DOCSLIB.ORG

Role of the Contractile Vacuole Complex As A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of the Contractile Vacuole Complex As A ROLE OF THE CONTRACTILE VACUOLE COMPLEX AS A TRAFFICKING HUB IN TRYPANOSOMA CRUZI by SAYANTANEE NIYOGI (Under the Direction of Roberto Docampo) ABSTRACT Trypanosoma cruzi is the etiologic agent of Chagas disease. It contains a Contractile Vacuole Complex (CVC) that plays a vital role in the regulation of its cell volume and in its responses to osmotic stresses in all its life cycle stages. It is peculiar that though, T.cruzi is not a free-living organism it has a CVC; thus suggesting that the CVC could have functions beyond just osmoregulation as occurs in some other protists; where the CVC is involved in regulating calcium homeostasis and in the transfer of proteins to the surface. Besides, the approach of combined proteomic and bioinformatics analyses identified proteins localized to the CVC, several of them having trafficking roles, and implying to a potential novel role of the CVC. Here we used a combination of genetic and biochemical approaches to establish the contribution of the CVC as a trafficking hub. T. cruzi relies on protein secretion of glycosylphosphatidylinositol (GPI)-anchored surface proteins for invasion of host cells and establishment of infection. In this study we show that the CVC acts as a trafficking intermediate before GPI-anchored proteins reach the cell surface. Additionally we also identify CVC-located TcRab11 as a regulator of protein transport of GPI-anchored trans- sialidase to the plasma membrane, a process essential for the establishment of infection. Demonstration of the role of TcTS in infection has been previously difficult given the large number of genes encoding for this protein distributed through the genome of the parasite. We also studied the role of another CVC-located Rab. Rab32 is located in lysosome-related organelles (LRO) and since acidocalcisomes are LROs we investigated whether TcRab32 is needed for the structure and function of acidocalcisomes. By constructing GDP-bound dominant negative mutants of TcRab32 we were able to show a defect in trafficking, which ultimately affects parasite infectivity. This study with TcRab32 provides the link between the acidocalcisome and the contractile vacuole complex as observed in T. cruzi and in some other protists like Chlamydomonas reinhardtii and Dictyostelium discoideum. Our results are consistent with a role of the CVC in regulating membrane traffic to maintain the function of the acidocalcisome as well as traffic to the plasma membrane of T. cruzi. INDEX WORDS: T.cruzi, Contractile Vacuole Complex (CVC), acidocalcisomes, TcRab32, TcRab11, trans-sialidase, trafficking, membrane ROLE OF THE CONTRACTILE VACUOLE COMPLEX AS A TRAFFICKING HUB IN TRYPANOSOMA CRUZI by SAYANTANEE NIYOGI BSc., Asutosh College, Kolkata, India, 2006 MSc., University of Calcutta, Kolkata, India, 2008 A Dissertation Submitted to the Graduate Faculty of The University of Georgia in Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY ATHENS, GEORGIA 2014 © 2014 SAYANTANEE NIYOGI All Rights Reserved ROLE OF THE CONTRACTILE VACUOLE COMPLEX AS A TRAFFICKING HUB IN TRYPANOSOMA CRUZI by SAYANTANEE NIYOGI Major Professor: Roberto Docampo Committee: Boris Striepen Rick Tarleton Steve Hajduk Electronic Version Approved: Julie Coffield Interim Dean of the Graduate School The University of Georgia August 2014 iv DEDICATION Dedicated to Maa, Baba, Titli and Deep for their constant encouragement, support and unconditional love. v ACKNOWLEDGEMENTS I would like to thank my mentor Dr Docampo for the opportunity, the support, the time and patience he provided for me and the great projects he had lined up for me. He had to start right from scratch with me!! When I joined the lab, I did not have a lot of experience on the bench, in designing experiments. But thanks to him, I think I have become slightly better at it. I thank him for all that he has taught me, all the knowledge he imparted on me and guiding me all along. His love for science, his dedication to work has been an inspiration to me; that helped me to work hard on my projects with full sincerity. He has always been keen on answering my doubts, correcting my mistakes and also making sure that I do not repeat those mistakes. He always encouraged me to present my work both in external meetings as well as in internal seminars; something that has helped boost my level of confidence. I would also like to thank Dr Moreno for all her invaluable suggestions during lab meeting; which definitely made my dissertation a lot more solid. Also her review whenever I presented during a lab meeting or practiced for an upcoming seminar with her; is invaluable. I think I have learnt a lot about how important it is to be able to present your work and make sure that people can follow the talk from these discussions. Also I would like to thank my committee members Dr Striepen, Dr Tarleton and Dr Hajduk whose advice and suggestion added value to my thesis and towards the flow of the project. Thanks to Veronica who trained me in my first year and for her positive criticizm. I am and will be ever grateful to Melina for being the best lab manager and being a great vi friend; for always answering my questions and always encouraging me in the toughest of time. Thanks to Noelia who is a great friend and a wonderful labmate; she helped answer some of my doubts regarding the writing of the dissertation. And everyone else in the Docampo-Moreno lab; an environment that always inspired and taught me to work hard, help each other, to work together as a unit, discuss and share problems; and also taught me how important it is to recognize everyone’s contribution and also to be able to critically review each other’s as well as your own work. I can undoubtedly say these were the best 5 years of my life!! A big thank you to my parents; for giving us the best education and the best childhood. And most importantly making sure that we become nice human beings; something that I will carry with me wherever I go. They have made countless sacrifices to support me and my sister and give us a life which I know was very difficult for them to provide at the moment. My sister, for being my biggest cheerleader and for all the love she gives me. Though I am the elder one, but her wisdom and mature suggestions have definitely taught me a lot in life. Thank you to my brother-in-law who is more like my own brother; for all the encouragement, the sense of humor you keep pouring in at difficult times which always manages to bring a smile to my face on those days, when going gets tough. My gratitude to my parents-in-law for being understanding and very supportive throughout. And a big thank you to my husband for being my strength. Words will never do justice to what you mean to me. Thank you for being by my side, for backing me up when I fall down, for respecting my space and also being my biggest critique. You have indeed been my guide, my teacher and my best friend. Surprisingly all my worries disappeared after I vii came back home to him. The support and love from my family has been my biggest strength and instrumental in whatever I have been able to achieve. viii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS v LIST OF FIGURES xi CHAPTER 1 INTRODUCTION………………………………………………………………….1 Introduction…………………………………………………………………………….…...1 Structure of the Dissertation……………………………………………..…………………3 References ……………………………………………………………………….…………4 2 LITERATURE REVIEW…………………………………………………………..5 Trypanosoma cruzi and Chagas disease ……………………………………………………5 Life cycle of Trypanosoma cruzi …………………………………………………………..6 Contractile Vacuole Complex………………………………………………………………7 Acidocalcisomes…………………………………………………………………………..10 Traffic in trypanosomes…………………………………………………………………...13 Rab proteins………………………………………………………….……………………15 Tools to investigate the function of Rab proteins in vesicle fusion and transport mechanism……………………………………………………………………....16 GDP bound “OFF” stage of Rab proteins: examples……………………………………..18 Role of Rab32 protein in trafficking……………………………………………………...18 Role of Rab11 protein in trafficking………………………………………………………19 ix Rab protein prenylation and potential treatment of Chagas disease………………………20 Overview of Trypanosoma cruzi infection……………………………………………......21 GPI-anchored surface proteins…………………………………………………………....23 Trans-sialidase…………………………………………………………………………....24 References………………………………………………………………………………...27 3 RAB11 REGULATES TRAFFICKING OF TRANS-SIALIDASE TO THE PLASMA MEMBRANE THROUGH THE CONTRACTILE VACUOLE COMPLEX OF TRYPANOSOMA CRUZI ………………………………………………..45 Abstract……………………………………………………………………………………46 Author Summary…………………………………………………………………………..47 Introduction……………………………………………………………………………..…47 Results …………………………………………………………………………………….50 Discussion…………………………………………………………………………………59 Materials and Methods….………………………………………………………………...64 References………………………………………………………………………………...73 4 RAB32 IS ESSENTIAL FOR MAINTAINING FUNCTIONAL ACIDOCALCISOMES AND FOR GROWTH AND VIRULENCE OF TRYPANOSOMA CRUZI……………………………………………101 Abstract………………………………………………………………………………..…102 Author Summary ………………………………………………………………………...102 Introduction………………………………………………………………………………103 Results……………………………………………………………………………………105 Discussion……………………………………………………………………………......111 x Materials and methods…………………………………………………………………...113 References ……………………………………………………………………………….121 5 CONCLUSION…………………………………………………………………..139 Summary of key finding…………………………………………………………………139 Future work………………………………………………………………………………141 References ……………………………………………………………………………….147 xi LIST OF FIGURES Page Figure 2.1: Life cycle of T. cruzi…………………………………………………………………39
Load more

Recommended publications
  • Download the Abstract Book
    1 Exploring the male-induced female reproduction of Schistosoma mansoni in a novel medium Jipeng Wang1, Rui Chen1, James Collins1 1) UT Southwestern Medical Center. Schistosomiasis is a neglected tropical disease caused by schistosome parasites that infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs, yet our understanding of their sexual reproduction is limited because egg production is not sustained for more than a few days in vitro. Here, we explore the process of male-stimulated female maturation in our newly developed ABC169 medium and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. By performing an RNAi screen for genes whose expression was enriched in the female reproductive organs, we identify a single nuclear hormone receptor that is required for differentiation and maturation of germ line stem cells in female gonad. Furthermore, we screen genes in non-reproductive tissues that maybe involved in mediating cell signaling during the male-female interplay and identify a transcription factor gli1 whose knockdown prevents male worms from inducing the female sexual maturation while having no effect on male:female pairing. Using RNA-seq, we characterize the gene expression changes of male worms after gli1 knockdown as well as the female transcriptomic changes after pairing with gli1-knockdown males. We are currently exploring the downstream genes of this transcription factor that may mediate the male stimulus associated with pairing.
    [Show full text]
  • There Is Not a Latin Root Word Clear Your Desk Protist Quiz Grade Quiz
    There is not a Latin Root Word Clear your desk Protist Quiz Grade Quiz Malaria Fever Wars Classification Kingdom Protista contains THREE main groups of organisms: 1. Protozoa: “animal-like protists” 2. Algae: “plant-like protists” 3. Slime & Water Molds: “fungus-like protists” Basics of Protozoa Unicellular Eukaryotic unlike bacteria 65, 000 different species Heterotrophic Free-living (move in aquatic environments) or Parasitic Habitats include oceans, rivers, ponds, soil, and other organisms. Protozoa Reproduction ALL protozoa can use asexual reproduction through binary fission or multiple fission FEW protozoa reproduce sexually through conjugation. Adaptation Special Protozoa Adaptations Eyespot: detects changes in the quantity/ quality of light, and physical/chemical changes in their environment Cyst: hardened external covering that protects protozoa in extreme environments. Basics of Algae: “Plant-like” protists. MOST unicellular; SOME multicellular. Make food by photosynthesis (“autotrophic prostists”). Were classified as plants, BUT… – Lack tissue differentiation- NO roots, stems, leaves, etc. – Reproduce differently Most algal cells have pyrenoids (organelles that make and store starch) Can use asexual or sexual reproduction. Algae Structure: Thallus: body portion; usually haploid Body Structure: 1) unicellular: single-celled; aquatic (Ex.phytoplankton, Chlamydomonas) 2) colonial: groups of coordinated cells; “division of labor” (Ex. Volvox) 3) filamentous: rod-shaped thallus; some anchor to ocean bottom (Ex. Spyrogyra) 4) multicellular: large, complex, leaflike thallus (Ex. Macrocystis- giant kelp) Basics of Fungus-like Protists: Slime Molds: Water Molds: Once classified as fungi Fungus-like; composed of Found in damp soil, branching filaments rotting logs, and other Commonly freshwater; decaying matter. some in soil; some Some white, most yellow parasites.
    [Show full text]
  • Unique Characteristics of the Kinetoplast DNA Replication
    CHAPTER 2 Unique Characteristics of the Kinetoplast DNA Replication Machinery Provide Potential Drug Targets in Trypanosomatids Dotan Sela, Neta Milman, Irit Kapeller, Aviad Zick, Rachel Bezalel, Nurit Yaffe and Joseph Shlomai* Reevaluating the Kinetoplast as a Potential Target for Anti-Trypanosomal Drugs inetoplast DNA (kDNA) is a remarkable DNA structure found in the single mitohondrion of flagellated protozoa of the order Kinetoplastida. In various parasitic Kspecies of the family Trypanosomatidae, it consists of 5,000-10,000 duplex DNA minicircles (0.5-10 kb) and 25-50 maxicircles (20-40 kb), which are linked topologically into a two dimensional DNA network. Maxicircles encode for typical mitochondrial proteins and ribosomal RNA, whereas minicircles encode for guide RNA (gRNA) molecules that function in the editing of maxicircles’ mRNA transcripts. The replication of kDNA includes the dupli- cation of free detached minicircles and catenated maxicircles, and the generation of two prog- eny kDNA networks. It is catalyzed by an enzymatic machinery, consisting of kDNA replica- tion proteins that are located at defined sites flanking the kDNA disk in the mitochondrial matrix (for recent reviews on kDNA see refs. 1-8). The unusual structural features of kDNA and its mode of replication, make this system an attractive target for anti-trypanosomal and anti-leishmanial drugs. However, in evaluating the potential promise held in the development of drugs against mitochondrial targets in trypanosomatids, one has to consider the observations that dyskinetoplastic (Dk) bloodstream forms of trypanosomes survive and retain their infectivity, despite the substantial loss of their mitochondrial genome (recently reviewed in ref. 9). Survival of Dk strains has led to the notion that kDNA and mitochondrial functions are dispensable for certain stages of the life cycle of trypanosomatids.
    [Show full text]
  • Microorganisms – Protists: Euglena
    Microorganisms – Protists: Euglena Euglena are unicellular organisms classified into the Kingdom Protista, and the Phylum Euglenophyta. All euglena have chloroplasts and can make their own food by photosynthesis. They are not completely autotrophic though, euglena can also absorb food from their environment. Euglena usually live in quiet ponds or puddles. Euglena move by a flagellum (plural flagella), which is a long whip-like structure that acts like a little motor. The flagellum is located on the anterior (front) end, and twirls in such a way as to pull the cell through the water. It is attached at an inward pocket called the reservoir. Color and label the reservoir grey. Color and label the flagellum black. The Euglena is unique in that it is both heterotrophic (must consume food) and autotrophic (can make its own food). Chloroplasts within the euglena trap sunlight that is used for photosynthesis and can be seen as several rod-like structures throughout the cell. Color and label the chloroplasts green. Euglena also have an eyespot at the anterior end that detects light, it can be seen near the reservoir. This helps the euglena find bright areas to gather sunlight to make their food. Color and label the eyespot red. Euglena can also gain nutrients by absorbing them across their cell membrane, hence they become heterotrophic when light is not available, and they cannot photosynthesize. The euglena has a stiff pellicle outside the cell membrane that helps it keep its shape, though the pellicle is somewhat flexible, and some euglena can be observed scrunching up and moving in an inchworm type fashion.
    [Show full text]
  • Autophagy in Trypanosomatids
    Cells 2012, 1, 346-371; doi:10.3390/cells1030346 OPEN ACCESS cells ISSN 2073-4409 www.mdpi.com/journal/cells Review Autophagy in Trypanosomatids Ana Brennand 1,†, Eva Rico 2,†,‡ and Paul A. M. Michels 1,* 1 Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, postal box B1.74.01, B-1200 Brussels, Belgium; E-Mail: [email protected] 2 Department of Biochemistry and Molecular Biology, University Campus, University of Alcalá, Alcalá de Henares, Madrid, 28871, Spain; E-Mail: [email protected] † These authors contributed equally to this work. ‡ Present Address: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, King’s Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +32-2-7647473; Fax: +32-2-7626853. Received: 28 June 2012; in revised form: 14 July 2012 / Accepted: 16 July 2012 / Published: 27 July 2012 Abstract: Autophagy is a ubiquitous eukaryotic process that also occurs in trypanosomatid parasites, protist organisms belonging to the supergroup Excavata, distinct from the supergroup Opistokontha that includes mammals and fungi. Half of the known yeast and mammalian AuTophaGy (ATG) proteins were detected in trypanosomatids, although with low sequence conservation. Trypanosomatids such as Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for serious tropical diseases in humans. The parasites are transmitted by insects and, consequently, have a complicated life cycle during which they undergo dramatic morphological and metabolic transformations to adapt to the different environments.
    [Show full text]
  • The Intestinal Protozoa
    The Intestinal Protozoa A. Introduction 1. The Phylum Protozoa is classified into four major subdivisions according to the methods of locomotion and reproduction. a. The amoebae (Superclass Sarcodina, Class Rhizopodea move by means of pseudopodia and reproduce exclusively by asexual binary division. b. The flagellates (Superclass Mastigophora, Class Zoomasitgophorea) typically move by long, whiplike flagella and reproduce by binary fission. c. The ciliates (Subphylum Ciliophora, Class Ciliata) are propelled by rows of cilia that beat with a synchronized wavelike motion. d. The sporozoans (Subphylum Sporozoa) lack specialized organelles of motility but have a unique type of life cycle, alternating between sexual and asexual reproductive cycles (alternation of generations). e. Number of species - there are about 45,000 protozoan species; around 8000 are parasitic, and around 25 species are important to humans. 2. Diagnosis - must learn to differentiate between the harmless and the medically important. This is most often based upon the morphology of respective organisms. 3. Transmission - mostly person-to-person, via fecal-oral route; fecally contaminated food or water important (organisms remain viable for around 30 days in cool moist environment with few bacteria; other means of transmission include sexual, insects, animals (zoonoses). B. Structures 1. trophozoite - the motile vegetative stage; multiplies via binary fission; colonizes host. 2. cyst - the inactive, non-motile, infective stage; survives the environment due to the presence of a cyst wall. 3. nuclear structure - important in the identification of organisms and species differentiation. 4. diagnostic features a. size - helpful in identifying organisms; must have calibrated objectives on the microscope in order to measure accurately.
    [Show full text]
  • Can Protozoa Prove the Beginning of the World?
    Southeastern University FireScholars Classical Conversations Spring 2020 Can Protozoa Prove the Beginning of the World? Karina L. Burton Southeastern University - Lakeland, [email protected] Follow this and additional works at: https://firescholars.seu.edu/ccplus Part of the Cell Biology Commons, and the Evolution Commons Recommended Citation Burton, Karina L., "Can Protozoa Prove the Beginning of the World?" (2020). Classical Conversations. 9. https://firescholars.seu.edu/ccplus/9 This Term Paper is brought to you for free and open access by FireScholars. It has been accepted for inclusion in Classical Conversations by an authorized administrator of FireScholars. For more information, please contact [email protected]. 1 Can Protozoa Prove the Beginning of the World? Karina L. Burton Classical Conversations: Challenge 4; Southeastern University ENGL 1233: English Composition II Grace Veach April 16, 2020 2 Abstract Protozoa are magnificent creatures. They exhibit all of the functions intrinsic to living organisms: irritability, metabolism, growth and reproduction. Within these functions, there are numerous examples of mutations that occur in order for organisms to adapt to their given environments. Irritability is demonstrated in protozoa by their use of pseudopodia, flagella, or cilia for motility; it has been shown that such locomotors exhibit diversity while maintaining similar protein and chemical structures that appear to be a result of evolutionary processes. Metabolism in protozoa is similar to that of larger animals, but their diet is unique. They primarily feast upon bacteria, which have begun mutating to evade easy ingestion and digestion by protozoa, therefore increasing their survival rate and making it necessary for protozoa to adapt.
    [Show full text]
  • The Life Cycle of Trypanosoma (Nannomonas) Congolense in the Tsetse Fly Lori Peacock1,2, Simon Cook2,3, Vanessa Ferris1,2, Mick Bailey2 and Wendy Gibson1*
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Peacock et al. Parasites & Vectors 2012, 5:109 http://www.parasitesandvectors.com/content/5/1/109 RESEARCH Open Access The life cycle of Trypanosoma (Nannomonas) congolense in the tsetse fly Lori Peacock1,2, Simon Cook2,3, Vanessa Ferris1,2, Mick Bailey2 and Wendy Gibson1* Abstract Background: The tsetse-transmitted African trypanosomes cause diseases of importance to the health of both humans and livestock. The life cycles of these trypanosomes in the fly were described in the last century, but comparatively few details are available for Trypanosoma (Nannomonas) congolense, despite the fact that it is probably the most prevalent and widespread pathogenic species for livestock in tropical Africa. When the fly takes up bloodstream form trypanosomes, the initial establishment of midgut infection and invasion of the proventriculus is much the same in T. congolense and T. brucei. However, the developmental pathways subsequently diverge, with production of infective metacyclics in the proboscis for T. congolense and in the salivary glands for T. brucei. Whereas events during migration from the proventriculus are understood for T. brucei, knowledge of the corresponding developmental pathway in T. congolense is rudimentary. The recent publication of the genome sequence makes it timely to re-investigate the life cycle of T. congolense. Methods: Experimental tsetse flies were fed an initial bloodmeal containing T. congolense strain 1/148 and dissected 2 to 78 days later. Trypanosomes recovered from the midgut, proventriculus, proboscis and cibarium were fixed and stained for digital image analysis.
    [Show full text]
  • Sexual Development in Plasmodium Parasites: Knowing When It’S Time to Commit
    REVIEWS VECTOR-BORNE DISEASES Sexual development in Plasmodium parasites: knowing when it’s time to commit Gabrielle A. Josling1 and Manuel Llinás1–4 Abstract | Malaria is a devastating infectious disease that is caused by blood-borne apicomplexan parasites of the genus Plasmodium. These pathogens have a complex lifecycle, which includes development in the anopheline mosquito vector and in the liver and red blood cells of mammalian hosts, a process which takes days to weeks, depending on the Plasmodium species. Productive transmission between the mammalian host and the mosquito requires transitioning between asexual and sexual forms of the parasite. Blood- stage parasites replicate cyclically and are mostly asexual, although a small fraction of these convert into male and female sexual forms (gametocytes) in each reproductive cycle. Despite many years of investigation, the molecular processes that elicit sexual differentiation have remained largely unknown. In this Review, we highlight several important recent discoveries that have identified epigenetic factors and specific transcriptional regulators of gametocyte commitment and development, providing crucial insights into this obligate cellular differentiation process. Trophozoite Malaria affects almost 200 million people worldwide and viewed under the microscope, it resembles a flat disc. 1 A highly metabolically active and causes 584,000 deaths annually ; thus, developing a After the ring stage, the parasite rounds up as it enters the asexual form of the malaria better understanding of the mechanisms that drive the trophozoite stage, in which it is far more metabolically parasite that forms during development of the transmissible form of the malaria active and expresses surface antigens for cytoadhesion. the intra‑erythrocytic developmental cycle following parasite is a matter of urgency.
    [Show full text]
  • The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma Brucei in the Mammalian Bloodstream
    pathogens Review The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma brucei in the Mammalian Bloodstream Eleanor Silvester †, Kirsty R. McWilliam † and Keith R. Matthews * Institute for Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, King’s Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, UK; [email protected] (E.S.); [email protected] (K.R.McW.) * Correspondence: [email protected]; Tel.: +44-131-651-3639 † These authors contributed equally to this work. Received: 23 May 2017; Accepted: 22 June 2017; Published: 28 June 2017 Abstract: African trypanosomes cause devastating disease in sub-Saharan Africa in humans and livestock. The parasite lives extracellularly within the bloodstream of mammalian hosts and is transmitted by blood-feeding tsetse flies. In the blood, trypanosomes exhibit two developmental forms: the slender form and the stumpy form. The slender form proliferates in the bloodstream, establishes the parasite numbers and avoids host immunity through antigenic variation. The stumpy form, in contrast, is non-proliferative and is adapted for transmission. Here, we overview the features of slender and stumpy form parasites in terms of their cytological and molecular characteristics and discuss how these contribute to their distinct biological functions. Thereafter, we describe the technical developments that have enabled recent discoveries that uncover how the slender to stumpy transition is enacted in molecular terms. Finally, we highlight new understanding of how control of the balance between slender and stumpy form parasites interfaces with other components of the infection dynamic of trypanosomes in their mammalian hosts.
    [Show full text]
  • The Life Cycle of Trypanosoma Cruzi
    Tyler et al. THE LIFE CYCLE OF TRYPANOSOMA CRUZI K. M. Tyler, C. L. Olson and D. M. Engman Departments of Microbiology-Immunology and Pathology Feinberg Medical School of Northwestern University, Chicago, IL 60611 ABSTRACT Since the discovery of Trypanosoma cruzi as the parasite that causes Chagas disease, nearly a century ago, the details of the organism's life cycle have fascinated scientists. T. cruzi is a single-celled eukaryote with a complex life cycle alternating between reduviid bug vectors and vertebrate hosts. It is able to adapt via the process of cellular differentiation to replicate within the diverse environments represented of the insect's gut and host cell cytoplasm. These adaptive transformations take the form of coordinated changes in morphology, metabolism and cell cycle regulation. Different life cycle stages of T. cruzi show dramatically different protein and RNA profiles, which are the end result of unusual mechanisms for regulating gene expression. In recent years, new molecular techniques have been brought to bear on the life cycle dramatically increasing our knowledge of the strategies employed by the parasite to ensure its continued survival. INTRODUCTION Chagas disease The etiologic agent of the chronic and often fatal Chagas disease is the American trypanosome, Trypanosoma cruzi , a flagellated protozoan of the order Kinetoplastida. The survival of T. cruzi is dependent on the successful transmission between, and the colonization of, two radically different environments: the midgut of the reduviid bug vector and the cytoplasm of the mammalian host cell. As is true of all infections, interruption of the pathogen's life cycle will lead to eradication of the disease.
    [Show full text]
  • A PRELIMINARY NOTE on TETRAMITUS, a STAGE in the LIFE CYCLE of a COPROZOIC AMOEBA by MARTHA BUNTING
    294 Z6OL6G Y.- M. BUNTING PROC. N. A. S. A PRELIMINARY NOTE ON TETRAMITUS, A STAGE IN THE LIFE CYCLE OF A COPROZOIC AMOEBA By MARTHA BUNTING DEPARTMENT OF ZOOLOGY, UNIVERSITY OF PENNSYLVANIA Communicated July 24, 1922 In 1920 a study of the Entamoeba of the rat was begun and in a culture on artificial medium a number of Coprozoic amoeba appeared, one of which exhibited a flagellate phase which seems to be identical with Tetramitus rostratus Perty.1 The appearance of flagellate phases in cultures of Coprozoic amoeba (Whitmore,2 etc.) as well as of soil amoeba (Kofoid,1 Wilson,4 etc.) has been recorded a number of times, but the flagellates which appeared were relatively simple in organization and very transitory in occurrence. Fur- thermore, some of the simpler flagellates have been observed (Pascher5) to lose their flagella and become amoeboid. In the case here described, however, there is a transformation of a simple amoeba into a relatively complex flagellate which multiplies for several days then returns to the amoeboid condition and becomes encysted. Tetramitus rostratus has been studied by a number of investigators since its discovery in 1852, by Perty,' yet no one has given a full account of its life history. The lack of cysts in previous accounts, mentioned by Dobell and O'Connor,6 is explained by the transformation into an amoeba before encystment. It is believed that this animal presents the extreme in transformations of this sort and serves to emphasize the close relationship between amoebae and flagellates, and the need for careful studies of life cycles, in pure cultures where possible, in investigations of coprozoic and other Protozoa.
    [Show full text]