Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Using tissue cell culture to make a protein or polypeptide
Patent
1998-06-29
2000-08-01
Campell, Bruce R.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Using tissue cell culture to make a protein or polypeptide
536 231, 536 237, 4353201, 435 711, 435325, 514 1, C07H 2302, C07H 2304, C12N 1500, C12P 2104, A01N 6100
Patent
active
060965215
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The present invention concerns the new adherence gene alpB from Helicobacter pylori and the polypeptide coded thereby. The gene, the polypeptide and an antibody directed against the polypeptide can be used to diagnose, prevent and treat a Helicobacter infection.
The occurrence of spiral bacteria in the human gastric mucous membrane has been known for a long time (Bizzozero, 1893). The fact that these are pathogenic germs was, however, not realised until the successful isolation and culture of this bacterium by Marshall and Warren (Warren and Marshall, 1983; Marshall et al., 1984) from the gastric mucous membrane of a patient with a gastric ulcer (ulcus ventriculi). As the first analyses showed the isolated microorganisms were gram-negative, spiral bacteria with an extremely high motility and the unusual ability of being able to survive in a strongly acidic environment (up to ca. pH 1.5). The germs which were originally denoted Campylobacter pylori were finally classified on the basis of biochemical and morphological characteristics in the newly established genus "Helicobacter" (Goodwin et al., 1989).
The importance of Helicobacter pylori infection and the implications of this discovery already became clear within a few years. Epidemiological investigations by Taylor and Blaser (1991) showed that the H. pylori infection occurs world-wide and that ca. 50% of the population are infected with this bacterium, the infection rate being higher in the developing countries than in industrialised countries. Furthermore it was observed that the probability of a chronic H. pylori infection increases drastically with increasing age. Hence the H. pylori infection is among the most frequent chronic bacterial infections of humans.
Today it is known that the infection inevitably leads to the induction of a bacterial gastritis (type B gastritis) in humans. Moreover it is assumed that H. pylori also plays a causal role in the development of gastric and duodenal ulcers (ulcus ventriculi and ulcus duodeni) as well as some forms of gastric carcinoma (adenocarcinoma) (Lee et al., 1993; Solnick and Tompkins, 1993). Even the MALT (mucosa associated lymphoid tissue) lymphomas of the stomach which occur more rarely and are regarded as precursors of B cell tumours of the immune system are also presumably a result of H. pylori infection. An antibacterial treatment of such patients with the successful eradication (total elimination) of H. pylori leads to a healing of gastric ulcers as well as of low grade MALT lymphomas (Sipponen and Hyvarinen, 1993; Isaacson and Spencer, 1993; Stolte and Eidt, 1993).
A sequel of a long-term infection with H. pylori is atrophic gastritis, a degeneration of the mucous, acid or pepsin-producing cells of the stomach epithelium which has to be regarded as a pre-cancerous lesion. According to a statistic of the types of cancer which occurred world-wide most frequently in 1980, gastric carcinoma is in second place but with a declining tendency (Parkin et al., 1988). Two studies have recently shown a statistically significant correlation between H. pylori infection and the occurrence of gastric carcinoma (intestinal type); both came to the conclusion that ca. 60% of all gastric carcinomas that occur are probably due to a H. pylori infection (Parsonnet et al., 1991; Nomura et al., 1991). Furthermore investigations by Sipponen (1992) show that in many industrialised countries more than 20% of infected persons contract an ulcer of the stomach or of the duodenum during their life whereas this risk is negligibly small in persons with a normal gastric mucosa. This means that these frequent gastro-duodenal diseases must be regarded as infectious diseases and treated appropriately (Alper, 1993). A treatment which eliminates a chronic H. pylori infection that is already present leads to a healing of a gastritis, a gastric or duodenal ulcer or a MALT lymphoma. Thus a prophylactic treatment which prevents a H. pylori infection (e.g. immunization) as well as a treatment which eliminates a H. pylori infection
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Blum Andre
Corthesy-Theulaz Irene
Haas Rainer
Meyer Thomas F.
Odenbreit Stefan
Campell Bruce R.
Chen S
Max-Planck-Gesellschaft zur Forderung der Wissenschaften
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