细菌蛋白酶的致病作用

细菌通过分泌胞外蛋白酶来分解宿主蛋白质,并激活血管舒张素－派肽级联系统,为其生长,繁殖提供所需要的营养物质,同时,细菌蛋白酶能破坏补体和（或）免疫球蛋白,从而使细菌逃避宿主的防御机制,保证其级在宿主体内生存,由此可见,蛋白酶在细菌感染过程中起重要作用。因此,人工合成不影响宿主蛋白酶的活性,而能特异地抑制某些特定细菌蛋白酶的蛋白酶抑制剂,可能是一种有用的抗菌物质,用以治疗细菌感染。     

细菌周膜研究的最新进展

作者于１９９５年５月２８日至６月３日出席在俄罗斯第二大城市—圣彼得堡召开的第十次国际固氮会议。会议内容不仅囊括几乎所有生物固氮领域,也包括一些化学固氮研究。现就该会议论文籍中有关细菌周膜研究的是新资料介绍给同行,作为对我１９９５年在《生命科学》第１期上发表的有关《豆科类的体周膜功能》一文的进一步完善和补充。     

病原弧菌的致病机理

由弧菌属细菌 (Vibriospp.)引起的弧菌病 (Vibriosis)是在世界各地海水养殖鱼、虾、贝类等动物中普遍流行、危害最大的细菌性疾病。在已知的弧菌中,有 10多种是海洋养殖动物的病原菌。长期以来,人们对病原弧菌的致病性研究一直是利用分离菌株对养殖动物进行各种方式的人工感染,通过观察实验动物是否发病来判断病原弧菌的致病性,而对弧菌病的发生、发展等过程缺乏深入的了解。由于对病原弧菌致病机理的研究最终将会为弧菌病的防治提供可靠的科学依据,近十年来,对病原弧菌的致病机理研究已成为对弧菌病研究的重点和最活跃的研究领域,研究工作主要包括对常见的病原弧菌在养殖动物体内外环境中的生     

嗜吞噬细胞无形体致病机理的研究进展

嗜吞噬细胞无形体是一种侵染中性粒细胞专性细胞内寄生的革兰阴性菌,其所致疾病为人粒细胞无形体病（HGA）,是一种经蜱传播的人兽共患病。它感染中性粒细胞后可诱发机体产生炎症免疫反应,最终导致免疫抑制及潜在疾病引起的各种继发感染和器官衰竭,甚至危及生命。近年来该病原体日益受到人们的关注和重视。就嗜吞噬细胞无形体致病机理研究的进展进行了综述。     

铜绿假单胞菌致病力和致病机理研究进展

铜绿假单胞菌是在临床上引起多种感染的重要的致病菌 ,其致病机理复杂而多样。综述了国内外近年来研究铜绿假单胞菌的结构、胞外产物的致病机理。了解铜绿假单胞菌的致病机理对预防及治疗其引起的感染具有指导意义。     

结核分枝杆菌的致病机理

结核病仍是全球健康的主要威胁,其致病菌结核分枝杆菌的致闰机理与众不同。脂类代谢在致病中具有重要的作用。巨噬细胞被入侵的细菌修的机理也是研究细菌持续感染致病的重要突破点,研究细菌的致病机理可以为开发新的疫苗和治疗药物奠定坚实的基础。     

蛋白质组学在病毒致病机理研究中的应用

近年来,蛋白质组学技术成为医学研究的热点。蛋白质组学是高通量的分析正常及病理条件下机体、组织、细胞或亚细胞成分中的全部蛋白质。对不同空间、不同时间上动态变化的蛋白质组的整体进行比较,分析不同蛋白质组之间在表达数量、表达水平和修饰状态上的差异。蛋白质组学分析作为对生物代谢调控分析的技术手段,以病毒为研究的对象和工具,该技术的研究主要集中在新蛋白的发现、致病机理、疫苗的研制及耐药机制等方面。本文主要概述了蛋白质组学在一些动物传染病病毒致病方面研究和应用,分析了蛋白质组学技术对蛋白功能研究存在的问题和未来发展趋势,以便使研究者了解该技术使用的现状,提供理论参考。     

细菌分类学课程改革的探索与实践

从更新和充实教学内容、融应用实例和科研成果于教学、改进教学方法和教学手段等3个主要方面对细菌分类学课程进行改革,使古老的分类学增添了新的活力,提高了教学效果和质量。     

多胺与细菌病原的致病性

多胺是一类具有两个以上氨基的脂肪族化合物,它们在生物体内含量的动态平衡受合成、转运、降解及互换等过程的影响,多胺及其合成和转运系统与病原菌的致病性相关.本文综述了多胺在细菌毒力因子的转录和翻译、细菌生物膜的合成、细菌对抗生素的抗性、细菌对抗宿主的酸性胁迫和氧化胁迫、细菌对抗宿主的先天免疫防御机制、细菌致病性生物分子的合成等方面的重要作用.     

Interplay between Clathrin and Rab5 Controls the Early Phagocytic Trafficking and Intracellular Survival of Brucella abortus within HeLa cells

Lipid raft-associated clathrin is essential for host-pathogen interactions during infection. Brucella abortus is an intracellular pathogen that circumvents host defenses, but little is known about the precise infection mechanisms that involve interaction with lipid raft-associated mediators. The aim of this study was to elucidate the clathrin-mediated phagocytic mechanisms of B. abortus. The clathrin dependence of B. abortus infection in HeLa cells was investigated using an infection assay and immunofluorescence microscopy. The redistribution of clathrin in the membrane and in phagosomes was investigated using sucrose gradient fractionation of lipid rafts and the isolation of B. abortus-containing vacuoles, respectively. Clathrin and dynamin were concentrated into lipid rafts during B. abortus infection, and the entry and intracellular survival of B. abortus within HeLa cells were abrogated by clathrin inhibition. Clathrin disruption decreased actin polymerization and the colocalization of B. abortus-containing vacuoles with clathrin and Rab5 but not lysosome-associated membrane protein 1 (LAMP-1). Thus, our data demonstrate that clathrin plays a fundamental role in the entry and intracellular survival of B. abortus via interaction with lipid rafts and actin rearrangement. This process facilitates the early intracellular trafficking of B. abortus to safe replicative vacuoles.     

The Chlamydia effector chlamydial outer protein N (CopN) sequesters tubulin and prevents microtubule assembly

Chlamydia species are obligate intracellular pathogens that utilize a type three secretion system to manipulate host cell processes. Genetic manipulations are currently not possible in Chlamydia, necessitating study of effector proteins in heterologous expression systems and severely complicating efforts to relate molecular strategies used by Chlamydia to the biochemical activities of effector proteins. CopN is a chlamydial type three secretion effector that is essential for virulence. Heterologous expression of CopN in cells results in loss of microtubule spindles and metaphase plate formation and causes mitotic arrest. CopN is a multidomain protein with similarity to type three secretion system "plug" proteins from other organisms but has functionally diverged such that it also functions as an effector protein. We show that CopN binds directly to αβ-tubulin but not to microtubules (MTs). Furthermore, CopN inhibits tubulin polymerization by sequestering free αβ-tubulin, similar to one of the mechanisms utilized by stathmin. Although CopN and stathmin share no detectable sequence identity, both influence MT formation by sequestration of αβ-tubulin. CopN displaces stathmin from preformed stathmin-tubulin complexes, indicating that the proteins bind overlapping sites on tubulin. CopN is the first bacterial effector shown to disrupt MT formation directly. This recognition affords a mechanistic understanding of a strategy Chlamydia species use to manipulate the host cell cycle.     

Inhibition of colony-spreading activity of Staphylococcus aureus by secretion of δ-hemolysin

Staphylococcus aureus spreads on the surface of soft agar, a phenomenon we termed "colony spreading." Here, we found that S. aureus culture supernatant inhibited colony spreading. We purified δ-hemolysin (Hld, δ-toxin), a major protein secreted from S. aureus, as a compound that inhibits colony spreading. The culture supernatants of hld-disrupted mutants had 30-fold lower colony-spreading inhibitory activity than those of the parent strain. Furthermore, hld-disrupted mutants had higher colony-spreading ability than the parent strain. These results suggest that S. aureus negatively regulates colony spreading by secreting δ-hemolysin.     

The 1.8 Å cholix toxin crystal structure in complex with NAD+ and evidence for a new kinetic model

Certain Vibrio cholerae strains produce cholix, a potent protein toxin that has diphthamide-specific ADP-ribosyltransferase activity against eukaryotic elongation factor 2. Here we present a 1.8 Å crystal structure of cholix in complex with its natural substrate, nicotinamide adenine dinucleotide (NAD⁺). We also substituted hallmark catalytic residues by site-directed mutagenesis and analyzed both NAD⁺ binding and ADP-ribosyltransferase activity using a fluorescence-based assay. These data are the basis for a new kinetic model of cholix toxin activity. Further, the new structural data serve as a reference for continuing inhibitor development for this toxin class.     

Characterization of Streptokinases from Group A Streptococci Reveals a Strong Functional Relationship That Supports the Coinheritance of Plasminogen-binding M Protein and Cluster 2b Streptokinase

Group A streptococcus (GAS) strains secrete the protein streptokinase (SK), which functions by activating host human plasminogen (hPg) to plasmin (hPm), thus providing a proteolytic framework for invasive GAS strains. The types of SK secreted by GAS have been grouped into two clusters (SK1 and SK2) and one subcluster (SK2a and SK2b). SKs from cluster 1 (SK1) and cluster 2b (SK2b) display significant evolutionary and functional differences, and attempts to relate these properties to GAS skin or pharynx tropism and invasiveness are of great interest. In this study, using four purified SKs from each cluster, new relationships between plasminogen-binding group A streptococcal M (PAM) protein and SK2b have been revealed. All SK1 proteins efficiently activated hPg, whereas all subclass SK2b proteins only weakly activated hPg in the absence of PAM. Surface plasmon resonance studies revealed that the lower affinity of SK2b to hPg served as the basis for the attenuated activation of hPg by SK2b. Binding of hPg to either human fibrinogen (hFg) or PAM greatly enhanced activation of hPg by SK2b but minimally influenced the already effective activation of hPg by SK1. Activation of hPg in the presence of GAS cells containing PAM demonstrated that PAM is the only factor on the surface of SK2b-expressing cells that enabled the direct activation of hPg by SK2b. As the binding of hPg to PAM is necessary for hPg activation by SK2b, this dependence explains the coinherant relationship between PAM and SK2b and the ability of these particular strains to generate the proteolytic activity that disrupts the innate barriers that limit invasiveness.     

Domain Analyses Reveal That Chlamydia trachomatis CT694 Protein Belongs to the Membrane-localized Family of Type III Effector Proteins

The Chlamydia trachomatis type three-secreted effector protein CT694 is expressed during late-cycle development yet is secreted by infectious particles during the invasion process. We have previously described the presence of at least two functional domains within CT694. CT694 was found to interact with the human protein Ahnak through a C-terminal domain and affect formation of host-cell actin stress fibers. Immunolocalization analyses of ectopically expressed pEGFP-CT694 also revealed plasma membrane localization for CT694 that was independent of Ahnak binding. Here we provide evidence that CT694 contains multiple functional domains. Plasma membrane localization and CT694-induced alterations in host cell morphology are dependent on an N-terminal domain. We demonstrate that membrane association of CT694 is dependent on a domain resembling a membrane localization domain (MLD) found in anti-host proteins from Yersinia, Pseudomonas, and Salmonella spp. This domain is necessary and sufficient for localization and morphology changes but is not required for Ahnak binding. Further, the CT694 MLD is able to complement ExoS ΔMLD when ectopically expressed. Taken together, our data indicate that CT694 is a multidomain protein with the potential to modulate multiple host cell processes.