结核分枝杆菌对宿主细胞凋亡效应的调控研究

由结核分枝杆菌（MTB）引起的结核病是严重危害人类健康的重大传染病,全世界约有1/3的人口潜伏感染MTB。近几年随着耐多药MTB和HIV混合感染的流行,使结核病控制形势更加严峻。细胞凋亡是生物有机体一种古老的免疫防御反应,在帮助机体清除胞内菌过程中发挥关键作用。已有研究结果表明,结核分枝杆菌对宿主细胞凋亡的调控过程非常复杂,即表现为有双重性：有些基因能促进凋亡,而有些则表现为抑制效应,且本研究组初步的研究结果表明细菌的毒力与凋亡有一定的内在联系,但是相关的分子机制还很不清楚。因此,鉴定MTB基因组中与凋亡相关的基因可以为研究细菌和宿主细胞之间的相互作用奠定基础,并且有助于研发新的药物靶标和候选疫苗。     

树突状细胞在抗结核分枝杆菌感染中的作用

树突状细胞（Dendritic cells,DCs）是最有效的抗原呈递细胞.DCs能够摄取外来物质,包括结核分枝杆菌（Mycobacterium tuberculosis,MTB）,并将其呈递给效应性淋巴细胞,激发宿主对抗病原微生物感染的免疫反应.因此,树突状细胞与结核分枝杆菌的相互作用在感染初期机体发动免疫应答中十分重要.研究树突状细胞和结核分枝杆菌间的相互作用,有利于从根本上了解细菌-宿主作用机理,为阐明结核分枝杆菌逃避免疫的机制提供依据.     

结核分枝杆菌的抗逆性与致病性研究进展

结核病是由结核分枝杆菌(Mycobacterium tuberculosis,MTB)复合群感染导致的人畜共患传染病,在新型冠状病毒感染暴发前是全球死亡人数最多的单一传染病。结核病致死率高,主要原因是其致病菌结核分枝杆菌具有极强的毒力且可以抵御多种外界环境胁迫因子。本文主要介绍结核分枝杆菌对理化胁迫的耐受性,以及结核分枝杆菌的耐药性、致病性与免疫性,为深入研究结核病的发病机制和研发新型的抗结核药物提供理论指导。     

结核分枝杆菌分泌蛋白调控巨噬细胞自噬诱导持续性感染

巨噬细胞的自噬作用能够保护宿主抵抗结核分枝杆菌的感染;而持续性感染的MTB(Mycobacterium tuberculosis)可以从自噬体中逃逸或抑制自噬的发生,从而在宿主体内长期存活。尽管相关机制不明确,但胞内存活的MTB分泌蛋白在持续性感染时发挥了重要作用。它可以通过抑制巨噬细胞自噬维持蛋白质稳定性和在胞内长期存活,导致LTBI(latent TB infection)的发生。综述了MTB的四种分泌蛋白(Eis、Pkn G、Sap M和Hsp16. 3)在持续性感染中调节巨噬细胞自噬的作用,可能为发现LTBI新的生物标志物和药物新靶点提供有效思路。     

MSMEG3150调控耻垢分枝杆菌细胞壁的结构与生物膜的形成

目的 探讨耻垢分枝杆菌中MSMEG＿3150蛋白的功能。方法 构建耻垢分枝杆菌MSMEG＿3150过表达株;采用CRISPRi技术构建耻垢分枝杆菌MSMEG＿3150沉默株。使用MSMEG＿3150过表达株、沉默株和野生型菌株进行实验研究。测定细菌生长曲线;刚果红实验检测细菌表面疏水性。透射电镜、扫描电镜等观察菌体形态、结构。LC-MS测定脂肪酸含量。结晶紫染色定量生物膜形成。结果 过表达MSMEG＿3150导致菌体变长、细胞壁增厚,生长速度加快,脂质含量增多,增强细菌表面的疏水性,促进生物膜形成。结论 MSMEG＿3150可能通过调控耻垢分枝杆菌细胞壁的脂质含量和表面疏水性从而影响细菌的生长特性及生物膜的形成。     

细菌细胞壁肽聚糖的研究

肽聚糖是真细菌细胞壁中特有的成分,因其在细菌细胞壁的生理功能中发挥着主要作用,而成为目前细菌细胞壁方面研究的主题.介绍了细菌细胞壁肽聚糖的化学组成、结构特点、分类、分离纯化、生物合成、生物学功能及应用前景等.     

徐州地区结核分枝杆菌耐多药、广泛耐药情况调查

目的:分析徐州地区结核分枝杆菌(MTB)临床分离株对一、二线抗结核药物耐药情况,了解本地耐多药结核(MDR-TB)、广泛耐药结核病(XDR-TB)所占比例。方法:对627例涂阳肺结核患者的痰标本采用改良罗氏培养法进行结核分枝杆菌培养,同时对培养出的MTB分别进行异烟肼(H)、利福平(R)、链霉素(S)、乙胺丁醇(E)、丁胺卡那霉素(Amk)、左氧氟沙星(Lfx)药物敏感性试验。结果:比例法检测627株MTB分离株中,单耐63例,多耐28例,耐多药125例,广泛耐药18例。结论:徐州地区耐药情况严重,尤其耐多药、广泛耐药结核病比例较高,为本地区结核病控制增加难度。     

猪胸膜放线杆菌中黏附素的研究进展

胸膜肺炎放线杆菌(Actinobacillus pleuropneumoniae,APP)是引起猪传染性胸膜肺炎疾病的病原菌,APP引起猪致病的毒力因子有多种,其中黏附素作为细菌粘附宿主的第一步中的关键作用被广泛关注.黏附是APP感染宿主的第一步,分泌到革兰氏阴性菌表面的自转运黏附索调节着细菌对宿主细胞的黏附,是重要的...     

猪链球菌2型毒力相关因子研究进展

猪链球菌2型是在世界范围内影响养猪业和人类健康的一种重要的人兽共患传染病。猪链球菌2型毒力因子在致病过程中发挥了重要的作用。但是对猪链球菌2型的致病机制和关键毒力因子仍然不确定,使有效的防治该病成为一个难题。本研究对猪链球菌2型已发现的毒力因子和新发现的毒力因子进行综述,为防治该病提供科学依据和参考。     

结核分枝杆菌酰基辅酶A脱氢酶的晶体学初步研究

结核病是人类健康的重要威胁.随着多药耐药和广泛耐药结核分枝杆菌菌株,以及结核分枝杆菌与人类免疫缺陷病毒共感染现象的出现,寻找新的更安全有效的药物靶标迫在眉睫.对来自结核分枝杆菌的潜在药物靶标进行蛋白三维结构的阐释是研究抗结核药物的有力手段之一.酰基辅酶A脱氢酶在结核分枝杆菌的脂肪酸合成酶系统中发挥着重要的作用,有可能成...     

Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice

Tuberculosis is the leading cause of death in the world resulting from a single bacterial infection. Despite its enormous burden on world health, little is known about the molecular mechanisms of pathogenesis of Mycobacterium tuberculosis. Bacterial multiplication and concomitant tissue damage within an infected host, including experimentally infected mice, occurs primarily in the lungs-the favoured niche of M. tuberculosis. Although it has been proposed that the distinctive cell wall of M. tuberculosis is important for virulence, rigorous genetic proof has been lacking. Here, using signature-tagged mutagenesis, we isolated three attenuated M. tuberculosis mutants that cannot synthesize or transport a complex, cell wall-associated lipid called phthiocerol dimycocerosate (PDIM) which is found only in pathogenic mycobacteria. Two mutants have transposon insertions affecting genes implicated in PDIM synthesis; the third has a disruption in a gene encoding a large transmembrane protein required for proper subcellular localization of PDIM. Synthesis and transport of this complex lipid is only required for growth in the lung; all three mutants are unaffected for growth in the liver and spleen. This clearly shows that a lipid is required for M. tuberculosis virulence.     

国槐成熟种子胚乳与子叶解剖结构及贮藏物质的比较

利用组织化学方法观察了国槐成熟种子胚乳和子叶的显同与亚显微结构，结果表明：成熟胚乳细胞多糖贮藏于细胞上，除糊粉层外，胚乳细胞几乎完全由半乳甘露聚糖所填充，原生质体被挤压收缩成很小的不规则形状，其中有贮藏蛋白体，无淀粉粒。面成熟子叶叶肉细胞脱水收缩，胞质中主要被蛋白体，脂体和少量淀粉所填充，大部分细胞器消失。     

Reconstitution of a phospholipid flippase from rat liver microsomes

The endoplasmic reticulum is the principal site of synthesis and initial incorporation of membrane lipids in eukaryotic cells; the enzymes of glycerolipid biosynthesis are exclusively located on its cytoplasmic surface. To maintain a phospholipid bilayer in this organelle, newly synthesized phospholipids must be translocated to the lumenal surface. Consistent with this are measurements indicating that movement of phospholipids across microsomal membranes is rapid, with a half-time less than 5 min (refs 3 and 4). Rapid movement of phospholipids has also been detected across the plasma membrane of Bacillus megaterium, another site of de novo lipid biosynthesis. The rapid transmembrane movement of phosphatidylcholine has not been detected, however, in vesicles prepared from microsomal lipids. These latter data suggest involvement in the endoplasmic reticulum of a phospholipid-translocating protein, as was first proposed by Bretscher who called it 'flippase'. Here we report reconstitution of a phospholipid flippase from rat liver microsomes into lipid vesicles.     

Role of cholesterol and lipid organization in disease

Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.     

Selenium-dependent glutathione peroxidasesA highlight of the role of phospholipid hydroperoxide glutathione peroxidase in protection against oxidative damage

Since the discovery that selenium is an integral component of the active site of the mammalian glutathione peroxidase, four members of the glutathione peroxidase family have been characterised: classical cellular glutathione peroxidase, gastrointestinal glutathione peroxidase; plasma glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase ( PHGPx) . They are products of different genes and have different specificities on hydrogen peroxide and lipid hydroperoxides, the latter are generated by free radicals and can damage cell membranes and disrupt cellular functions. Interestingly, PHGPx is not only active on phospholipid hydroperoxide, but also active on thymine hydroperoxide (a model compound for DNA damage) and protein hydroperoxides. This review highlights the role of PHGPx in protection against peroxidative damage of lipids, protein and DNA.     

风兜地钱基本组织细胞超微结构观察

用透射电镜观察风兜地钱垢基本组织，可以分辨出三种不同类型的细胞：（１）薄壁细胞。基本组织主要由这种细胞构成，在这种细胞之间主要靠胞间连丝联络；（２）蛋白质储藏细胞。单个地分布在近气室底部；（３）脂肪贮藏细胞，体积明显大于周围细胞，分布在原叶体近下表皮部位。     

Linearly concatenated cyclobutane lipids form a dense bacterial membrane

Lipid membranes are essential to the functioning of cells, enabling the existence of concentration gradients of ions and metabolites. Microbial membrane lipids can contain three-, five-, six- and even seven-membered aliphatic rings, but four-membered aliphatic cyclobutane rings have never been observed. Here we report the discovery of cyclobutane rings in the dominant membrane lipids of two anaerobic ammonium-oxidizing (anammox) bacteria. These lipids contain up to five linearly fused cyclobutane moieties with cis ring junctions. Such 'ladderane' molecules are unprecedented in nature but are known as promising building blocks in optoelectronics. The ladderane lipids occur in the membrane of the anammoxosome, the dedicated intracytoplasmic compartment where anammox catabolism takes place. They give rise to an exceptionally dense membrane, a tight barrier against diffusion. We propose that such a membrane is required to maintain concentration gradients during the exceptionally slow anammox metabolism and to protect the remainder of the cell from the toxic anammox intermediates. Our results further illustrate that microbial membrane lipid structures are far more diverse than previously recognized.     

基于生物信息学的结核杆菌候选药靶基因的分析筛选

结核分支杆菌(Mycobacterium tuberculosis,MTB)是结核病的致病菌,MTB基因组和蛋白质组的研究为筛选新的抗MTB药物提供了可能．鉴于前人所做的工作,目前比较一致的意见是：与MTB细胞壁的合成相关的酶类,尤其是与脂肪酸合成和降解相关的酶类,是筛选抗结核杆菌药物的理想靶标．选取与脂肪酸合成、分解、转运相关的187个基因,分析blast结果,剔除与人和其他生物(如大肠杆菌等)蛋白序列相似性大于60％的基因．利用相关生物软件挑选出至少有一个糖基位点且具有溶剂可及性的抗原基因9个．本研究为以后分析药靶基因编码蛋白质的三维结构、利用现有的生物技术和有关的化合物对候选药靶进行功能研究、在细胞水平加以验证打下基础．     

Phosphoinositides in cell regulation and membrane dynamics

Inositol phospholipids have long been known to have an important regulatory role in cell physiology. The repertoire of cellular processes known to be directly or indirectly controlled by this class of lipids has now dramatically expanded. Through interactions mediated by their headgroups, which can be reversibly phosphorylated to generate seven species, phosphoinositides play a fundamental part in controlling membrane-cytosol interfaces. These lipids mediate acute responses, but also act as constitutive signals that help define organelle identity. Their functions, besides classical signal transduction at the cell surface, include regulation of membrane traffic, the cytoskeleton, nuclear events and the permeability and transport functions of membranes.