Toxoplasma Gondii

The Model Apicomplexan. Perspectives and Methods

1st Edition - March 2, 2007
Imprint: Academic Press
Editors: Louis M. Weiss, Kami Kim
Language: English
eBook ISBN:
9 7 8 - 0 - 0 8 - 0 4 7 5 0 1 - 1

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 carrie… Read more

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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.

Preface
Acknowledgements
Chapter 1: The History and Life Cycle of Toxoplasma gondii
- Publisher Summary
- 1.1 INTRODUCTION
- 1.2 THE ETIOLOGICAL AGENT
- 1.3 PARASITE MORPHOLOGY AND LIFE CYCLE
- 1.4 TRANSMISSION
- 1.5 TOXOPLASMOSIS IN HUMANS
- 1.6 TOXOPLASMOSIS IN OTHER ANIMALS
- 1.7 DIAGNOSIS
- 1.8 TREATMENT
- 1.9 PREVENTION AND CONTROL
- ACKNOWLEDGEMENTS
Chapter 2: The Ultrastructure of Toxoplasma gondii
- Publisher Summary
- 2.1 INTRODUCTION
- 2.2 INVASIVE STAGE ULTRASTRUCTURE AND GENESIS
- 2.3 COCCIDIAN DEVELOPMENT IN THE DEFINITIVE HOST
- 2.4 DEVELOPMENT IN THE INTERMEDIATE HOST
Chapter 3: Population Structure and Epidemiology of Toxoplasma gondii
- Publisher Summary
- 3.1 INTRODUCTION
- 3.2 MARKERS FOR GENETIC STUDIES
- 3.3 PARASITE POPULATION GENETICS
- 3.4 FACTORS AFFECTING TRANSMISSION AND GENETIC EXCHANGE
- 3.5 MOLECULAR EPIDEMIOLOGICAL STUDIES
- 3.6 TOXOPLASMA GENOTYPE AND BIOLOGICAL CHARACTERISTICS
- 3.7 TOXOPLASMA GENOTYPE AND HUMAN DISEASE
- 3.8 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 4: Clinical Disease and Diagnostics
- Publisher Summary
- 4.1 INTRODUCTION
- 4.2 CLINICAL DISEASE
- 4.3 DIAGNOSIS OF INFECTION WITH TOXOPLASMA GONDII IN THE HUMAN HOST
- 4.4 TREATMENT OF TOXOPLASMOSIS
Chapter 5: Ocular Disease Due to Toxoplasma gondii
- Publisher Summary
- 5.1 INTRODUCTION
- 5.2 HISTORICAL FEATURES OF OCULAR TOXOPLASMOSIS
- 5.3 EPIDEMIOLOGY
- 5.4 THE MECHANISM OF TISSUE DAMAGE IN OCULAR TOXOPLASMOSIS
- 5.5 HOST FACTORS IN OCULAR TOXOPLASMOSIS
- 5.6 PARASITE FACTORS IN OCULAR INFECTION
- 5.7 ANIMAL MODELS
- 5.8 CLINICAL CHARACTERISTICS
- 5.9 DIAGNOSTIC TESTS AND PATHOLOGY
- 5.10 THE TREATMENT AND MANAGEMENT OF OCULAR TOXOPLASMOSIS
- 5.11 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 6: Toxoplasmosis in Wild and Domestic Animals
- Publisher Summary
- 6.1 INTRODUCTION
- 6.2 TOXOPLASMOSIS IN WILDLIFE
- 6.3 TOXOPLASMOSIS IN ZOOS
- 6.4 TOXOPLASMA GONDII AND ENDANGERED SPECIES
- 6.5 TOXOPLASMOSIS IN PETS
- 6.6 DOMESTIC FARM ANIMALS
- 6.7 FISH, REPTILES, AND AMPHIBIANS
Chapter 7: Toxoplasma Animal Models and Therapeutics
- Publisher Summary
- 7.1 INTRODUCTION
- 7.2 CONGENITAL TOXOPLASMOSIS
- 7.3 OCULAR TOXOPLASMOSIS
- 7.4 CEREBRAL TOXOPLASMOSIS
Chapter 8: Biochemistry and Metabolism of Toxoplasma gondii
- Publisher Summary
- 8.1 INTRODUCTION
- 8.2 CARBOHYDRATE METABOLISM
- 8.3 GLYCOLIPID ANCHORS
- 8.4 NUCLEOTIDE BIOSYNTHESIS
- 8.5 NUCLEOSIDE TRIPHOSPHATE HYDROLASE (NTPase)
Chapter 9: The Apicoplast and Mitochondrion of Toxoplasma gondii
- Publisher Summary
- 9.1 INTRODUCTION
- 9.2 THE APICOPLAST
- 9.3 THE MITOCHONDRION
- 9.4 PERSPECTIVES
- ACKNOWLEDGEMENTS
Chapter 10: Calcium Storage and Homeostasis in Toxoplasma gondii
- Publisher Summary
- 10.1 INTRODUCTION
- 10.2 FLUORESCENCE METHODS TO STUDY CALCIUM HOMEOSTASIS IN T. GONDII
- 10.3 REGULATION OF [Ca2+]i IN T. GONDII
- 10.4 CALCIUM STORAGE
- 10.5 Ca2+ FUNCTION IN T. GONDII
- 10.6 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 11: Toxoplasma Secretory Proteins and their Roles in Cell Invasion and Intracellular Survival
- Publisher Summary
- 11.1 INTRODUCTION
- 11.2 INVASION: A RAPID AND ACTIVE PROCESS DEPENDING ON GLIDING MOTILITY
- 11.3 INVASION: TIGHTLY COUPLED SECRETION MACHINERY
- 11.4 MICRONEMES
- 11.5 RHOPTRIES
- 11.6 DENSE GRANULES
- 11.7 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 12: Alterations in Host-Cell Biology due to Toxoplasma gondii
- Publisher Summary
- 12.1 INTRODUCTION
- 12.2 OBSERVED CHANGES IN HOST-CELL BIOLOGY
- 12.3 MEDIATORS OF ALTERATIONS IN HOST-CELL BIOLOGY
- 12.4 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 13: Bradyzoite Development
- Publisher Summary
- 13.1 INTRODUCTION
- 13.2 BRADYZOITE AND TISSUE CYST MORPHOLOGY AND BIOLOGY
- 13.3 THE DEVELOPMENT OF TISSUE CYSTS AND BRADYZOITES IN VITRO
- 13.4 THE CELL CYCLE AND BRADYZOITE DEVELOPMENT
- 13.5 THE STRESS RESPONSE AND BRADYZOITES
- 13.6 SIGNALING PATHWAYS AND BRADYZOITE FORMATION
- 13.7 THE IDENTIFICATION OF BRADYZOITE-SPECIFIC GENES
- 13.8 CYST WALL AND MATRIX ANTIGENS
- 13.9 SURFACE ANTIGENS
- 13.10 METABOLIC DIFFERENCES BETWEEN BRADYZOITES AND TACHYZOITES
- 13.11 GENETIC STUDIES ON BRADYZOITE BIOLOGY
- 13.12 SUMMARY
- ACKNOWLEDGEMENTS
Chapter 14: Development and Application of Classical Genetics in Toxoplasma gondii
- Publisher Summary
- 14.1 INTRODUCTION
- 14.2 BIOLOGY OF TOXOPLASMA
- 14.3 ESTABLISHMENT OF TRANSMISSION GENETICS
- 14.4 DEVELOPMENT OF MOLECULAR GENETICS TOOLS
- 14.5 APPLICATION OF GENETIC MAPPING
- 14.6 FUTURE CHALLENGES
- ACKNOWLEDGEMENTS
Chapter 15: Genetic Manipulation of Toxoplasma gondii
- Publisher Summary
- 15.1 INTRODUCTION
- 15.2 THE MECHANICS OF MAKING TRANSGENIC PARASITES
- 15.3 USING TRANSGENIC PARASITES TO STUDY THE FUNCTION OF PARASITE GENES
- 15.4 PERSPECTIVES
- 15.5 THE TOXOPLASMA MANIATIS: A SELECTION OF DETAILED PROTOCOLS FOR PARASITE CULTURE, GENETIC MANIPULATION, AND PHENOTYPIC CHARACTERIZATION
- ACKNOWLEDGEMENTS
Chapter 16: Gene Regulation
- Publisher Summary
- 16.1 INTRODUCTION
- 16.2 THE TRANSCRIPTOME OF TOXOPLASMA
- 16.3 TRANSCRIPTIONAL CONTROL IN TOXOPLASMA
- 16.4 CHROMATIN REMODELING IN TOXOPLASMA
- 16.5 EVIDENCE OF POST-TRANSCRIPTIONAL MECHANISMS IN TOXOPLASMA
- 16.6 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 17: The Secretory Protein Repertoire and Expanded Gene Families of Toxoplasma gondii and Other Apicomplexa
- Publisher Summary
- 17.1 INTRODUCTION
- 17.2 THE EC PROTEIN REPERTOIRE OF TOXOPLASMA GONDII
- 17.3 MICRONEME, RHOPTRY, AND DENSE-GRANULE PROTEINS
- 17.4 THE LCCL DOMAIN-CONTAINING PROTEINS
- 17.5 THE ARTICULINS
- 17.6 CONCLUSIONS
Chapter 18: Comparative Aspects of Nucleotide and Amino-acid Metabolism in Toxoplasma gondii and other Apicomplexa
- Publisher Summary
- 18.1 INTRODUCTION
- 18.2 PURINES
- 18.3 PYRIMIDINES
- 18.4 AMINO ACIDS
Chapter 19: Toxoplasma as a Model System for Apicomplexan Drug Discovery
- Publisher Summary
- 19.1 INTRODUCTION
- 19.2 UNDERSTANDING MECHANISMS OF CURRENT THERAPIES
- 19.3 VALIDATION OF SOME POTENTIAL APICOMPLEXAN TARGETS
- 19.4 EMPIRIC SCREENING FOR SMALL-MOLECULE INHIBITORS
- 19.5 VALIDATION OF cGMP-DEPENDENT PROTEIN KINASE (PKG) – A CASE STUDY
- 19.6 FUTURE OUTLOOK
- ACKNOWLEDGEMENTS
Chapter 20: Proteomics of Toxoplasma gondii
- Publisher Summary
- 20.1 INTRODUCTION
- 20.2 FUNDAMENTALS OF PROTEOMICS
- 20.3 WHICH PROTEOME? PROTEOMES AND SUBPROTEOMES OF T. GONDII
- 20.4 MASS-SPECTROMETRY ANALYSIS OF T. GONDII PROTEINS
- 20.5 CAN PROTEOMICS BE QUANTITATIVE?
- 20.6 APPLICATION OF PROTEOMICS TO THE STUDY OF T. GONDII
- 20.7 SUB-PROTEOMES OF T. GONDII
- 20.8 PROTEOMICS ANALYSIS OF THE RHOPTRY ORGANELLES OF T. GONDII
- 20.9 PROTEOMICS ANALYSIS OF EXCRETORY/SECRETORY PROTEINS OF T. GONDII
- 20.10 OTHER SUB-PROTEOME STUDIES OF T. GONDII
- 20.11 THE DYNAMIC PROTEOME OF T. GONDII
- 20.12 PROTEOMICS AS A TOOL TO DISSECT THE HOST IMMUNE RESPONSE TO INFECTION
- 20.13 CHEMICAL PROTEOMICS
- 20.14 DATABASE MANAGEMENT OF T. GONDII PROTEOMICS DATA
- 20.15 CONCLUSION AND PERSPECTIVES
- ACKNOWLEDGEMENTS
Chapter 21: Cerebral Toxoplasmosis: Pathogenesis and Host Resistance
- Publisher Summary
- 21.1 INTRODUCTION
- 21.2 PRODUCERS OF INTERLEUKIN (IL)-12 REQUIRED FOR IFN-γ PRODUCTION
- 21.3 PRODUCERS OF IFN-γ
- 21.4 THE INVOLVEMENT OF OTHER CYTOKINES AND REGULATORY MOLECULES IN RESISTANCE
- 21.5 INVOLVEMENT OF HUMORAL IMMUNITY IN RESISTANCE
- 21.6 IFN-γ-INDUCED EFFECTOR MECHANISMS
- 21.7 EFFECTOR CELLS IN THE BRAIN WITH ACTIVITY AGAINST T. GONDII
- 21.8 THE ROLE OF CELLS HARBORING T. GONDII IN THE BRAIN
- 21.9 HOST GENES INVOLVED IN REGULATING RESISTANCE
- 21.10 GENETIC FACTORS OF T. GONDII DETERMINING DEVELOPMENT OF TE AND VIRULENCE
- 21.11 IMMUNE EFFECTOR MECHANISMS IN OCULAR TOXOPLASMOSIS
- 21.12 IMMUNE EFFECTOR MECHANISMS IN CONGENITAL TOXOPLASMOSIS
- 21.13 CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 22: Innate Immunity in Toxoplasma gondii Infection
- Publisher Summary
- 22.1 INTRODUCTION
- 22.2 ENTEROCYTES
- 22.3 NEUTROPHILS
- 22.4 DENDRITIC CELLS
- 22.5 MACROPHAGES
- 22.6 B CELLS
- 22.7 SIGNALING PATHWAYS
- 22.8 NK AND NKT CELLS
- 22.9 INTESTINAL ADAPTIVE IMMUNE RESPONSE
- 22.10 PARASITE ANTIGENS THAT TRIGGER THE INNATE RESPONSE
- 22.11 CONCLUSIONS
Chapter 23: Adaptive Immunity and Genetics of the Host Immune Response
- Publisher Summary
- 23.1 INTRODUCTION
- 23.2 MOUSE GENETIC STUDIES
- 23.3 STUDIES OF LEWIS AND FISHER RATS
- 23.4 STUDIES IN HUMANS CONCERNING GENES THAT CONFER RESISTANCE OR SUSCEPTIBILITY AND USE OF MURINE MODELS WITH HUMAN TRANSGENES
- 23.5 INFLUENCE OF PARASITE STRAIN ON IMMUNE RESPONSE AND DISEASE
- 23.6 GENERAL ASPECTS OF IMMUNITY
- 23.7 IMMUNOLOGICAL CONTROL IN ANIMAL MODELS
- 23.8 IMMUNOLOGICAL CONTROL IN HUMANS
- 23.9 INFLUENCE OF CO-INFECTION WITH OTHER PARASITES
- 23.10 PREGNANCY AND CONGENITAL DISEASE
- 23.11 SUMMARY AND CONCLUSIONS
- ACKNOWLEDGEMENTS
Chapter 24: Vaccination Against Toxoplasmosis: Current Status and Future Prospects
- Publisher Summary
- 24.1 INTRODUCTION
- 24.2 SCOPE OF PROBLEM AND POTENTIAL BENEFITS OF VACCINATION
- 24.3 CURRENT STATUS OF VACCINES FOR INTERMEDIATE HOSTS
- 24.4 THE RODENT AS A MODEL TO STUDY CONGENITAL DISEASE AND VACCINATION
- 24.5 REVIEW OF VACCINES FOR THE DEFINITIVE HOST – CATS
- 24.6 INSIGHTS FROM OTHER COCCIDIAL PARASITES
- 24.7 FUTURE STRATEGIES TO DESIGN NEW VACCINES FOR COCCIDIAL PARASITES IN GENERAL AND T. GONDII IN PARTICULAR
- ACKNOWLEDGMENTS
Epilogue
INDEX

Louis M. Weiss

Louis M. Weiss, MD, MPH 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.

Affiliations and expertise

Professor of Medicine and Pathology, Albert Einstein College of Medicine of Yeshiva University, NY, USA

Kami Kim

Dr. Kami Kim is a physician-scientist who joined the USF faculty in 2017 as a Professor of Internal Medicine (Infectious Diseases and International Medicine) and Professor of Global Health. Her laboratory focuses upon understanding the pathogenesis of toxoplasmosis and malaria, parasitic diseases of global significance. The Toxoplasma projects use a multidisciplinary systems biology approach to understand how the parasite senses and responds to changes in its host. Using a combination of epigenomics, genetics and proteomics, her group is studying how the parasite transitions from the pathogenic tachyzoite form to the persistent bradyzoite form. She is investigating the epigenetic and genetic factors that govern the host response to parasites. Dr. Kim is a fellow of the American Academy of Microbiology and the Infectious Disease Society of America as well as an elected member of the Association for American Physicians and the American Society for Clinical Investigation.

Affiliations and expertise

Professor of Internal Medicine (Infectious Diseases and International Medicine) and Professor of Global Health, University of South Florida, USF Medicine International, Tampa, Florida

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