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E-Book

E-Book, Englisch, 801 Seiten

Weiss MD / Kim MD Toxoplasma Gondii

The Model Apicomplexan. Perspectives and Methods
1. Auflage 2011
ISBN: 978-0-08-047501-1
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

The Model Apicomplexan. Perspectives and Methods

E-Book, Englisch, 801 Seiten

ISBN: 978-0-08-047501-1
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark



Toxoplasmosis is caused by a one-celled protozoan parasite known as Toxoplasma gondii. In the United States, it is estimated that approximately 30% of cats, the primary carriers, have been infected by T. gondii. Most humans contract toxoplasmosis by eating cyst-contaminated raw or undercooked meat, vegetables, or milk products or when they come into contact with the T. gondii eggs from cat feaces while cleaning a cat's litterbox, gardening, or playing in a sandbox. Approx 1 in 4 (more than 60 million) people in the USA are infected with the parasite, and in the UK between 0.5 and 1% of individuals become infected each year. By the age of 50, 40% of people test positive for the parasite. The predilection of this parasite is for the central nervous system (CNS) causing behavioral and personality alterations as well as fatal necrotizing encephalitis, and is especially dangerous for HIV infected patients.
Though there have been tremendous strides in our understanding of the biology of Toxoplasma gondii in the last decade, there has been no systemic review of all of the information that has accumulated. Toxoplasma gondii provides the first comprehensive summary of literature on this organism by leading experts in the field who were responsible for organising the 7th International Congress on Toxoplasmosis in May 2003. It offeres systematic reviews of the biology of this pathogen as well as descriptions of the methods and resources used. Within the next year the T. gondii genome will be completed making this an indispensable research resource for biologists, physicians, parasitologists, and for all those contemplating experiments using T. gondii.
* Serves as a model for understanding invasion of host cells by parasites, immune response, motility, differentiation, phylogenetics, evolution and organelle acquisition
* Discusses the protocols related to genetic manipulation, cell biology and animal models while also providing reference material on available resources for working with this organism

Louis M. Weiss M.D., M.P.H is Professor of Medicine (Division of Infectious Diseases) and Professor of Pathology (Division of Parasitology and Tropical Medicine) of the Albert Einstein College of Medicine, Bronx, New York. Dr. Weiss received his M.D. and M.P.H degrees from the Johns Hopkins University in 1982. He then completed a residency in Internal Medicine at the University of Chicago and a fellowship in Infectious Diseases at the Albert Einstein College of Medicine. Following this fellowship, he joined the faculty at Einstein where he is currently a Professor of Pathology and Medicine. His laboratory group has an active research program on parasitic diseases with a research focus on Toxoplasma gondii, the Microsporidia and Trypanosoma cruzi. Dr. Weiss is the author of over 200 publications and the editor of 3 books on parasitology. He is a fellow of the American College of Physicians, Infectious Disease Society of America and the American Academy of Microbiology. Dr. Weiss is the Co-Director of the Einstein Global Health Center.

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1;Front cover;1
2;Toxoplasma gondii;4
3;Copyright page;5
4;Contents;8
5;Contributors;16
6;Preface;20
7;Acknowledgements;22
8;Chapter 1: The History and Life Cycle of Toxoplasma gondii;24
8.1;1.1 INTRODUCTION;24
8.2;1.2 THE ETIOLOGICAL AGENT;24
8.3;1.3 PARASITE MORPHOLOGY AND LIFE CYCLE;25
8.4;1.4 TRANSMISSION;28
8.5;1.5 TOXOPLASMOSIS IN HUMANS;31
8.6;1.6 TOXOPLASMOSIS IN OTHER ANIMALS;33
8.7;1.7 DIAGNOSIS;33
8.8;1.8 TREATMENT;34
8.9;1.9 PREVENTION AND CONTROL;34
8.10;ACKNOWLEDGEMENTS;35
8.11;REFERENCES;35
9;Chapter 2: The Ultrastructure of Toxoplasma gondii;42
9.1;2.1 INTRODUCTION;42
9.2;2.2 INVASIVE STAGE ULTRASTRUCTURE AND GENESIS;42
9.3;2.3 COCCIDIAN DEVELOPMENT IN THE DEFINITIVE HOST;52
9.4;2.4 DEVELOPMENT IN THE INTERMEDIATE HOST;62
9.5;REFERENCES;69
10;Chapter 3: Population Structure and Epidemiology of Toxoplasma gondii;72
10.1;3.1 INTRODUCTION;72
10.2;3.2 MARKERS FOR GENETIC STUDIES;73
10.3;3.3 PARASITE POPULATION GENETICS;76
10.4;3.4 FACTORS AFFECTING TRANSMISSION AND GENETIC EXCHANGE;90
10.5;3.5 MOLECULAR EPIDEMIOLOGICAL STUDIES;92
10.6;3.6 TOXOPLASMA GENOTYPE AND BIOLOGICAL CHARACTERISTICS;93
10.7;3.7 TOXOPLASMA GENOTYPE AND HUMAN DISEASE;94
10.8;3.8 CONCLUSIONS;98
10.9;ACKNOWLEDGEMENTS;99
10.10;REFERENCES;99
11;Chapter 4: Clinical Disease and Diagnostics;104
11.1;4.1 INTRODUCTION;104
11.2;4.2 CLINICAL DISEASE;104
11.3;4.3 DIAGNOSIS OF INFECTION WITH TOXOPLASMA GONDII IN THE HUMAN HOST;107
11.4;4.4 TREATMENT OF TOXOPLASMOSIS;115
11.5;REFERENCES;117
12;Chapter 5: Ocular Disease Due to Toxoplasma gondii;124
12.1;5.1 INTRODUCTION;124
12.2;5.2 HISTORICAL FEATURES OF OCULAR TOXOPLASMOSIS;125
12.3;5.3 EPIDEMIOLOGY;126
12.4;5.4 THE MECHANISM OF TISSUE DAMAGE IN OCULAR TOXOPLASMOSIS;128
12.5;5.5 HOST FACTORS IN OCULAR TOXOPLASMOSIS;129
12.6;5.6 PARASITE FACTORS IN OCULAR INFECTION;130
12.7;5.7 ANIMAL MODELS;131
12.8;5.8 CLINICAL CHARACTERISTICS;134
12.9;5.9 DIAGNOSTIC TESTS AND PATHOLOGY;140
12.10;5.10 THE TREATMENT AND MANAGEMENT OF OCULAR TOXOPLASMOSIS;144
12.11;ACKNOWLEDGEMENTS;147
12.12;REFERENCES;147
13;Chapter 6: Toxoplasmosis in Wild and Domestic Animals;156
13.1;6.1 INTRODUCTION;156
13.2;6.2 TOXOPLASMOSIS IN WILDLIFE;156
13.3;6.3 TOXOPLASMOSIS IN ZOOS;163
13.4;6.4 TOXOPLASMA GONDII AND ENDANGERED SPECIES;165
13.5;6.5 TOXOPLASMOSIS IN PETS;165
13.6;6.6 DOMESTIC FARM ANIMALS;167
13.7;6.7 FISH, REPTILES, AND AMPHIBIANS;169
13.8;REFERENCES;170
14;Chapter 7: Toxoplasma Animal Models and Therapeutics;176
14.1;7.1 INTRODUCTION;176
14.2;7.2 CONGENITAL TOXOPLASMOSIS;177
14.3;7.3 OCULAR TOXOPLASMOSIS;186
14.4;7.4 CEREBRAL TOXOPLASMOSIS;193
14.5;REFERENCES;200
15;Chapter 8: Biochemistry and Metabolism of Toxoplasma gondii;208
15.1;8.1 INTRODUCTION;208
15.2;8.2 CARBOHYDRATE METABOLISM;209
15.3;8.3 GLYCOLIPID ANCHORS;216
15.4;8.4 NUCLEOTIDE BIOSYNTHESIS;217
15.5;8.5 NUCLEOSIDE TRIPHOSPHATE HYDROLASE (NTPase);222
15.6;REFERENCES;224
16;Chapter 9: The Apicoplast and Mitochondrion of Toxoplasma gondii;230
16.1;9.1 INTRODUCTION;230
16.2;9.2 THE APICOPLAST;231
16.3;9.3 THE MITOCHONDRION;252
16.4;9.4 PERSPECTIVES;259
16.5;ACKNOWLEDGEMENTS;259
16.6;REFERENCES;259
17;Chapter 10: Calcium Storage and Homeostasis in Toxoplasma gondii;268
17.1;10.1 INTRODUCTION;268
17.2;10.2 FLUORESCENCE METHODS TO STUDY CALCIUM HOMEOSTASIS IN T. GONDII;268
17.3;10.3 REGULATION OF [Ca2+]i IN T. GONDII;271
17.4;10.4 CALCIUM STORAGE;273
17.5;10.5 Ca2+ FUNCTION IN GONDII;281
17.6;10.6 CONCLUSIONS;283
17.7;ACKNOWLEDGEMENTS;284
17.8;REFERENCES;284
18;Chapter 11: Toxoplasma Secretory Proteins and their Roles in Cell Invasion and Intracellular Survival;288
18.1;11.1 INTRODUCTION;288
18.2;11.2 INVASION: A RAPID AND ACTIVE PROCESS DEPENDING ON GLIDING MOTILITY;289
18.3;11.3 INVASION: TIGHTLY COUPLED SECRETION MACHINERY;291
18.4;11.4 MICRONEMES;294
18.5;11.5 RHOPTRIES;312
18.6;11.6 DENSE GRANULES;322
18.7;11.7 CONCLUSIONS;329
18.8;ACKNOWLEDGEMENTS;330
18.9;REFERENCES;330
19;Chapter 12: Alterations in Host-Cell Biology due to Toxoplasma gondii;340
19.1;12.1 INTRODUCTION;340
19.2;12.2 OBSERVED CHANGES IN HOST-CELL BIOLOGY;341
19.3;12.3 MEDIATORS OF ALTERATIONS IN HOST-CELL BIOLOGY;352
19.4;12.4 CONCLUSIONS;357
19.5;ACKNOWLEDGEMENTS;358
19.6;REFERENCES;358
20;Chapter 13: Bradyzoite Development;364
20.1;13.1 INTRODUCTION;364
20.2;13.2 BRADYZOITE AND TISSUE CYST MORPHOLOGY AND BIOLOGY;365
20.3;13.3 THE DEVELOPMENT OF TISSUE CYSTS AND BRADYZOITES IN VITRO;367
20.4;13.4 THE CELL CYCLE AND BRADYZOITE DEVELOPMENT;370
20.5;13.5 THE STRESS RESPONSE AND BRADYZOITES;371
20.6;13.6 SIGNALING PATHWAYS AND BRADYZOITE FORMATION;373
20.7;13.7 THE IDENTIFICATION OF BRADYZOITE-SPECIFIC GENES;374
20.8;13.8 CYST WALL AND MATRIX ANTIGENS;375
20.9;13.9 SURFACE ANTIGENS;379
20.10;13.10 METABOLIC DIFFERENCES BETWEEN BRADYZOITES AND TACHYZOITES;380
20.11;13.11 GENETIC STUDIES ON BRADYZOITE BIOLOGY;381
20.12;13.12 SUMMARY;383
20.13;ACKNOWLEDGEMENTS;383
20.14;REFERENCES;384
21;Chapter 14: Development and Application of Classical Genetics in Toxoplasma gondii;390
21.1;14.1 INTRODUCTION;390
21.2;14.2 BIOLOGY OF TOXOPLASMA;390
21.3;14.3 ESTABLISHMENT OF TRANSMISSION GENETICS;396
21.4;14.4 DEVELOPMENT OF MOLECULAR GENETICS TOOLS;399
21.5;14.5 APPLICATION OF GENETIC MAPPING;401
21.6;14.6 FUTURE CHALLENGES;408
21.7;ACKNOWLEDGEMENTS;409
21.8;REFERENCES;409
22;Chapter 15: Genetic Manipulation of Toxoplasma gondii;414
22.1;15.1 INTRODUCTION;414
22.2;15.2 THE MECHANICS OF MAKING TRANSGENIC PARASITES;415
22.3;15.3 USING TRANSGENIC PARASITES TO STUDY THE FUNCTION OF PARASITE GENES;419
22.4;15.4 PERSPECTIVES;426
22.5;15.5 THE TOXOPLASMA MANIATIS: A SELECTION OF DETAILED PROTOCOLS FOR PARASITE CULTURE, GENETIC MANIPULATION, AND PHENOTYPIC CHARACTERIZATION;426
22.6;REFERENCES;438
22.7;ACKNOWLEDGEMENTS;438
23;Chapter 16: Gene Regulation;442
23.1;16.1 INTRODUCTION;442
23.2;16.2 THE TRANSCRIPTOME OF TOXOPLASMA;443
23.3;16.3 TRANSCRIPTIONAL CONTROL IN TOXOPLASMA;447
23.4;16.4 CHROMATIN REMODELING IN TOXOPLASMA;453
23.5;16.5 EVIDENCE OF POST-TRANSCRIPTIONAL MECHANISMS IN TOXOPLASMA;459
23.6;16.6 CONCLUSIONS;460
23.7;ACKNOWLEDGEMENTS;461
23.8;REFERENCES;461
24;Chapter 17: The Secretory Protein Repertoire and Expanded Gene Families of Toxoplasma gondii and Other Apicomplexa;468
24.1;17.1 INTRODUCTION;468
24.2;17.2 THE EC PROTEIN REPERTOIRE OF TOXOPLASMA GONDII;471
24.3;17.3 MICRONEME, RHOPTRY, AND DENSE-GRANULE PROTEINS;478
24.4;17.4 THE LCCL DOMAIN-CONTAINING PROTEINS;481
24.5;17.5 THE ARTICULINS;482
24.6;17.6 CONCLUSIONS;483
24.7;REFERENCES;483
25;Chapter 18: Comparative Aspects of Nucleotide and Amino-acid Metabolism in Toxoplasma gondii and Other Apicomplexa;488
25.1;18.1 INTRODUCTION;488
25.2;18.2 PURINES;489
25.3;18.3 PYRIMIDINES;507
25.4;18.4 AMINO ACIDS;518
25.5;REFERENCES;520
26;Chapter 19: Toxoplasma as a Model System for Apicomplexan Drug Discovery;528
26.1;19.1 INTRODUCTION;528
26.2;19.2 UNDERSTANDING MECHANISMS OF CURRENT THERAPIES;530
26.3;19.3 VALIDATION OF SOME POTENTIAL APICOMPLEXAN TARGETS;533
26.4;19.4 EMPIRIC SCREENING FOR SMALL-MOLECULE INHIBITORS;536
26.5;19.5 VALIDATION OF cGMP-DEPENDENT PROTEIN KINASE (PKG) – A CASE STUDY;538
26.6;19.6 FUTURE OUTLOOK;549
26.7;ACKNOWLEDGEMENTS;553
26.8;REFERENCES;553
27;Chapter 20: Proteomics of Toxoplasma gondii;564
27.1;20.1 INTRODUCTION;564
27.2;20.2 FUNDAMENTALS OF PROTEOMICS;566
27.3;20.3 WHICH PROTEOME? PROTEOMES AND SUB-PROTEOMES OF T. GONDII;568
27.4;20.4 MASS-SPECTROMETRY ANALYSIS OF T. GONDII PROTEINS;569
27.5;20.5 CAN PROTEOMICS BE QUANTITATIVE?;570
27.6;20.6 APPLICATION OF PROTEOMICS TO THE STUDY OF T.GONDII;573
27.7;20.7 SUB-PROTEOMES OF T.GONDII;573
27.8;20.8 PROTEOMICS ANALYSIS OF THE RHOPTRY ORGANELLES OF T.GONDII;574
27.9;20.9 PROTEOMICS ANALYSIS OF EXCRETORY/SECRETORY PROTEINS OF T. GONDII;578
27.10;20.10 OTHER SUB-PROTEOME STUDIES OF T. GONDII;578
27.11;20.11 THE DYNAMIC PROTEOME OF T. GONDII;579
27.12;20.12 PROTEOMICS AS A TOOL TO DISSECT THE HOST IMMUNE RESPONSE TO INFECTION;580
27.13;20.13 CHEMICAL PROTEOMICS;582
27.14;20.14 DATABASE MANAGEMENT OF T. GONDII PROTEOMICS DATA;584
27.15;20.15 CONCLUSION AND PERSPECTIVES;585
27.16;ACKNOWLEDGEMENTS;586
27.17;REFERENCES;586
28;Chapter 21: Cerebral Toxoplasmosis: Pathogenesis and Host Resistance;590
28.1;21.1 INTRODUCTION;590
28.2;21.2 PRODUCERS OF INTERLEUKIN (IL)-12 REQUIRED FOR IFN-y PRODUCTION;591
28.3;21.3 PRODUCERS OF IFN-y;592
28.4;21.4 THE INVOLVEMENT OF OTHER CYTOKINES AND REGULATORY MOLECULES IN RESISTANCE;595
28.5;21.5 INVOLVEMENT OF HUMORAL IMMUNITY IN RESISTANCE;598
28.6;21.6 IFN-y INDUCED EFFECTOR MECHANISMS;598
28.7;21.7 EFFECTOR CELLS IN THE BRAIN WITH ACTIVITY AGAINST T. GONDII;601
28.8;21.8 THE ROLE OF CELLS HARBORING T. GONDII IN THE BRAIN;603
28.9;21.9 HOST GENES INVOLVED IN REGULATING RESISTANCE;605
28.10;21.10 GENETIC FACTORS OF T.GONDII DETERMINING DEVELOPMENT OF TE AND VIRULENCE;606
28.11;21.11 IMMUNE EFFECTOR MECHANISMS IN OCULAR TOXOPLASMOSIS;606
28.12;21.13 CONCLUSIONS;607
28.13;21.12 IMMUNE EFFECTOR MECHANISMS IN CONGENITAL TOXOPLASMOSIS;607
28.14;ACKNOWLEDGEMENTS;609
28.15;REFERENCES;609
29;Chapter 22: Innate Immunity in Toxoplasma gondii Infection;616
29.1;22.1 INTRODUCTION;616
29.2;22.2 ENTEROCYTES;616
29.3;22.3 NEUTROPHILS;618
29.4;22.4 DENDRITIC CELLS;619
29.5;22.5 MACROPHAGES;620
29.6;22.6 B CELLS;621
29.7;22.7 SIGNALING PATHWAYS;621
29.8;22.8 NK AND NKT CELLS;623
29.9;22.9 INTESTINAL ADAPTIVE IMMUNE RESPONSE;625
29.10;22.10 PARASITE ANTIGENS THAT TRIGGER THE INNATE RESPONSE;626
29.11;22.11 CONCLUSIONS;626
29.12;REFERENCES;628
30;Chapter 23: Adaptive Immunity and Genetics of the Host Immune Response;632
30.1;23.1 INTRODUCTION;632
30.2;23.2 MOUSE GENETIC STUDIES;638
30.3;23.3 STUDIES OF LEWIS AND FISHER RATS;675
30.4;23.4 STUDIES IN HUMANS CONCERNING GENES THAT CONFER RESISTANCE OR SUSCEPTIBILITY AND USE OF MURINE MODELS WITH HUMAN TRANSGENES;676
30.5;23.5 INFLUENCE OF PARASITE STRAIN ON IMMUNE RESPONSE AND DISEASE;679
30.6;23.6 GENERAL ASPECTS OF IMMUNITY;687
30.7;23.7 IMMUNOLOGICAL CONTROL IN ANIMAL MODELS;697
30.8;23.8 IMMUNOLOGICAL CONTROL IN HUMANS;702
30.9;23.9 INFLUENCE OF CO-INFECTION WITH OTHER PARASITES;717
30.10;23.10 PREGNANCY AND CONGENITAL DISEASE;718
30.11;23.11 SUMMARY AND CONCLUSIONS;720
30.12;ACKNOWLEDGEMENTS;720
30.13;REFERENCES;720
31;Chapter 24: Vaccination Against Toxoplasmosis: Current Status and Future Prospects;744
31.1;24.1 INTRODUCTION;744
31.2;24.2 SCOPE OF PROBLEM AND POTENTIAL BENEFITS OF VACCINATION;744
31.3;24.3 CURRENT STATUS OF VACCINES FOR INTERMEDIATE HOSTS;748
31.4;24.4 THE RODENT AS A MODEL TO STUDY CONGENITAL DISEASE AND VACCINATION;768
31.5;24.5 REVIEW OF VACCINES FOR THE DEFINITIVE HOST – CATS;770
31.6;24.6 INSIGHTS FROM OTHER COCCIDIAL PARASITES;771
31.7;24.7 FUTURE STRATEGIES TO DESIGN NEW VACCINES FOR COCCIDIAL PARASITES IN GENERAL AND T. GONDII IN PARTICULAR;773
31.8;ACKNOWLEDGMENTS;775
32;Epilogue;784
33;Index;786



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