Patogénese Molecular, Unidade dos Retrovirus e Infecções Associadas, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

MARIA PODINOVSKAIA

Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

STEVEN A. PORCELLI

Department of Microbiology and Immunology and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461

SLADJANA PRISIC

Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115

ALEXANDER S. PYM

KwaZulu-Natal Research Institute for TB and HIV (K-RITH), Nelson R. Mandela School of Medicine, 719 Umbilo Road, Durban, South Africa

SAHADEVAN RAMAN

National Emerging Infectious Diseases Laboratory, Boston University, Boston, MA 02215

KYU Y. RHEE

Department of Medicine, Weill Cornell Medical College, 1300 York Avenue A-431A, New York, NY 10065

JACOBS P. RICHARDS

Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261

G. MARCELA RODRIGUEZ

Public Health Research Institute Center & Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103

ERIC J. RUBIN

Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115

DAVID G. RUSSELL

Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

VIKRAM SAINI

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294

NEERAJ K. SAINI

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461

SANKARAN SANDHYA

Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India

CHRISTOPHER M. SASSETTI

University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655

DIRK SCHNAPPINGER

Department of Microbiology and Immunology, Weill Medical College, and Program in Molecular Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065

GARY SCHOOLNIK

Department of Medicine and Department of Microbiology and Immunology, Stanford Medical School, Stanford, CA 94305

OLGA T. SCHUBERT

Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli Strasse 16, 8093 Zurich, Switzerland

WANLIANG SHI

Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205

ADRIE J. C. STEYN

KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa, and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294

TIMOTHY P. STINEAR

Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia

NEELIMA SUKUMAR

Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

PHILIP SUPPLY

CNRS UMR 8204; INSERM, U1019; Center for Infection and Immunity of Lille, Institut Pasteur de Lille; and Université Lille Nord de France, Lille, France

HOWARD TAKIFF

Laboratorio de Genética Molecular, CMBC, IVIC, Caracas, Venezuela

SHUMIN TAN

Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

VANESSA TRAN

Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8

ANDREJ TRAUNER

Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115

BRIAN C. VANDERVEN

Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

CATHERINE VILCHÈZE

Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461

DIGBY F. WARNER

Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, P/Bag X3, Rondebosch 7700, South Africa

RYAN M. WELLS

KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa, and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294

DOUGLAS B. YOUNG

Mycobacterial Research Division, National Institute for Medical Research, London NW7 1AA, United Kingdom

YING ZHANG

Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, and Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China

WENHONG ZHANG

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China

Index

A

ABC transporter, in trehalose transport, 365, 369

Abrahams, G. L., 503

Acadian phage, 128

acc genes, 615–616

Accelerator, in asymmetric growth, 716

Accurate-mass retention time values, 342

aceA gene, 146

Acetamidase system, switches, 225, 228

Acetylated PIMs, 545–546

Acetylation, 247, 289

Acetyl-CoA carboxylase, 615–616

N-Acetylglucosamine, in lysis, 122

N-Acetylglucosamine rhamnose linker, in peptidoglycan synthesis, 520

N-Acetylglycosylases, in lysis, 122

N-Acetylmuramidases, in lysis, 122

N-Acetyl-muramyl-l-alanine amidases, in lysis, 122, 124

Acetyltransferase, 307

Acid stress, 193

genome changes due to, 732

PZA activity and, 484

Acidobacteria, STPKs of, 682

Acidothermus cellulolyticus, Pup-proteasome system of, 669

Acinetobacter baumannii, drug susceptibility in, 714

Acinetoferrin, 378

Aconitase, 330–331

AcpM protein, 443

Acr2 protein, 213

Actinobacteria, 27

energetics of, 396

STPKs of, 682

stress response of, 193

Actinomycetales, 310

Activation loops, in STPKs, 685–687

Active site pockets, 269–270

N-Acylated glucosamine (GlcNAc), in peptidoglycan, 513, 515–517

Acyltransferases, 563, 574

Acyltrehaloses, 572–579

Adams, K. N., 715

Adaptive immunity, evasion of, 756–762

Adaptive response, in signal transduction, 681

AddAB protein, 658

Adenosine deaminase, 639

Adenosine kinase, 639–640

S-Adenosylmethionine, 311

S-Adenosylmethionine-dependent methyltransferase, 619

Adenylate cyclases, in cyclic AMP signaling, 281, 283–285

Adenylosuccinate synthase, 637

Adephagia phage, 106

AdnAB protein, 658, 660

Ag85 antigens, 755–756

ahp genes and Ahp proteins, 151, 232, 304, 417, 436, 733

Airborne pathogens, biosafety requirements for, 4–5

Akhter, Y., 188

Alanine dehydrogenase, 245–246

Alanine ligase, 515

Alanine racemase, 232, 500, 515

l-Alanyl-d-glutamine-meso-diaminopimelyl-d-alanine, 513

Alber, M., 365

AlbG protein, 469

Albicidin, 469

Aldridge, B. B., 716

Alkyl hydroperoxidase, 304

Alkyl hydroperoxide reductase, 733

Allelic exchange reactions, 17–18

Alma phage, 97

Almeida, D., 418

Alonso, S., 735

Alpha/beta hydrolases, 268

Alpha-glucans, 362, 370–372

Alpha-mycolic acids, 613

alr gene, 414

Alternative sigma factor density, 138

Alternator, in asymmetric growth, 716

Alveolar surface area, 301

Amidophosphoribosyltransferase, 636

Amikacin, resistance to, 419–420

Aminoglycosides, resistance to, 414, 419–420

5-Aminoimdazole-4-carboxyamide ribonucleotide transformylase, 637

Aminoimidazole moiety, in dNTP synthesis, 641–642

Amplification, in ChIP-Seq, 163

Amurin, 121

Anaerobic conditions, PZA activity and, 483

Anaplerosis, 333–334

Andersen, S. J., 647

Anderson, R. J., 611

Annotation, structural, 261–280

Anoosheh, S., 139

Anti-anti-sigma factors, 138, 681

Antigen 85, 245, 366

Antigen(s), as immunological decoys, 755–756

Antigen presenting cells, infection of, 752–753

Antigenic peptides, for vaccines, 252–253

Antiholins, 122

Antimicrobial peptides, 735–736

Antimycobacterial agents, see Drug(s); specific agents

Antioxidants

ergothioneine as, 312

in lung, 301

Antisense RNAs, 189–192, 232

Anti-sigma factors, 303

Apa protein, 247

aph gene, 4

Apoptosis, blocking of, 762

aprABC gene, 212, 732

Arabinase, 536

d-Arabino-d-mannan, 590

Arabinofuranosyl (Araf) residues, 536, 540–541

Arabinofuranosyltransferase, 539–540

Arabinogalactan, 350, 535–541, 614

Arabinose, in arabinogalactan, 536

Arabinosyltransferases, 418–419

AraC protein, 226, 229

Araf (arabinofuranosyl) residues, 536, 540–541, 547–548

Araucaria, 83

Aravind, A., 671

ARC (AAA ATP forming ring-shaped complexes), 667

ArcB, 214

ArcBA proteins, 399

Argaman, L., 198

Arginase, 304

Arginine, nitric oxide generation from, 301

Arnvig, K. B., 193, 198, 199

Ars proteins, 212, 402

Artemis genome browser, 184

Artifacts, in ChIP-Seq, 164

Arylamine N-acetyltransferase, 442

asd gene, 515

asino1 gene, 190

Aspartate carbamoyltransferase, 638

Aspartate semialdehyde dehydrogenase, 5

Aspartokinase, 5

ASpks protein, 191

asRNAs

detection of, 199

function of, 189–190, 200

Assembly genes, of phages, 93–95

Atc protein, in ChIP-Seq, 166–167

Atmospheric pressure chemical ionization, 342, 344

ATP7 transporters, 734

atp genes, 640

ATP, synthesis of, 390–391, 402–403

ATPase, in virulence, 36

atpBEFHAGDC operon, 402

atpE gene, 414, 423

att sites, 4, 101, 104, 106–107

Attachment, in biofilm formation, 774

Attenuation indicator lipid, 581, 585

Autoinducers, in biofilm formation, 774

Autophagy, 735–736, 748, 751

Autoregulation, 214, 217

Auxotrophic mutants, 4–5

Auxotrophy, amino acid, 395

Avery, Oswald, 7

Av-Gay, Y., 306

Azides, 482, 483

B

Babitzke, P., 189

Babsiella phage, 83

Bach, H., 699

Bacillus

energetics of, 401

sigma factors of, 138

Bacillus anthracis

cAMP signaling in, 281, 290

noncoding RNAs of, 199

Bacillus subtilis

in biofilms, 775

buffers of, 311

cell envelope composition of, 569

defenses against reactive species, 305

DNA replication in, 642, 644, 649

double-strand DNA break repair in, 658, 660–661

drug susceptibility in, 715

genetic switches in, 226

metallobiology of, 383

noncoding RNAs of, 188, 192, 196, 199

nucleotide metabolism in, 638

prophage of, 126

Pup-proteasome system of, 676

sigma factors of, 148

STPKs of, 690

BACTEC-MGIT, 463

Bacterioferritin, 245–246, 380

Bacteriophage(s), see also Mycobacteriophage(s)

lysis of, 121–133

Bacteriophage lambda, 10–11, 15–17, 105–106, 121

Bacteriophage recombineering of electroporated DNA (BRED) technique, 104–105

Bacteroides, alternative sigma factor-density of, 138

BAKA phage, 83, 97

Banerjee, S. K., 144

Banfield, J. F., 668

Bar codes, for transposons, 18–19

Bardarov, Stoyan, 13–14

Barnyard phage, 99

Battesti, A., 191

Bcp proteins, 304

BDM31343, 495, 497

Beadle, George, 6

Beaucher, J., 148

Beckman, E. M., 614

Beclin-1, 736

Bedaquiline, 4, 414, 423, 487, 493, 498, 501

Benzoic acid, for PZA enhancement, 483–484

Beresford, N. J., 699, 701

Berney, M., 403

Berthelot, M., 361

Beste, D. J., 334, 494

Bet DNA pairing enzyme, 107–108

Beta-lactams, resistance to, 423, 498, 525–526

Bethlehem phage, 98, 128

bfr genes and Bfr proteins, 380–381, 729, 734

BglII, 14

Bibb, Mervyn, 11

Bigger, Joseph, 716, 718

BigNuz phage, 104

Billman-Jacobe, H., 589

Binding sites, for transcription factors, ChIP-Seq mapping of, 161–181

bioA gene, 232

Biocyc Pathway/Genome databases, 177

Biofilm-associated proteins, 774

Biofilms, 19–20, 773–784

changes induced by, 715

characteristics of, 774–775

drug efficacy and, 715–716

formation of, 777, 779–780

genetics of, 777–779

history of hypothesis, 773–774

mycolic acids in, 614

as persistence strategy, 775–777

phenotype resistance of, 779

population-level studies of, 721

single-cell studies of, 721

Bioinformatics

for lipidomics, 353–354

structural, 263

Biological validation, of target, 500

Bioluminescence gene, 14

Biomarkers

mycobacterial lipids as, 356

for Mycobacterium tuberculosis, 254

Biosignatures, 254

Biotin carboxylase, 615

Bishai, W. R., 106–107, 674

blaC gene and BlaC protein, 423, 526

Blanchard, J. S., 306, 325

Blasco, B., 168

BLAST, 262

BLASTN, 90, 101

Blind deconvolution, in ChIP-Seq, 166

Bloom, Barry, 10–11

BMHI, 14

bom sites, 65–68

Boomer phage, 128

Bordetella pertussis, cAMP signaling in, 281, 290

Botella, H., 735

Bott, M., 400

Bound sites, in ChIP-Seq, 168, 171

BP phage, 95, 97, 104–106

BRACIL algorithm, in ChIP-Seq, 166

Branched-chain keto acid dehydrogenase, 329

Braun's lipoprotein, 522

BRED (bacteriophage recombineering of electroporated DNA) technique, 104–105

Brennan, Patrick, 11

Brodie, A. F., 389, 569

“Bronx box,” 14

Broxmeyer, L., 130

Brujita phage, 104, 106

Bsz2 phage, 99

Buffers, for ChIP-Seq, 178

Burkholderia cenocepacia, noncoding RNAs of, 199

Burns, K. E., 670, 672

Buruli ulcers, 777

Bxb1 phage, 101, 103, 106, 107

Bxz1 phage, 105, 127, 129

Bxz2 phage, 101, 106

C

Calamita, H., 143

Calcium, in mycobacteria, 734

Caldwell, D. E., 774

Cali phage, 83

Calmette, Albert, 49–52

cAMP and macrophage regulator (Cmr), 285, 287–288

cAMP signaling, see Cyclic AMP signaling

Campbell, G. R., 736

cAMP-receptor protein (CRP), 282, 285–289

Campylobacter jejuni

drug susceptibility in, 714–715

noncoding RNAs of, 199

Candida albicans

cAMP signaling in, 282

drug susceptibility in, 718

drug targets in, 503

Canetti, Georges, 32–33, 779

Canonical endolysins, 122

Canonical holins, 122

Canonical promoter signal, in ChIP-Seq, 173

Capping motifs, 542–543, 548

Capreomycin, resistance to, 414, 420–421

Capsular polysaccharides, 590–592

Carbamoyltransferase, 638

Carbon metabolism, central, 323–339

Carbon monoxide dehydrogenase, 399

Carbonyl cyanide m-chlorophenylhydrazone, 482

N5-Carboxyaminoimdazole ribonucleotide (CAIR), 636–637

Carboxylic acids, short-chain, metabolism of, 329

Carboxymycobactin, 377–379, 592

Carboxy-mycolic acids, 613

Carboxypeptidases, 520, 521

Carboxytransferase, 615

CarD protein, 233, 637

Cardiolipids, 541

Cardiolipin, 561–562

Carotenes, 570–571

Carotenoids, 30, 570–571

Carriere, Christian, 13–14

Cas proteins, 197

Casonato, S., 144

CASP experiments, 262

Caspase activation and recruitment domain, 749–750

Catabolite activator protein, 227

Catalão, M. J., 124–125

Catalase-peroxidase enzymes, 304

Catalytic/ATP binding domain, of histidine kinase, 209

CATH database, 263

Cathelicidin, 736

Cathepsins, 759

Cation diffusion facilitator family, 381

CatS protein, 759

CD1 molecules, lipid antigen presentation by, 762

cdd genes, 641

cds genes, 562

Cell envelope, 28

acyltrihaloses in, 572–579

capsular polysaccharides in, 590–592

composition of, 559–561

glycolipids in, see Glycolipids

glycopeptidolipids in, 587–590

isoprenoids in, 563–572

layers of, 559–561

mannosyl phosphomycoketides in, 579–580

peptidoglycans in, 513–533

phenolic glycolipids in, 581–587

phospholipids in, 561–563

phthiocerol dimycocerosates in, 581–587

plasma membrane of, 349–353, 587

polysaccharides in, 590–592

triglycerides in, 561–563

Cell(s), septation of, 525

Cell wall

arabinogalactan in, 535–541

composition of, 212

lipidomics of, 341–360

phosphatidyl-myo-inositol glycolipids of, 541–550

proteomics of, 245

recycling of, 522

Cellular redox ratio, 313

Central carbon metabolism, 323–339

definition of, 323

Emden-Meyerhof-Parnas pathway in, 325–328

energy sources for, 324–325

glycoxylate shunt, 333–334

methylcitrate cycle in, 333–334

pentose phosphate pathway in, 328–329

pyruvate dehydrogenase complex in, 329

schematic representation of, 323

short-chain carboxylic acids in, 329

tricarboxylic acid cycle in, 330–334

CentroidFold program, 200

ceo genes, 443

CESTET (conditional expression-specialized transduction essentiality test), 535, 544

CFP-10 protein, 29, 35, 247

Chah phage, 128

Chao, J. D., 697

Chaperone-like proteins, 124

Chaperones, 189, 213

Charlie phage, 104, 106, 128, 130

Chatterjee, D., 589

Chauhan, R., 141, 144

Che8 phage, 99, 127, 129

Che9c phage, 104–105, 108

Che9d phage, 127, 128

Che12 phage, 130

Che92 phage, 84, 91–93

Chemical scaffolds, 501–503

Chemical tractability (druggability), 273–276

Chemoinformatic analysis, 501

Chen, S., 198

Chenodeoxycholate, 587

Chi site, 658

ChIP-on-chip analysis, 148

ChIP-Seq (chromatin immunoprecipitation followed by sequencing), 161–181

comprehensive mapping in, 166–168

control experiments in, 162–163

data analysis in, 163–166

data availability in, 176–178

diagram of, 162

extensive binding in, 175–176

nonpromoter binding in, 173–175

in prokaryotes, 171–173

protocol for, 162–163, 177–178

validation of, 168–171

Chiradia, L. D., 701

ChiZ protein, 525

Chloride

genome changes due to, 732

in mycobacteria, 734

5-Chloro pyrazinamide, 484

Chlorobium tepidum, carbon metabolism in, 330

Cholesterol metabolism, 495–497, 757–758

Chorismate, 582

Chp protein, 366–367, 574

Chromatin immunoprecipitation, followed by sequencing (ChIP-Seq), 161–181

Chromatography, for mycolic acids, 612–613

Chromosomal gene transfer, 62–68, 106

Ciprofloxacin, 421, 456, 461, 466, 469, 713

Cirello, Jeffrey, 15

cis-Encoded base pairing RNAs, 189–191

Citric synthase, 330

Cjw1 phage, 128

cKD mutants, 232

Clark-Curtiss, Josephine E., 9–10

Class II transcriptional transactivator, 757

Classroom Undergraduate Research Experience (CURE), 84

Clastogens, 658

Claviceps purpurea, 310

Clavulanate, 526

Cleaving peptides, 668

ClgR protein, 145–146

Clofazimine, resistance to, 423

Cloning, direct, 104–105

Cloning-based screen approach, for RNA, 198–199

Clostridium difficile, resistance in, 468

Clostridium perfringens, resistance in, 468

Clostridium, sigma factors of, 138

Clp proteases, 249, 774

ClpXP protease, 104, 230

Cluster(s), in mycobacteriophage organization, 82, 84–90

Cluster K family phages, 13

Clustered, regularly interspaced short palindromic repeats (CRISPRs), 33, 100, 196–197

cma genes and Cma proteins, 265, 620

cmk genes, 641

Cmr (cAMP and macrophage regulator), 285, 287–288

CmrR protein, 384

Cmt proteins, 381

C-mycosides, 587

cmyt genes, 541

Cobalamin riboswitch, 187–188

CobC protein, 638

Coimmunoprecipitation, of RNAs, 200

Cole, Stewart, 16–18

Collins, D. M., 140

Collins, P. B., 433

Colony-forming units, plating of, 251–252

Comparative genome analysis

of phages, 90–93

for RNA, 199–200

Comparative lipidomics, 345, 347

Comparative modeling, for structural information, 262–263

Comparative proteomics, 243–246

Complement receptor, 747

Complex I, Complex II, Complex III, and Complex IV enzymes

in electron transport chain, 400

in growth, 390–391

structures of, 391–396

Compound libraries, 500–501

Compound-driven target selection, 494

Computational methods, for RNA prediction, 197–198

Condition tree analysis, 729

Conditional expression-specialized transduction essentiality test (CESTET), 535, 544

Conjugation, 7

chromosomal transfer in, 62–68

classical (oriT-mediated), 62–63, 65

distributive conjugal transfer, 68–76

genetic requirements for, 67

paradoxes in, 67–68

plasmid transfer in, 62–64

Conservons, 468

Consumption, see Tuberculosis

Control experiments, in ChIP-Seq, 162–163

Controlled proteolysis, 230, 231

Cook, G. M., 403

Cooperative binding, in ChIP-Seq, 166

CopA protein, 383

Copper, in mycobacteria, 381–384, 734

Copurification, of sRNAs, 200

Cord factor (trehalose dimycolate), 127, 350, 353, 362

Core particle, of proteasomes, 668, 670, 675

Corndog phage, 125, 127–129

Coronin-1, 751

Corynebacteriaceae, nucleotide metabolism in, 636

Corynebacterium

mycolic acids of, 613

Pup-proteasome system of, 669

Corynebacterium diphtheriae, metallobiology of, 379

Corynebacterium glutamicum

arabinogalactan of, 536, 538–541

cAMP signaling in, 282

carbon metabolism in, 334

cell envelope composition of, 559

energetics of, 399–400, 403

genetic switches in, 226

mycolic acids of, 622

phosphatidyl-myo-inositol glycolipids of, 545–547

Pup-proteasome system of, 670

redox sensors in, 302

STPKs of, 683, 696

trehalose in, 364

Cosmids, 4, 11, 105–106

Costerton, J. W, 774

Courthouse gene, 99

Cowley, S., 696

Cox, J. S., 586

Cox, Jeffery, 15

Coxsackie virus, Pup-proteasome system of, 674

crgA gene, 525

Crick, Francis, 7

CRISPRs (clustered, regularly interspaced short palindromic repeats), 33, 100, 196–197

Cross-correlation function, in ChIP-Seq, 164

Cross-presentation, of antigens, 759

CRP (cAMP-receptor protein), 282, 285–289

crRNAs (CRISPRs), 33, 100, 196–197

crt genes and Crt proteins, 30, 570–571

Cryptococcus neoformans, cAMP signaling in, 282

CSDevonv method, 166

CsgD protein, 774

CsoR protein, 382, 384

Csr proteins, 189, 198, 200

Cta proteins, 400

ctaBCDE gene, 389–390, 400

ctp genes and Ctp proteins, 381–383, 734, 735

Ctr1 protein, 734–735

C-type leptin receptor (mincle), 353, 614, 647, 747, 750

CURE (Classroom Undergraduate Research Experience), 84

Curtiss, Roy, III, 7, 9–10

cwlM gene, 522–523

CwsA protein, 525

Cyanide, 482

cycA gene, 414

Cyclic AMP receptor protein, 52

Cyclic AMP signaling, 281–295

adenylate cyclases in, 281, 283–285

cAMP production and secretion in, 290–291

control of, 289–299

CRP regulon in, 288–289

in gene regulation, 286–287

host cell interactions in, 290–291

lysine acetylase in, 289

mechanisms of, 281–282

in metabolism, 286–287

organisms using, 281–282

overview of, 281–282

regulation of, 285–286

transcription factors in, 287–288

Cyclic AMP, synthesis of, 404

Cyclic monophosphate binding proteins, 285–286

Cyclopropanation, 621–622

Cyclopropane synthases, 265, 624

Cycloserine

resistance to, 414, 422, 515

target of, 500

cydA genes, 401

cydABCD gene, 389–390

Cystein ligase, 307

Cytidine deaminase, 641

Cytidylate kinase, 641

Cytochrome c oxidase, 400

aa 3-type, 389–390

bc 1-aa 3-type, 400

bd-type, 389–390, 400–401

Cytochrome oxidase, copper in, 381

Cytoplasmic membrane, lysis of, 122

Cytoprotectant, ergothioneine as, 312

Cytosol, proteomics of, 245

Cytotoxicity, of phages, 95

D

D4 phage, 99–100

D19 phage, 11

D29 phage, 95, 99, 108, 127–129

Dac proteins, 521–522

Dainese, E., 145, 152

Dallman, H. G., 648

DAP (meso-diaminopimelate), 513–516, 518

Darwin, K. H., 667, 670, 672, 674, 734

DAS+4 tag, Switches, 229–230

Dassie bacillus, 35, 37, 51

Data analysis, in lipidomics, 347–348

DATs (2,3-di-O-acyltrehaloses), 575–577

Davies, Julian, 8–9

Davis, Ron, 10

Davy, K.W., 714

dcd genes, 641

DD5 phage, 128

DDD (F1F0-ATP synthase), 391, 402–403, 482

ddl gene, 414

de Steenwinkel, J. E M., 713

DECAL (differential expression using customized amplification libraries), 442

Decaprenol-1-monophosphoryl-2-keto-β-erythro-pentofuranose (DPX), 539

Decaprenyl-5-phosphoribose (DPR), 539

Decaprenyl diphosphate (Dec-PP), 518–519

Decaprenyl phosphate (Dec-P), 349–350, 517–519, 567–568

Decaprenyl phosphoryl-4-phosphoribose (DPPR), 539

Decoys, immunological, 755–756

Dec-P (decaprenyl phosphate), 349–350, 517–519, 567–568

Dec-PP (decaprenyl diphosphate), 518–519

Degradation, of proteins, Pup-proteasome system in, 667–680

Degradosomes, 196

Dehydrolipoamide acyltransferase, 674

Dehydroquinase, 273

Delamanid, 487, 493

Deltaproteobacteria, STPKs of, 682

Demethylmenaquinone, 569

Dendritic cells, infection of, 753

1-Deoxy-d-xylulose-5-phosphate reductoisomerase, 565–566

1-Deoxy-d-xylulose-5-phosphate synthase, 563, 565

Deoxynucleotide triphosphates (dNTPs), biosynthesis of, 636–642

Depupylase, 672

Depupylation, 671–672

Dessication, double-strand DNA breaks in, 657

Detergents, for waxy cultures, 715

Detoxification

of copper, 734

of isoniazide, 442

mycothiol for, 309

truncated hemoglobins in, 305

Deubiquitylases, 669–672

DfrA protein, 503

Dhar, N., 401

D'Herelle, Felix, 108–109

Diacylglycerol, 544–545

2,3-Diacyltrehalose, 368

meso-Diaminopimelate (DAP), 513–516, 518

Diaminopimelic acid, 5, 9

Diarylquinolines, 403

Dibutyryl cAMP, 286–287

DiChiara, J. M, 198–199

Dietzia, mycolic acids of, 613

Differential expression using customized amplification libraries (DECAL), 442

Diglyceride acyltransferases, 562

Dihydrofolate reductase, 232, 273, 444, 500

Dihydrolipoamide transferase, 733

Dihydrolipoyl dehydrogenase, 331

Dihydrolipoyllysine-residue acetyltransferase, 329, 331

Dihydroorotate, 638

1,4-Dihydroxy-2-naphthoate, 569

Dihydroxyacetone kinase, 327

Dimer and phosphotransferase domain, of histidine kinase, 209

Dimerization

of STPKs, 685–686

in two-component regulatory systems, 211, 216

Dimethylallyl diphosphate, 563, 565–566

Dimycolyl diarabinoglycerol, 614

din genes and Din proteins, 644–645

Dinitrobenzamide derivatives (DNBs), 539, 549–550

Dinitrophenol, 482

2,3-Di-O-acyltrehaloses (DATs), 575–577

Diphosphatidylglycerol, 561

4-Diphosphocytidyl-2C-methyl-d-erythritol, 565–566

4-Diphosphocytidyl-2C-methyl-d-erythritol phosphate, 566

dipZ gene, 151

Direct cloning, 104–105

Direct plating, for phage isolation, 82

Direct transcriptional silencing, 232

Direct transitional repression, 232

Dispersal, in biofilm formation, 774–775

Distributive conjugal transfer, 68–76

evolutionary effects of, 71–75

as genetic mapping tool, 75–76

indel formation in, 74–75

mating identity switch in, 75

mid genes in, 75–76

models for, 68–70

mosaicism in, 68, 72–74

in native mycobacterial species, 71–74

vs. oriT-mediated conjugation, 68

reproductive success and, 74

spontaneous mutation and, 74

unanswered questions about, 71

Disulfide bonding, 305

Disulfide reductases, 304

Disulfide stress, 303

DivIVA protein, 525, 527

DivIVC protein, 527

DlaT protein, 733

DNA

as active factor in gene transfer, 7

double-stranded, 82, 123

extracellular, 774

replication of, 642–649

DNA binding protein, 380

dna genes and Dna proteins, for replication, 642–649

DNA gyrases, 421, 457–463, 468

DNA ligases, 273

DNA microarrays, for sigma factors, 141–143, 145, 147–148, 151

DNA polymerases, 95, 642–645

DNA topoisomerases, fluoroquinolones targeting, 457–459

DnaA boxes, 645

DNA/RNA-binding 3-helical bundle, 268

dN/dS (nonsynonymous vs. synonymous) ratios, 33

DocB7 phage, 130

Domagk, G., 431

dop gene and Dop protein, 671–675

Dori phage, 101

Dormant infections, 713

DosR/S/T in, 302

electron transport in, 404

persisters in, 718

proteomics of, 245–246, 253

redox potential and, 300

Dorrestein, P. C., 674

Dos regulon, 213, 697, 729–730

Dose-responsiveness, in gene expression, 231

DosR protein, 166, 175–176, 193, 199, 212, 249

DosR/DevR proteins, 401–402

DosRS-DosT system, 402

DosR/S/T dormancy regulon, 302

DosRST system, 217

DosT/DosS/DosR system, 404

Double-strand DNA breaks

causes of, 657

repair of, 657–666

homologous recombination method for, 658–660

nonhomologous end joining in, 660–662

in pathogenesis, 663–664

single-strand annealing in, 662–663

dpr genes and Dpr proteins, 539, 549–550

Drr AB protein, 467, 586

Drug(s), development of, 253–254

structural considerations in, 273–276

targets for, 493–509

Drug resistance

aminoglycosides, 414, 419–420

bedaquiline, 4, 414, 423

beta-lactams, 423

capreomycin, 414, 420–421

ciprofloxacin, 713

cycloserine, 414, 422, 515

definitions of, 413, 712

detection of, 423

efflux pumps in, 714–715

ethambutol, 4, 414, 418–419, 548–549

ethionamide, 4, 395, 414, 421–422, 431–453

fluoroquinolones, 455–478

genomics and, 423–424

historical review of, 431

isoniazid, 4, 395–396, 414, 416–417, 431–453, 434–446

linezolid, 414

mechanisms of, 7–9, 19–20, 414

molecular basis of, 413–429

new drug development for, 253–254, 493–509

oxazolidinones, 422–423

para-aminosalicylic acid, 414, 422

proteomics for, 245

prothionamide, 421–422

pyrazinamide, 414, 417–418, 479–493

quinolones, 414, 421

redox environment and, 301–302

reversal of, 498

rifamycin, 414–416, 713

streptomycin, 7–9, 414

susceptibility testing for, 14

WhiB family and, 303

Drug sensitivity, definition of, 712

Drug susceptibility, 711–725; see also Drug resistance

definition of, 711

drug tolerance, 712–720, 723

persistence, see Persistence and persisters

testing for, 14

Drug targets, 273–276

BTZs, 549–550

DNBs, 549–550

ethambutol, 548–549

ethionamide, 434–435

fluoroquinolones, 457–458

isoniazid, 434–435

modification of, 414

multiple, single inhibitor for, 498

mycolic acids, 621

new, 493–509

current status of, 494–495

expanding screening for, 500–503

genetic approaches to, 494

relevant biology for, 495–498

replication properties and, 648–649

overexpression of, 499–500

pyrazinamide, 480–484

serine/threonine protein kinases as, 700–701

specificity of, 273, 495

SQ109, 549

Drug tolerance

asymmetric growth in, 716–717

in biofilms, 775, 779

definition of, 712

heritable, 716

persister population in, 716, 718–720

population-level, 712–714

Druggability, 273–276, 495

DS6A phage, 101

DsbE-like protein, 151

DtxR protein, 380, 383–384

DU1 and DU2, 55–56

Dubos, R. J., 572, 774

dUDP-Rha, 536–538

Duplication, tandem, 55

dut genes and Dut proteins, 640–641

dxs gene and Dxs protein, 563, 565