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1.
Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.  相似文献   

2.
Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ectopic assembly of tight-junction components at sites of bacterial attachment, and altering the composition and function of the apical-junctional complex. Long-term CagA delivery to polarized epithelia caused a disruption of the epithelial barrier function and dysplastic alterations in epithelial cell morphology. CagA appears to target H. pylori to host cell intercellular junctions and to disrupt junction-mediated functions.  相似文献   

3.
Olson JW  Maier RJ 《Science (New York, N.Y.)》2002,298(5599):1788-1790
The gastric pathogen Helicobacter pylori is known to be able to use molecular hydrogen as a respiratory substrate when grown in the laboratory. We found that hydrogen is available in the gastric mucosa of mice and that its use greatly increased the stomach colonization by H. pylori. Hydrogenase activity in H. pylori is constitutive but increased fivefold upon incubation with hydrogen. Hydrogen concentrations measured in the stomachs of live mice were found to be 10 to 50 times as high as the H. pylori affinity for hydrogen. A hydrogenase mutant strain is much less efficient in its colonization of mice. Therefore, hydrogen present in animals as a consequence of normal colonic flora is an energy-yielding substrate that can facilitate the maintenance of a pathogenic bacterium.  相似文献   

4.
人幽门螺杆菌（H.pylori）是慢性胃炎和消化性溃疡的主要病因，并与胃癌的发生密切相关。幽门螺杆菌的致病机理与其致病性和宿主免疫应答有关，尤以幽门螺杆菌的毒性占主导地位。最新研究表明，约60%的幽门螺杆菌分离株具有分泌空泡毒素（VacA）的能力，并且血清中其相应抗体的出现与消化性溃疡的发生高度平行。综述了VacA的制备和纯化，理化特性，蛋白质结构，编码基因，致病机理及其单克隆抗体等方面的研究进展。  相似文献   

5.
The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA(+)) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.  相似文献   

6.
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7.
采用AutoDock软件将一系列已有的硝基咪唑衍生物与尿素酶晶体三维结构进行分子对接研究,以便更好地理解该系列抑制剂与尿素酶的结合方式以及酶-底物复合物与作用机理相关的结构与特征。同时,还考察了一组硝基咪唑衍生物抑制活性与分子对接软件预测的结合能之间的相关性,证明分子对接技术是一种可行的尿素酶抑制剂筛选方法。  相似文献   

8.
Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.  相似文献   

9.
Airborne transmission of influenza A/H5N1 virus between ferrets   总被引：1，自引：0，他引：1  
Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.  相似文献   

10.
Human fertilization begins when spermatozoa bind to the extracellular matrix coating of the oocyte, known as the zona pellucida (ZP). One spermatozoan then penetrates this matrix and fuses with the egg cell, generating a zygote. Although carbohydrate sequences on the ZP have been implicated in sperm binding, the nature of the ligand was unknown. Here, ultrasensitive mass spectrometric analyses revealed that the sialyl-Lewis(x) sequence [NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc], a well-known selectin ligand, is the most abundant terminal sequence on the N- and O-glycans of human ZP. Sperm-ZP binding was largely inhibited by glycoconjugates terminated with sialyl-Lewis(x) sequences or by antibodies directed against this sequence. Thus, the sialyl-Lewis(x) sequence represents the major carbohydrate ligand for human sperm-egg binding.  相似文献   

11.
Plants have evolved a powerful immune system to defend against infection by most microbial organisms. However, successful pathogens, such as Pseudomonas syringae, have developed countermeasures and inject virulence proteins into the host plant cell to suppress immunity and cause devastating diseases. Despite intensive research efforts, the molecular targets of bacterial virulence proteins that are important for plant disease development have remained obscure. Here, we show that a conserved P. syringae virulence protein, HopM1, targets an immunity-associated protein, AtMIN7, in Arabidopsis thaliana. HopM1 mediates the destruction of AtMIN7 via the host proteasome. Our results illustrate a strategy by which a bacterial pathogen exploits the host proteasome to subvert host immunity and causes infection in plants.  相似文献   

12.
Specific suppression of immune responses   总被引：17，自引：0，他引：17  
The models we have discussed in detail demonstrate specific suppression of immune reactivity produced in normal adult animals by antibody and antigen. The mechanism of homeostasis of suppression in these models depends on continued exposure to antigen and on an active response by the host. The active response may include production of antibody directed against specific receptors as well as antibody directed against antigen. Thus, specific regulation of both antibody and cell mediated immunity to an antigen might be achieved by the use of only the biological agents of the response: antigen, antibody, and possibly antibody to receptors. The general implication is that these same biological agents are responsible for autoregulation of immune reactions occurring in nature. Presumably, these agents may be used to suppress or reverse immune responses for appropriate clinical objectives.  相似文献   

13.
益生菌保健和治疗作用的研究进展   总被引：1，自引：0，他引：1  
刘长建  姜波  刘秋 《安徽农业科学》2009,37(20):9357-9359
益生菌是一类对宿主机体健康有益的低致病性或无致病性微生物。大量研究表明,益生菌除能促进营养物质的消化、吸收,还对胃肠道疾病、癌症、免疫力低下、婴儿过敏、肝病、高血压、Helicobacter pylori感染等症具有预防和治疗效果。其中的机理有广泛的研究,但仍无定论。  相似文献   

14.
The soil-borne necrotrophic fungus Rhizoctonia solani is one of destructive fungi causing severe yield losses in various important crops. However, the host defense mechanisms against the invasion of this pathogen are poorly understood. In this study, we employed an iTRAQ-based quantitative proteomic approach to investigate host proteins responsive to R. solani using the resistant rice cultivar YSBR1. As a whole, we identified 319 differentially accumulated proteins (DAPs) after inoculation of rice plants with R. solani. Functional categorization analysis indicates that these DAPs cover a broad range of functions. Notably, a substantial portion of the DAPs are involved in cell redox homeostasis, carbohydrate metabolism, and phenylpropanoid biosynthesis, or belong to pathogenesis-related proteins, indicating that these processes/proteins play important roles in host defense against R. solani. Interestingly, all of the DAPs involved in photosynthesis and chlorophyll biosynthetic processes, and part of the DAPs involved in phenylpropanoid biosynthesis, show reduced accumulation after R. solani infection, suggesting that R. solani probably inhibits host photosynthetic system and phenylpropanoid biosynthesis to facilitate infection and colonization. In conclusion, our results provide both valuable resources and new insights into the molecular mechanisms underlying rice and R. solani interaction.  相似文献   

15.
幽门螺杆菌（Hp）是人体内常见的病原微生物,现发现其与胃癌的发生密切相关。VacA作为Hp感染的一种主要并且重要的毒力因子,推测其在胃癌发生过程中可能起着较为重要的作用。对VacA基因、蛋白的分子结构和研究现状以及VacA诱发细胞毒性的机制做一综述。  相似文献   

16.
Immune interferon gamma (IFN-γ) is essential for mammalian host defense against intracellular pathogens. IFN-γ induces nearly 2000 host genes, yet few have any assigned function. Here, we examined a complete mouse 65-kilodalton (kD) guanylate-binding protein (Gbp) gene family as part of a 43-member IFN-γ-inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes. Family-wide loss-of-function analysis found that at least four Gbps--Gbp1, Gbp6, Gbp7, and Gbp10--conferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals. These Gbps solicited host defense proteins, including the phagocyte oxidase, antimicrobial peptides, and autophagy effectors, to kill intracellular bacteria. Thus, specific 65-kD Gbps coordinate a potent oxidative and vesicular trafficking program to protect the host from infection.  相似文献   

17.
The interface between an infectious agent and its host represents the ultimate battleground for survival: The microbe must secure a niche for replication, whereas the host must limit the pathogen's advance. Among the host's arsenal of antimicrobial factors, the type 1 interferons (IFNs) induce potent defense mechanisms against viruses and are key in the host-virus standoff. Viruses have evolved multiple tricks to avoid the immediate antiviral effects of IFNs and, in turn, hosts have adapted use of this innate cytokine system to galvanize multiple additional layers of immune defense. The plasticity that exists in these interactions provides us with a lesson in détente.  相似文献   

18.
Natural killer (NK) cells are lymphocytes that can be distinguished from T and B cells through their involvement in innate immunity and their lack of rearranged antigen receptors. Although NK cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based activation motif (ITAM)-containing transmembrane molecule for expression and signal transduction. Thus, NK cells use receptors functionally resembling ITAM-coupled T and B cell antigen receptors to provide vital innate host defense.  相似文献   

19.
The phytophagous insect, Epiblema strenuana, is an effective biocontrol agent against Am-brosia and Parthenium, and was introduced to China in 1990 to control Ambrosia artemisiifolia. After asmall scale release in Hunan Province, E. strenuana established and begun to spread. Host specificity andfeeding studies in Hunan have indicated that there are four host plants in China, A. artemisiifolia, A. trifi-da, Xanthium sibiricum and Parthenium hysterophorus. These plants are all weeds that need to be con-trolled. However, there are still some different views among scientists about the merits of this release becauseof potential effects on non-target species such as Helianthus annuus, and uncertainty about climatic suitabili-ty. To address these concerns, the CLIMEX system was used to predict the possibility of establishment of E.strenuana with A. artemisii f olia , A. tri fida , and P. hysterophorus at 85 meteorological locations. Also,the probability of E. strenuana co-establishing with A. artemisiifolia, A. trifida or P. hysterophorus wasevaluated quantitatively by bioclimatic risk index (BCRI) transferred from ecoclimate index (EI). Moreover,the hypothetical adaptation of E. strenuana to H. annuus as a host, were evaluated by bioclimate matching.These results help to predict the potential spread of A. artemisiifolia, A. trifida, P. hysterophorus and e-valuate the merits of further releases of E. strenuana in China.  相似文献   

20.
Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.  相似文献   

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