CARBOHYDRATE-DEPENDENT INTERACTIONS BETWEEN C ELEGANS AND ITS PATHOGENS

秀丽隐杆线虫与其病原体之间依赖于碳水化合物的相互作用

• 批准号: 8170902
• 负责人: JONATHAN HODGKIN
• 金额: $ 4.45万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170902
• 关键词: Bacteria; Biochemistry; Caenorhabditis elegans; Carbohydrates; Computer Retrieval of Information on Scientific Projects Database; DNA Sequence; Enzymes; Exhibits; Family; Funding; Genetic; Glucuronic Acids; Glycoconjugates; Glycosphingolipids; Golgi Apparatus; Grant; Infection; Institution; Lesion; Manuscripts; Methods; Modeling; Nematoda; Pathway interactions; Phenotype; Polysaccharides; Predisposition; Printing; Publications; Research; Research Personnel; Resistance; Resistance to infection; Resources; Series; Source; Structure; United States National Institutes of Health; loss of function; mutant; novel; pathogen; research study; sugar nucleotide

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The C. elegans cuticle is infected by the nematode bacterial pathogen Microbacterium nematophilum. In screens for C. elegans mutants with altered susceptibility to infection, several bus (bacteria unswollen) mutants were isolated and exhibited increased resistance to infection. DNA sequencing experiments and homology searches suggest strongly that glycoconjugate biosynthetic enzymes may be disrupted in these mutants. The srf-3 mutants contain genetic lesions in a Golgi nucleotide sugar transporter and are also resistant to M. nematophilum infection, supporting the notion that the bus phenotype is due to a loss of function in one or more glycoconjugate pathways. We are carrying out analysis of the glycoconjugates of the several bus mutants. Since homology does not necessarily accurately predict function, we are investigating several glycoconjugate classes in tandem. We are performing mass spectrometric analysis of N- and O-glycans and glycosphingolipids of the mutants and are comparing the results for these to the corresponding glycans of the wild-type C. elegans N2 bristol strain using methods we have developed and adapted to the C. elegans model. We have observed that the mutants have a series of higher-mass O-glycans that contain glucuronic acid as an internal residue and represent a novel family of glycans. The structures of these nnovel compounds have been determined and the manuscript describing the results has been accepted for publication in the Jounal of Biological Chemistry (E Palaima et al., The caenorhabditis elegans bus-2 mutant reveals a new class of O-glycansaffecting bacterial resistance.J Biol Chem. 2010 Apr 12; [Epub ahead of print] ).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 秀丽隐杆线虫角质层是由线虫细菌病原体微分细菌感染的。 在秀丽隐杆线虫突变体易感性感染的筛查中，分离了几种总线（细菌无陈便的）突变体，并表现出对感染的耐药性的增加。 DNA测序实验和同源性搜索强烈表明，在这些突变体中可能会破坏糖缀合物生物合成酶。 SRF-3突变体在高尔基核苷酸糖转运蛋白中含有遗传病变，并且对黑胞芽孢杆菌感染具有抗性，这支持了这样一种观点，即BUS表型是由于一种或多个糖氯二酮轭途径中的功能丧失所致。 我们正在对几个总线突变体的糖缀合物进行分析。 由于同源性不一定能准确预测功能，因此我们正在研究串联的几个糖缀合物类。我们正在对突变体的N-和O-聚糖和糖磷脂进行质谱分析，并将其结果与野生型C. C. elegans n2 Bristol菌株的相应聚糖进行比较，并使用我们开发并适应了C. exlelans模型。我们已经观察到这些突变体具有一系列含有葡萄糖酸作为内部残基的高质量O-聚糖，代表了新型聚糖家族。 The structures of these nnovel compounds have been determined and the manuscript describing the results has been accepted for publication in the Jounal of Biological Chemistry (E Palaima et al., The caenorhabditis elegans bus-2 mutant reveals a new class of O-glycansaffecting bacterial resistance.J Biol Chem. 2010 Apr 12; [Epub ahead of print] ).