?Trypanosoma brucei
Trypanosoma Brucei Brucei TREU667 (Bloodstream form, phase contrast picture. Black bar indicates 10µm.)
Scientific classification
Kingdom: Protista Phylum: Euglenozoa Class: Kinetoplastea Order: Trypanosomatida Genus: Trypanosoma Species: T. brucei
Subspecies
T. b. brucei T. b. gambiense T. b. rhodesiense Image File history File linksMetadata Tb_brucei. ... Scientific classification or biological classification is how biologists group and categorize extinct and living species of organisms (as opposed to folk taxonomy). ... Typical phyla Protists (IPA: ) are a heterogeneous group of living things, comprising those eukaryotes that are not animals, plants, or fungi. ... Classes Euglenoidea Kinetoplastea Diplonemea Postgaardea The Euglenozoa are a large group of flagellate protozoa, dominated by the euglenids and kinetoplastids. ... Orders Trypanosomatida Bodonida The kinetoplastids are a group of flagellate protozoa, including a number of parasites responsible for serious diseases in humans and other animals, as well as various forms found in soil and aquatic environments. ... Genera Blastocrithidia Crithidia Endotrypanum Herpetomonas Leishmania Leptomonas Phytomonas Trypanosoma Wallaceina Trypanosomes are a group of kinetoplastid protozoa distinguished by having only a single flagellum. ... Trypanosoma is a notable genus of trypanosomes, a monophyletic group of unicellular parasitic protozoa. ...

Trypanosoma Brucei is a notable parasitic species of Trypanosoma. The species causes African trypanosomaiasis (or sleeping sickness) in humans and animals in Africa. There are 3 sub-species of T.brucei; T.b.brucei, T.b.gambiense and T.b.rhodesiense. Sleeping sickness or African trypanosomiasis is a parasitic disease in people and in animals. ... For other uses, see Africa (disambiguation). ...

The entirely parasitic species has two hosts - its insect vector and mammalian host. Because of the large difference between these hosts the cell undergoes complex changes to facilitate its survival in the insect gut and the mammalian bloodstream. It also features a unique and notable variable surface glycoprotein (VSG) coat in order to avoid the host's immune system. There is an urgent need for the development of new drug therapies as current treatments can prove fatal to the patient as well as the trypanosomes. Classes & Orders See taxonomy Insects are invertebrate animals of the Class Insecta, the largest and (on land) most widely-distributed taxon within the phylum Arthropoda. ... Traditionally in medicine, a vector is an organism that does not cause disease itself but which spreads infection by conveying pathogens from one host to another. ... Orders Subclass Monotremata Monotremata Subclass Marsupialia Didelphimorphia Paucituberculata Microbiotheria Dasyuromorphia Peramelemorphia Notoryctemorphia Diprotodontia Subclass Placentalia Xenarthra Dermoptera Desmostylia Scandentia Primates Rodentia Lagomorpha Insectivora Chiroptera Pholidota Carnivora Perissodactyla Artiodactyla Cetacea Afrosoricida Macroscelidea Tubulidentata Hyracoidea Proboscidea Sirenia The mammals are the class of vertebrate animals primarily characterized by the presence of mammary...

The trypanosome cytoskeleton is the subject of considerable research. The cytoskeleton, as the structure behind mitosis, locomotion and surface binding, is vital for viability and so is a target of interest for drug development. The eukaryotic cytoskeleton. ... Mitosis is the process by which a cell separates its duplicated genome into two identical halves. ...

The Infection: Trypanosomaiasis

Main article: African Trypanosomaiasis

The insect vector for T.brucei is the tsetse fly. The parasite lives in the gut of the fly (procyclic form), until it migrates to the salivary glands for injection to the mammalian host on binding. The parasite lives within the bloodstream (bloodstream form) where it can reinfect the fly vector after biting. Later during a T.brucei infection the parisite may migrate to other areas of the host. A T.brucei infection may be transferred human to human via bodily fluid exchange, primarily blood transfer. Binomial name Glossina morsitans The tsetse fly, Glossina morsitans, is a fly (order Diptera) that eats blood from animals, including humans. ...

There are three different sub-species of T.brucei cause different variants of Trypanosomaiasis.

• T.b.gambiense - Causes slow onset chronic trypanosomaiasis.
• T.b.rhodesiense - Causes fast onset acute trypanosomaiasis.
• T.b.brucei - Causes animal African trypanosomaiasis (or Nagana), along with several other parasites.

Nagana, also called Animal African Trypanosomiasis, is a disease of vertebrate animals. ...

The Cell Structure

The structure of the cell is fairly typical of eukaryotes, see eukaryotic cell. All major organelles are seen, including the nucleus, mitochondria, endoplasmic reticulum, etc. Main unusual features include the single large mitochondria with a condensed mitochondrial DNA structure, and its association with the basal body of the flagellum, unucually the cytoskeleton organisation mechanism of the cell. The cell also features a dense coat of variable surface glycoproteins (VSGs). Cells in culture, stained for keratin (red) and DNA (green). ... Kingdoms Animalia - Animals Fungi Plantae - Plants Protista A eukaryote is an organism with a complex cell or cells, in which the genetic material is organized into a membrane-bound nucleus or nuclei. ... Kingdoms Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. ... In cell biology, the nucleus (from Latin nucleus or nuculeus, kernel) is found in all eukaryotic cells and contains the nuclear genes which form most of the cells genetic material. ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... The endoplasmic reticulum (endoplasmic meaning within the cytoplasm, reticulum meaning little net) or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport (e. ... Mitochondrial DNA (mtDNA) is DNA that is located in mitochondria. ... A basal body is a short cylindrical array of microtubules plus their associated proteins found at the base of a eukaryotic cell cilium or flagellum. ... A flagellum (plural, flagella) is a whip-like organelle that many unicellular organisms, and some multicellular ones, use to move about. ... The eukaryotic cytoskeleton. ...

Trypanosomatid cellular forms.

Trypanosomatids show specific cellular forms:

• Amastigote - Basal body anterior of nucleus, with a short, essentially non-functional, flagellum.
• Promastigote - Basal body anterior of nucleus, with a long detached flagellum.
• Epimastigote - Basal body anterior of nucleus, with a long flagellum attached along the cell body.
• Trypomastigote - Basal body posterior of nucleus, with a long flagellum attached along the cell body.

T.brucei can be found in any of these forms, with the typical procyclic and bloodstream forms in the trypomastigote structure.

The Genome

The genome of T.brucei is made up of: In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ...

• 11 large chromosomes of 1 to 6 megabase pairs.
• 6 intermediate chromosomes of 300 to 600 kilobase pairs.
• Around 100 mini chromosomes of around 50 to 100 kilobase pairs. These may be present in multiple copies per haploid genome.

The large chromosomes contain most genes, while the small chromosomes tend to carry genes involved in antigenic variation, including the VSG genes. The genome has been sequenced and is available online www.genedb.org. Figure 1: Chromosome. ... Haploid (meaning simple in Greek) cells have only one copy of each chromosome. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ...

The mitochondrial genome is found condensed into the kinetoplast, an unusual feature unique to the the kinetoplastea class. It and the basal body of the flagellum are strongly associated via a cytoskeletal structure. A basal body is a short cylindrical array of microtubules plus their associated proteins found at the base of a eukaryotic cell cilium or flagellum. ... A flagellum (plural, flagella) is a whip-like organelle that many unicellular organisms, and some multicellular ones, use to move about. ...

The VSG Coat

The surface of the trypanosome is made up from a uniform coat of variable surface glycoproteins (VSGs). This coat has two roles:

• A physical barrier blocking recognition of the cell by the non-specific immune response of the mammalian host and hiding invariant surface proteins (such as ion chanels, receptors, etc.) from specific immune system recognition.
• A variable surface to the cell, allowing variation and adaptation to avoid the specific immune system.

The coat is highly variable - there are thought to be many hundred alternative copies of the gene in the genome. In each cell, and throughout a population of cells within the host, the same coat protein is expressed, but this expression is unstable and is likely to change with the next generation. Rates of switching of up to 1 in 50 cells per generation have been seen. The immune system is composed of a complex constellation of cells, organs and tissues, arranged in an elaborate and dynamic communications network and equipped to optimize the response against invasion by pathogenic organisms. ... The immune system is composed of a complex constellation of cells, organs and tissues, arranged in an elaborate and dynamic communications network and equipped to optimize the response against invasion by pathogenic organisms. ...

The protein is made up of a highly variable N terminal domain of around 300 to 350 amino acids, and a more conserved C terminal domain of around 100 amino acids. The c terminal domain forms a structural bundle of 4 alpha helixes, while the N teminal domain forms a 'halo' around the helixes. The tertiary stucture of this halo is well conserved (supprisingly, given that the actual amino acid sequences vary widely), allowing close packing into the physical barrier the VSGs are required to form. The VSGs are anchored to the cell membrane via a GPI anchor - a covelant linkage from the c terminus, through around 4 sugars, to a phosphatidyl-inositol phospholipid acid which lies in the cell membrane. Proteins are amino acid chains, made up from 20 different L-α-amino acids, also referred to as residues, that fold into unique three-dimensional protein structures. ... Proteins are amino acid chains, made up from 20 different L-α-amino acids, also referred to as residues, that fold into unique three-dimensional protein structures. ... Drawing of a cell membrane A cell membrane, plasma membrane or plasmalemma is a selectively permeable lipid bilayer coated by proteins which comprises the outer layer of a cell. ... A GPI anchor (phosphatidyl-inositol glycane) is a common modification of the C-terminus of membrane-attached proteins. ... Two schematic representations of a phospholipid. ...

The genome contains many copies of possible VSG genes. Around 20 are found on the large and intermediate chromosomes which are active and potentially transcribed (although only one per cell ever will be). Around 100 are found near the telomeres of the mini chromosomes. These are not active, but if moved via recombination to an active transcription site will produce a functional VSG protein. Finally around 1000 are found in repeated sections in the interior of the chromosomes. These are generally inactive, typically with omitted sections or premature stop codons, but are important in the evolution of new VSG genes. It is estimated up to 10% of the T.brucei genome may be made up of VSG genes or pseudogenes. A telomere is a region of highly repetitive DNA at the end of a chromosome, which functions as an aglet. ... Recombination usually denotes a genetic event that occurs during the formation of sperm and egg cells (especially in areas of study of biology topics). ... A pseudogene is a nucleotide sequence that is part of the genome of an organism that appears to code for a gene product (typically a protein) but does not (or no longer does so). ...

Upon infection the trypanosome originally expresses a particular VSG. As the host's immune system generates a specific response to this coat protein this selects against expression of that VSG, lowering the population of trypanosomes. At this point a cell will start expressing an alternative VSG, and can repopulate. The overall effect of this boom and bust population cycle due to the predator/prey relationship with the hosts immune system leads to a succession of bouts of infection, each with a different VSG coat protein being expressed.

The Cytoskeleton

The cytoskeleton is predominantly made up of microtubules, forming a subpellicular corset. The microtubules lie parallel to each other along the long axis of the cell, with the number of microtubules at any point roughly proportional to the circumference of the cell at that point. As the cell grows (including for mitosis) additional microtubules grow between the existing tubules, leading to semiconservative inheritance of the cytoskeleton. The microtubules are orientated + at the posterior and - at the anterior. The eukaryotic cytoskeleton. ... Microtubules are protein structures found within cells. ...

Microfilament and intermediate filaments also play an important role in the cytoskeleton, but these generally overlooked. This article or section should be merged with actin Microfilaments or actin filaments are made up of two twisted monomeric actin subunits. ... // Intermediate filaments(IFs) are a component of the cytoskeleton - important structural components of living cells. ...

Flagellar Structure

Trypanosoma Brucei flagellar structure.

The trypanosome flagellum has two main structures. It is made up of a typical flagellar axoneme which lies parallel to the paraflagellar rod, a lattice structure of proteins unique to the kinetoplastida, euglenoids and dinoflagellates. Families Bodonidae Trypanosomatidae The kinetoplastids are a group of flagellate protozoa, including a number of parasites responsible for serious diseases in humans and other animals, as well as various forms found in soil and aquatic environments. ... The euglenids are one of the best-known groups of flagellates, commonly found in freshwater especially when rich in organic materials, with a few marine and endosymbiotic members. ... Classes Dinophyceae Noctiluciphyceae Syndiniophyceae The dinoflagellates are a large group of flagellate protists. ...

The microtubules of the flagellar axoneme lie in the normal 9+2 arrangement, orientated with the + at the anterior end and the - in the basal body. The a cytoskeletal structure extends from the basal body to the kinetoplast. The flagellum is bound to the cytoskeleton of the main cell body by four specialised microtubules, which run parallel and in the same direction to the flagellar tubulin. The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ...

The flagellar function is twofold - locomotion via oscilations along the attached flagellum and cell body, and attatchment to the fly gut during the procyclic phase.

Mitotic Process

Trypanosome cell cycle (procyclic form).

The mitotic division of T.brucei is unusual in terms of the cytoskeletal process. The basal body, unlike a centrosome of most eukaryotic cells, plays an important role in the organisation of the spindle. The centrosome is the main microtubule organizing center (MTOC) of the cell as well as a regulator of cell-cycle progression. ...

Stages of mitosis:

1. The basal body replicates, both remaining associated with the kinetoplast.
2. The kinetoplast undergoes replication, and the daughter kinetoplasts are separated by the basal bodies.
3. The second flagellum grows while the nucleus undergoes replication.
4. The mitochondria divides, and cytokinesis progresses from the anterior to posterior end.
5. The division resolves. The daughter cells may stay connected for a significant length of time after cytokinesis is complete.