幽门螺杆菌在胃内定植的相关影响因素

胃内定植是引起幽门螺杆菌（Helicobacter pylori,H. pylori）感染的先决条件。H. pylori可穿过胃黏液层并与胃上皮细胞相互作用。这个定植过程主要受到H. pylori动力和尿素酶的影响。同时H. pylori形态、胃内pH、外膜蛋白及益生菌等也在其中扮演重要角色。该研究主要对H. pylori胃内定植过程中的相关影响因素进行综述。     

Helicobacter pylori– coccoid forms and biofilm formation

Electron microscopic studies have shown that Helicobacter pylori occurs in three stages: spiral forms, coccoid forms and degenerative forms. The spiral forms are viable, culturable, virulent and can colonize experimental animals and induce inflammation. The coccoid forms may also be viable but are nonculturable, less virulent and are less likely to colonize and induce inflammation in experimental animals than the spiral forms. The degenerative forms are pyknotic, nonculturable, coccoid forms of dead H. pylori . These forms cannot be cultured and the cell membrane has disintegrated but gene material can be detected by PCR in water supplies. There is no substantial evidence for viable H. pylori persisting in water supplies. Epidemiological studies suggest that environmental water is a risk factor for H. pylori infection when compared with tap water, and formation of H. pylori biofilm cannot be excluded. Helicobacter pylori does not seem to take part in biofilm formation in the oral cavity even though the bacterium may be detected.     

Bacterial factors that mediate colonization of the stomach and virulence of Helicobacter pylori

Helicobacter pylori is a Gram-negative microaerophilic organism that colonizes the gastric mucosa of humans. Helicobacter pylori is one of the most common infections in humans and results in the development of gastritis in all infected individuals, although the majority of people are asymptomatic. A subset of infected people develop serious disease including duodenal ulceration and gastric cancer. Helicobacter pylori exhibits many striking characteristics. It lives in the hostile environment of the stomach and displays a very strict host and tissue tropism. Despite a vigorous immune response, infection persists for the lifetime of the host unless eradicated with antimicrobials. Why H. pylori is so pathogenic in some individuals and not in others is unknown but is thought to be due to a variety of host, environmental and bacterial factors. In this review, some of the bacterial factors that mediate colonization of the gastric mucosa and play a role in the pathogenesis of this organism have been considered.     

Helicobacter pylori AddAB helicase-nuclease and RecA promote recombination-related DNA repair and survival during stomach colonization

Helicobacter pylori colonization of the human stomach is characterized by profound disease-causing inflammation. Bacterial proteins that detoxify reactive oxygen species or recognize damaged DNA adducts promote infection, suggesting that H. pylori requires DNA damage repair for successful in vivo colonization. The molecular mechanisms of repair remain unknown. We identified homologues of the AddAB class of helicase-nuclease enzymes, related to the Escherichia coli RecBCD enzyme, which, with RecA, is required for repair of DNA breaks and homologous recombination. H. pylori mutants lacking addA or addB genes lack detectable ATP-dependent nuclease activity, and the cloned H. pylori addAB genes restore both nuclease and helicase activities to an E. coli recBCD deletion mutant. H. pylori addAB and recA mutants have a reduced capacity for stomach colonization. These mutants are sensitive to DNA damaging agents and have reduced frequencies of apparent gene conversion between homologous genes encoding outer membrane proteins. Our results reveal requirements for double-strand break repair and recombination during both acute and chronic phases of H. pylori stomach infection.     

Evolution of the Helicobacter pylori vacuolating cytotoxin in a human stomach

We describe two subclones of Helicobacter pylori, isolated contemporaneously from a human stomach, which differ markedly in the vacuolating cytotoxin gene, vacA, but whose near identity in sequences outside this locus implies a very recent common origin. The differences are consistent with homologous recombination with DNA from another strain and result in a changed vacA midregion and, importantly, in changed toxicity.     

Living dangerously: how Helicobacter pylori survives in the human stomach

Helicobacter pylori was already present in the stomach of primitive humans as they left Africa and spread through the world. Today, it still chronically infects more than 50% of the human population, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. To succeed in these long-term associations, H. pylori has developed a unique set of virulence factors, which allow survival in a unique and hostile ecological niche--the human stomach.     

Mucocytes with micronuclei and sowing with the coccoid forms of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in a mucous membrane of human stomach

In accordance with the solution of IARC, the Helicobacter pylori (H. pylori) refers to carcinogens of the first group. As the carcinogenic factors have a mutagen effect, we have undertaken the cytogenetic testing of 62 patients with chronic nonatrophic gastritis (40 of which have H. pylori-associated gastritis) by account of the micronuclei in mucocytes of tectorial-pit epithelium of the mucous membrane of the antral region of the stomach. The detection of H. pylori cells in the mucous membrane of the stomach (SMM) was performed with the help of immunocytochemical method that permitted us to visualize both the bacillar and coccoid forms, as well as to evaluate the degree of sowing of SMM with the coccoid forms of H. pylori. In the patient group with H. pylori-associated gastritis, the frequency rate of mucocytes with micronuclei in SMM appears to be considerably higher than in the group of patients whose SMM was not infected with H. pylori (P < 0,05). A high scale of sowing with the coccoid forms of H. pylori was accompanied by a significantly heightened level of mucocytes with micronuclei in the SMM. In connection with this and on the basis of modern notions of carcinogenesis, based on mutagen modifications in somatic cells, patients that exhibit high sowing with coccoid forms of H. pylori may be placed in the group of heightened oncologic hazards.     

Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection.     

Carcinogenic role of tumor necrosis factor-alpha inducing protein of Helicobacter pylori in human stomach

Helicobacter pylori is the definitive carcinogen for stomach cancer and is known to induce proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF-alpha is an endogenous tumor promoter, we identified the TNFalpha inducing protein (Tipalpha) gene family, and confirmed Tipalpha and HP-MP1 as new carcinogenic proteins of H. pylori.Tipalpha protein is unique to H. pylori, and this paper shows the strong tumor promoting activity of Tipalpha gene family, in cooperation with Ras protein and its mechanisms of action in relation to NF-kappaB activation, and discusses the carcinogenic role of Tipalpha in stomach cancer. Our recent finding showing that penicillin-binding proteins of other bacteria are weak homologues of Tipalpha is also discussed.     

Carbohydrate-dependent inhibition of Helicobacter pylori colonization using porcine milk

Breast milk has a well-known anti-microbial effect, which is in part due to the many different carbohydrate structures expressed. This renders it a position as a potential therapeutic for treatment of infection by different pathogens, thus avoiding the drawbacks of many antibiotics. In a previous study, we showed that pigs express the Helicobacter pylori receptors, sialyl Lewis x (Le x) and Le b, on various milk proteins. Here, we investigate the pig breed- and individual-specific expression of these epitopes, as well as the inhibitory capacity of porcine milk on H. pylori binding and colonization. Milk proteins from three different pig breeds were analysed by western blotting using antibodies with known carbohydrate specificity. An adhesion assay was used to investigate the capacity of pig milk to inhibit H. pylori binding to neoglycoproteins carrying Le b and sialyl-di-Le x. alpha1,3/4-fucosyltransferase transgenic FVB/N mice, known to express Le b and sialyl Le x in their gastric epithelium, were colonized by H. pylori and were subsequently treated with Le b- and sialyl Le x-expressing or nonexpressing porcine milk, or water (control) only. The degree of H. pylori colonization in the different treatment groups was quantified. The expression of the Le b and sialyl Le x carbohydrate epitopes on pig milk proteins was breed- and individual specific and correlated to the ability of porcine milk to inhibit H. pylori adhesion in vitro and H. pylori colonization in vivo. Milk from certain pig breeds may have a therapeutic and/or prophylactic effect on H. pylori infection.     

Oxidative cellular damage associated with transformation of Helicobacter pylori from a bacillary to a coccoid form

Exposure to unfavorable conditions results in the transformation of Helicobacter pylori, a gastric pathogen, from a bacillary form to a coccoid form. The mechanism and pathophysiological significance of this transformation remain unclear. The generation of the superoxide radical by H. pylori has previously been shown to inhibit the bactericidal action of nitric oxide, the concentration of which is relatively high in gastric juice. With the use of chemiluminescence probes, both the quality and quantity of reactive oxygen species generated by H. pylori have now been shown to change markedly during the transformation from the bacillary form to the coccoid form. The transformation of H. pylori was associated with oxidative modification of cellular proteins, including urease, an enzyme required for the survival of this bacterium in acidic gastric juice. Although the cellular abundance of urease protein increased during the transformation, the specific activity of the enzyme decreased and it underwent aggregation. Specific activities of both superoxide dismutase and catalase in H. pylori also decreased markedly during the transformation. The transformation of H. pylori was also associated with oxidative modification of DNA, as revealed by the generation of 8-hydroxyguanine, and subsequent DNA fragment. These observations indicate that oxidative stress elicited by endogenously generated reactive oxygen species might play an important role in the transformation of H. pylori from the bacillary form to the coccoid form.     

Mucosal immune responses are related to reduction of bacterial colonization in the stomach after therapeutic Helicobacter pylori immunization in mice

The aim of this study was to investigate the capacity of oral and parenteral therapeutic immunization to reduce the bacterial colonization in the stomach after experimental Helicobacter pylori infection, and to evaluate whether any specific immune responses are related to such reduction. C57BL/6 mice were infected with H. pylori and thereafter immunized with H. pylori lysate either orally together with cholera toxin or intraperitoneally (i.p.) together with alum using immunization protocols that previously have provided prophylactic protection. The effect of the immunizations on H. pylori infection was determined by quantitative culture of H. pylori from the mouse stomach. Mucosal and systemic antibody responses were analyzed by ELISA in saponin extracted gastric tissue and serum, respectively, and mucosal CD4+ T cell responses by an antigen specific proliferation assay. Supernatants from the proliferating CD4+ T cells were analyzed for Th1 and Th2 cytokines. The oral, but not the parenteral therapeutic immunization induced significant decrease in H. pylori colonization compared to control infected mice. The oral immunization resulted in markedly elevated levels of serum IgG+M as well as gastric IgA antibodies against H. pylori antigen and also increased H. pylori specific mucosal CD4+ T cell proliferation with a Th1 cytokine profile. Although the parenteral immunization induced dramatic increases in H. pylori specific serum antibody titers, no increases in mucosal antibody or cellular immune responses were observed after the i.p. immunization compared to control infected mice. These findings suggest that H. pylori specific mucosal immune responses with a Th1 profile may provide therapeutic protection against H. pylori.     

Placental acquisition of maternal specific IgG and Helicobacter pylori colonization in infancy

Background. Colonization with Helicobacter pylori generally occurs in infancy, and the microorganism is often acquired from close family members. Rate of infant colonization may be affected by maternal immune status. Methods. To investigate the potential protective effect of anti‐H. pylori immunoglobulin G (IgG) acquired via the placenta, 65 mothers and their infants were studied from the infant's birth for 1 year. Circulating IgG antibodies were measured by enzyme‐linked immunosorbent assay (ELISA) in cord blood and every 8 weeks. Immunoblotting was performed on sera from infants with significant increases in IgG levels. Rate of infant H. pylori colonization was measured by ¹³C urea breath tests every 4 weeks from the age of 12 weeks. Results. Maternal and infant cord blood specific IgG levels were correlated (R² = .747, p < .001). Infant H. pylori specific IgG fell 5‐fold compared to maternal levels over the first 6 months of life, and rose subsequently in many cases, with the development of novel immunoblot patterns. There were no significant associations between the age at first positive urea breath test and maternal or infant cord specific H. pylori IgG levels. Conclusions. Transplacentally acquired specific IgG antibody does not protect infants from colonization by H. pylori.     

球形幽门螺杆菌对SGC-7901细胞增殖的影响

目的:了解球形幽门螺杆菌对体外培养细胞增殖的影响.方法:采用抗生素诱导幽门螺杆菌标准菌株NCTC11637球变,将弯曲形和球形菌的菌悬液(1×108个/ml)作5倍梯度稀释,而后分别加入胃癌上皮细胞SGC-7901,共孵育3 d后,用MTT法检测SGC-7901细胞增殖的情况.结果:高浓度的弯曲形和球形幽门螺杆菌(＞8×107个/ml)可明显抑制细胞的增殖(P＜0.05);低浓度的球形幽门螺杆菌(＜1.28×105个/ml)可明显促进细胞的增殖(P＜0.05).结论:球形幽门螺杆菌在体外可影响SGC-7901细胞的增殖.     

The relation of Helicobacter pylori with dysplasia and stomach neoplasms in Costa Rica]

Occurrence of the bacterium Helicobacter pylori was compared for two Costa Rican sites with contrasting levels of gastric cancer incidence, Poás (incidence 15.13%) and Puriscal (83.53%). A sample of 185 adults of similar age and sex proportions was studied in each site, using both H. pylori antiserum tests and gastroscopy to collect two biopsies per case. No clear association between H. pylori and gastric cancer was found.