Helicobacter pylori: Difference between revisions

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[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=324548] Blaser, Martin J and Atherton, John C."''Helicobacter pylori'' persistence: biology and disease". J Clin Invest. 2004 February 1; 113(3): 321–333.
[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=324548] Blaser, Martin J and Atherton, John C."''Helicobacter pylori'' persistence: biology and disease". J Clin Invest. 2004 February 1; 113(3): 321–333.
2. http://www.cdd.com.au/html/expertise/diseaseinfo/helicobacter.html


Marshall, Barry J, McCallum, Richard W and Guerrant, Richard L. "''Helicobacter pylori'' in peptic ulceration and gastritis." Blackwell Scientific Publications 1991; 24-25, 58
Marshall, Barry J, McCallum, Richard W and Guerrant, Richard L. "''Helicobacter pylori'' in peptic ulceration and gastritis." Blackwell Scientific Publications 1991; 24-25, 58

Revision as of 06:48, 4 June 2007

A Microbial Biorealm page on the genus Helicobacter pylori

Classification

Higher order taxa

Bacteria (Domain); Proteobacteria (Phylum); Epsilon Proteobacteria (Class); Campylobacterales (Order); Helicobacteraceae (Family); Helicobacter (Genus)

Species

NCBI: Taxonomy

Helicobacter pylori

Description and significance

Helicobacter pylori is a Gram negative organism that has a helical or spiral shaped with 6-8 flagella at one end. The size of the organism measures about 2-4 μm x 0.5-1.0 μm. H. pylori is found in a very acidic environment, a pH of 2.0 or less. It is cultured in microaerobic (low oxygen conditions) but it adapts to high oxygen at high culture densities. It is commonly found inside the lining of the stomach and the duodenum. H. pylori is a slow growing organism that can cause peptic ulcers and gastritis that can lead to gastric cancer and gastric MALT lymphoma (mucosa-associated lyphoid tissue).

It was first observed in 19th century that curved bacteria were living in the lining of the stomach, but growing and isolating the bacteria was neglected. H. pylori was later isolated in Perth, Western Australia by Barry Marshall and Robin Warren in 1983. They discovered that H. pylori was related to peptic ulcers. To prove this evidence, the organism was cultured from the stomach, and concluded that H. pylori was the bacteria that caused peptic ulcers and gastritis. [3] In 2005, Marshall and Warren received the Nobel Prize in physiology or medicine for their discovery of the Helicobacter pylori. [5]

Helicobacter pylori was initially named Campylobacter pylordis because it appeared that the organism was similar to other Campylobacters, it showed similar appearances with the campylobacter jejuni. Using rRNA hybridation sequencing, H. pylori was shown that it was different from the Campylobacter genus. H.pylori was separated into its own genus Helicobacter in 1989. The Helicobacter reflects to the appearances of the organism, helical in vivo, but often rodlike in vitro. [Marshall]

Genome structure

The two strains of the genomes have been completely sequenced. H. pylori 26695 and J99. Both were sequenced using a random shotgun approaching from libraries of cloned chromosonal fragments of ~2.5kb. The 26695 genome was 24kb larger than the J99, but both of the genomes had G+C% of 39%. Both genomes had similar average lenths of coding sequences, coding density and the bias of initiation codons. The orgin of replication of the genome J99 was not clearly identifiable. [Mobley]

The genome of Helicobacter pylori strain "26695" is circular and contains 1,667,867 base pairs, and strain "J99" contains 1,643,831 base pairs. 300 bp encodes for membrane proteins, and 1590 bp are predicted coding sequences. The chromosome of the organism contains genes that encodes the urease gene cluster, cytotoxins in the membrane, and the cag pathogenicity island. In 1989, CagA gene was found and identified as the marker strain of the risk of peptic ulcers and gastric cancer. The CagA pathogenicity island recognizes the type IV secretion system, which CagA proteins are moved to the host cells. [1]

The DNA content of H. pylori has GC range of 35-38% which catergorized itself to the Campylobacter species. However, the comparisons of the 16S ribosomal RNA showed that H. pylori was different from Campylobacter but similar to Wolinella succinogenes. which its GC range was 42-49%. H. pylori was placed into its own genus, Helicobacter. after the analysis of the ultrastructure, fatty acid composition and biochemical tests which proved different for H. pylori and W. succinogenes [Marshall]

The analysis of H. pylori sequences specifies the diversity and the development of the organism. H. pylori sequences shows that the recombination and the clone between the strain linkage is uncertain, and the recombination is based on the repetitive DNA sequences that permits the high frequency deletion and duplication of the DNA. The genome contains sequences that encodes for the membrane proteins. For example, the F1F0 ATP synthase complex, various oxidoreductases such as cytochrome o, and some transporters. [Modlin] Sequences show that H. pylori obtains a “well developed systems for motility, for scavenging iron, and for DNA restriction and modification.” [6] Helicobacter pylori are capable to uptake DNA from other H. pylori. Due to the uncertainty of the strain linkages, recombination occurs because of the repetitive DNA squences, which allows high frequency deletion and duplication and mismatch inbetween the strands. Lack of mismatch repairing can increase in frequency of random variation but it can also convert the gene which can bring down the diversity of the organism. [1]

Cell structure and metabolism

Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces.

The motility of H. pylori depends on the flagella which is driven by the proton motive force. The motility and the shape of the bacteria is specifically adapted to the gastric mucus. The flagella have a molecular weight of 50,000-62,000 The shape helps the bacteria to move easily in viscous environments. They do not only provide motility but they have bulbs on the ends of the flagella which favors the adhesion. The flagella is 4μm in length (average), and the diameter is measured 30nm. [Mobley]

The genome of H. pylori has homologs of all the enzymes and is required for the assembly of peptidoglycan by the use of precursors of the cytoplasmic synthesis. After the transport through the cytoplasmic membrance, the precursors are embodied into the peptidoglycan layer by penicillin-binding proteins. The peptidoglycan of H. pylori differs from the E. coli. H. pylori peptidoglycan has muropeptides with pentapeptide side chains that ends with glysine. Through the genome, F0 proton-channeling complex (a,b,c subunits) and catalytic, peripheral headpiece of the F1 have all been identified.[Mobley]

Through the analysis of the genome 26695 and J99, H. pylori does not use complex carbohydrates as energy sources. The only carbohydrate used by H. pylori is glucose. It is metabolized via the Entner Douderoff pathway (reaction that catabolize glucose to pyruvate using glycolysis or pentose phosphate pathway). But it is likely used for anabolic biosynthesis rather than catabolic production. The primary source of pyruvate in H. pylori are lactate, L-alanine, L-serine, D-Amino acids rather than glucose or malate. It has been reported that fermentation of pyruvate produces Acetate. J99 contains homologs to the pta (phosphate acetyl transferase) and ackA (acetate kinase) genes. The 26695 pta has a frameshift mutation which inactivates the gene product.

The urease is a potent virulence factor for H. pylori. Urease is central to H. pylori's metabolism and virulence and helps colonize n the gastric mucosa. Urease: NH2C=ONH2 + H2O ---> NH3 + NH2-COOH and NH2COOH + 2H2O ---> NH3 + H2CO3. This reaction increases in pH. H. pylori synthesizes a huge amount of urease. They use it to convert urea into ammonia and bicarbonate to counteract the low acidity of the stomach. With high urease activity, H. pylori can protect the bacterium from acid damage by buffering the cell and the environment. The hydrolysis of urea molecules in the gastric juices creates ammmonia which acts as an acceptor for the H+ ions to increase the local pH. H. pylori demonstrates the highest activity of acidity. The enzyme must be consistantly available for the organism to survive in the acidic environment. The defense of the body cannot fight H .pylori because killer T cells and white cells cannot easily get through the lining of the stomach. As the defense cells die, the H. pylori feeds off the superoxide radicals on the stomach lining of the cells.

H. pylori increases its diversity by the changes in acidity, nutrient availability, and gastric epithelium.

Ecology

Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.

Pathology

Helicobacter pylori is known for peptic ulcers and gastritis. The organism weakens the mucous lining of the stomach and allows acid to enter to the sensitive coating of the stomach. The acid and the bacteria irritates the lining and causes a ulcer. It is very common to humans, and animals. Half of the population is infected by H. pylori. Since it is a slow growing bacterium, they have the organism, but don't get ulcer or gastritis. H. pylori is able to adapt and survive in the acidic environment of the stomach because the conversion of urea to bicarbonate and ammonia neutralizes the gastric acid. The motility of the bacteria, the flagella and the shape favors colonization which allows spiral shape to excavate through the lining.

The protein cagA has an increasing host response. The function is unknown but it is part of the pathogenicity island which has a region that contains 40 genes, and appears to affect virulence. This island contains DNA with different base compared to the rest of the genome. [Modlin] CagA is coexpressed with VacA. VacA is known as a gene that is mosaic. It shows a clear pathway for the secreted toxins that contribute to the virulence and the colonization in many ways. [4] Another gene that is mostly identified with virulence is iceA. iceA shows a clear relationship between expression and clinical outcome of the genes. There are number of membrance inserted proteins which involves with the export of proteins within the pathogenicity island. It is sometimes difficult to the infection of H. pylori by using its genomic base. In Asia, CagA is not the marker for pathogenesis contrast to Western countries. [Modlin]

Several spiral shaped looking like H. pylori bacteria have been found in the gastric mucosa in animals like cats, dogs, baboons and ferrets. They are often called gastric Campylobacter like organisms, but they do not cause gastritis or ulcer. Macaca mulatta, M. nemestrina and baboons seem to be the only animals that natually harbor H. pylori. Using ELISA and immunoperoxidase staining, the antibodies of the H. pylori was found in serum. [Marshall]

Most people with H. pylori do not show symptoms, usually they are asymptomatic. But people with the infection are likely to develop peptic ulcers. Symptoms in patients can be pain in the upper abdomen, nausea, vomiting, loss of appetite, and indigestion.

Application to Biotechnology

Does this organism produce any useful compounds or enzymes? What are they and how are they used?

In the H. pylori," Lys gene is found as a autolytic (break down of tissue) enzyme that degrades the walls of Gram positive and negative bacteria. It was found in the unrelated clinical strain. The gene is expressed in vitro, and lytic activity is on both Gram positive and negative cell walls. The hydrolytic action of the protein was confirmed by the clone and the expression of the gene. [2]

Current Research

Enter summaries of the most recent research here--at least three required

References

[1] Blaser, Martin J and Atherton, John C."Helicobacter pylori persistence: biology and disease". J Clin Invest. 2004 February 1; 113(3): 321–333.

2. http://www.cdd.com.au/html/expertise/diseaseinfo/helicobacter.html

Marshall, Barry J, McCallum, Richard W and Guerrant, Richard L. "Helicobacter pylori in peptic ulceration and gastritis." Blackwell Scientific Publications 1991; 24-25, 58

[2] Marsich, Eleonora, Zuccato, Pierfrancesco, Rizzie, Sonia, Vetere, Amedeo, Tonin, Enrico, and Paoletti, Sergio. "Helicobacter pylori Expresses an Autolytic Enzyme: Gene Identification, Cloning, and Theoretical Protein Structure" J Bacteriol. 2002 November; 184(22): 6270–6279.

Megraud, F. "Taxonomy and Biology of Helicobacter pylori- a comment". "Helicobacter pylori, Gastritis and Peptic Ulcer". Springer-Verlag Berlin Heidelberg 1990; 59

Mobley, Harry L.T, Mendz, George L. and Hazell, Stuart L. "Helicobacter pylori physiology and genetics". ASM Press 2001; 69-71, 75-76, 300

Modlin, Irvin M. and Sachs, George. "Acid Related Diseases, Biology and treatment" Lippincott Williams and Wilkins 2004; 461-462, 479-481.

[3] NCBI Entrez Genome Project. "Helicobacter pylori 26695"

[4] NCBI Entrez Genome Project. Cover TL, Blanke SR. "Helicobacter pylori VacA, a paradigm for toxin multifunctionality."

[5] The Nobel Prize in Physiology or Medicine 2005 awarded to Barry J. Marshall and J. Robin Warren "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease".

[6] Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou L, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Hickey EK, Berg DE, Gocayne JD, Utterback TR, Peterson JD, Kelley JM, Cotton MD, Weidman JM, Fujii C, Bowman C, Watthey L, Wallin E, Hayes WS, Borodovsky M, Karp PD, Smith HO, Fraser CM, Venter JC. "The complete genome sequence of the gastric pathogen Helicobacter pylori." Nature 1997. 388(6642): 515-6








[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Edited by Katherine Park student of Rachel Larsen and Kit Pogliano