Molecular and Cellular Biology of Pathogenic Trypanosomatids

Book Series: Frontiers in Parasitology

Volume 1

by

Marcelo Santos da Silva, Maria Isabel N. Cano

DOI: 10.2174/97816810840531170101
eISBN: 978-1-68108-405-3, 2017
ISBN: 978-1-68108-406-0
ISSN: 2542-4211 (Print)
ISSN: 2542-422X (Online)



Recommend this eBook to your Library



Every year millions of people living in tropical areas across the globe, are affected by trypanosomatids – the parasites causing Chaga...[view complete introduction]

Table of Contents

Foreword

- Pp. i-iii (3)

Walter Colli

Download Free

Preface

- Pp. iv-v (2)

Marcelo Santos da Silva and Maria Isabel N. Cano

Download Free

List of Contributors

- Pp. vi-vii (2)

Marcelo Santos da Silva and Maria Isabel N. Cano

Download Free

The Cellular Organization of Trypanosomatids During Life Cycle

- Pp. 3-60 (58)

Simone Guedes Calderano, Nilmar Silvio Moretti, Christiane Araujo, Marcelo S. da Silva, Teresa Cristina Leandro de Jesus, Loyze P. Oliveira de Lima, Mariana de Camargo Lopes, Leonardo da Silva Augusto, Julia Pinheiro Chagas da Cunha, Maria Carolina Elias and Sergio Schenkman

View Abstract Purchase Chapter

Trypanosomatid Genome Organization and Ploidy

- Pp. 61-103 (43)

João Luís Reis-Cunha, Hugo Oswaldo Valdivia and Daniella Castanheira Bartholomeu

View Abstract Purchase Chapter

Chromosomes Ends and Telomere Biology of Trypanosomatids

- Pp. 104-133 (30)

Miguel Angel Chiurillo, Cristiane Regina Antonio, Marjorie Mendes Marini, Renata Torres de Souza and José Franco da Silveira

View Abstract Purchase Chapter

Nuclear and Kinetoplast DNA Replication in Trypanosomatids

- Pp. 134-194 (61)

Marcelo S. da Silva, Maria Alejandra Viviescas, Raphael Souza Pavani, Edna Gicela Ortiz, Camila B. Storti and Maria Isabel N. Cano

View Abstract Purchase Chapter

Genome Maintenance in Trypanosomatids

- Pp. 195-260 (66)

Gonzalo Cabrera, Viviane G. Silva, Isabela C. Mendes, Carlos R. Machado and Richard McCulloch

View Abstract Download Free

Mechanisms Controlling Gene Expression in Trypanosomatids

- Pp. 261-290 (30)

Santuza M. R. Teixeira and Bruna M. Valente

View Abstract Purchase Chapter

Virulence Factors and Immune Evasion in Leishmania spp.

- Pp. 291-345 (55)

Jose M. Requena and Manuel Soto

View Abstract Purchase Chapter

Virulence Factors and Immune Evasion in Trypanosoma cruzi

- Pp. 346-393 (48)

Jorge González, Bessy Gutiérrez, José L. Vega and Jorge E. Araya

View Abstract Purchase Chapter

Molecular Tools and Strategies for Diagnosis of Chagas Disease and Leishmaniasis

- Pp. 394-453 (60)

Alejandro G. Schijman, Juan M. Burgos and Paula L. Marcet

View Abstract Purchase Chapter

New Chemotherapy Against Trypanosomiasis and Leishmaniasis

- Pp. 454-530 (77)

Jair L. de Siqueira-Neto

View Abstract Purchase Chapter

Recombinant Vaccines Against Pathogenic Trypanosomatids

- Pp. 531-585 (55)

Priscila Martins Andrade Denapoli, Alba Marina Gimenez and Maurício Martins Rodrigues

View Abstract Purchase Chapter

Subject Index

- Pp. 586-595 (10)

Marcelo Santos da Silva and Maria Isabel N. Cano

Download Free

Foreword

Since 1970, due to important financing programs, Brazilian scientists have been able to practice Biology while studying trypanosomatids, mainly Trypanosoma cruzi and Leishmania spp. The Annual Meeting in Caxambu since 1974, focusing on Trypanosoma cruzi at the beginning, and later extending the interest to other parasites, particularly Leishmania, were the catalysts of a scientific boom in Brazilian biology. Many young and enthusiastic students have been trained by the pioneers in the morphology, physiology, biochemistry, immunology and molecular biology of trypanosomatids, including vectorial transmission and clinical aspects of the diseases. The Caxambu meetings also brought to Brazil renowned scientists of the field who established important and long-lasting connections with Brazilians. After 2005, the field has gained momentum after the publication in Science of the complete genome of three species of the order Kinetoplastida, namely Leishmania major, Trypanosoma cruzi and Trypanosoma brucei. This e-book is a consequence of the Brazilian scientific activities in the field in the last 45 years. Maria Isabel Cano is my scientific grand-daughter and Marcelo Santos da Silva got his Ph.D. under her supervision.

The first chapter deals with the cellular organization of trypanosomatids during the life cycle. This group diverged early in evolution and due to this fact their members conserved certain characteristics not found in other eukaryotes as organelles like glycosomes, reservosomes and acidocalcisomes, among other cell compartments. Differences between species and between the distinct life cycle forms of each organism are comprehensively discussed.

Chapter 2 unveils the fascinating area of the trypanosomatid genomes. Information has been made available by the Tritryps project that provided major insights into the genome structure and organization of these parasites. While T. brucei presents subtelomeric expansion of genes related to antigenic variation, T. cruzi and Leishmania genomes contain species-specific genes related to cellular invasion and survival inside the mammalian host cells. As control of gene expression operates mainly at a post-transcriptional level in trypanosomatids, gene copy number variation is probably an efficient mechanism to enhance gene expression and increase sequence variability. Among the Tritryps, T. cruzi presents the most striking expansion of species-specific multigene families, which could be related to the ability of the parasite to infect any nucleated cell of a broad range of mammals. Chromosomal copy number variation is also well tolerated by these parasites, allowing the expansion of a whole set of genes simultaneously. The functional implications of these chromosomal expansions to the parasite biology are still to be determined.

Chapter 3 clarifies the function of chromosome ends and telomeres in trypanosomatid biology. These structures, in addition to the preservation of chromosomal integrity, play a major role in survival. The telomeric repeat (5'-TTAGGG-3')n is conserved among trypanosomatid species, but adjacent subtelomeric sequences vary between species and chromosomes within the same cell. For example, size and gene content of T. cruzi subtelomeres differ in each chromosome due to differences in the abundance and organization of these genes, whereas in Leishmania spp. subtelomeres show a more conserved organization.

Chapter 4 is a pleasant travel on nuclear and kinetoplast DNA replication in trypanosomatids. These organisms exhibit both conserved and unique non-conserved features in the DNA replication machinery. Curiously, the trypanosomatid pre-replication complex differs from other eukaryotes, having features similar to those of Archaea. The completion of DNA replication, at trypanosomatid telomeres, apparently is similar to other eukaryotes, although the processing of the leading and lagging telomeres required to generate the 3' overhangs, which serve as telomerase substrate, remains unknown. DNA replication in trypanosomatids initiates almost simultaneously in the nucleus and the kinetoplast, suggesting that regulation of DNA synthesis in the two DNA-containing organelles may be coordinated. The kinetoplast DNA consists of mini- and maxi-circles, which are replicated by many proteins with, as yet, unknown mechanisms of action. The complex DNA replication mechanisms, independently acting in both kinetoplast and nucleus, are reviewed.

Chapter 5 discusses mechanisms by which trypanosomatids maintain genome integrity and preserve faithful DNA replication despite multiple environmental aggressions. A growing body of evidence on how trypanosomatids recognize and repair damages is reviewed.

Chapter 6 explores one of the most fascinating features that make trypanosomatids unique organisms in the biological world. Despite being eukaryotic organisms they constitutively synthesize polycistronic mRNAs from separate gene clusters. Control of gene expression is not carried out at the DNA level but relies upon post-transcriptional mechanisms. This chapter aptly discusses the common post-transcriptional pathways for most genes, although many regulatory strategies within species of the group differ from each other. It is argued that these complex and diversified regulatory machineries allow rapid responses of these organisms to drastic environmental changes during their life cycle.

Chapters 7 and 8 describe virulence factors and the immune evasion in Leishmania spp and Trypanosoma cruzi, respectively. These parasites co-evolved with their hosts – mammalian and insects – for several millions of years and developed specialized strategies to evade the immune system by overcoming both innate and adaptive immune responses. The role of different species of molecules as virulence factors is discussed.

Diagnosis, chemotherapy, and potential recombinant vaccines are discussed in the ensuing chapters 9, 10 and 11, respectively. The diseases caused by kinetoplastids, called neglected diseases since they are predominant in poorer tropical countries having scarce resources, are responsible for thousands of deaths per year. No vaccines are available for these diseases. Presently, drug therapies are not very effective because the few available drugs are toxic, and treatment is costly. Comprehensively, methods of vector control are insufficient, despite the Southern Cone initiative in the nineties by which transmission of Trypanosoma cruzi in the domicile and outdoors by Triatoma infestans, at least in some countries, has been controlled. Chapter 9, stresses the need for reliable and specific diagnostic tests for epidemiological surveys, surveillance for vectorial transmission, blood screening, screening of pregnant women and their newborns, and in individual patients. The chapter summarizes the most commonly used molecular tools described to date to detect T. cruzi infection and to identify and genotype Leishmania spp. Chapter 10 discusses the present status of the chemotherapy area, emphasizing the screening assays that led to a few drugs reaching the stage of a clinical trial after a selection from millions of molecules tested. A milestone has been set for the year 2020, by the London Declaration: control of Chagas disease and leishmaniasis, and elimination of Human African Trypanosomiasis. Advances to achieve these goals are presented in this chapter. Finally, Chapter 11 deals with the research efforts on the development of recombinant vaccines against trypanosomatids, most of which are at the stage of preclinical experimentation. It is hoped that these efforts can be translated into efficient human vaccines.

This book is being edited in electronic form. In addition to the PDF edition accessible online, it will be aired in open access electronic media. Any reader can also have access to a printed version and also to individual chapters offered by the authors themselves. Thus, it is hoped that biologists, graduate students and post-doctoral researchers benefit with this up-to-date and competent review of the present literature on trypanosomatids.

Prof. Walter Colli
University of São Paulo
Brazil


Preface

Among the pathogenic trypanosomatids are the etiological agents of leishmaniasis, African trypanosomiasis and Chaga’s disease, protozoa parasites belonging respectively, to the genus Leishmania and Trypanosoma. The diseases are high prevalent in tropical areas of the globe and according to WHO cause thousands of new cases and deaths every year. It is worth noting though that international migration made Chaga’s disease and leishmaniasis becoming an issue also in many developing countries in Europe, Canada, USA, Australia, and Japan. Although the number of new cases and deaths from Chaga’s disease had decreased in the last decade, the millions of chronically infected persons who are at risk for developing cardiovascular and/or digestive pathology make Chaga’s disease one of the leading causes of cardiovascular morbidity and premature death in Latin America. Human African trypanosomiasis (HAT), also known as sleeping sickness, is endemic in sub-Saharan countries and is caused by T. brucei gambiense and T. b. rhodesiense. The number of HAT cases has been decreasing in the last years due to very active control efforts although according to a recent WHO report, country or regional averages may be misleading since the burden of the disease falls very heavily on some areas. HAT patients require lots of care and disease diagnosis and treatment can be costly and time-consuming. However, in many Africa countries diagnostics and HAT drugs are provided free of charge. Leishmaniasis in its turn is still considered a dangerous menace, principally to the poor, with about 12 million people currently infected. Depending on the species leishmaniasis can be expressed in different clinical forms, with the cutaneous form being the most common, causing self-limiting skin ulcer or a highly disfiguring scar, to the disfiguring and mutilating mucocutaneous form, and the visceral form is the most severe and fatal if not treated. All these diseases are still challenges to overcome since the absence of effective vaccines, and the toxicity of current anti-parasite drugs, in addition to the emergence of drug-resistant parasite strains and HIV co-infections are non-transposable barriers to disease control. Thus, many research initiatives have been direct to understand parasite biology and its interactions with different hosts, as well as the mechanisms of disease pathogenesis, of drug resistance and genome organization and maintenance, with the aim of the development of more efficient diagnostic tools and non-toxic and effective drugs and vaccines.

In this eBook, experts review and explore current knowledge about the molecular and cellular biology of trypanosomatids, highlighting the most important and actual discoveries in each research field. Topics covered include cell organization during development; genome organization and maintenance; control of gene expression; nuclear and kinetoplast DNA replication; mechanisms of DNA damage repair; virulence factors and immune evasion; new methods for molecular diagnosis; new therapeutic tools and recombinant vaccine biology.

We believe that the eBook content will be of keen interest to undergraduates, graduate students and principally to the Parasitology community and researchers working in related fields.

We would like to thank the contributing authors of this book for their time, expertise, and for making this eBook novel, educational, and informative and Professor Walter Colli for written the Forward.

Finally, we would like to express our gratitude to Mr. Shehzad Naqvi, the Senior Manager Publications from Bentham Science Publishers for his continuous help.

Dr. Marcelo Santos da Silva
Instituto Butantan
São Paulo
Brazil

Dr. Maria Isabel N. Cano
Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP)
Botucatu, São Paulo
Brazil

List of Contributors

Editor(s):
Marcelo Santos da Silva
Instituto Butantan
São Paulo
Brazil


Maria Isabel N. Cano
Universidade Estadual Paulista, “Júlio de Mesquita Filho” (UNESP)
São Paulo
Brazil




Contributor(s):
Alba Marina Gimenez
Universidade Federal de São Paulo, São Paulo
Brazil


Alejandro G. Schijman
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Ciudad de Buenos Aires
Argentina


Bessy Gutiérrez
University of Antofagasta, Antofagasta
Chile


Bruna M. Valente
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Camila B. Storti
Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Botucatu, São Paulo
Brazil


Carlos R. Machado
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Christiane Araújo
Instituto Butantan, São Paulo
Brazil


Cristiane Regina Antonio
Universidade Federal de São Paulo, São Paulo
Brazil


Daniella Castanheira Bartholomeu
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Edna Gicela Ortiz Morea
Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Botucatu, São Paulo
Brazil


Gonzalo Cabrera
Universidad de Chile, Santiago
Chile


Hugo Oswaldo Valdivia
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Isabela C. Mendes
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Jair L. Siqueira-Neto
University of California San Diego, La Jolla
USA


João Luís Reis-Cunha
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Jorge Araya
University of Antofagasta, Antofagasta
Chile


Jorge González
University of Antofagasta, Antofagasta
Chile


José Franco da Silveira
Universidade Federal de São Paulo, São Paulo
Brazil


José L. Vega
University of Antofagasta, Antofagasta
Chile


Jose M. Requena
Universidad Autónoma de Madrid, Madrid
Spain


Juan M. Burgos
Universidad Nacional de San Martín, Provincia de Buenos Aires
Argentina


Julia Pinheiro C. da Cunha
Instituto Butantan, São Paulo
Brazil


Leonardo da Silva Augusto
Universidade Federal de São Paulo, São Paulo
Brazil


Loyze P. Oliveira de Lima
Instituto Butantan, São Paulo
Brazil


Manuel Soto
Universidad Autónoma de Madrid, Madrid
Spain


Marcelo Santos da Silva
Instituto Butantan, São Paulo
Brazil


Maria Alejandra Viviescas
Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Botucatu, São Paulo
Brazil


Maria Carolina Elias
Instituto Butantan, São Paulo
Brazil


Maria Isabel Nogueira Cano
Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Botucatu, São Paulo
Brazil


Mariana de Camargo Lopes
Instituto Butantan, São Paulo
Brazil


Marjorie Mendes Marini
Universidade Federal de São Paulo, São Paulo
Brazil


Maurício Martins Rodrigues
Universidade Federal de São Paulo, São Paulo
Brazil


Miguel Angel Chiurillo
Universidade de Campinas, Campinas
Brazil


Nilmar Silvio Moretti
Universidade Federal de São Paulo, São Paulo
Brazil


Paula L. Marcet
Center for Diseases, Control and Prevention (CDC), Atlanta
United States of America


Priscila Martins Andrade Denapoli
Universidade Federal de São Paulo
Brazil


Raphael Souza Pavani
Instituto Butantan, São Paulo
Brazil


Renata Torres de Souza
Universidade Federal de São Paulo, São Paulo
Brazil


Richard McCulloch
University of Glasgow, Glasgow
UK


Santuza M. R. Teixeira
Universidade Federal de Minas Gerais, Minas Gerais
Brazil


Sergio Schenkman
Universidade Federal de São Paulo, São Paulo
Brazil


Simone Guedes Calderano
Instituto Butantan, São Paulo
Brazil


Teresa Cristina Leandro
Teresa Cristina Leandro de Jesus Instituto Butantan, São Paulo
Brazil


Viviane G. Silva
Universidade Federal de Minas Gerais, Minas Gerais
Brazil




Advertisement



Webmaster Contact: info@benthamscience.org Copyright © 2017 Bentham Science