结核分枝杆菌相关毒力基因的研究进展

在结核病的发生过程中,毒力起着重要的作用,因为只有毒力菌株才可致病.结核菌的毒力可以理解为其引起结核病的能力,而致病性与毒力因子总是联系在一起的.结核菌是典型的胞内寄生菌,但只有有毒株才能在细胞内存活和繁殖.毒力因子在毒力株的巨噬细胞复制中起关键作用,目前对毒力相关基因及毒力因子作用机制知之甚少.本文将对几个研究较多的毒力相关基因作一综述.     

结核分枝杆菌相关毒力基因的研究进展

在结核病的发生过程中,毒力起着重要的作用,因为只有毒力菌株才可致病.结核菌的毒力可以理解为其引起结核病的能力,而致病性与毒力因子总是联系在一起的.结核菌是典型的胞内寄生菌,但只有有毒株才能在细胞内存活和繁殖.毒力因子在毒力株的巨噬细胞复制中起关键作用,目前对毒力相关基因及毒力因子作用机制知之甚少.本文将对几个研究较多的毒力相关基因作一综述.     

结核分枝杆菌相关毒力基因的研究进展

在结核病的发生过程中,毒力起着重要的作用,因为只有毒力菌株才可致病.结核菌的毒力可以理解为其引起结核病的能力,而致病性与毒力因子总是联系在一起的.结核菌是典型的胞内寄生菌,但只有有毒株才能在细胞内存活和繁殖.毒力因子在毒力株的巨噬细胞复制中起关键作用,目前对毒力相关基因及毒力因子作用机制知之甚少.本文将对几个研究较多的毒力相关基因作一综述.     

铜绿假单胞菌密度感应系统调控的毒力因子的致病作用

铜绿假单胞菌可以产生多种毒力因子,是引起细菌慢性持续感染的重要原因之一.其密度感应系统与其毒力因子的合成密切相关.近年,有大量研究发现其分泌的毒力因子可以影响宿主的免疫系统,产生致病作用.因此,现在就毒力因子的致病作用的相关研究作一综述.     

幽门螺杆菌毒力因子及其诱发胃癌作用机制研究进展

幽门螺杆菌（Hp）属于革兰阴性菌,可以在人胃内存活并定植。Hp能够利用其毒力因子调节宿主炎症反应,破坏胃黏膜,其感染的长期结局包括胃癌和胃黏膜相关淋巴组织淋巴瘤等恶性肿瘤,是与胃癌相关的Ⅰ类致癌物。与Hp生存相关的毒力因子主要是脲酶,在脲酶的帮助下,Hp可以在pH值极低的胃内生存,形成持久感染;与Hp定植相关的毒力因子包括外部炎症蛋白A、Hp外膜蛋白Q、血型抗原结合黏附素,这些毒力因子与宿主胃上皮细胞相互作用,帮助Hp在胃黏膜定植,增加癌前病变及胃癌发生风险;与Hp致病相关的毒力因子包括细胞毒素相关基因A、空泡细胞毒素、外膜囊泡、γ-谷氨酰转肽酶、高温需求蛋白A等,Hp在胃上皮细胞存活、黏附并成功定植后,上述毒力因子进一步诱导炎症反应,促进细胞增殖、侵袭和转移,促使胃部炎症向胃癌转化。深入研究Hp毒力因子诱导胃癌发生的机制,有助于为胃癌的诊断和治疗提供新思路和方法。     

N-钙黏蛋白在烟曲霉黏附及侵袭内皮细胞中的作用

目的 探讨N-钙黏蛋白在内皮细胞黏附吞噬烟曲霉过程中的作用.方法 观察提取人脐静脉内皮细胞蛋白与烟曲霉的结合过程,了解N-钙黏蛋白是否可与烟曲霉结合,建立内皮细胞黏附及吞噬烟曲霉的体外模型,通过单克隆抗体阻断上皮细胞膜受体N-钙黏蛋白,再次观察脐静脉内皮细胞黏附及吞噬烟曲霉情况.结果 脐静脉内皮细胞膜蛋白N-钙黏蛋白可与烟曲霉结合,抗体阻断N-钙黏蛋白后,脐静脉内皮细胞黏附和吞噬烟曲霉能力明显下降.结论 N-钙黏蛋白是脐静脉内皮细胞黏附吞噬烟曲霉孢子的相关受体.     

幽门螺杆菌毒力致病因子研究进展

幽门螺杆菌( Helicobacter pylori, H pylori)感染是一种世界范围内常见的慢性感染, 可致多种疾病, 如: 慢性胃炎, 十二指肠溃疡, 胃黏膜相关的淋巴样组织淋巴瘤及胃腺癌. 不同疾病是由H pylori和宿主之间复杂的致病机制导致. 近年来, 学者们对H pylori毒力致病因子的研究取得了长足进展, 为揭开H pylori感染的致病机制奠定了基础. 本文就H pylori毒力致病因子CagA、VacA、BabA、SabA、OipA、DupA等的最新研究进展进行了综述.     

结核桿菌的特性和构造与其致病力的关系

在考虑结核病的决定因素时,应同时注意到组织环境(Tissue environment)的特征与结核杆菌本身的性质。但是人们在考虑结核病时,常常只注意到微生物的性质,我们也先由这方面谈起。一结核杆菌的性质与其毒力的关系 1.细菌代谢特征与毒力的关系:分枝杆菌属中各个菌株的代谢特征是不同的,我们有理由相信其中某些不同之点是与毒力相关。当我们以常用方法,加蚁酸盐(Formate),醋酸盐(acetate)、丙酸盐(propionate)、丁酸盐(butyrate)或乳酸盐(Lactate)作为基质     

Chemerin研究进展

Chemerin是一种免疫调节因子,在炎性反应相关的一系列蛋白酶作用下可对白细胞产生趋化作用,并参与炎性反应.同时chemerin也是一种调节脂肪细胞生成、代谢及葡萄糖稳态的脂肪因子,其参与了肥胖及代谢综合征的发生、发展.近年来研究发现chemerin对糖尿病及代谢综合征具有一定的诊断意义,且其有可能成为治疗相关疾病的新靶点.     

河南省某一淡水养殖环节中非O1/O139群霍乱弧菌毒力基因及分子分型分析

目的 了解河南省淡水养殖环节中非O1/O139群霍乱弧菌毒力基因分布及分子分型情况。方法 对河南省淡水养殖环节中50株非O1/O139群霍乱弧菌和3株病人来源菌株进行全基因测序,利用PubMLST-Vc数据库分析其序列分型(ST),利用最小生成树关系图分析进化关系,通过VFDB数据库获得其毒力基因分布。结果 来源于淡水养殖环节和来源于病人的非O1/O139群霍乱弧菌53株菌株均具有黏附、趋化运动、抗吞噬、毒素及酶类等功能的8类毒力相关因子基因,缺失辅助定植、毒素共调、分泌等功能的毒力相关因子基因和副霍乱肠毒素等4个毒素基因。部分毒力相关因子或部分菌株的毒力相关因子毒力基因不全。与3株来源于病人的菌株相比,二者毒力因子基因携带情况相近,除MSHA Ⅳ型菌毛毒力因子mshA基因、荚膜多糖wbuB基因、wbfY基因、rmlB基因、血红素受体hutA基因及Ⅲ型分泌系统vscC2和vcrD2基因外,部分菌株二者携带相同的毒力因子基因。53株非O1/O139群霍乱弧菌分属19个ST型,ST4和ST5是优势ST型,养殖环节来源的菌株与病人来源的菌株分属不同的ST型。19个ST型等位基因位点变异差异数在1~7个,其中分离自淡水养殖环节的非O1/O139群霍乱弧菌菌株17个ST型等位基因位点变异差异数在1~7个,病人来源的非O1/O139群霍乱弧菌菌株2个ST型与分离自淡水养殖环节的非O1/O139群霍乱弧菌菌株ST1、ST2、ST6和ST10属同一簇,与ST1有6个等位基因位点存在差异。结论 河南省淡水养殖环节非O1/O139群霍乱弧菌菌株MLST分型多样化,携带多种毒力相关因子,不同来源菌株携带的毒力基因相同,虽然分属不同的ST型,但还是存在食品安全风险,提醒有关部门采取措施进行防控。     

Stress and coping: the psychoneuroimmunology of HIV/AIDS

A considerable body of evidence, reviewed in this chapter, suggests that psychosocial factors play an important role in progression of HIV infection, its morbidity and mortality. Psychosocial influences relating to faster disease progression include life-event stress, sustained depression, denial/avoidance coping, concealment of gay identity (unless one is rejection-sensitive), and negative expectancies. Conversely, protective psychosocial factors include active coping, finding new meaning, and stress management. In studying long survivors of HIV/AIDS, our group has found protective effects on health of life involvement, collaborative relationship with doctor, emotional expression, depression (conversely), and perceived stress (conversely). Reviewed and discussed are psychoneuroimmunological pathways by which immune and neuroendocrine mechanisms might link psychosocial factors with health and long survival. Finally, biological factors are also a major determinant of disease progression and include genetics and age of the host, viral strain and virulence, medication and several immune response factors on which psychosocial influences could impact.     

A Haemophilus ducreyi CpxR deletion mutant is virulent in human volunteers

Haemophilus ducreyi 35000HP contains a homolog of the CpxRA 2-component signal transduction system, which controls the cell envelope stress response system in other gram-negative bacteria and regulates some important H. ducreyi virulence factors. A H. ducreyi cpxR mutant was compared with its parent for virulence in the human challenge model of experimental chancroid. The pustule formation rate in 5 volunteers was 33% (95% confidence interval [CI], 1.3%-65.3%) at 15 parent sites and 40% (95% CI, 18.1%-61.9%) at 15 mutant sites (P = .35). Thus, the cpxR mutant was not attenuated for virulence. Inactivation of the H. ducreyi cpxR gene did not reduce the ability of this mutant to express certain proven virulence factors, including the DsrA serum resistance protein and the LspA2 protein, which inhibits phagocytosis. These results expand our understanding of the involvement of the CpxRA system in regulating virulence expression in H. ducreyi.     

Effects of the twin-arginine translocase on secretion of virulence factors,stress response,and pathogenesis

A novel secretion pathway originally found in plants has recently been discovered in bacteria and termed TAT, for "twin-arginine translocation," with respect to the presence of an Arg-Arg motif in the signal sequence of TAT-secreted products. However, it is unknown whether the TAT system contributes in any way to virulence through the secretion of factors associated with pathogenesis or stress response. We found that the opportunistic pathogen Pseudomonas aeruginosa produces several virulence factors that depend on the TAT system for proper export to the periplasm, outer membrane, or extracellular milieu. We identified at least 18 TAT substrates of P. aeruginosa and characterized the pleiotropic phenotypes of a tatC deletion mutant. The TAT system proved essential for the export of phospholipases, proteins involved in pyoverdine-mediated iron-uptake, anaerobic respiration, osmotic stress defense, motility, and biofilm formation. Because all these traits have been associated with virulence, we studied the role of TAT in a rat lung model. A tatC mutant did not cause the typical multifocal pulmonary abscesses and did not evoke a heavy inflammatory host response compared with wild type, indicating that tatC mutant cells are attenuated for virulence. Because the TAT apparatus is well conserved among important bacterial pathogens yet absent in mammalian cells, it represents a potential target for novel antimicrobial compounds.     

The modulation of Plasmodium falciparum virulence as a factor in the self-regulation of the malarial parasitic system

Higher Plasmodium falciparum virulence is one of the major factors that contributes to the development of severe malaria and leads to death. However, the nature of virulence and its time course are not so far fully understood. The authors have made a published data-based hypothesis that the virulence of P. falciparum strains circulating in the malaria endemic areas of tropical Africa is not strictly genetically determined. The virulence of P. falciparum increases with its passage through the non-immune organisms of the infected persons. This mechanism of virulence modulation ensures the survival of the parasite in the human population with a considerable communal immunity. To test the validity of the hypothesis, the authors have used a mathematical analytical method to assess the published data on malaria mortality in some areas of tropical Africa. The results of the analysis have shown close values of actual and expected data.     

Cronobacter sakazakii: stress survival and virulence potential in an opportunistic foodborne pathogen

A characteristic feature of the opportunistic foodborne pathogen Cronobacter sakazakii is its ability to survive in extremely arid environments, such as powdered infant formula, making it a dangerous opportunistic pathogen of individuals of all age groups, especially infants and neonates. Herein, we provide a brief overview of the pathogen; clinical manifestations, environmental reservoirs and our current understanding of stress response mechanisms and virulence factors which allow it to cause disease.     

Inorganic polyphosphate is essential for long-term survival and virulence factors in Shigella and Salmonella spp

The importance of inorganic polyphosphate (poly P) and poly P kinase (PPK), the enzyme principally responsible for its synthesis, has been established previously for stationary-phase survival of Escherichia coli and virulence in Pseudomonas aeruginosa. The gene (ppk) that encodes PPK is highly conserved among many bacterial pathogens, including Shigella and Salmonella spp. In view of the phylogenetic similarity of the enteropathogens and the frequency with which virulence factors are expressed in stationary phase, the ppk gene of pathogenic Shigella flexneri, Salmonella enterica serovar Dublin, and Salmonella enterica serovar typhimurium have been cloned and deleted. In some of these mutants lacking ppk, the phenotypes included features indicative of decreased virulence such as: (i) growth defects, (ii) defective responses to stress and starvation, (iii) loss of viability, (iv) polymyxin sensitivity, (v) intolerance to acid and heat, and (vi) diminished invasiveness in epithelial cells. Thus PPK may prove, as it has with P. aeruginosa, to be an attractive target for antibiotics, with low toxicity because PPK is not found in higher eukaryotes.     

肝螺杆菌致病机制的研究进展

肝螺杆菌是一种人兽共患病病原,可引发多系统疾病。其致病性与毒力因子有关,细胞致死性肿胀毒素会阻断细胞在G2/M期生长,引起细胞凋亡,同时还能激活NF-κB通路,释放细胞因子,引发炎症;鞭毛蛋白、粘附素、铁蛋白DPS、抗氧化酶、尿素酶等,利于肝螺杆菌定植、生长和发挥致病作用;毒力基因包含一个Ⅵ型分泌系统(T6SS),可将毒力相关基因编码的毒力蛋白释放到机体中,引起机体免疫反应。本文阐述了肝螺杆菌毒力因子对机体损伤的作用机制,旨在为深入了解肝螺杆菌致病机制提供参考。     

Cronobacter sakazakii: stress survival and virulence potential in an opportunistic foodborne pathogen

A characteristic feature of the opportunistic foodborne pathogen Cronobacter sakazakii is its ability to survive in extremely arid environments, such as powdered infant formula, making it a dangerous opportunistic pathogen of individuals of all age groups, especially infants and neonates. Herein, we provide a brief overview of the pathogen; clinical manifestations, environmental reservoirs and our current understanding of stress response mechanisms and virulence factors which allow it to cause disease.     

The alternative sigma factor katF (rpoS) regulates Salmonella virulence.

Nutrient limitation is a critical signal in Salmonella virulence gene regulation. The katF (rpoS) gene mediates the expression of the Salmonella spv plasmid virulence genes during bacterial starvation. A katF Salmonella mutant has increased susceptibility to nutrient deprivation, oxidative stress, acid stress, and DNA damage, conditions which are relevant to the intraphagosomal environment of host macrophages. Moreover, the katF mutant has significantly reduced virulence in mice. katF encodes an alternative sigma factor of RNA polymerase which coordinately regulates Salmonella virulence.     

Competence-programmed predation of noncompetent cells in the human pathogen Streptococcus pneumoniae: genetic requirements

Natural competence for genetic transformation is the best-characterized feature of the major human pathogen Streptococcus pneumoniae. Recent studies have shown the virulence of competence-deficient mutants to be attenuated, but the nature of the connection between competence and virulence remained unknown. Here we document the release, triggered by competent cells, of virulence factors (e.g., the cytolytic toxin pneumolysin) from noncompetent cells. This phenomenon, which we name allolysis, involves a previously undescribed bacteriocin system consisting of a two-peptide bacteriocin, CibAB, and its immunity factor, CibC; the major autolysin, LytA, and lysozyme, LytC; and a proposed new amidase, CbpD. We show that CibAB are absolutely required for allolysis, whereas LytA and LytC can be supplied either by the competent cells or by the targeted cells. We propose that allolysis constitutes a competence-programmed mechanism of predation of noncompetent cells, which benefits to the competent cells and contributes to virulence by coordinating the release of virulence factors.