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Helicobacter pylori

2007 Schools Wikipedia Selection. Related subjects: Organisms

               iHelicobacter pylori
            Scientific classification

   Kingdom: Bacteria
   Phylum:  Proteobacteria
   Class:   Epsilon Proteobacteria
   Order:   Campylobacterales
   Family:  Helicobacteraceae
   Genus:   Helicobacter
   Species: H. pylori

                                Binomial name

   Helicobacter pylori
   ((Marshall et al. 1985) Goodwin et al. 1989)

   Helicobacter pylori is a bacterium that infects the mucus lining of the
   stomach and duodenum. Many cases of peptic ulcers, gastritis, and
   duodenitis are caused by H. pylori infection. However, many who are
   infected do not show any symptoms of disease. Helicobacter bacteria are
   the only known microorganisms that can thrive in the highly acidic
   environment of the stomach. Its helical shape (hence the name
   helicobacter) is thought to have evolved to penetrate and colonize the
   mucus lining.

History

   In 1875, German scientists found spiral bacteria in the lining of the
   human stomach; the bacteria could not be grown in culture and the
   results were eventually forgotten.

   In 1892, the Italian researcher Giulio Bizzozero described spiral
   bacteria living in the acidic environment of the stomach of dogs.

   Professor Walery Jaworski of the Jagiellonian University in Kraków
   investigated sediments of gastric washings obtained from humans in
   1899. Among some rod-like bacteria, he also found bacteria with a
   characteristic spiral shape, which he called Vibrio rugula. He was the
   first to suggest a possible role of this organism in the pathogeny of
   gastric diseases. This work was included in the "Handbook of Gastric
   Diseases" but it did not have much impact as it was written in Polish.

   The bacterium was rediscovered in 1979 by Australian pathologist Robin
   Warren, who did further research on it with Barry Marshall beginning in
   1981; they isolated the organisms from mucosal specimens from human
   stomachs and were the first to successfully culture them. In their
   original paper, Warren and Marshall contended that most stomach ulcers
   and gastritis were caused by colonization with this bacterium, not by
   stress or spicy food as had been assumed before.

   The medical community was slow to recognize the role of this bacterium
   in stomach ulcers and gastritis, believing that no bacterium could
   survive for long in the acidic environment of the stomach. The
   community began to come around after further studies were done,
   including one in which Marshall drank a Petri dish of H. pylori,
   developed gastritis, and the bacteria were recovered from his stomach
   lining, thereby satisfying three out of the four Koch's postulates.
   Marshall's gastritis later resolved without treatment. Marshall and
   Warren went on to show that antibiotics are effective in the treatment
   of gastritis. In 1994, the National Institutes of Health (USA)
   published an opinion stating that most recurrent gastric ulcers were
   caused by H. pylori, and recommended that antibiotics be included in
   the treatment regimen. Evidence has been accumulating to suggest that
   duodenal ulcers are also associated with H. pylori infection. In 2005,
   Warren and Marshall were awarded the Nobel Prize in Medicine for their
   work on H. pylori.

   Before the appreciation of the bacterium's role, stomach ulcers were
   typically treated with medicines that neutralize stomach acid or
   decrease its production. While this worked well, the ulcers very often
   reappeared. A traditional medication against gastritis was bismuth
   subsalicylate. It was often effective, but fell out of use, since its
   mechanism of action was a mystery. Nowadays it is quite clear that it
   is due to the bismuth salt acting as an antibiotic. Today, many stomach
   ulcers are treated with antibiotics effective against H. pylori.

   The bacterium was initially named Campylobacter pyloridis, then C.
   pylori (after a correction to the Latin grammar) and in 1989, after DNA
   sequencing and other data showed that the bacterium did not belong in
   the Campylobacter genus, it was placed in its own genus, Helicobacter.
   The name pylori comes from the Greek word pylorus, which means
   gatekeeper, and refers to the pyloric valve (the circular opening
   leading from the stomach into the duodenum).

   While H. pylori remains the most important known bacteria to inhabit
   the human stomach, several other species of the Helicobacter genus have
   now been identified in other mammals and some birds, and some of these
   can infect humans. Helicobacter species have also been found to infect
   the livers of certain mammals and to cause liver disease.

Structure of the bacterium

   H. pylori is a spiral-shaped gram-negative bacterium, about 3
   micrometres long with a diameter of about 0.5 micrometre. It has 4–6
   flagella. It is microaerophilic, i.e. it requires oxygen but at lower
   levels than those contained in the atmosphere. It contains a
   hydrogenase and obtains energy by oxidizing molecular hydrogen (H[2])
   that was produced by other intestinal bacteria. It tests positive for
   oxidase and catalase.
   Molecular model of H. pylori urease enzyme
   Enlarge
   Molecular model of H. pylori urease enzyme

   With its flagella and its helical shape, the bacterium drills into the
   mucus layer of the stomach, and then can be found in a number of
   locations: in the mucus, attached to epithelial cells, or inside
   vacuoles in epithelial cells. It produces adhesins which bind to
   membrane-associated lipids and carbohydrates and help its adhesion to
   epithelial cells. It excretes the enzyme urease, which converts urea
   into ammonia and bicarbonate. The release of ammonia is beneficial to
   the bacterium since it partially neutralizes the very acidic
   environment of the stomach (whose very purpose is to kill bacteria).
   Ammonia is, however, toxic to the epithelial cells, and with other
   products of H. pylori, including protease, catalase, and
   phospholipases, causes damage to those cells.

   Some strains of the bacteria have a particular mechanism for
   "injecting" the inflammatory agent peptidoglycan from their own cell
   wall into epithelial stomach cells. (See below for "cagA pathogenicity
   island" in the section "Genome studies of different strains".) It
   remains unknown how this mechanism is advantageous to the bacterium.

   Under conditions of environmental stress, Helicobacter will convert
   from the spiral to a coccoid form. This coccoid form of the organism
   has not been cultured, but has been found in the water supply in the US
   and is apparently involved in the epidemiology of the bacterium. The
   coccoid form has also been found to be able to adhere to gastric
   epithelial cells in vitro.

Infection and diagnosis

   Immunohistochemical staining of Helicobacter from a gastric biopsy.
   Enlarge
   Immunohistochemical staining of Helicobacter from a gastric biopsy.

   Infection may be symptomatic or asymptomatic (without visible ill
   effects). It is estimated that up to 70% of infection is asymptomatic.

   The bacteria have been isolated from feces, saliva and dental plaque of
   infected patients, which suggests gastro-oral or fecal-oral as possible
   transmission routes.

   It is estimated that about 2/3 of the world population are infected by
   the bacterium. Actual infection rates vary from nation to nation - the
   West (Western Europe, North America, Australasia) having rates around
   25% and the Third World much higher. In the latter, it is common,
   probably due to poor sanitary conditions, to find infections in
   children. In the United States, infection is primarily in the older
   generations (about 50% for those over the age of 60 compared with 20%
   under 40 years) and the poorest. This is largely attributed to higher
   hygiene standards and widespread use of antibiotics. However,
   antibiotic resistance is appearing in H. pylori. There are already many
   metronidazole resistant strains in Europe, the United States, and
   developing countries.

   It is widely believed that in the absence of treatment, H. pylori
   infection persists for life; the human immune system is not able to
   eradicate it. However, despite the dominance of this belief among
   physicians, there is actually no epidemiological evidence to support it
   and increasing evidence to the contrary. Because H. pylori infection is
   not generally detected at onset or during the acute phase, the
   proportion of acute infections that persist is not known, but several
   studies that followed the natural history in populations have reported
   apparent spontaneous elimination.

   One can test for H. pylori infection with blood antibody or stool
   antigen tests, or with the carbon urea breath test (in which the
   patient drinks ^14C- or ^13C-labelled urea, which the bacterium
   metabolizes producing labelled carbon dioxide that can be detected in
   the breath), or endoscopy to provide a biopsy sample for testing for
   the presence of urease " rapid urease test", histology or microbial
   culture.

   None of these test methods are completely failsafe. Blood antibody
   tests, for example, range from 76% to 84% sensitivity. Medication can
   affect H. pylori urease activity and give "false negatives" with the
   urea-based tests.

Treatment

   H. pylori colonized on the surface of regenerative epithelium
   (Warthin-Starry's silver)
   Enlarge
   H. pylori colonized on the surface of regenerative epithelium
   (Warthin-Starry's silver)

   In patients who are asymptomatic, treatment is not usually recommended.

   In gastric ulcer patients where H. pylori is detected, normal procedure
   is eradication to allow the ulcer to heal. The standard first-line
   therapy is a one week triple-therapy. The Sydney gastroenterolgist
   Thomas Borody invented the first triple therapy in 1987. Today the
   standard triple therapy is amoxicillin, clarithromycin and a proton
   pump inhibitor such as omeprazole – though sometimes a different proton
   pump inhibitor is substituted, or metronidazole is used in place of
   amoxicillin in those allergic to penicillin. Such a therapy has
   revolutionised the treatment of gastric ulcers and has made a cure to
   the disease possible, where previously symptom-control using antacids,
   H[2]-antagonists or proton pump inhibitors alone was the only option.

   Unfortunately, an increasing number of infected individuals are found
   to harbour bacteria resistant to first-line antibiotics. This results
   in initial treatment failure and requires additional rounds of
   antibiotic therapy. For resistant cases, a quadruple therapy may be
   used. Bismuth compounds are also effective in combination with the
   above drugs. For the treatment of clarithromycin- resistant strains of
   H. pylori the use of levofloxacin as part of the therapy has been
   recommended.

   There is some preliminary evidence that regular consumption of broccoli
   sprouts might eradicate H. pylori.

   Some evidence suggested that consumption of mastic gum might be able to
   control or even eradicate H. pylori, but later studies showed this not
   to be the case.

   A study done on mongolian gerbils indicates that green tea extract can
   suppress H. pylori growth.

   As explained below, some authors suggest that an H. pylori infection
   may be protective against certain diseases of the esophagus and cardia.
   Therefore, a more cautious approach than complete eradication may be
   necessary in some cases.

Gastric cancer connection

   Gastric cancer and gastric MALT lymphoma (lymphoma of the
   mucosa-associated lymphoid tissue) have been associated with H. pylori,
   and the bacterium has been categorized as a group I carcinogen by the
   International Agency for Research on Cancer (IARC). While the
   association is reasonably strong, it is not entirely clear that there
   is a causal relationship involved.

   Two related mechanisms by which H. pylori could promote cancer are
   under investigation. One mechanism involves the enhanced production of
   free radicals near H. pylori and an increased rate of host cell
   mutation. The other proposed mechanism has been called a "perigenetic
   pathway" and involves enhancement of the transformed host cell
   phenotype by means of alterations in cell proteins such as adhesion
   proteins. It has been proposed that H. pylori induces inflammation and
   locally high levels of TNF-alpha and/or interleukin 6. According to the
   proposed perigenetic mechanism, inflammation-associated signaling
   molecules such as TNF-alpha can alter gastric epithelial cell adhesion
   and lead to the dispersion and migration of mutated epithelial cells
   without the need for additional mutations in tumor suppressor genes
   such as genes that code for cell adhesion proteins.

Acid reflux and esophageal cancer

   The infection rate with H. pylori has been decreasing in developing
   countries, presumably because of improved hygiene and increased use of
   antibiotics. Accordingly, the incidence of gastric cancer in the U.S.
   has fallen by 80 percent from 1900 to 2000. However, gastroesophageal
   reflux disease and cancer of the esophagus have increased dramatically
   during the same period. In 1996, Martin J. Blaser put forward the
   theory that H. pylori might also have a beneficial effect: by
   regulating the acidity of the stomach contents, it lowers the impact of
   regurgitation of stomach acids into the esophagus. While some favorable
   evidence has been accumulated, as of 2005 the theory is not universally
   accepted.

Genome studies of different strains

   EM photograph of H. pylori
   Enlarge
   EM photograph of H. pylori

   Several strains are known, and the genomes of two have been completely
   sequenced. The genome of the strain "26695" consists of about 1.7
   million base pairs, with some 1550 genes. The two sequenced strains
   show large genetic differences, with up to 6% of the nucleotides
   differing.

   Study of the H. pylori genome is centered on attempts to understand
   pathogenesis, the ability of this organism to cause disease. There are
   62 genes in the "pathogenesis" category of the genome database. Both
   sequenced strains have an approximately 40 kb long Cag pathogenicity
   island (a common gene sequence believed responsible for pathogenesis)
   that contains over 40 genes. This pathogenicity island is usually
   absent from H. pylori strains isolated from humans who are carriers of
   H. pylori but remain asymptomatic.

   The cagA gene codes for one of the major H. pylori virulence proteins.
   Bacterial strains that have the cagA gene are associated with an
   ability to cause severe ulcers. The cagA gene codes for a relatively
   long (1186 amino acid) protein. The CagA protein is transported into
   human cells where it may disrupt the normal functioning of the
   cytoskeleton. The Cag pathogenicity island has about 30 genes that code
   for a complex type IV secretion system. After attachment of H.pylori to
   stomach epithelial cells, the CagA protein is injected into the
   epithelial cells by the type IV secretion system. The CagA protein is
   phosphorylated on tyrosine residues by a host cell membrane-associated
   tyrosine kinase. Pathogenic strains of H. pylori have been shown to
   activate the epidermal growth factor receptor (EGFR), a membrane
   protein with a tyrosine kinase domain. Activation of the EGFR by H.
   pylori is associated with altered signal transduction and gene
   expression in host epithelial cells that may contribute to
   pathogenesis. It has also been suggested that a c-terminal region of
   the cagA protein (amino acids 873-1002) can regulate host cell gene
   transcription independent of protein tyrosine phosphorylation. It is
   thought, due to cagA's low GC content relative to the rest of the
   helicobacter genome, that the gene was acquired by horizontal transfer
   from another cagA+ bacterial species.

   Each human population has a characteristic distribution of H. pylori
   strains that typically infect members of that population. This allows
   researchers to use H. pylori to study human migration patterns. It
   could be established that H. pylori in Amazon Indians has East Asian
   rather than European origins, suggesting that it arrived with the
   original immigrants at least 11,000 years ago.

   Retrieved from " http://en.wikipedia.org/wiki/Helicobacter_pylori"
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   with only minor checks and changes (see www.wikipedia.org for details
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