Trypanosoma brucei: Difference between revisions

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In general, the cellular structure of Trypanosoma brucei is similar to all other eukaryotes. There are however, a few differences.
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.<ref>[http://www.ncbi.nlm.nih.gov/sites/entrezDb=pubmed&Cmd=ShowDetailView&TermToSearch=8885223&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus Rudenko G, McCulloch R, Dirks-Mulder A, Borst P. 'Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei.'. 1996 Sep.]</ref>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'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.<ref>[http://www.ncbi.nlm.nih.gov/sites/entrezDb=pubmed&Cmd=ShowDetailView&TermToSearch=16246022&ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum van Hellemond JJ, Opperdoes FR, Tielens AG. "The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei.". 2005 Nov.]</ref> The Citric Acid Cycle is not functioning as a cycle itself, but parts of its pathways are being used in T. brucei.
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.<ref>[http://www.ncbi.nlm.nih.gov/sites/entrezDb=pubmed&Cmd=ShowDetailView&TermToSearch=16246022&ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum van Hellemond JJ, Opperdoes FR, Tielens AG. "The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei.". 2005 Nov.]</ref> The Citric Acid Cycle is not functioning as a cycle itself, but parts of its pathways are being used in T. brucei.

Revision as of 22:19, 25 August 2007

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.[1] 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.[2]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.

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

(1)Frank SA, Barbour AG. "Within-host dynamics of antigenic variation". 'Infection Genetics and Evolution'. 2006. p. 146-146.

(2)Lythgoe KA, Morrison LJ, Read AF, Barry JD. "Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation". 'Proceedings of The National Academy of Sciences of The United States of America'. 2007 May 8. p. 8095-8100.

(3)Taylor JE, Rudenko G. "Switching trypanosome coats: what's in the wardrobe?". 2006 Aug 14.

(4)Rudenko G, McCulloch R, Dirks-Mulder A, Borst P. "Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei". 1996 Sep.

(5)van Hellemond JJ, Opperdoes FR, Tielens AG. "The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei". 2005 Nov.

(6)Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Böhme U, Hannick L, Aslett MA, Shallom J, Marcello L, Hou L, Wickstead B, Alsmark UC, Arrowsmith C, Atkin RJ, Barron AJ, Bringaud F, Brooks K, Carrington M, Cherevach I, Chillingworth TJ, Churcher C, Clark LN, Corton CH, Cronin A, Davies RM, Doggett J, Djikeng A, Feldblyum T, Field MC, Fraser A, Goodhead I, Hance Z, Harper D, Harris BR, Hauser H, Hostetler J, Ivens A, Jagels K, Johnson D, Johnson J, Jones K, Kerhornou AX, Koo H, Larke N, Landfear S, Larkin C, Leech V, Line A, Lord A, Macleod A, Mooney PJ, Moule S, Martin DM, Morgan GW, Mungall K, Norbertczak H, Ormond D, Pai G, Peacock CS, Peterson J, Quail MA, Rabbinowitsch E, Rajandream MA, Reitter C, Salzberg SL, Sanders M, Schobel S, Sharp S, Simmonds M, Simpson AJ, Tallon L, Turner CM, Tait A, Tivey AR, Van Aken S, Walker D, Wanless D, Wang S, White B, White O, Whitehead S, Woodward J, Wortman J, Adams MD, Embley TM, Gull K, Ullu E, Barry JD, Fairlamb AH, Opperdoes F, Barrell BG, Donelson JE, Hall N, Fraser CM, Melville SE, El-Sayed NM. "The genome of the African trypanosome Trypanosoma brucei". Wellcome Trust Sanger Institute. 2005 Jul 15.

(7)Eva Gluenz, Michael K. Shaw, Keith Gull. "Structural asymmetry and discrete nucleic acid subdomains in the Trypanosoma brucei kinetoplast". 2007. Molecular Microbiology 64 (6), p. 1529–1539