Franklin et al. 2001
Helicobacter typhlonius is a Gram-negative bacterium and opportunistic pathogen found in the genus Helicobacter. There are only thirty five known species in this genus, which was discovered in 1982. H. typhlonius has a small number of close relatives, including Helicobacter muridarum, Helicobacter trogontum, and Helicobacter hepaticus, with the latter being the closest relative and much more prevalent.
H.typhlonius is one of 35 known species of Helicobacter. It was previously named Helicobacter sp. strain MIT 97-6910 by Fox et al. but was changed to its current name by Franklin et al. after discovering a genetically and morphologically identical organism that causes proliferative typhlocolitis, also known as irritable bowel disease. Some close relatives of H. typhlonius include Helicobacter muridarum, Helicobacter trogontum, Helicobacter hepaticus, and Helicobacter pylori.
Helicobacter typhlonius is motile due to its single sheathed flagellum. It has a spiral morphology, and its size is 0.3-μm by 2- to 3-μm. It is capable of ammonia assimilation, urea production, and phosphoribosyl pyrophosphate biosynthesis. H. typhlonius is also urease-negative which is known to assist in survival and proliferation of microbes in acidic gastric environments. Additionally, it can only grow in microaerobic conditions (a very small amount of oxygen), not in aerobic or anaerobic conditions.
Helicobacter typhlonius was isolated from the feces of immunocompromised mice by James G. Fox and Craig L. Franklin in two separate laboratories in the year 1999. The mice suffered from irritable bowel syndrome, which was caused by H. typhlonius, but the mechanism of the infection was unknown. Polymerase chain reaction (PCR) was used to copy the DNA sequence of the bacteria to be examined. PCR was an ideal method, due to the unique intervening genome sequence that is easily recognized by PCR. The sequences were then analyzed using the Sequence Analysis Software Package (Wisconsin Package, version 10.0; Genetics Computer Group, Inc., Madison Wis.). The biochemical results of PCR tests as well as phenotypic test results of all other 32 known species of Helicobacter were compared to the results given by the newly isolated species. After observing the results and declaring H.typhlonius a new species of Helicobacter, a new phylogenetic tree for the genus Helicobacter was created.
The full genome was determined using Single Molecule, Real Time (SMRT) sequencing in 2015 by Frank et al. Using hierarchical genome assembly process (HGAP), the sequences were assembled into a single long read.
The genome of H. typhlonius is 1,920,000 base pairs in length. There are 2,117 protein-coding genes and 43 RNA genes with a GC-content of 38.8%. Compared to other members of the genus Helicobacter such as H. hepaticus and H. pylori, H. typhlonius has a larger genome. Furthermore, H. typhlonius has a GC-content that is similar to H. hepaticus. While roughly 75% of protein coding genes were shared between H. hepaticus and H. typhlonius, 468 unique protein coding genes were identified in H. typhlonius which comprises about 2% of its entire genome.
Additionally, the genome contains a distinct pathogenicity island with a lower GC-content and flanked by repeats. This island is around 650,000 base pairs and compromises 75 protein coding genes which includes a type IV secretion system (T4SS) that is responsible for secreting toxins to assist in virulence.
Helicobacter typhlonius is a microaerophile capable of oxidative phosphorylation using oxygen as a terminal electron acceptor. In this species, fermentation of pyruvate and Acetyl-CoA to acetate is possible in the absence of oxygen. Additionally, carbohydrate breakdown includes both sucrose and mannose and amino acid degradation includes citrulline, aspartate, glutamate, and glutamine. H. typhlonius is also capable of arginine biosynthesis through the urea cycle.
Helicobacter typhlonius can grow at 37 degrees Celsius, as well as 42 degrees Celsius; however, it cannot be grown at 25 degrees Celsius or in the presence of 1.5% Sodium Chloride. The typical spiral morphology can also change into cocci when grown in the presence of 1% glycine, but growth rate remains the same. Growth optima of H. typhlonius is microaerobic conditions. It is typically found in the gastrointestinal tract of immunodeficient rodents and humans and is characterized by a 166 base pair intervening sequence in its 16s rRNA, which has been previously detected by 16s rRNA gene sequence analysis.
Helicobacter typhlonius is known to cause irritable bowel syndrome in both humans and animals; therefore, it is used to study IBD pathogenesis and treatment. Along with this, some research has linked H. typhlonius with the regulation of intestinal tumors. From studying Apc mutant mice, researchers were able to use polymerase chain reaction amplification to observe certain segments of DNA and narrow down the cause to two possible bacterial species: Akkermansia muciniphila and Helicobacter typhlonius. A positive correlation was established between the prevalence of these bacteria and tumor size. It has also been found that H. typhlonius causes typhlocolitis in mice that are immunocompromised. Typhlocolitis is characterized by inflammation and necrosis of the mucosal lining in the intestinal tract, specifically cecal, colonic, and the small intestine.
- Franklin CL, Gorelick PL, Riley LK, Dewhirst FE, Livingston RS, Ward JM, Beckwith CS, Fox JG (November 2001). "Helicobacter typhlonius sp. nov., a Novel Murine Urease-Negative Helicobacter Species". Journal of Clinical Microbiology. 39 (11): 3920–6. doi:10.1128/JCM.39.11.3920-3926.2001. PMC 88465. PMID 11682508.
- Frank J, Dingemanse C, Schmitz AM, Vossen RH, van Ommen GJ, den Dunnen JT, Robanus-Maandag EC, Anvar SY (2016-01-08). "The Complete Genome Sequence of the Murine Pathobiont Helicobacter typhlonius". Frontiers in Microbiology. 6: 1549. doi:10.3389/fmicb.2015.01549. PMC 4705304. PMID 26779178.
- Chichlowski M, Sharp JM, Vanderford DA, Myles MH, Hale LP (December 2008). "Helicobacter typhlonius and Helicobacter rodentium differentially affect the severity of colon inflammation and inflammation-associated neoplasia in IL10-deficient mice". Comparative Medicine. 58 (6): 534–41. PMC 2710754. PMID 19149410.
- Chichlowski, Maciej; Hale, Laura P (2009-02-15). "Effects of Helicobacter Infection on Research: The Case for Eradication of Helicobacter from Rodent Research Colonies". Comparative Medicine. 59 (1): 10–17. PMC 2703140.
- Scavizzi F, Raspa M (January 2006). "Helicobacter typhlonius was detected in the sex organs of three mouse strains but did not transmit vertically". Laboratory Animals. 40 (1): 70–9. doi:10.1258/002367706775404390. PMID 16460591.
- Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (January 2017). "KEGG: new perspectives on genomes, pathways, diseases and drugs". Nucleic Acids Research. 45 (D1): D353–D361. doi:10.1093/nar/gkw1092. PMC 5210567. PMID 27899662.
- Dingemanse C, Belzer C, van Hijum SA, Günthel M, Salvatori D, den Dunnen JT, Kuijper EJ, Devilee P, de Vos WM, van Ommen GB, Robanus-Maandag EC (November 2015). "Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice". Carcinogenesis. 36 (11): 1388–96. doi:10.1093/carcin/bgv120. PMID 26320104.
- Taylor NS, Xu S, Nambiar P, Dewhirst FE, Fox JG (July 2007). "Enterohepatic Helicobacter species are prevalent in mice from commercial and academic institutions in Asia, Europe, and North America". Journal of Clinical Microbiology. 45 (7): 2166–72. doi:10.1128/JCM.00137-07. PMC 1933014. PMID 17507523.
- Barthold, SW; Smith, AL; Lord, PF; Bhatt, PN; Jacoby, RO; Main, AJ (August 1, 1982). "Epizootic coronaviral typhlocolitis in suckling mice". Laboratory Animal Science. 32 (4). ISSN 0023-6764.