Handbook of Tuberculosis

1201 Pages·2008·60.439 MB·English

by  Stefan H. E. Kaufmann, Paul van Helden, Eric Rubin, Warwick J. Britton

HandbookofTuberculosis
Edited by
Stefan H. E. Kaufmann
and Eric Rubin
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Handbook of Tuberculosis
Molecular Biology and Biochemistry
Edited by
Stefan H. E. Kaufmann and Eric Rubin
TheEditors AllbookspublishedbyWiley-VCHarecarefully
produced.Nevertheless,authors,editors,and
publisherdonotwarranttheinformationcontained
Prof.Dr.Dr.h.c.StefanH.E.Kaufmann
inthesebooks,includingthisbook,tobefreeof
MaxPlanckInstituteforInfectionBiology
errors.Readersareadvisedtokeepinmindthat
DepartmentofImmunology
statements,data,illustrations,proceduraldetailsor
Charitéplatz1
10117Berlin otheritemsmayinadvertentlybeinaccurate.
Germany
[email protected] LibraryofCongressCardNo.: appliedfor
BritishLibraryCataloguing-in-PublicationData
Prof.Dr.EricRubin
Acataloguerecordforthisbookisavailablefromthe
HarvardMedicalSchool
BritishLibrary.
DepartmentofMicrobiologyandMolecularGenetics
200LongwoodAve.
Boston,MA02115 Bibliographicinformationpublishedby
USA theDeutscheNationalbibliothek
DieDeutscheNationalbibliothekliststhis
[email protected]
publicationintheDeutscheNationalbibliografie;
detailed bibliographicdataareavailableinthe
Internetathttp://dnb.d-nb.de.
2008WILEY-VCHVerlagGmbH&Co.KGaA,
Weinheim
Allrightsreserved(includingthoseoftranslationinto
otherlanguages).Nopartofthisbookmaybe
reproducedinanyform–byphotoprinting,
microfilm,oranyothermeans–nortransmittedor
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Printedonacid-freepaper
ISBN:978-3-527-31886-5
V
Contents
ListofContributors XIII
Foreword XVII
Timeline XXI
Introduction XXIII
Preface XXIX
1 BiochemistryoftheCellEnvelopeofMycobacterium tuberculosis 1
Dean C.Crick,LuisQuadri,PatrickJ.Brennan
1.1 OverviewoftheCellEnvelopeofM.tuberculosis 1
1.2 FreeLipidsandLipoglycansAssociatedwiththeOuterLayerof
theCellWallofM.tuberculosis 4
1.3 ThemAGPComplex 7
1.3.1 MycolicAcids 7
1.3.2 AG 8
1.3.3 PG 9
References 11
2 PolyketidesandPolyketide-ContainingGlycolipidsofMycobacterium
tuberculosis:Structure,BiosynthesisandBiologicalActivities 21
ChristopheGuilhotandMamadou Daffé
2.1 Introduction 21
2.1.1 OrganizationandCompositionoftheEnvelopeofM.tuberculosis 21
2.1.2 BiosynthesisofLipidsfromtheCellEnvelope:Roleof
PolyketideSynthases 24
2.2 BiosynthesisofPolyketidesinM.tuberculosis 25
2.2.1 TheMas-LikeFamily:FormationofMethyl-Branched
FattyAcids 25
2.2.2 ThePpsCluster:SynthesisofPhthiocerolandPhenolphthiocerol 27
2.2.3 MycolicCondensation:RoleofPks13 29
2.2.4 MbtCandMbtD:Synthesisofthe -HydroxybutyrateBlock
ofMycobactins 29
HandbookofTuberculosis:MolecularBiologyandBiochemistry.EditedbyStefanH.E.KaufmannandEricRubin
Copyright 2008WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-31886-5
VI Contents
2.2.5 Pks12:FormationofMycoketide 30
2.2.6 OrphanPks 30
2.3 BiosynthesisandTranslocationofthePolyketide-Derived
LipidsinM.tuberculosis 31
2.3.1 PGLsandDIMs 32
2.3.1.1 ActivationofthePksSubstrates 32
2.3.1.2 ModificationofthePhthiocerolandPhenolphthiocerolChains 32
2.3.1.3 ReleaseofthePolyketidesandTransferontotheirAcceptors 33
2.3.1.4 FormationoftheSaccharidicAppendageofPGL 34
2.3.1.5 Translocation 35
2.3.2 Trehalose-ContainingLipids 36
2.3.2.1 TrehaloseMonomycolateandTDM 36
2.3.2.2 SLs 36
2.3.2.3 PATandDAT 37
2.3.2.4 LOS 37
2.3.3 Mannosyl- -1-Phosphomycoketides 38
2.4 RoleofPolyketide-DerivedLipidsinM.tuberculosisBiology 38
2.4.1 ContributiontotheFunctionsoftheCellEnvelope 39
2.4.2 ContributiontoM.tuberculosisPathogenicity 40
2.4.2.1 EarlyInteractionwithHostCells 40
2.4.2.2 IntracellularFateofM.tuberculosis 40
2.4.2.3 MultiplicationandPersistencewithintheHost 41
2.4.2.4 ModulationoftheHostImmuneResponses 42
2.5 Conclusions 44
References 45
3 PhysiologyofMycobacterium tuberculosis 53
DigbyF.Warner,ValerieMizrahi
3.1 Introduction 53
3.2 PhysiologyandVirulence 53
3.3 KeyFeaturesofTuberculosis 54
3.4 PhysiologyofM.tuberculosis 55
3.4.1 StructureandCompositionoftheCellWall 55
3.4.2 CellularMetabolisminM.tuberculosis 57
3.4.3 RegulatedPhysiologicalAdaptability 58
3.4.4 ToleranceofDamageCausedbyHostImmuneEffectors 59
3.4.5 SlowGrowthandStatesofLowMetabolicActivity 60
3.5 DeterminantsofVirulenceinM.tuberculosis 61
3.6 PhysiologyandDrugDiscovery 62
3.6.1 EssentialandConditionallyEssentialGenesinM.tuberculosis 62
3.6.2 DependenceofM.tuberculosisGeneFunctiononthe
InfectionModel 63
3.6.3 CurrentTrends 63
3.7 Conclusions 64
References 65
Contents VII
4 NutrientUptakebyMycobacteria 71
MichaelNiederweis
4.1 Introduction 71
4.2 CellEnvelopeofMycobacteria 72
4.2.1 PermeabilityBarriersinMycobacterialCellEnvelopes 72
4.2.2 PrinciplePathwaysofNutrientsAcrosstheMycobacterial
CellEnvelope 73
4.3 TransportAcrossMycobacterialOuterMembranes 74
4.3.1 Porin-MediatedDiffusionofHydrophilicSolutes 74
4.3.2 DirectDiffusionofHydrophobicSolutesThroughthe
CellMembranes 76
4.4 TransportAcrosstheInnerMembrane 76
4.4.1 TransportersofCarbon-ContainingCompounds 76
4.4.1.1 TransportersofCarbohydrates 76
4.4.1.2 TransportersofLipids 80
4.4.2 TransportersofPhosphorus-ContainingSolutes 81
4.4.3 TransportersofSulfur-ContainingSolutes 82
4.4.4 TransportersofNitrogen-ContainingSolutes 82
4.4.5 TransportersofInorganicCations 83
4.4.6 TransportersofOtherSolutes 84
References 84
5 IronUptakebyMycobacterium tuberculosis 91
LuisE.N.Quadri
5.1 TheBattleforIronbetweenM.tuberculosisanditsHost 91
5.2 StructuresofMBTsandCMBTsfromM.tuberculosis 92
5.3 ChromosomalLociInvolvedinMBTandCMBTBiosynthesis
andTransport 93
5.4 RegulationofGenesInvolvedinMBT/CMBT-Mediated
IronAcquisition 95
5.5 PhenotypeofM.tuberculosisStrainswithMutationsinGenes
oftheMBT/CMBTSystem 96
5.6 EnzymologicalStudiesofProteinsInvolvedinMBTandCMBT
Biosynthesis 97
5.7 CurrentWorkingModelfortheBiosynthesisofMBTsandCMBTs 98
5.8 MBTandCMBTTraffickingandSequestrationofIroninthe
Host 100
5.9 ReleaseofIronfromtheFe3 -MBT/CMBTComplexes 102
5.10 InhibitionofIronUptakeinM.tuberculosis:ANovel
AvenueforExplorationofPotentialAnti-TuberculosisDrugs 103
References 105
6 ProteinTransportinMycobacterium tuberculosis 111
Justin A.McDonough,Miriam Braunstein
6.1 Introduction 111
VIII Contents
6.2 SecPathway 112
6.3 SecPathwayinM.tuberculosis 113
6.4 LipoproteinProcessingandExportinM.tuberculosis 113
6.5 AConnectionbetweenSecExportandProteinGlycosylation
inM.tuberculosis 114
6.6 SecA1andSecA2inM.tuberculosis 114
6.7 TatPathway 116
6.8 TatPathwayinM.tuberculosis 118
6.9 ESX-1PathwayinM.tuberculosis 119
6.10 PEandPPEProteinExportinM.tuberculosis 123
6.11 Conclusions 124
References 125
7 ThePEandPPEProteinFamiliesofMycobacterium tuberculosis 131
GiovanniDelogu,StewartT.Cole,RolandBrosch
7.1 Introduction 131
7.2 ThePEProteinFamily 131
7.2.1 ThePE_PGRSSubfamily 133
7.2.2 GeneExpressioninthePE_PGRSSubfamily 133
7.2.3 CellularLocalizationofPE_PGRSProteins 136
7.2.4 ImmunologyandHostResponsetoPE_PGRSProteins 136
7.2.5 GeneticVariationinthePE_PGRSSubfamily 138
7.3 ThePPEProteinFamily 139
7.4 PE/PPEProteinsandtheESAT-6Family 140
7.4.1 PE/PPEGenesandESX-1 140
7.4.2 PE/PPEGenesandESX-5 141
7.5 EvolutionofPE/PPEGenes 142
References 144
8 VirulenceandPersistenceMechanismsofMycobacterium
tuberculosis 151
Helena I.Boshoff,Ramandeep Singh,Clifton E.Barry 3rd
8.1 Introduction 151
8.2 ApproachestoDefiningVirulence/PersistenceFactorsof
M.tuberculosis 152
8.2.1 UseofTargetedGeneticMutantsinAnimalModels 152
8.2.2 Whole-GenomeScanningApproaches 160
8.2.3 Epidemiology-DrivenApproaches 161
8.3 ClassificationofStrain-IndependentVirulence/Persistence
Factors 162
8.3.1 IntermediateMetabolismandNutrientUptake 162
8.3.2 RespiratoryPathways 164
8.3.3 Lipids 165
8.3.4 CellWall-AssociatedProteins 167
8.3.5 RepairandDetoxificationSystems 168
Contents IX
8.3.6 SignalTransductionandTranscription 169
8.4 Strain-DependentVirulence/PersistenceFactors 171
8.5 PersistenceMechanismsinLatentDisease 173
8.6 Conclusions 175
References 175
9 GenomicsoftheMycobacterium tuberculosisComplex 193
Stephen V.Gordon,AlexanderS.Pym
9.1 Introduction 193
9.2 GenomeStructure 194
9.3 RepetitiveDNA 195
9.4 ThePEandPPEProteins 196
9.5 GeneExpression 197
9.6 Physiology 197
9.7 DrugTargets 200
9.8 AntigenMining 201
9.9 Evolution 202
9.10 Conclusions 205
References 205
10 TranscriptomicsandTranscriptionalRegulation 213
DirkSchnappinger
10.1 Introduction 213
10.2 TranscriptionofHousekeepingGenes 213
10.3 Alternative Factors 217
10.4 RegulationbyAccessoryTranscriptionFactors 223
10.4.1 Two-ComponentSystems 223
10.4.2 Metal-DependentTranscriptionalRegulators 225
10.4.3 RegulationbyCyclicAMP(cAMP) 227
10.5 RegulationoftheM.tuberculosisTranscriptomeDuring
Infections 227
References 232
11 ProteomicsofMycobacterium tuberculosis 241
Karen M.Dobos,John T.Belisle
11.1 HistoryofProteomics 241
11.2 TheM.tuberculosisProteomeinthePre-GenomeEra 241
11.3 TheM.tuberculosisProteomeinthePost-GenomeEra 243
11.4 Conclusions 253
References 253
12 TheProteomeofMycobacterium tuberculosisinThreeDimensions 261
MatthiasWilmanns,Stefan H.E.Kaufmann
12.1 FromStructuralBiologytoStructuralGenomics 261
12.2 The3DStructuresofM.tuberculosisProteins 262
X Contents
12.3 The3DStructuresofProtein–LigandInteractions
InvolvingM.tuberculosisTargets 271
12.4 The3DStructuresofM.tuberculosisHostProtein–Ligand
Interactions 273
12.5 Structure-BasedDiscoveryofFunctionsofM.tuberculosisProteins 275
12.6 Structure-BasedDiscoveryofInhibitorsAgainstM.tuberculosis
Proteins 277
12.7 FuturePerspectivesinM.tuberculosisStructuralBiology 278
References 279
13 MolecularMechanismsofDormancyandResuscitation 287
TigeR.Rustad,Ashley M.Sherrid,DavidR.Sherman
13.1 RoleofLatencyintheGlobalTuberculosisEpidemic 287
13.2 ImportantQuestionsofLatencyandResuscitation 288
13.2.1 CatchingtheDormantBacillusatHome 288
13.2.2 TheMetabolicandReplicativeStateofinvivoM.tuberculosis
fromLatentInfections 290
13.3 ModelsofLatency 290
13.3.1 invivoLatencyModels:ACatalogofMycobacterialAbuse 290
13.3.2 TheHypoxicModelofLatency 291
13.3.2.1 Rationale 291
13.3.2.2 ModelsofHypoxia-InducedLatency 292
13.3.2.3 TheDosR-RegulatedInitialResponsetoHypoxia 294
13.3.3 invivoModelsofLatency 295
13.4 ResuscitationofTuberculosis 296
13.4.1 PrevalenceandPredisposingFactors 296
13.4.1.1 TheApices:AFavorableLocation 297
13.4.2 ModelsofReactivation 297
13.5 ConclusionsandForwardDirections 298
References 299
14 Mycobacterium tuberculosis:LifeandDeathinthePhagosome 307
DavidG.Russell
14.1 Introduction 307
14.2 TheTwoFacesoftheMacrophage 308
14.3 TheIntraphagosomalEnvironmentinRestingMacrophages 308
14.4 HowstheBugDoIt? 311
14.5 Okay,SoThatstheRestingMacrophage,WhatHappens
WhenYouActivateIt? 313
14.6 TheKillingPhagosome 313
14.7 TheImmuneInterface 314
14.8 Inside-OutManipulationoftheHost 316
14.9 Conclusions 316
References 317