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Characterization of Moraxella catarrhalis lipooligosaccharide serotypes.

机译:卡他莫拉氏菌脂低聚糖血清型的表征。

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摘要

Moraxella catarrhalis, a gram-negative mucosal pathogen, is the third most common cause of bacterial infections associated with otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease (COPD). A major component of the outer membrane of these bacteria is the glycolipid, termed lipooligosaccharide (LOS). In M. catarrhalis , LOS consists of a lipid A molecule attached to a di-KDO molecule linked to a series of branched hexose sugar residues. M. catarrhalis can be divided into three serotypes based on the LOS structure that the strain expresses. A majority of clinical isolates express either serotype A or serotype B LOS, while very few isolates express serotype C. Little is known about the synthesis and addition of sugar residues of these complex molecules, in addition to the relevance these molecules have during infection. The LOS expressed by Haemophilus influenzae and Neisseria species has been shown to be important in infection and these biologically active glycolipids share some similar epitopes to M. catarrhalis LOS. To begin to ascertain if individual carbohydrate residues and substitutions of M. catarrhalis LOS are important in various steps of pathogenesis, the biosynthesis of the LOS molecule must be understood. This study identified the full set of LOS glycosyltransferases (lgt ) responsible for constructing the LOS molecule for each serotype. There were six genes identified that are required for the various LOS serotype structures, in addition to multiple alleles. Mutations in each gene encoding these glycosyltransferases resulted in a specifically truncated LOS structure. These truncated structures were used to analyze the human serum antibody response to various LOS epitopes developed in COPD patients that experience an exacerbation induced by a M. catarrhalis infection. New human antibodies were detected in a set of patients to both serotype specific structures and various internal and terminal oligosaccharide epitopes. To better understand the disproportion of LOS serotypes isolated in the clinical setting, a strain that is capable of expressing each serotype individually was constructed to begin to dissect why serotype A and B strains appear much better suited for colonization or infection in the human host. This study has allowed a better understanding of the assembly of the M. catarrhalis LOS molecule in order to learn the role of LOS in the human host.
机译:卡他莫拉氏菌是革兰氏阴性黏膜病原体,是儿童与中耳炎相关的细菌感染的第三大最常见原因,而慢性阻塞性肺疾病(COPD)患者病情加重。这些细菌的外膜的主要成分是糖脂,称为脂寡糖(LOS)。在粘膜炎莫拉氏菌中,LOS由连接至di-KDO分子的脂质A分子组成,该di-KDO分子与一系列分支的己糖残基相连。根据该菌株表达的LOS结构,可将粘膜炎莫拉氏菌分为三种血清型。大多数临床分离株表达A型或B型LOS,而很少分离株表达C型。除这些分子在感染过程中的相关性外,对这些复杂分子的糖残基的合成和添加知之甚少。流感嗜血杆菌和奈瑟氏球菌物种表达的LOS已显示在感染中很重要,这些具有生物活性的糖脂具有与卡他莫拉氏菌LOS相似的表位。为了开始确定卡他氏菌LOS的单个碳水化合物残基和取代在发病的各个步骤中是否重要,必须了解LOS分子的生物合成。这项研究确定了负责构建每种血清型的LOS分子的全套LOS糖基转移酶(lgt)。除了多个等位基因外,还鉴定出了六个LOS血清型结构所需的基因。编码这些糖基转移酶的每个基因中的突变均导致LOS结构发生特异性截短。这些截短的结构用于分析人COPD患者中发生的各种LOS表位的血清抗体应答,这些COPD患者经历了由卡他莫拉菌感染引起的病情加重。在一组患者中检测到针对血清型特异性结构以及各种内部和末端寡糖表位的新人类抗体。为了更好地理解在临床环境中分离出的LOS血清型的比例,构建了能够单独表达每种血清型的菌株,以开始剖析为什么血清型A和B菌株看起来更适合在人类宿主中定植或感染。这项研究可以更好地了解粘膜炎莫拉氏菌LOS分子的组装,从而了解LOS在人类宿主中的作用。

著录项

  • 作者

    Schwingel, Johanna M.;

  • 作者单位

    State University of New York at Buffalo.;

  • 授予单位 State University of New York at Buffalo.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 119 p.
  • 总页数 119
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 关键词

  • 入库时间 2022-08-17 11:38:28

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