Tropheryma whipplei: Difference between revisions

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The most interesting thing about ''Tropheryma whipplei'' is the fact that it has such a tiny genome.  "Dr Stephen Bentley, who led the team at The Wellcome Trust Sanger Institute, said, 'This really is a wolf in sheep's clothing. Within this amazingly small genome, it has packed a sophisticated array of tools to escape our defence mechanisms. It's an incredibly adept operator which can tell us a great deal about bacteria and their evolution'" (5).  It is the "master of disguise", as even though it has only caused a few cases of disease and, once again, has such a small genome, it really molds itselfs to its environment in a noteworthy way.  Just to put into perspective how small it is, most bacterial genomes are three to four times larger, code for about 3,000 genes as opposed to around 800, and have hardly any repetitive DNA.  ''T. whipplei'' has about five percent of its DNA sequences repeated which also aides in its ability to deviate itself over and over again.  It "carries a set of DNA sequences unlike anything previously seen in bacterial genomes." This is the case because it, as far as research has come to discover, selects new regions that it then incorporates into the genes that encodes its single outer coating; this is the reason why Dr. Stephen is quoted saying it is like a wolf in sheep's clothing, because it never gives its host a chance to realize what it is, as it is constantly morphing and changing into something repeatedly different.  Not only does it disguise itself in this manner, but it also takes the membranes from the host cells to "hide" in as well.  Hence, with these two forms of camouflage, the body doesn't or has a hard time detecting the presence of ''T. whipplei'', as it hides itself in the lining of the human gut, where it gains its energy (5).     
The most interesting thing about ''Tropheryma whipplei'' is the fact that it has such a tiny genome.  "Dr Stephen Bentley, who led the team at The Wellcome Trust Sanger Institute, said, 'This really is a wolf in sheep's clothing. Within this amazingly small genome, it has packed a sophisticated array of tools to escape our defence mechanisms. It's an incredibly adept operator which can tell us a great deal about bacteria and their evolution'" (5).  It is the "master of disguise", as even though it has only caused a few cases of disease and, once again, has such a small genome, it really molds itselfs to its environment in a noteworthy way.  Just to put into perspective how small it is, most bacterial genomes are three to four times larger, code for about 3,000 genes as opposed to around 800, and have hardly any repetitive DNA.  ''T. whipplei'' has about five percent of its DNA sequences repeated which also aides in its ability to deviate itself over and over again.  It "carries a set of DNA sequences unlike anything previously seen in bacterial genomes." This is the case because it, as far as research has come to discover, selects new regions that it then incorporates into the genes that encodes its single outer coating; this is the reason why Dr. Stephen is quoted saying it is like a wolf in sheep's clothing, because it never gives its host a chance to realize what it is, as it is constantly morphing and changing into something repeatedly different.  Not only does it disguise itself in this manner, but it also takes the membranes from the host cells to "hide" in as well.  Hence, with these two forms of camouflage, the body doesn't or has a hard time detecting the presence of ''T. whipplei'', as it hides itself in the lining of the human gut, where it gains its energy (5).     


Even though it is so small, it still is well equipped for its metabolic activities.  However, there are deficiencies of ten amino acids in the biosynthetic pathways.  For example, there is a lack of thioredoxin and thioredoxin reductase gene homologues (4).  Thioredoxin is usually in its reduced state in an NADPH-dependent reaction, acting as an electron donor.  ''T. whipplei'' also has a mutation in the DNA gyrase, which relates to the fact that it is resistant to quinolone antibiotic (4).      
Even though it is so small, it still is well equipped for its metabolic activities.  However, there are deficiencies of ten amino acids in the biosynthetic pathways.  For example, there is a lack of thioredoxin and thioredoxin reductase gene homologues (4).  Thioredoxin is usually in its reduced state in an NADPH-dependent reaction, acting as an electron donor.  ''T. whipplei'' also has a mutation in the DNA gyrase, which relates to the fact that it is resistant to quinolone antibiotic (4). Because of its metabolic deficiencies, like the major energy producing system, which is the Kreb's or TCA it must get the nutrients it needs from the environment, in this case the stomach lining.  It also has to rely on its host for the synthesis of essential amino acids like arginine and histidine, as it cannot produce these for itself either(5).         


==Ecology==
==Ecology==

Revision as of 09:10, 5 June 2007

Classification

Higher order taxa

Cellular Organisms; Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma; Tropheryma Whipplei (1).

Genus

Genus: Tropheryma Species: Whipplei

Description and significance

Description

Tropheryma whipplei is rod shaped, a gram-postive bacterium (3). It was finally isolated in eukaryotic cells in the year 2000 and propagated in culture at thirty-seven degrees Celsius, but was believed to resist culturalization for a long time (2). In fact, it still can only be cultured if part of its eukaryotic host. The isolation from human cells and the culturalization has allowed more characterization, including sequencing its genome that has resulted in 808 predicted protein-coding gene sequences, even though it grows at a very slow rate of about four to seventeen days. It was first described by the pathologist George H. Whipple in 1907. Still not much is known about the biology of this bacterium, but it wasn't even believed to be a pathogen until it was studied using electron microphotographs of affected tissues in 1961, which was when it was discovered that indeed it is (3). It has a 0.92-Mb genome, placing it in a high-G+C-content gram-positive bacterial group in comparison with others, such as Actinobacteria that have lower G+C contents. Because it is a reduced genomic species, it does not have many genes regulating transcription. This lack of regulation is believed to be the case because inside the host cells the environment is apparently rather stable, and so T. whipplei does not need extensive regulation (2). The way it infects its host and the nautral habitat from which T. whipplie arises is not very well understood as of yet, but it is known to need to live in an aerobic environment that is host-associated (3). However, because it lacks most regulatory components, it seems apparent that this enviornmental agent is capable of adapting to a wide range of stressful conditions, especially in relation to temperature (2).

It is mesophilic, meaning it grows best at moderate temperatures ranging between twenty-five and forty degrees Celsius. Its optimal temperature is thirty-seven degrees Celsius (3). However, Tropheryma whipplei has a special ability as even though it is not affected by heat shock, it can modify its transcriptome following cold shock at a temperature of four degrees Celsius; this proves that although it lacks a lot of typical regulatory elements, it still has a highly adaptive response to thermal stresses that would be typical with its potential environmental origin being that of something assumably at lower temperatures (something still being studied), thereby allowing it to live and adapt in cold conditions (2). It is beneficial for T. whipplei to be able to adapt to a varying range of temperatures because it has no motility (3), but because it has the great ability to adapt during cold shock that is the reason why it is being studied, as well as the fact that it is the pathogen that causes the fatal Whipple diease, as described below within the pathogen section.

Genome structure

Description

It is important for Tropheryma whipplei to have its genome sequenced, because with a 0.92 Mb genome (2), it is the only known human pathogen with a reduced genome sequence within the class of Actinobacteria. This means that this pathogen is the smallest known within its class. It has a circular genome of 927,303 base pairs. T. whipplei has a low G+C content at 46%. Yet, it was originally considered high because 552/808 identified Open Reading Frames have their closest homologues within other actinobacteria class genomes (4). An OFR is important to determine once a gene has been sequenced, as it deals with where the encoded proteins are first transcribed into messenger RNA and then translated into a protein. A particular nucleotide will start and another will stop (known as a stop codon) translation; this is an ORF. Due to its small genomic size, much has yet to be discovered.

Cell structure and metabolism

The most interesting thing about Tropheryma whipplei is the fact that it has such a tiny genome. "Dr Stephen Bentley, who led the team at The Wellcome Trust Sanger Institute, said, 'This really is a wolf in sheep's clothing. Within this amazingly small genome, it has packed a sophisticated array of tools to escape our defence mechanisms. It's an incredibly adept operator which can tell us a great deal about bacteria and their evolution'" (5). It is the "master of disguise", as even though it has only caused a few cases of disease and, once again, has such a small genome, it really molds itselfs to its environment in a noteworthy way. Just to put into perspective how small it is, most bacterial genomes are three to four times larger, code for about 3,000 genes as opposed to around 800, and have hardly any repetitive DNA. T. whipplei has about five percent of its DNA sequences repeated which also aides in its ability to deviate itself over and over again. It "carries a set of DNA sequences unlike anything previously seen in bacterial genomes." This is the case because it, as far as research has come to discover, selects new regions that it then incorporates into the genes that encodes its single outer coating; this is the reason why Dr. Stephen is quoted saying it is like a wolf in sheep's clothing, because it never gives its host a chance to realize what it is, as it is constantly morphing and changing into something repeatedly different. Not only does it disguise itself in this manner, but it also takes the membranes from the host cells to "hide" in as well. Hence, with these two forms of camouflage, the body doesn't or has a hard time detecting the presence of T. whipplei, as it hides itself in the lining of the human gut, where it gains its energy (5).

Even though it is so small, it still is well equipped for its metabolic activities. However, there are deficiencies of ten amino acids in the biosynthetic pathways. For example, there is a lack of thioredoxin and thioredoxin reductase gene homologues (4). Thioredoxin is usually in its reduced state in an NADPH-dependent reaction, acting as an electron donor. T. whipplei also has a mutation in the DNA gyrase, which relates to the fact that it is resistant to quinolone antibiotic (4). Because of its metabolic deficiencies, like the major energy producing system, which is the Kreb's or TCA it must get the nutrients it needs from the environment, in this case the stomach lining. It also has to rely on its host for the synthesis of essential amino acids like arginine and histidine, as it cannot produce these for itself either(5).

Ecology

Tropheryma whipplei is suspected to have an environmental origin (2).

Pathology

Description


Tropheryma whipplei is indeed a pathogen that causes disease in human beings. This not well-understood pathogen is responsible for causing Whipple disease. This disease is destructive to many of the bodies systems. It causes intestinal malabsorption that leads to cachexia (2). Cachexia is a physical wasting away of the body, and is often caused by disease such as advanced cancer, AIDS, and also in the case of Whipple disease. This wasting syndrome leads to a loss of weight, fat, and muscle, as in healthy people the body adjusts to lose its nutrients much more gradually during a state of starvation, but in the case of cachexia the body will not make any such necessary adjustments. Unfortunately, Whipple disease also effects not only the digestive system, but also the cardiac and central nervous systems as well (2). If left untreated, this pathogen is fatal. Yet, even if antibiotic treatment is given, clinical relapses in the form of cerebral issues can ensue (2). Symptoms include diarrhea and abdominal pain (3).

Application to Biotechnology

Current Research

References

1. Bischoff, Joe, et al. "Tropheryma whipplei." Taxonomy Browser. 10 Jan. 2007. NCBI. 1 June 2007

    <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/
    wwwtax.cgi?mode=Info&id=2039&lvl=3&p=mapview&p=has_linkout&p=blast_url&p=genome_blast&lin=f&keep=1&sr
    chmode=1&unlock>. 

2. Crapoulet, Nicolas, et al. "Global Transcriptome Analysis of Tropheryma whipplei in Response to

    Temperature Stresses." Journal of Bacteriology 188.14 (July 2006): 28-39. American Society for
    Microbiology. Ed. Jack Kenney. 24 Apr. 2006. PubMed Central. 30 May 2007
    <http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1539978>. 

3. Raoult D et al., "Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome.", Genome Res, 2003

    Aug;13 (8):1800-9
    <http://www.ncbi.nlm.nih.gov/sites/entrez?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=95>.

4. "Tropheryma whipplei genome database." Structural and Genomic Information Laboratory (IGS). Ed. H.

    Ogata. 27 Feb. 2002. National Center for Scientific Research. 3 June 2007
    <http://www.igs.cnrs-mrs.fr/mgdb/Tropheryma/>. 


5. Von Herbay, Dr. Axel. "Undercover Infective - Cracking the Code of a Quiet Killer." Wellcome Trust

    Sanger Institute (Feb. 2003). Wellcome Trust Sanger Institute. 25 Jan. 2007. Wellcome Trust
    Genome Campus. 2 June 2007 <http://www.sanger.ac.uk/Info/Press/2003/030221.shtml>. 


Edited by Sophia Gevorkian, student of Rachel Larsen and Kit Pogliano.