Cover -- Half Title -- Title Page -- Copyright -- Contents -- Contributors -- Preface -- I. Genomes, Genomics, and Genetic Exchange -- Chapter 1: Gene Transfer in Mycobacterium tuberculosis: Shuttle Phasmids to Enlightenment -- OVERVIEW OF KEY MUTATIONS THAT FACILITATED GENE TRANSFER IN M. TUBERCULOSIS -- TB TRANSMISSION ESTABLISHED TB CAUSALITY -- GENE TRANSMISSION ESTABLISHED PHENOTYPE CAUSALITY -- ELUCIDATING THE MECHANISMS OF’DRUG KILLING: THE STREPTOMYCIN EXAMPLE -- TRANSFER OF GENES FROM PATHOGENIC MYCOBACTERIA INTO THE SURROGATE HOST E. COLI: GREAT PROMISE WITH LIMITATIONS -- INTRODUCTION OF FOREIGN DNA INTO MYCOBACTERIA: SHUTTLE PHASMIDS AND THE DEVELOPMENT OF A PLASMID TRANSFORMATION SYSTEM FOR M. SMEGMATIS -- SECOND GENERATION SHUTTLE PHASMIDS: REPORTER MYCOBACTERIOPHAGES, TRANSPOSON DELIVERY, AND SPECIALIZED TRANSDUCTION -- HIGH-THROUGHPUT SPECIALIZED TRANSDUCTION -- IMAGINING A WORLD WITHOUT TB -- References -- Chapter 2: Mycobacterial Pathogenomics and Evolution -- INTRODUCTION -- MYCOBACTERIAL GENOMICS -- INSIGHTS INTO THE MACROEVOLUTION OF M. TUBERCULOSIS BASED ON COMPARISON WITH M. MARINUM AND MYCOBACTERIUM KANSASII -- MICROEVOLUTIONARY GENOMICS OF THE TUBERCLE BACILLI -- MYCOBACTERIAL SYSTEMS DISCOVERED BY GENOMICS THAT ARE INVOLVED IN PATHOGENICITY -- CONCLUSIONS AND PERSPECTIVES -- References -- Chapter 3: BCG Vaccines -- HISTORY OF BCG SUBSTRAINS -- BCG AS AN ATTENUATED MEMBER OF THE M. TUBERCULOSIS COMPLEX -- MOLECULAR EVOLUTION AND THE DERIVATION OF BCG SUBSTRAINS -- MOLECULAR EVOLUTION AND THE PROPAGATION OF BCG SUBSTRAINS -- CONCLUSION AND PERSPECTIVES: ATTENUATION OF VIRULENCE AND PROTECTIVE EFFICACY -- REFERENCES -- Chapter 4: Distributive Conjugal Transfer: New Insights into Horizontal Gene Transfer and Genetic Exchange in Mycobacteria -- CLASSICAL oriT-MEDIATED CONJUGATION: A BRIEF OVERVIEW.

MYCOBACTERIAL CONJUGATION -- DISTRIBUTIVE CONJUGAL TRANSFER -- DCT AS AN ENGINE FOR MYCOBACTERIAL EVOLUTION -- DCT AS A GENETIC MAPPING TOOL -- SUMMARY AND FUTURE PROSPECTSFOR DCT -- References -- Chapter 5: Molecular Genetics of Mycobacteriophages -- INTRODUCTION -- GENERAL ASPECTS OF MYCOBACTERIOPHAGES -- MYCOBACTERIOPHAGE GENOMICS -- MYCOBACTERIOPHAGE-HOST INTERACTIONS -- INTEGRATION SYSTEMS -- MYCOBACTERIOPHAGE GENE EXPRESSIONAND ITS REGULATION -- GENETIC MANIPULATION OF MYCOBACTERIOPHAGES -- APPLICATIONS FOR MYCOBACTERIAL GENETICS -- PERSPECTIVES: PAST, PRESENT, AND FUTURE -- References -- Chapter 6: Genetics of Phage Lysis -- THE LYSIS PLAYERS -- MYCOBACTERIOPHAGE-MEDIATED LYSIS -- APPLICATIONS OF THE LYSIS PROPERTIES -- CONCLUDING REMARKS -- References -- II. Gene Expression and Regulation -- Chapter 7 : Sigma Factors: Key Molecules in Mycobacterium tuberculosis Physiology and Virulence -- THE σ FACTORS OF MYCOBACTERIUM TUBERCULOSIS -- CONCLUDING REMARKS -- References -- Chapter 8: Transcription Factor Binding Site Mapping Using ChIP-„Seq -- ChIP-Seq METHOD AND PROTOCOL -- DATA ANALYSIS -- COMPREHENSIVE MAPPING OF TF BINDING SITES IN M. TUBERCULOSIS -- VALIDATION OF THE ChIP-Seq SYSTEM -- THE DIVERSITY OF TF BINDING IN PROKARYOTES -- NONPROMOTER TF BINDING -- EXTENSIVE TF BINDING -- TBDB AND DATA AVAILABILITY -- APPENDIX -- References -- Chapter 9: Noncoding RNA in Mycobacteria -- WHAT IS ncRNA? -- STRESS RESPONSES OF INTERGENIC sRNAs -- OTHER M. TUBERCULOSIS ncRNAs -- HOW TO IDENTIFY ncRNA -- GLOSSARY -- References -- Chapter 10: Two-Component Regulatory Systems of Mycobacteria -- INTRODUCTION -- SPECIFIC SYSTEMS -- CONCLUSION -- References -- Chapter 11: Regulated Expression Systems for Mycobacteria and Their Applications -- GENETIC SWITCHES FOR CONTROLLING GENE EXPRESSION IN MYCOBACTERIA.

COMMON AND DISTINCTIVE FEATURES OF’THE DIFFERENT REGULATORY SYSTEMS AND STRATEGIES -- APPLICATIONS -- CONCLUSIONS AND FUTURE PERSPECTIVES -- References -- III. The Mycobacterial Proteome -- Chapter 12: Mycobacterium tuberculosis in the Proteomics Era -- COMPARATIVE PROTEOMICS -- FUNCTIONAL PROTEOMICS -- TARGETED PROTEOMICS -- IMPACT OF PROTEOMICS ON TB INTERVENTION AND DIAGNOSTICS -- References -- Chapter 13: Structural Annotation of the Mycobacterium tuberculosis Proteome -- OBTAINING A STRUCTURAL PROTEOME -- FUNCTIONAL INSIGHTS FROM PROTEIN STRUCTURES -- COVERAGE OF M. TUBERCULOSIS STRUCTURAL PROTEOME AND ANNOTATION -- FEATURES OF THE M. TUBERCULOSIS STRUCTURAL PROTEOME -- LEVELS OF ANNOTATION -- STRUCTURAL PROTEOME AND ITS IMPACT ON PATHOGENESIS AND VIRULENCE -- INSIGHTS INTO TWO-COMPONENT SYSTEMS -- APPLICATION IN DRUG DISCOVERY -- CURRENTLY EXPLORED TARGETS FOR STRUCTURE-BASED ANTI-TB DRUG DISCOVERY -- NEW TARGET IDENTIFICATION: STRUCTURAL ASSESSMENT OF DRUGGABILITY -- STRUCTURE-BASED LEAD DESIGN -- CONCLUSIONS -- References -- Chapter 14: Cyclic AMP Signaling in Mycobacteria -- CYCLIC AMP IS A UNIVERSAL SECONDMESSENGER USED BY PATHOGENS AND THEIR HOSTS -- NUCLEOTIDE CYCLASES IN M. TUBERCULOSIS -- REGULATION OF cAMP PRODUCTION -- DIVERSE ROLES FOR cAMP WITHIN MYCOBACTERIA -- EMERGING ROLES FOR cAMP SIGNALINGIN MYCOBACTERIAL GENEREGULATION AND METABOLISM -- cAMP-ASSOCIATED TRANSCRIPTION FACTORS: Cmr AND CRPMt -- DEFINING THE CRPMt REGULON ANDBINDING MOTIF -- STRUCTURE AND FUNCTION OF CRP Mt -- THE PROTEIN LYSINE ACETYLASE Rv0998 -- MORE MAKING THAN BREAKING OF’cAMP’IN MYCOBACTERIA? -- cAMP PRODUCTION, SECRETION, AND HOST CELL INTERACTIONS -- CONCLUSIONS AND FUTURE DIRECTIONS -- References -- IV. Metabolism -- Chapter 15: The Physiology and Genetics of Oxidative Stress in Mycobacteria -- REDOX HOMEOSTASIS -- OXIDATIVE STRESS.

REDOX ENVIRONMENT OF THE LUNG -- REDOX SENSORS OF M. TUBERCULOSIS -- THIOLS AS REDOX BUFFERS AND CELLULAR DETOXIFIERS -- MEASUREMENT OF THE REDOX STATE’IN MYCOBACTERIA -- CONCLUSIONS AND FUTURE CHALLENGES -- References -- Chapter 16: Metabolomics of Central Carbon Metabolism in Mycobacterium tuberculosis -- CARBOHYDRATE METABOLISM -- EMP PATHWAY AND GLUCONEOGENIC COUNTERPARTS -- THE PPP -- METABOLISM OF SHORT-CHAIN CARBOXYLIC ACIDS -- PDH COMPLEX -- TCA CYCLE -- GLYOXYLATE SHUNT AND THE METHYLCITRATE CYCLE -- CONCLUDING REMARKS -- References -- Chapter 17: Mycobacterial Lipidomics -- METABOLOMICS AS A DISCIPLINE -- ORGANISM-WIDE LIPIDOMIC DETECTION -- TARGETED AND GLOBAL LIPIDOMICS -- LIPID IDENTIFICATION -- MYCOBACTERIAL LIPIDS -- MYCOBACTERIAL LIPIDOMIC METHODS -- BIOLOGICAL STUDIES USING LIPIDOMICS -- SUMMARY AND CONCLUSION -- References -- Chapter 18: Genetics of Mycobacterial Trehalose Metabolism -- TREHALOSE: A UBIQUITOUS AND UNIVERSAL SUGAR -- FUNCTIONS OF TREHALOSE IN MYCOBACTERIA -- TREHALOSE DE NOVO BIOSYNTHESIS -- TREHALOSE DEGRADATION -- BIOSYNTHESIS OF TREHALOSE-„DERIVED GLYCOLIPIDS -- TREHALOSE UPTAKE AND RECYCLING -- CONVERSION OF TREHALOSE TO’ALPHA-GLUCANS -- CONCLUDING REMARKS -- References -- Chapter 19: Metallobiology of Tuberculosis -- THE BATTLE FOR IRON -- ZINC AND COPPER: NEVER’TOO’LITTLE’OR TOO MUCH -- FUTURE DIRECTIONS -- References -- Chapter 20: Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria -- OVERVIEW OF MYCOBACTERIAL RESPIRATION AND OXIDATIVE PHOSPHORYLATION -- ENERGETICS OF MYCOBACTERIA DURING’GROWTH AND NONGROWTH CONDITIONS -- ELECTRON DONORS FUELING RESPIRATION IN MYCOBACTERIA -- TERMINAL ELECTRON ACCEPTOR UTILIZATION -- ELECTRON ACCEPTOR UTILIZATION’UNDER HYPOXIA -- ATP SYNTHESIS BY THE F1F0 -ATP SYNTHASE -- CONTROL OF ELECTRON TRANSPORT CHAIN EXPRESSION AND OXIDATIVE PHOSPHORYLATION.

References -- V. Genetics of Drug Resistance -- Chapter 21: Molecular Basis of Drug Resistance in Mycobacterium tuberculosis -- DEFINITIONS OF DRUG-RESISTANT TB -- MECHANISMS OF DRUG RESISTANCE -- FIRST-LINE AGENTS -- INJECTABLE AGENTS -- SECOND-LINE AGENTS -- OTHER DRUGS -- NOVEL AGENTS -- DIAGNOSTIC TOOLS FOR DETECTING DRUG-RESISTANT M. TUBERCULOSIS -- GENOMICS AND DRUG RESISTANCE -- References -- Chapter 22: Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis : Genes, Mutations, and Causalities -- THE EMERGENCE OF DRUG RESISTANCE -- MODE OF ACTION OF INH AND ETH -- MECHANISMS OF RESISTANCE TO’INH’AND ETH -- CONCLUSIONS AND THE FUTURE -- References -- Chapter 23: The Molecular Genetics of Fluoroquinolone Resistance in Mycobacterium tuberculosis -- FQs AND THEIR INTRODUCTION INTO’ANTI-TB THERAPY -- THE FQ DRUG TARGET -- FQs POISON THE TYPE II TOPOISOMERASES -- INTERACTIONS WITH DIFFERENT FQs AND’RELATION OF STRUCTURE TO RESISTANT DEVELOPMENT -- FQ RESISTANCE WITHOUT GYRASE MUTATIONS -- CONCLUSIONS -- References -- Chapter 24: Mechanisms of Pyrazinamide Action and Resistance -- THE HISTORY: THE UNUSUAL DISCOVERY AND THE ROLLER COASTER OF PZA -- IMPORTANCE OF PZA IN SHORTENING’TB THERAPY -- MECHANISMS OF PZA ACTION -- TARGETS OF PZA -- MECHANISMS OF PZA RESISTANCE -- IMPLICATIONS OF PZA FOR DEVELOPING A NEW GENERATION OF PERSISTER DRUGS -- CONCLUSIONS -- References -- Chapter 25: Genetic Strategies for Identifying New Drug Targets -- CURRENT TARGET-BASED DRUGDISCOVERY IN MYCOBACTERIUM TUBERCULOSIS -- TARGETING BIOLOGY THAT IS RELEVANT’FOR INFECTION -- USING DRUG SCREENS TO PROSPECTFORNEW TARGETS -- BIOLOGICALLY RELEVANT TARGET VALIDATION -- FINDING MORE AND BETTER COMPOUNDS -- CONCLUDING REMARKS -- References -- VI. Genetics of Membrane and Cell Wall Biosynthesis -- Chapter 26: Genetics of Peptidoglycan Biosynthesis.

GENETICS OF PG PRECURSOR SYNTHESIS.