A群链球菌疫苗研究：历史的要略和新的视角

化脓性链球菌通常是指Lancefield分类中的A群链球菌(GAS),它是一群革兰阳性致病菌,能引起人们包括咽炎、腥红热、化脓性筋膜炎和链球菌毒素中毒性休克综合症(streptococcal toxic shock syndrome,STSS)等在内的广泛的疾病。感染后遗症有急性风湿热(acute rheumatic fever,ARF),并发病症有风湿性心脏病(rheumatic heart disease,RHD),     

葡萄球菌和链球菌超抗原及其在人类疾病中的作用

本文介绍超抗原对于Ｔ细胞的作用方式,几种主要超抗原的来源和致病机制,以及葡萄球菌和链球菌超抗原与某些人类疾病如中毒性休克综合征（ＴＳＳ）、烫伤样皮肤综合征、皮肤粘膜淋巴结综合征、类风湿性关节炎、自身免疫性中枢神经系统紊乱、滴状牛皮癣等的关系。     

化脓性链球菌溶血素O活性结构重组蛋白的制备

生物信息分析化脓性链球菌溶血素O(streptolysin O,Slo)蛋白结构表明,Slo蛋白除含有由461氨基酸残基组成的溶血活性结构域Thiol_cytolysin外,在N端还有一跨膜结构域。利用pET101-GENE蛋白表达系统,成功构建出表达具有Slo活性重组蛋白的重组子,采用镍柱亲和层析分离技术,纯化目的蛋白;纯化蛋白SDS-PAGE检测分析表明,重组蛋白与预测的溶血活性结构域的分子量相一致;溶血实验显示,纯化重组蛋白具有溶血活性。以纯化的重组蛋白为免疫原,对大鼠进行4次免疫,所获得免疫血清经 Elisa检测,抗Slo血清效价达到 1 ∶12 800;Western blot检测猪链球菌、马链球菌和化脓性链球菌中的链球菌溶血素结果显示,抗Slo多克隆抗体仅能与化脓性链球菌溶血素O发生反应,表明研究制备的化脓性链球菌溶血素O活性结构重组蛋白抗原具有较好的特异性,所制备的抗原Slo 可用于进一步开发抗链球菌溶血素O(ASO)试剂盒。     

β-溶血型链球菌与银屑病发病、发生及发展的研究现状

银屑病的发病与链球菌感染的相关性近年来得到人们的密切关注.银屑病是一类由T细胞介导的自身免疫性疾病,链球菌抗原可在易感人群中诱发或加重银屑病并使银屑病慢性持续存在.从β-溶血型链球菌诱发银屑病相关的细胞壁、细胞膜、CpG DNA序列及其他相关蛋白的自身抗原及β-溶血型链球菌通过活化T细胞、抗原抗体反应途径、通过作用机体的基因改变遗传易感性诱发银屑病的可能作用途径几方面,阐述β-溶血型链球菌与银屑病发病、发生及发展的研究现状.     

ELISA检测奶牛乳房炎疫苗效果方法的建立

建立一种检测抗乳房炎疫苗抗体的酶联免疫吸附试验(ELISA)方法,用于免疫后具有保护性效果的抗体水平。通过对细胞抗原制备、最佳抗原包被浓度的确定、抗原包被和封闭最佳条件确定、酶标抗体的最佳工作浓度及作用时间等反应体系的筛选和确定,建立了检测抗乳房炎疫苗抗体的间接ELISA方法。结果表明,金黄色葡萄球菌(Staphylococcus aureus)、无乳链球菌(Streptococcus agalactiae)、停乳链球菌(Streptococcus dysgalactiae)抗原最佳包被质量浓度分别为5 mg.L-1、10 mg.L-1、10 mg.L-1;包被条件为4℃过夜;用2%人血白蛋白作为封闭剂最佳封闭条件是37℃封闭30 min;酶标抗体最佳作用时间为30 min。结论攻毒试验表明,疫苗免疫后,血清中抗体滴度达到或超过免疫前2倍时,奶牛即具有较好的乳腺保护效力。这一指标可作为疫苗效力检验的标准。     

肺炎链球菌相关毒力因子及其作用的研究进展

肺炎链球菌(Streptococcus pneumonia,S.pn)是导致黏膜疾病(如中耳炎、肺炎)和系统性疾病(包括败血症和脑膜炎)等严重疾病的主要病原体之一。肺炎链球菌毒力因子分为荚膜多糖、S.pn相关蛋白、细胞壁及细胞壁多糖三大类,其中荚膜多糖为最主要的毒力因子,也是疫苗中最有效的成分。毒力因子在S.pn入侵机体及引发疾病的过程中起着重要的作用。因此,毒力因子及作用的研究,不仅对预防和治疗肺炎链球菌的感染有着重要的意义,并为研发安全、有效的多糖疫苗提供一定的技术支持。现就肺炎链球菌毒力因子及其作用作一综述。     

A族β溶血性链球菌与猩红热的相关研究

A族β溶血性链球菌（beta—haemolyticgroup A Streptococcusisolate,GAS）又称为酿脓链球菌（Strepto—coccus pyogenes）,是一种常见的致病性化脓性革兰阳性球菌,猩红热是由GAS引起的儿童常见呼吸道传染病。近年来,随着严重侵袭性GAS感染在欧美一些国家再次增多,猩红热在一些国家中的发病率也在升高。简要介绍GAS的分型、超抗原及耐药与猩红热之间的关系。     

肺炎链球菌粘附和毒力因子A研究进展

肺炎链球菌（Streptococcus pneumoniae,SP）普遍定植于呼吸道,是人类重要的侵袭性病原菌之一,是社区获得性肺炎、中耳炎、脑膜炎、菌血症、鼻窦炎的主要病原菌。肺炎链球菌粘附和毒力因子A（pneumococcal adherence and virulence factor A,PavA）是肺炎链球菌早期感染和侵袭过程中关键的毒力因子。体外试验表明,缺失PavA的肺炎链球菌的突变株其粘附和侵入上皮细胞和内皮细胞的能力明显下降。作为一种保护性抗原,其诱导的细胞和体液免疫可以有效的抵抗肺炎链球菌的感染,是肺炎链球菌新一代疫苗的候选蛋白。但是,PavA在肺炎链球菌与人肺上皮细胞交互对话中作用机制的研究尚属空白,本文就肺炎链球菌粘附和毒力因子A得最新研究进展作一综述。     

肺炎链球菌表面黏附素A(PsaA)的研究进展

肺炎链球菌表面黏附素A(PsaA)是各型肺炎链球菌共有的种特异性表面结合脂蛋白,具有较好的免疫原性,在肺炎链球菌黏附呼吸道粘膜过程中起关键作用,PsaA的编码基因psaA在遗传上高度保守,PsaA是目前肺炎链球菌抗原研究的热点之一。本文就十年来PsaA的研究进展作一简要综述。     

14型肺炎链球菌荚膜多糖纯化工艺中两种去除蛋白方法的比较

目的苯酚抽提法和脱氧胆酸钠沉淀法去除14型肺炎链球菌荚膜多糖中蛋白质的效果比较。方法将3批次14型肺炎链球菌发酵培养液经超滤、乙醇沉淀等方法初步纯化后,平分成两份,分别采用苯酚抽提法和脱氧胆酸钠沉淀法去除蛋白,通过比较多糖收获量、多糖组分检定结果、多糖分子质量、多糖抗原活性、多糖核磁共振图谱,以此评价这两种蛋白去除方法的效果。结果与苯酚抽提法相比,脱氧胆酸钠沉淀法制备的14型肺炎链球菌纯化荚膜多糖除收获量较高,蛋白和核酸杂质含量较低外,氨基己糖含量、多糖分子质量、抗原活性和多糖核磁共振图谱的检定分析结果无显著性差异(P>0.1)。结论作为14型肺炎链球菌荚膜多糖纯化工艺中的除蛋白方法,脱氧胆酸钠沉淀法优于苯酚抽提法。     

Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner

Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC –II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.     

高毒力A组链球菌致病机制研究进展

A组链球菌(Group A Streptococcus,GAS)常导致咽炎和皮肤感染,也能引起严重侵袭性感染.根据其表面M蛋白编码基因emm可将GAS分为200多型,严重侵袭性感染多由高毒力株引起,以emm1、emm3、emm12、emm28和emm89型常见.研究发现高毒力GAS株中CovRS基因突变可导致细菌逃逸固...     

鲍曼不动杆菌VI型分泌系统功能蛋白的研究及应用新进展

细菌VI型分泌系统（type VI secretion system,T6SS）作为一个动态多蛋白复合体,各元件之间分工明确,转运各种效应蛋白作用于竞争细菌获得自我生长优势。鲍曼不动杆菌（Acinetobacter baumannii,Ab）通过T6SS介导细菌在微生物群落中的竞争能力,影响其耐药进化、宿主侵袭感染等过程。其中,缬氨酸-甘氨酸-精氨酸G蛋白三聚体（valine-glycine repeat protein G,VgrG）、脯氨酸-丙氨酸-丙氨酸-精氨酸重复序列蛋白（proline-alanine-alanine-arginine,PAAR）、溶血素共调节蛋白（hemolysin-coregulated protein,Hcp）和效应-免疫（effector-immunity,E-I）对发挥着关键作用。有关T6SS的研究总结虽然很多,但是鲜有文章系统概述其临床应用前景,因为这对T6SS功能蛋白的鉴定、特性、转运机制等基础研究的进展提出了挑战。本文通过综述鲍曼不动杆菌中T6SS的分布、主要功能蛋白的特性及转运机制的研究进展,结合T6SS的应用案例,提供其应用的可行性证据。以期进一步推动鲍曼不动杆菌VI型分泌系统基因和功能的研究,为开发新型抗感染疫苗、筛选合适的靶点抑制剂及生产工程化药物递送工具提供新的思路。     

肺炎链球菌荚膜多糖O-乙酰化修饰的研究进展

肺炎链球菌表面覆盖着一层荚膜,由多糖组成,是肺炎链球菌关键的毒力因子和重要的抗原,也是细菌分型的依据。强毒血清型的荚膜多糖被制成糖疫苗在抗感染方面发挥了巨大作用。荚膜多糖结构复杂,经常被O-乙酰化修饰,这些多变的化学修饰扮演着重要的生物学角色。本文对肺炎链球菌荚膜多糖O-乙酰化修饰的研究进展进行了介绍,包括荚膜多糖的遗传基础、合成途径和血清学特征,荚膜多糖的O-乙酰化修饰的化学结构及其相应的O-乙酰基转移酶,O-乙酰化修饰的化学鉴定和生物学功能。同时,我们也总结了多糖O-乙酰化修饰在肺炎链球菌微进化中的作用和对糖疫苗的影响,并对今后的研究进行了展望。本综述旨在为研究荚膜多糖的O-乙酰化修饰的致病机制奠定基础,也为糖疫苗的设计提供指导。     

Cytokine storm in COVID-19: from viral infection to immune responses,diagnosis and therapy

The COVID-19 outbreak is emerging as a significant public health challenge. Excessive production of proinflammatory cytokines, also known as cytokine storm, is a severe clinical syndrome known to develop as a complication of infectious or inflammatory diseases. Clinical evidence suggests that the occurrence of cytokine storm in severe acute respiratory syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely associated with the rapid deterioration and high mortality of severe cases. In this review, we aim to summarize the mechanism of SARS-CoV-2 infection and the subsequent immunological events related to excessive cytokine production and inflammatory responses associated with ACE2-AngII signaling. An overview of the diagnosis and an update on current therapeutic regimens and vaccinations is also provided.     

Vomocytosis: What we know so far

Vomocytosis, or nonlytic exocytosis, has been reported for Cryptococcus neoformans since 2006. Since then, the repertoire of vomocytosing pathogens and host cells has increased and so have the molecular components linked to vomocytosis occurrence. Nonetheless, the mechanism underlying this phenomenon, whether it is triggered by the host or the pathogen, and how it affects disease progression are still unresolved. This review contains a summary of the main findings regarding vomocytosis and the outstanding questions puzzling scientists to this day.     

Opposing roles of IL-10 in acute bacterial infection

Interleukin-10 (IL-10) is recognized as an anti-inflammatory cytokine that downmodulates inflammatory immune responses at multiple levels. In innate cells, production of this cytokine is usually triggered after pathogen recognition receptor (PRR) engagement by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patters (DAMPs), as well as by other soluble factors. Importantly, IL-10 is frequently secreted during acute bacterial infections and has been described to play a key role in infection resolution, although its effects can significantly vary depending on the infecting bacterium. While the production of IL-10 might favor host survival in some cases, it may also result harmful for the host in other circumstances, as it can prevent appropriate bacterial clearance. In this review we discuss the role of IL-10 in bacterial clearance and propose that this cytokine is required to recover from infection caused by extracellular or highly pro-inflammatory bacteria. Altogether, we propose that IL-10 drives excessive suppression of the immune response upon infection with intracellular bacteria or in non-inflammatory bacterial infections, which ultimately favors bacterial persistence and dissemination within the host. Thus, the nature of the bacterium causing infection is an important factor that needs to be taken into account when considering new immunotherapies that consist on the modulation of inflammation, such as IL-10. Indeed, induction of this cytokine may significantly improve the host’s immune response to certain bacteria when antibiotics are not completely effective.     

Agrobacterium Rhizogenes rolB and rolD Genes: Regulation and Involvement in Plant Development

Rol genes belong to the T-DNA which is transferred by Agrobacterium rhizogenes into plant cells. Each of these genes affects plant development and is regulated by the host. In this review, after a brief historical background, the most intriguing aspects of past and current research on rolB and rolD genes are highlighted and discussed.     

Energetic stress in the honeybee Apis mellifera from Nosema ceranae infection

Parasites are dependent on their hosts for energy to reproduce and can exert a significant nutritional stress on them. Energetic demand placed on the host is especially high in cases where the parasite-host complex is less co-evolved. The higher virulence of the newly discovered honeybee pathogen, Nosema ceranae, which causes a higher mortality in its new host Apis mellifera, might be based on a similar mechanism. Using Proboscis Extension Response and feeding experiments, we show that bees infected with N. ceranae have a higher hunger level that leads to a lower survival. Significantly, we also demonstrate that the survival of infected bees fed ad libitum is not different from that of uninfected bees. These results demonstrate that energetic stress is the probable cause of the shortened life span observed in infected bees. We argue that energetic stress can lead to the precocious and risky foraging observed in Nosema infected bees and discuss its relevance to colony collapse syndrome. The significance of energetic stress as a general mechanism by which infectious diseases influence host behavior and physiology is discussed.