Trypanosoma brucei
A Microbial Biorealm page on the genus Trypanosoma brucei
Classification
Higher order taxa
Kingdom: Eukaryota; Phylum: Euglenozoa; Order: Kinetoplastida; Family: Trypanosomatidae; Genus: Trypanosoma; SubGenus: Trypanozoon; Species: Trypanosoma brucei
Species
Genus: Trypanosoma Species: brucei Sub-species: Trypanosoma brucei brucei,Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense,Trypanosoma brucei TREU927.
Description and Significance
The eukaryotic Trypanosoma brucei is one of the parasitic species from the Trypanosoma genus. It exists in two forms: an insect vector, and once inside the bloodstream, a mammalian host. T. brucei exists as its insect vector in the tsetse fly. Once the tsetse fly bites a mammal, the microbe enters the bloodstream where it transforms into the mammalian host form, and is then capable of mutating and invading the central nervous system, (CNS). Once inside the CNS, it has the ability to inflict African trypanosomiasis, (sleeping sickness).
The complete genome of T. brucei has been sequenced; this is important because it is key information that is used to research possible cures for Trypanosomiasis.
Describe the appearance, habitat, etc. of the organism, and why it is important enough to have its genome sequenced. Describe how and where it was isolated.
Include a picture or two (with sources) if you can find them.
Genome structure
Describe the size and content of the genome. How many chromosomes? Circular or linear? Other interesting features? What is known about its sequence?Does it have any plasmids? Are they important to the organism's lifestyle?
The genome of T. brucei has 11 megabased-size chromosomes, ranging from one to six megabasepairs, which do not condense during mitosis.(6)It is predicted to have 9068 genes, with about 904 pseudogenes, and 1700 genes that are specific for T. brucei. The G+C content is 46.4%.
The genome of T. brucei has surface antigens that allow the bacteria to escape from being noticed by the immune system.(1) T. brucei is capable of continuously changing the expression of these antigens to effectively hide from antibodies. It is thought that there are around 806 VSG's in the genome.
The circular mitochondrial genome in T. brucei is enclosed in the kintetoplast, which is positioned at the base of the flagellum.(7) T. brucei has about 100 minichromosomes as well.
The cytoskeleton of T. brucei can be divided into three main classes: microtubules, intermediate filaments, and actin microfilaments.(6)
Cell structure and metabolism
In general, the cellular structure of Trypanosoma brucei is similar to all other eukaryotes. There are however, a few differences. T. brucei's cell surface has, (in addition to its surface antigens), a thick layer of proteins, called Variant Surface Glycoprotein (VSG's) genes. These allow the surface antigens to mutate, by switching variants.(2) Having over 1000 VSG genes and psuedogenes, T. brucei is able to switch variants frequently. Trascription occurs one gene at a time, from one of many telomeric VSG expression sites.(3) In order to switch an active VSG gene, DNA rearrangements must occur, to switch the old VSG gene with a new one. Using the bloodstream form of T. brucei, scientists in the Netherlands discovered that telomere exchange, thought to be rare, was indeed occuring. The scientists marked a VSG gene with a hygromycin resistance gene, allowed the gene to undergo variation, and selected switched Trypanosomes. The drug sensitivity and polymerase chain reactions (PCR), revealed that telomere exchange had taken place.(4) Interestingly enough, of the 806 VSG's in the genome of T. brucei, only about 7% of them are thought to be fully functional!
T. brucei also has unusual Citric Acid Cycles and a single large mitochondria. In the insect vector host, the Citric Acid Cycle is not used to generate energy; rather parts of the Citric Acid Cycle are suggested to be used for: acetyl-CoA transport into cytosol, degradation of proline and glutamate to succinate, and the formation of malate(5) The Citric Acid Cycle is not functioning as a cycle itself, but parts of its pathways are being used in T. brucei.
It is very important to understand the cell's metabolism, as it is a key target for new drug synthesis. Most of the research done on T. brucei's metabolism is on the microbe's lifecycle; however, T. brucei has shown to be a the most metabolically restrictive species of the Trypanosoma genus.(6) It is thought that horizontal gene transfer from bacteria to the Tritryp lineage is the cause of this versatility. The Tritryp lineage has many essential genes that are required for the uptake/degredation of glucose. By targeting drugs to alter the pathways that use glucose, (glycolysis, the Citric Acid Cycle, or the pentose phosphate shunt), one could potentially discover new medicines for African Trypanosomiasis. Although about 50% of the genes of T. brucei have no known function, as of yet, many more biochemical pathways have yet to be discovered.
Ecology
Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.
Pathology
How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.
Trypanosoma brucei resides in the tsetse flys salivary glands. Once the fly bites a mammal, (human or animal), the trypanosomes get injected into the lyphatic system, and eventually pass into the bloodstream. After about
Application to Biotechnology
Does this organism produce any useful compounds or enzymes? What are they and how are they used?
Current Research
Enter summaries of the most recent research here--at least three required
References
Edited by Shannon Chan
(3)Taylor JE, Rudenko G. "Switching trypanosome coats: what's in the wardrobe?". 2006 Aug 14.