Helicobacter hepaticus ATCC51449

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A Microbial Biorealm page on the genus Helicobacter hepaticus ATCC51449


Higher order taxa

Cellular Organisms; Bacteria; Proteobacteria; Delta/Epsilon Subdivisions; Epsilonproteobacteria; Campylobacterales; Helicobacteraceae; Helicobacter; Helicobacter hepaticus ATCC51449


Helicobacter hepaticus

NCBI: Taxonomy Genome: H. hepaticus ATCC51449

Description and significance

Helicobacter hepaticus ATCC514459 is a Gram-negative, spiral (anywhere from one to seven spirals) shaped bacteria. It is usually between 0.2 to 0.3 µm in diameter and 1.5 to 5.0 µm long. It is a microaerophilic organism since it requires oxygen to live, but can live in environments that contain less oxygen than atmospheric levels. Like other species of Helicobacter, Helicobacter hepaticus can be found in the mucosal layer of the gastrointestinal tract or in liver tissue. In mice, it has been found to cause chronic hepatitis, liver cancer, and inflammatory bowel disease. Its importance in humans is not fully understood yet. (EMBL-EBI)

Helicobacter hepaticus was first isolated from hepatic tissue when a spiral bacterium was able to be cultivated on blood agar plates incubated at 37ºC under anaerobic or microaerobic conditions. Ultrastructural morphologic examination, biochemical characteristics examination, and 16S rRNA gene sequencing were all used to characterize Helicobacter hepaticus. (Rice 129-30)

Helicobacter hepaticus (Image by: Marie Lefevre)

Genome structure

Helicobacter hepaticus has a circular genome consisting of 1,799,146 base pairs, which are thought to encode for 1,875 proteins. It has 35.9% GC content and 938 of its proteins are orthologous with Helicobacter pylori, 953 are orthologous with Campylobacter jejuni, and 821 are orthologous with both Helicobacter pylori and Campylobacter jejuni. The genome also contains a 71 kb genomic island HHGI1 that differs in GC content from the rest of the genome. The genomic island encodes three components of a type IV secretion system. A type IV secretion system is a conjugation system that allows for the transporting of DNA or proteins. Five other strains of Helicobacter hepaticus that are known to cause liver disease lacked anywhere from 85 to 229 genes, including large parts of the genomic island HHGI1. (Suerbaum S)

Cell structure and metabolism

Helicobacter hepaticus has bipolar sheathed flagella for motility. However, unlike other Helicobacter species, Helicobacter hepaticus does not have the periplasmic fibers that envelope the bacterial cell.

Helicobacter hepaticus has a strong urease activity. Urease is an enzyme that catalyzes the hyrdolysis of urea into bicarbonate and ammonia, both of which neutralize gastric acid and therefore allows the bacteria to colonize the acidic environment that the gastrointestinal tract can be. Helicobacter hepaticus tests positive in both oxidase and catalase tests. The oxidase test shows the presence of cytochrome c oxidases which show that a cell would be capable of using oxygen to produce energy via an Electron Transport Chain. The catalase test further proves this ability since catalase is an enzyme that decomposes hydrogen peroxide (a Reactive Oxygen Species) into water and oxygen. Helicobacter hepaticus can also gain energy anaerobically by reducing different compounds. It can reduce sulfur and produce hydrogen sulfide (H2S) and it can also reduce nitrate to nitrite. Helicobacter hepaticus is sensitive to the antibiotic metronidazole which kills anaerobic bacterium. It is resistant to the antibiotics nalidixic acid and cephalothin. (Rice 129-31))


Helicobacter hepaticus is an enterohepatic bacteria that can "infect the intestinal tracts and biliary trees of various mammals, including mice and humans, and are associated with chronic inflammatory diseases of the intestine, gallstone formation, and malignant transformation." (Sterzenbach) It is becoming and increasing concern in the biomedical research field where a recent study discovered that out of a sample of 79 mice from 34 sources, 62 of 79 mice had a Helicobacter infection and the, "Mice from 20 of the 34 institutions (59%) were most commonly colonized with Helicobacter hepaticus alone or in combination with other Helicobacter [species]." The potential of the impact the Helicobacter infections have on biomedical research experiments in vivo is therefore an important issue and under research. (Taylor)


As stated above, the HHGI1 genomic island encodes three basic components of a type IV secretion system which is a system of conjugation for DNA and protein transport. However, Helicobacter hepaticus lacks orthologs of Helicobacter pylori virulence factors such as adhesins, VacA cytotoxin, and almost all cag pathogenicity island proteins. Helicobacter hepaticus does have orthologs of Campylobacter jejuni adhesin PEB1 and the cytolethal distending toxin (CDT). These factors are what contribute to Helicobacter hepaticus' pathogenicity. (Suerbaum)

In addition, Helicobacter suppresses and evades the immune system in order to cause chronic inflammatory diseases. Helicobacter hepaticus produces soluble bacterial factors that reduce the ability of the Toll-like receptors TLR-4 (which binds to LPS) and TLR-5 (which binds to flagellin) to produce immune responses. The lysate of Helicobacter hepaticus and its soluble LPS also inhibited development of endotoxin tolerance to Escherichia coli LPS. Thus, suppression of immune responses by Helicobacter hepaticus may have wider effects on the entire intestinal flora, its homeostasis, and its inflammatory conditions. (Sterzenbach)

Current Research

In a paper entitled, “A Helicobacter hepaticus catalase mutant is hypersensitive to oxidative stress and suffers increased DNA damage,” the effect of the enzyme catalase on the life of Helicobacter hepaticus is investigated. A mutant strain was created that was deficient but not devoid of catalase activity. What they found was that wild type Helicobacter hepaticus cells were able to withstand environments at 6% oxygen, while the mutants could not survive at this same level. Furthermore, at optimal levels of oxygen for growth, the catalase mutant had severe growth inhibition. Finally, with treatment of hydrogen peroxide (100 mM for 6 minutes), wild type Helicobacter hepaticus cells were able to survive while the catalase mutants all died. Thus is was determined that the catalase enzyme plays a very important role as an antioxidant protein for Helicobacter hepaticus. (Hong)

In the, “Effects of Helicobacter hepaticus on the proteome of HEp-2 cells,” the effects of Helicobacter on human cells are investigated by examining the proteins produced by cells growing in the presence of Helicobacter hepaticus. “Enlargement, distension and elongation of HEp-2 cells were observed in co-cultures with H. hepaticus.” In addition, major killing of the HEp-2 cells was caused when the bacterial cell density reached 10^9 cfu/ml. With that number and the protein analysis, it was determined that Helicobacter hepaticus has a “multimodal action” of infection that occurs by the modulation of the expression of proteins necessary for various biological functions causing overall broad effects on the physiology of HEp-2 cells. (Okoli)

Another recent paper, “Enterohepatic Helicobacter species are Prevalent in Mice Obtained from Commercial and Academic Institutions in Asia, Europe, and North America,” discusses how prominent Helicobacter hepaticus and other Helicobacter species are amongst mice used for research in institutions and from commercial vendors. By using culture from cecal tissue of 79 mice from 34 sources, it was found that 62 out of 79 mice, or 78.5%, had some Helicobacter species cultured from their tissue. No Helicobacter was found in the mice that were advertised to be grown in Helicobacter free areas while one European source had mice infected with a new strain of Helicobacter, MIT 96-1001. Basically, the paper was trying to show how prominent Helicobacter infestations are in mice colonies used for research, and how the effects of the Helicobacter infections could have effects on biomedical research that some might not foresee. (Taylor)


EMBL-EBI http://www.ebi.ac.uk/2can/genomes/bacteria/Helicobacter_hepaticus.html

Hong Y, Wang G, Maier RJ. “A Helicobacter hepaticus catalase mutant is hypersensitive to oxidative stress and suffers increased DNA damage.” Journal Of Medical Microbiology. 2007 Apr; 56(Pt 4):557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17374900&query_hl=3&itool=pubmed_DocSum

NCBI http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=307

Okoli AS, Fox EM, Raftery MJ, Mendz GL. “Effects of Helicobacter hepaticus on the proteome of HEp-2 cells.” Antonie Van Leeuwenhoek. 2007 Mar 15; Epub http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17357813&query_hl=3&itool=pubmed_DocSum

Rice, Jerry M. "Helicobacter hepaticus, a Recently Recognized Bacterial Pathogen, Associated with Chronic Hepatitis and Hepatocellular Neoplasia in Laboratory Mice." Emerging Infectious Diseases. 1995. Volume 1, No. 4. p. 129-31. http://www.cdc.gov/ncidod/eid/vol1no4/rice2.htm

Sterzenbach T, Lee SK, Brenneke B, von Goetz F, Schauer DB, Fox JG, Suerbaum S, Josenhans C. “Inhibitory Effect of Enterohepatic Helicobacter hepaticus on Innate Immune Responses of Mouse Intestinal Epithelial Cells.” Infection and Immunity. 2007 Jun; 75(6):2717-28. Epub 2007 Mar 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17371851&query_hl=15&itool=pubmed_DocSum

Suerbaum S, Josenhans C, Sterzenbach T, Drescher B, Brandt P, Bell M, Droge M, Fartmann B, Fischer HP, Ge Z, Horster A, Holland R, Klein K, Konig J, Macko L, Mendz GL, Nyakatura G, Schauer DB, Shen Z, Weber J, Frosch M, Fox JG. "The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus." Proceedings of the National Academy of Sciences of the USA. 2003 Jun 24; 100(13):7901-6 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12810954&dopt=Abstract

Taylor NS, Xu S, Nambiar P, Dewhirst FE, Fox JG.“Enterohepatic Helicobacter species are Prevalent in Mice Obtained from Commercial and Academic Institutions in Asia, Europe, and North America.” Journal of Clinical Microbiology. 2007 May 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17507523&query_hl=15&itool=pubmed_DocSum

Edited by Arpan Patel, a student of Rachel Larsen