Toxoplasma Gondii (eBook)

Front cover 1
Toxoplasma gondii 4
Copyright page 5
Contents 8
Contributors 16
Preface 20
Acknowledgements 22
Chapter 1: The History and Life Cycle of Toxoplasma gondii 24
1.1 INTRODUCTION 24
1.2 THE ETIOLOGICAL AGENT 24
1.3 PARASITE MORPHOLOGY AND LIFE CYCLE 25
1.4 TRANSMISSION 28
1.5 TOXOPLASMOSIS IN HUMANS 31
1.6 TOXOPLASMOSIS IN OTHER ANIMALS 33
1.7 DIAGNOSIS 33
1.8 TREATMENT 34
1.9 PREVENTION AND CONTROL 34
ACKNOWLEDGEMENTS 35
REFERENCES 35
Chapter 2: The Ultrastructure of Toxoplasma gondii 42
2.1 INTRODUCTION 42
2.2 INVASIVE STAGE ULTRASTRUCTURE AND GENESIS 42
2.3 COCCIDIAN DEVELOPMENT IN THE DEFINITIVE HOST 52
2.4 DEVELOPMENT IN THE INTERMEDIATE HOST 62
REFERENCES 69
Chapter 3: Population Structure and Epidemiology of Toxoplasma gondii 72
3.1 INTRODUCTION 72
3.2 MARKERS FOR GENETIC STUDIES 73
3.3 PARASITE POPULATION GENETICS 76
3.4 FACTORS AFFECTING TRANSMISSION AND GENETIC EXCHANGE 90
3.5 MOLECULAR EPIDEMIOLOGICAL STUDIES 92
3.6 TOXOPLASMA GENOTYPE AND BIOLOGICAL CHARACTERISTICS 93
3.7 TOXOPLASMA GENOTYPE AND HUMAN DISEASE 94
3.8 CONCLUSIONS 98
ACKNOWLEDGEMENTS 99
REFERENCES 99
Chapter 4: Clinical Disease and Diagnostics 104
4.1 INTRODUCTION 104
4.2 CLINICAL DISEASE 104
4.3 DIAGNOSIS OF INFECTION WITH TOXOPLASMA GONDII IN THE HUMAN HOST 107
4.4 TREATMENT OF TOXOPLASMOSIS 115
REFERENCES 117
Chapter 5: Ocular Disease Due to Toxoplasma gondii 124
5.1 INTRODUCTION 124
5.2 HISTORICAL FEATURES OF OCULAR TOXOPLASMOSIS 125
5.3 EPIDEMIOLOGY 126
5.4 THE MECHANISM OF TISSUE DAMAGE IN OCULAR TOXOPLASMOSIS 128
5.5 HOST FACTORS IN OCULAR TOXOPLASMOSIS 129
5.6 PARASITE FACTORS IN OCULAR INFECTION 130
5.7 ANIMAL MODELS 131
5.8 CLINICAL CHARACTERISTICS 134
5.9 DIAGNOSTIC TESTS AND PATHOLOGY 140
5.10 THE TREATMENT AND MANAGEMENT OF OCULAR TOXOPLASMOSIS 144
ACKNOWLEDGEMENTS 147
REFERENCES 147
Chapter 6: Toxoplasmosis in Wild and Domestic Animals 156
6.1 INTRODUCTION 156
6.2 TOXOPLASMOSIS IN WILDLIFE 156
6.3 TOXOPLASMOSIS IN ZOOS 163
6.4 TOXOPLASMA GONDII AND ENDANGERED SPECIES 165
6.5 TOXOPLASMOSIS IN PETS 165
6.6 DOMESTIC FARM ANIMALS 167
6.7 FISH, REPTILES, AND AMPHIBIANS 169
REFERENCES 170
Chapter 7: Toxoplasma Animal Models and Therapeutics 176
7.1 INTRODUCTION 176
7.2 CONGENITAL TOXOPLASMOSIS 177
7.3 OCULAR TOXOPLASMOSIS 186
7.4 CEREBRAL TOXOPLASMOSIS 193
REFERENCES 200
Chapter 8: Biochemistry and Metabolism of Toxoplasma gondii 208
8.1 INTRODUCTION 208
8.2 CARBOHYDRATE METABOLISM 209
8.3 GLYCOLIPID ANCHORS 216
8.4 NUCLEOTIDE BIOSYNTHESIS 217
8.5 NUCLEOSIDE TRIPHOSPHATE HYDROLASE (NTPase) 222
REFERENCES 224
Chapter 9: The Apicoplast and Mitochondrion of Toxoplasma gondii 230
9.1 INTRODUCTION 230
9.2 THE APICOPLAST 231
9.3 THE MITOCHONDRION 252
9.4 PERSPECTIVES 259
ACKNOWLEDGEMENTS 259
REFERENCES 259
Chapter 10: Calcium Storage and Homeostasis in Toxoplasma gondii 268
10.1 INTRODUCTION 268
10.2 FLUORESCENCE METHODS TO STUDY CALCIUM HOMEOSTASIS IN T. GONDII 268
10.3 REGULATION OF [Ca2+]i IN T. GONDII 271
10.4 CALCIUM STORAGE 273
10.5 Ca2+ FUNCTION IN GONDII 281
10.6 CONCLUSIONS 283
ACKNOWLEDGEMENTS 284
REFERENCES 284
Chapter 11: Toxoplasma Secretory Proteins and their Roles in Cell Invasion and Intracellular Survival 288
11.1 INTRODUCTION 288
11.2 INVASION: A RAPID AND ACTIVE PROCESS DEPENDING ON GLIDING MOTILITY 289
11.3 INVASION: TIGHTLY COUPLED SECRETION MACHINERY 291
11.4 MICRONEMES 294
11.5 RHOPTRIES 312
11.6 DENSE GRANULES 322
11.7 CONCLUSIONS 329
ACKNOWLEDGEMENTS 330
REFERENCES 330
Chapter 12: Alterations in Host-Cell Biology due to Toxoplasma gondii 340
12.1 INTRODUCTION 340
12.2 OBSERVED CHANGES IN HOST-CELL BIOLOGY 341
12.3 MEDIATORS OF ALTERATIONS IN HOST-CELL BIOLOGY 352
12.4 CONCLUSIONS 357
ACKNOWLEDGEMENTS 358
REFERENCES 358
Chapter 13: Bradyzoite Development 364
13.1 INTRODUCTION 364
13.2 BRADYZOITE AND TISSUE CYST MORPHOLOGY AND BIOLOGY 365
13.3 THE DEVELOPMENT OF TISSUE CYSTS AND BRADYZOITES IN VITRO 367
13.4 THE CELL CYCLE AND BRADYZOITE DEVELOPMENT 370
13.5 THE STRESS RESPONSE AND BRADYZOITES 371
13.6 SIGNALING PATHWAYS AND BRADYZOITE FORMATION 373
13.7 THE IDENTIFICATION OF BRADYZOITE-SPECIFIC GENES 374
13.8 CYST WALL AND MATRIX ANTIGENS 375
13.9 SURFACE ANTIGENS 379
13.10 METABOLIC DIFFERENCES BETWEEN BRADYZOITES AND TACHYZOITES 380
13.11 GENETIC STUDIES ON BRADYZOITE BIOLOGY 381
13.12 SUMMARY 383
ACKNOWLEDGEMENTS 383
REFERENCES 384
Chapter 14: Development and Application of Classical Genetics in Toxoplasma gondii 390
14.1 INTRODUCTION 390
14.2 BIOLOGY OF TOXOPLASMA 390
14.3 ESTABLISHMENT OF TRANSMISSION GENETICS 396
14.4 DEVELOPMENT OF MOLECULAR GENETICS TOOLS 399
14.5 APPLICATION OF GENETIC MAPPING 401
14.6 FUTURE CHALLENGES 408
ACKNOWLEDGEMENTS 409
REFERENCES 409
Chapter 15: Genetic Manipulation of Toxoplasma gondii 414
15.1 INTRODUCTION 414
15.2 THE MECHANICS OF MAKING TRANSGENIC PARASITES 415
15.3 USING TRANSGENIC PARASITES TO STUDY THE FUNCTION OF PARASITE GENES 419
15.4 PERSPECTIVES 426
15.5 THE TOXOPLASMA MANIATIS: A SELECTION OF DETAILED PROTOCOLS FOR PARASITE CULTURE, GENETIC MANIPULATION, AND PHENOTYPIC CHARACTERIZATION 426
REFERENCES 438
ACKNOWLEDGEMENTS 438
Chapter 16: Gene Regulation 442
16.1 INTRODUCTION 442
16.2 THE TRANSCRIPTOME OF TOXOPLASMA 443
16.3 TRANSCRIPTIONAL CONTROL IN TOXOPLASMA 447
16.4 CHROMATIN REMODELING IN TOXOPLASMA 453
16.5 EVIDENCE OF POST-TRANSCRIPTIONAL MECHANISMS IN TOXOPLASMA 459
16.6 CONCLUSIONS 460
ACKNOWLEDGEMENTS 461
REFERENCES 461
Chapter 17: The Secretory Protein Repertoire and Expanded Gene Families of Toxoplasma gondii and Other Apicomplexa 468
17.1 INTRODUCTION 468
17.2 THE EC PROTEIN REPERTOIRE OF TOXOPLASMA GONDII 471
17.3 MICRONEME, RHOPTRY, AND DENSE-GRANULE PROTEINS 478
17.4 THE LCCL DOMAIN-CONTAINING PROTEINS 481
17.5 THE ARTICULINS 482
17.6 CONCLUSIONS 483
REFERENCES 483
Chapter 18: Comparative Aspects of Nucleotide and Amino-acid Metabolism in Toxoplasma gondii and Other Apicomplexa 488
18.1 INTRODUCTION 488
18.2 PURINES 489
18.3 PYRIMIDINES 507
18.4 AMINO ACIDS 518
REFERENCES 520
Chapter 19: Toxoplasma as a Model System for Apicomplexan Drug Discovery 528
19.1 INTRODUCTION 528
19.2 UNDERSTANDING MECHANISMS OF CURRENT THERAPIES 530
19.3 VALIDATION OF SOME POTENTIAL APICOMPLEXAN TARGETS 533
19.4 EMPIRIC SCREENING FOR SMALL-MOLECULE INHIBITORS 536
19.5 VALIDATION OF cGMP-DEPENDENT PROTEIN KINASE (PKG) – A CASE STUDY 538
19.6 FUTURE OUTLOOK 549
ACKNOWLEDGEMENTS 553
REFERENCES 553
Chapter 20: Proteomics of Toxoplasma gondii 564
20.1 INTRODUCTION 564
20.2 FUNDAMENTALS OF PROTEOMICS 566
20.3 WHICH PROTEOME? PROTEOMES AND SUB-PROTEOMES OF T. GONDII 568
20.4 MASS-SPECTROMETRY ANALYSIS OF T. GONDII PROTEINS 569
20.5 CAN PROTEOMICS BE QUANTITATIVE? 570
20.6 APPLICATION OF PROTEOMICS TO THE STUDY OF T.GONDII 573
20.7 SUB-PROTEOMES OF T.GONDII 573
20.8 PROTEOMICS ANALYSIS OF THE RHOPTRY ORGANELLES OF T.GONDII 574
20.9 PROTEOMICS ANALYSIS OF EXCRETORY/SECRETORY PROTEINS OF T. GONDII 578
20.10 OTHER SUB-PROTEOME STUDIES OF T. GONDII 578
20.11 THE DYNAMIC PROTEOME OF T. GONDII 579
20.12 PROTEOMICS AS A TOOL TO DISSECT THE HOST IMMUNE RESPONSE TO INFECTION 580
20.13 CHEMICAL PROTEOMICS 582
20.14 DATABASE MANAGEMENT OF T. GONDII PROTEOMICS DATA 584
20.15 CONCLUSION AND PERSPECTIVES 585
ACKNOWLEDGEMENTS 586
REFERENCES 586
Chapter 21: Cerebral Toxoplasmosis: Pathogenesis and Host Resistance 590
21.1 INTRODUCTION 590
21.2 PRODUCERS OF INTERLEUKIN (IL)-12 REQUIRED FOR IFN-y PRODUCTION 591
21.3 PRODUCERS OF IFN-y 592
21.4 THE INVOLVEMENT OF OTHER CYTOKINES AND REGULATORY MOLECULES IN RESISTANCE 595
21.5 INVOLVEMENT OF HUMORAL IMMUNITY IN RESISTANCE 598
21.6 IFN-y INDUCED EFFECTOR MECHANISMS 598
21.7 EFFECTOR CELLS IN THE BRAIN WITH ACTIVITY AGAINST T. GONDII 601
21.8 THE ROLE OF CELLS HARBORING T. GONDII IN THE BRAIN 603
21.9 HOST GENES INVOLVED IN REGULATING RESISTANCE 605
21.10 GENETIC FACTORS OF T.GONDII DETERMINING DEVELOPMENT OF TE AND VIRULENCE 606
21.11 IMMUNE EFFECTOR MECHANISMS IN OCULAR TOXOPLASMOSIS 606
21.13 CONCLUSIONS 607
21.12 IMMUNE EFFECTOR MECHANISMS IN CONGENITAL TOXOPLASMOSIS 607
ACKNOWLEDGEMENTS 609
REFERENCES 609
Chapter 22: Innate Immunity in Toxoplasma gondii Infection 616
22.1 INTRODUCTION 616
22.2 ENTEROCYTES 616
22.3 NEUTROPHILS 618
22.4 DENDRITIC CELLS 619
22.5 MACROPHAGES 620
22.6 B CELLS 621
22.7 SIGNALING PATHWAYS 621
22.8 NK AND NKT CELLS 623
22.9 INTESTINAL ADAPTIVE IMMUNE RESPONSE 625
22.10 PARASITE ANTIGENS THAT TRIGGER THE INNATE RESPONSE 626
22.11 CONCLUSIONS 626
REFERENCES 628
Chapter 23: Adaptive Immunity and Genetics of the Host Immune Response 632
23.1 INTRODUCTION 632
23.2 MOUSE GENETIC STUDIES 638
23.3 STUDIES OF LEWIS AND FISHER RATS 675
23.4 STUDIES IN HUMANS CONCERNING GENES THAT CONFER RESISTANCE OR SUSCEPTIBILITY AND USE OF MURINE MODELS WITH HUMAN TRANSGENES 676
23.5 INFLUENCE OF PARASITE STRAIN ON IMMUNE RESPONSE AND DISEASE 679
23.6 GENERAL ASPECTS OF IMMUNITY 687
23.7 IMMUNOLOGICAL CONTROL IN ANIMAL MODELS 697
23.8 IMMUNOLOGICAL CONTROL IN HUMANS 702
23.9 INFLUENCE OF CO-INFECTION WITH OTHER PARASITES 717
23.10 PREGNANCY AND CONGENITAL DISEASE 718
23.11 SUMMARY AND CONCLUSIONS 720
ACKNOWLEDGEMENTS 720
REFERENCES 720
Chapter 24: Vaccination Against Toxoplasmosis: Current Status and Future Prospects 744
24.1 INTRODUCTION 744
24.2 SCOPE OF PROBLEM AND POTENTIAL BENEFITS OF VACCINATION 744
24.3 CURRENT STATUS OF VACCINES FOR INTERMEDIATE HOSTS 748
24.4 THE RODENT AS A MODEL TO STUDY CONGENITAL DISEASE AND VACCINATION 768
24.5 REVIEW OF VACCINES FOR THE DEFINITIVE HOST – CATS 770
24.6 INSIGHTS FROM OTHER COCCIDIAL PARASITES 771
24.7 FUTURE STRATEGIES TO DESIGN NEW VACCINES FOR COCCIDIAL PARASITES IN GENERAL AND T. GONDII IN PARTICULAR 773
ACKNOWLEDGMENTS 775
Epilogue 784
Index 786