Tropheryma whipplei

# Overview
Tropheryma whipplei is a bacterium and the causative organism of Whipple's disease. While Tropheryma whipplei is categorized with the gram-positive Actinobacteria, the organism is commonly found to be gram-negative or gram-indeterminate when stained in the laboratory. Whipple himself probably observed the organisms as rod-shaped structures with silver stain in his original case, but no name was given to the organism until 1991 when the name Tropheryma whippelii was proposed after sections of the bacterial genome were sequenced. The name was changed to Tropheryma whipplei in 2001 (correcting the spelling of Whipple's name) after deposition in bacterial collections.

# Description
Tropheryma whipplei is a gram-positive rod-shaped bacterium. It was finally isolated in eukaryotic cells in the year 2000 and propagated in a culture at 37 degrees Celsius, but was believed to resist culturing for a long time. In fact, it still can only be cultured if part of its eukaryotic host is present. The isolation from human cells and the culturing 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 4 to 17 days.
It is mesophilic, meaning it grows best at moderate temperatures ranging between 25 and 40 degrees Celsius. Its optimal temperature is 37 degrees Celsius. 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 4 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 probably at lower temperatures (something still being studied), thereby allowing it to live and adapt in cold conditions.

# Structure

## Genome structure
Tropheryma whipplei has a 0.92 Mb genome, placing it in a high-GC-content gram-positive bacterial group. 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 is a reduced genomic species and it does not have many genes regulating transcription. It has a circular genome of 927,303 base pairs. Tropheryma whipplei has a low GC content at 46%. Yet, it was originally considered high because 552/808 identified open reading frames have their closest homologs within other Actinobacteria class genomes. An open reading frames (ORF) 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
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 defense mechanisms. It's an incredibly adept operator which can tell us a great deal about bacteria and their evolution'". 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 itself 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. Tropheryma 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 encode 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 Tropheryma whipplei, as it hides in the lining of the human gut, where it gains its energy. 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. Thioredoxin is usually in its reduced state in an NADPH-dependent reaction, acting as an electron donor. Tropheryma whipplei also has a mutation in the DNA gyrase, which relates to the fact that it is resistant to quinolone antibiotic. Because of its metabolic deficiencies, like the major energy producing system, which is the Krebs 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.

# Ecology
Tropheryma whipplei is suspected to have an environmental origin because its closest known relatives originated from the soil. However, Tropheryma whipplei is solely dependent on humans. Tropheryma whipplei inside its host is constantly reshaping itself and invade other organs. The fact that it is also very difficult to cultivate without human cells, makes understanding this pathogen harder.

# Pathogenesis
See Whipple's disease